bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-reported outcome measures for primary hyperparathyroidism: a systematic review of measurement properties
Authors: Liang George , Kaur Manraj N. , Wade Carrie G. , Edelen Maria O. , Bates David W. , Pusic Andrea L. , Liu Jason B.
Published: April 2024

Background

The quality of patient-reported outcome measures (PROMs) used to assess the outcomes of primary hyperparathyroidism (PHPT), a common endocrine disorder that can negatively affect patients’ health-related quality of life due to chronic symptoms, has not been rigorously examined. This systematic review aimed to summarize and evaluate evidence on the measurement properties of PROMs used in adult patients with PHPT, and to provide recommendations for appropriate measure selection.

Methods

After PROSPERO registration (CRD42023438287), Medline, EMBASE, CINAHL Complete, Web of Science, PsycINFO, and Cochrane Trials were searched for full-text articles in English investigating PROM development, pilot studies, or evaluation of at least one PROM measurement property in adult patients with any clinical form of PHPT. Two reviewers independently identified studies for inclusion and conducted the review following the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) Methodology to assess risk of bias, evaluate the quality of measurement properties, and grade the certainty of evidence.

Results

From 4989 records, nine PROM development or validation studies were identified for three PROMs: the SF-36, PAS, and PHPQoL. Though the PAS demonstrated sufficient test-retest reliability and convergent validity, and the PHPQoL sufficient test-retest reliability, convergent validity, and responsiveness, the certainty of evidence was low-to-very low due to risk of bias. All three PROMs lacked sufficient evidence for content validity in patients with PHPT.

Conclusions

Based upon the available evidence, the SF-36, PAS, and PHPQoL cannot currently be recommended for use in research or clinical care, raising important questions about the conclusions of studies using these PROMs. Further validation studies or the development of more relevant PROMs with strong measurement properties for this patient population are needed.
The effectiveness of knowledge-sharing techniques and approaches in research funded by the National Institute for Health and Care Research (NIHR): a systematic review
Authors: Baxter Helen , Bearne Lindsay , Stone Tracey , Thomas Clare , Denholm Rachel , Redwood Sabi , Purdy Sarah , Huntley Alyson Louise
Published: April 2024

Background

The National Institute of Health and Care Research (NIHR), funds, enables and delivers world-leading health and social care research to improve people’s health and wellbeing. To achieve this aim, effective knowledge sharing (two-way knowledge sharing between researchers and stakeholders to create new knowledge and enable change in policy and practice) is needed. To date, it is not known which knowledge sharing techniques and approaches are used or how effective these are in creating new knowledge that can lead to changes in policy and practice in NIHR funded studies.

Methods

In this restricted systematic review, electronic databases [MEDLINE, The Health Management Information Consortium (including the Department of Health’s Library and Information Services and King’s Fund Information and Library Services)] were searched for published NIHR funded studies that described knowledge sharing between researchers and other stakeholders. One researcher performed title and abstract, full paper screening and quality assessment (Critical Appraisal Skills Programme qualitative checklist) with a 20% sample independently screened by a second reviewer. A narrative synthesis was adopted.

Results

In total 9897 records were identified. After screening, 17 studies were included. Five explicit forms of knowledge sharing studies were identified: embedded models, knowledge brokering, stakeholder engagement and involvement of non-researchers in the research or service design process and organisational collaborative partnerships between universities and healthcare organisations. Collectively, the techniques and approaches included five types of stakeholders and worked with them at all stages of the research cycle, except the stage of formation of the research design and preparation of funding application. Seven studies (using four of the approaches) gave examples of new knowledge creation, but only one study (using an embedded model approach) gave an example of a resulting change in practice. The use of a theory, model or framework to explain the knowledge sharing process was identified in six studies.

Conclusions

Five knowledge sharing techniques and approaches were reported in the included NIHR funded studies, and seven studies identified the creation of new knowledge. However, there was little investigation of the effectiveness of these approaches in influencing change in practice or policy.
Clinical significance of RNA methylation in hepatocellular carcinoma
Authors: Bao Qiongling , Zeng Yifan , Lou Qizhuo , Feng Xuewen , Jiang Shuwen , Lu Juan , Ruan Bing
Published: April 2024

Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.
Super enhancer lncRNAs: a novel hallmark in cancer
Authors: Song Ping , Han Rongyan , Yang Fan
Published: April 2024

Super enhancers (SEs) consist of clusters of enhancers, harboring an unusually high density of transcription factors, mediator coactivators and epigenetic modifications. SEs play a crucial role in the maintenance of cancer cell identity and promoting oncogenic transcription. Super enhancer lncRNAs (SE-lncRNAs) refer to either transcript from SEs locus or interact with SEs, whose transcriptional activity is highly dependent on SEs. Moreover, these SE-lncRNAs can interact with their associated enhancer regions in cis and modulate the expression of oncogenes or key signal pathways in cancers. Inhibition of SEs would be a promising therapy for cancer. In this review, we summarize the research of SE-lncRNAs in different kinds of cancers so far and decode the mechanism of SE-lncRNAs in carcinogenesis to provide novel ideas for the cancer therapy.
Primary left ventricular leiomyosarcoma: a case report
Authors: Balachandran Vipin , Young Vanessa , Baillie Tina , James Allen
Published: April 2024

Cardiac leiomyosarcomas are a rare subset of the already infrequent, primary malignant cardiac neoplasia spectrum. The most common site for a primary leiomyosarcoma of the ventricle is on the right with fewer than five globally reported cases in the left ventricle. Most present with non-specific symptoms but attention is usually sought after the appearance of compressive symptoms or arrhythmias. We present a case of a left ventricular leiomyosarcoma in a 50-year old female patient that had a delayed diagnosis and its subsequent surgical resection and oncological management with docetaxel and gemcitabine. This case highlights the need for a high index of suspicion for cardiac masses especially if there are competing chronic diseases with similar symptomatology. Given the rare presentation of left ventricular leiomyosarcomas, case reports may provide valuable information that is otherwise unavailable.
Transversotrema hafniensis n. sp. infection in Poecilia reticulata by cercariae released from Melanoides tuberculata in Denmark
Authors: Buchmann Kurt , Kania Per Walter
Published: April 2024

Background

Exotic and ornamental fish are highly popular companion animals resulting in a significant transcontinental trade of fish, invertebrates and aquatic plants. A major issue is the diseases associated with these organisms, as they have a major impact on health of the fish in both public and private household aquaria. A secondary issue is the trade with these products, which potentially may expand the distribution area and spread a range of diseases to new habitats.

Results

We here describe how Poecilia reticulata (guppy), produced in a private household aquarium, were invaded by cercariae of an exotic trematode released by imported Melanoides tuberculata snails. The fish presented with severe clinical signs (tremor, flashing, scraping of body against objects). A standard parasitological examination and morphometric identification showed scale pocket infections with a digenean trematode species within the genus Transversotrema. Molecular identification by PCR, sequencing and phylogenetic analyses of a 2646 bp sequence encoding ribosomal RNA (partial 18 S, ITS1, 5.8 S, ITS2, partial 28 S) was performed. The 1107 bp sequence of mitochondrial DNA (cox1) showed that the parasite differed from previously described Transversotrema species in M. tuberculata. Morphometrics of adult and larval specimens of this isolate also differed from previously described freshwater species within the genus. The new species was described and is named after Copenhagen, for its geographic origin.

Conclusions

The genus Transversotrema comprises a range of species, adapted to a microhabitat in scalepockets of teleosts. A combination of morphological and molecular characterization techniques has been shown to provide a good differentiation between species. The fish were not purchased from a pet shop but produced in the home aquarium. This indicated that an infection pressure existed in the aquarium, where the source of infection was found to be exotic intermediate host snails M. tuberculata, which originally were imported and purchased from a pet shop. The potential spread of fish diseases associated with trade of fish and snails to new geographic regions, where climate conditions are favourable, is discussed.
A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301)
Authors: Spiliopoulou Pavlina , Kazmi Farasat , Aroldi Francesca , Holmes Thomas , Thompson David , Griffiths Lucinda , Qi Cathy , Parkes Matthew , Lord Simon , Veal Gareth J. , Harrison David J. , Coyle Vicky M. , Graham Jill , Jeffry Evans Thomas R. , Blagden Sarah P.
Published: April 2024

Purpose

5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU.

Patients and methods

NUC-3373 was administered as monotherapy to patients with advanced solid tumors refractory to standard therapy via intravenous infusion either on Days 1, 8, 15 and 22 (Part 1) or on Days 1 and 15 (Part 2) of 28-day cycles until disease progression or unacceptable toxicity. Primary objectives were maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) and schedule of NUC-3373. Secondary objectives included pharmacokinetics (PK), and anti-tumor activity.

Results

Fifty-nine patients received weekly NUC-3373 in 9 cohorts in Part 1 (n = 43) and 3 alternate-weekly dosing cohorts in Part 2 (n = 16). They had received a median of 3 prior lines of treatment (range: 0–11) and 74% were exposed to prior fluoropyrimidines. Four experienced dose-limiting toxicities: two Grade (G) 3 transaminitis; one G2 headache; and one G3 transient hypotension. Commonest treatment-related G3 adverse event of raised transaminases occurred in < 10% of patients. NUC-3373 showed a favorable PK profile, with dose-proportionality and a prolonged half-life compared to 5-FU. A best overall response of stable disease was observed, with prolonged progression-free survival.

Conclusion

NUC-3373 was well-tolerated in a heavily pre-treated solid tumor patient population, including those who had relapsed on prior 5-FU. The MTD and RP2D was defined as 2500 mg/m2 NUC-3373 weekly. NUC-3373 is currently in combination treatment studies.

Trial registration

Clinicaltrials.gov registry number NCT02723240. Trial registered on 8th December 2015. https://clinicaltrials.gov/study/NCT02723240.
Comparison of a multiplex PCR with DNA barcoding for identification of container breeding mosquito species
Authors: Reichl Julia , Prossegger Christina , Petutschnig Sarah , Unterköfler Maria Sophia , Bakran-Lebl Karin , Markowicz Mateusz , Indra Alexander , Fuehrer Hans-Peter
Published: April 2024

Background

Identification of mosquitoes greatly relies on morphological specification. Since some species cannot be distinguished reliably by morphological methods, it is important to incorporate molecular techniques into the diagnostic pipeline. DNA barcoding using Sanger sequencing is currently widely used for identification of mosquito species. However, this method does not allow detection of multiple species in one sample, which would be important when analysing mosquito eggs. Detection of container breeding Aedes is typically performed by collecting eggs using ovitraps. These traps consist of a black container filled with water and a wooden spatula inserted for oviposition support. Aedes mosquitoes of different species might lay single or multiple eggs on the spatula. In contrast to Sanger sequencing of specific polymerase chain reaction (PCR) products, multiplex PCR protocols targeting specific species of interest can be of advantage for detection of multiple species in the same sample.

Methods

For this purpose, we adapted a previously published PCR protocol for simultaneous detection of four different Aedes species that are relevant for Austrian monitoring programmes, as they can be found in ovitraps: Aedes albopictus, Aedes japonicus, Aedes koreicus, and Aedes geniculatus. For evaluation of the multiplex PCR protocol, we analysed 2271 ovitrap mosquito samples from the years 2021 and 2022, which were collected within the scope of an Austrian nationwide monitoring programme. We compared the results of the multiplex PCR to the results of DNA barcoding.

Results

Of 2271 samples, the multiplex PCR could identify 1990 samples, while species determination using DNA barcoding of the mitochondrial cytochrome c oxidase subunit I gene was possible in 1722 samples. The multiplex PCR showed a mixture of different species in 47 samples, which could not be detected with DNA barcoding.

Conclusions

In conclusion, identification of Aedes species in ovitrap samples was more successful when using the multiplex PCR protocol as opposed to the DNA barcoding protocol. Additionally, the multiplex PCR allowed us to detect multiple species in the same sample, while those species might have been missed when using DNA barcoding with Sanger sequencing alone. Therefore, we propose that the multiplex PCR protocol is highly suitable and of great advantage when analysing mosquito eggs from ovitraps.

Graphical Abstract
Mosquitoes in urban green spaces and cemeteries in northern Spain
Authors: Goiri Fátima , González Mikel A. , Cevidanes Aitor , Barandika Jesús F. , García-Peréz Ana L.
Published: April 2024

Background

Mosquitoes inhabiting urban green spaces and cemeteries in Europe represent a crucial facet of public health concern and contribute to the ecological balance. As urbanization intensifies, these areas increasingly serve as vital habitats for various mosquito species, fostering breeding grounds and increasing the risk of disease transmission.

Methods

A study was conducted in the three main cities (inland, coastal, and estuarine) of the Basque Country, northern Spain, to investigate the species composition, abundance, dynamic populations, larval habitats, and host preferences of mosquitoes in urban green spaces and cemeteries. CDC traps and dipping were used to collect mosquitoes for 2 years (2019–2020).

Results

A total of 21 mosquito species were identified, with Culex pipiens s.l. being the most abundant and widespread. The three ecological forms of Cx. pipiens were found, and Cx. pipiens pipiens was the most common in both green areas and cemeteries. Morphological identification together with molecular tools identified 65 COI sequences with high homology. The highest species richness was found in the inland city, followed by the coastal city and the estuarine city. Mosquito abundance was significantly higher in green areas compared to cemeteries and in the coastal and estuarine cities compared to the inland city. The investigation of larval breeding sites highlighted the dominance of Cx. pipiens s.l., particularly in semi-artificial ponds, diverse water-holding containers (tyres and buckets) and drainage systems in green areas; in cemeteries, most of the larvae were found in flowerpots and funerary urns. Seasonal activity exhibited variable peaks in mosquito abundance in the different cities, with a notable increase in July or August. Additionally, blood meal analysis revealed that Cx. pipiens s.l. fed on several common urban avian species.

Conclusions

Studies on mosquitoes are essential to understand their role in disease transmission and to design targeted and sustainable management strategies to mitigate the associated risks.

Graphical Abstract
Esophageal bronchogenic cyst treated with submucosal tunneling endoscopic resection: two case reports
Authors: Sha Hui , Jiang Zong-Dan
Published: April 2024

Introduction

Although esophageal bronchogenic cysts are benign diseases, they may be accompanied by serious complications and have the possibility of recurrence. Therefore, once confirmed, it is necessary to treat the esophagobronchial cyst when the contraindication is excluded. Endoscopic treatment is usually used for lesions with small diameter and shallow origin, and has the advantages of small surgical trauma and risk, which can reduce the psychological burden of patients to a certain extent, help them to recover quickly, and lower hospital costs.

Case presentation

Case 1 is a 54-year-old Han Chinese man admitted to our hospital who complained of difficulty swallowing in the past 6 months. Case 2 is a 41-year-old Han Chinese man who was hospitalized in the past 3 months due to chest discomfort. Endoscopic ultrasound revealed a hypoechoic cystic lesion arising from the muscularis propria. Submucosal tunneling endoscopic resection was performed using a dual knife, and a cystic mass was observed between the mucosa and the muscular layers of the esophagus. On locating the cyst, an incision was made on the oral side of the lesion for evacuation. The cyst wall was excised using endoscopic argon plasma coagulation. We successfully removed the esophageal bronchogenic cyst lesion in the intrinsic muscle layer using submucosal tunneling endoscopic resection.

Conclusion

Esophageal bronchogenic cysts are rare in clinical practice and lack specificity in clinical manifestations. Multiple methods can be used to determine the location and nature of the lesion and ultimately determine the treatment plan. Surgical resection and endoscopic treatment are two different treatment methods, and appropriate treatment plans need to be selected on the basis of the origin layer, size, and relationship with the esophagus of the lesion to reduce complications and improve prognosis.
Assessing microbially mediated vivianite as a novel phosphorus and iron fertilizer
Authors: Eshun Lordina Ekua , García-López Ana Maria , Recena Ramiro , Coker Victoria , Shaw Samuel , Lloyd Jonathan , Delgado Antonio
Published: April 2024

Background

Microorganisms can transform phosphorus (P)-enriched iron (Fe)-oxide sludge into products with higher P concentration or can directly promote the precipitation of P-rich compounds from water. However, there is no evidence of these products’ efficiency as fertilizers. This study aimed to assess the effectiveness of microbially mediated vivianite (biovivianite) as P and Fe  fertilizer for durum wheat and white lupin, respectively.

Results

To this end, two completely randomized block experiments were conducted with wheat (phosphorus (P) experiment) and white lupin (iron (Fe) experiment). The P and Fe sources used included biovivianite produced by microbial reduction of P-containing ferrihydrite at pH 6.5 (VivInsol6.5) and pH 7.0 (VivInsol7.0), biovivianite produced with soluble Fe(III) citrate (C6H5FeO7) in the presence of soluble phosphate at pH 7 (VivSol), and vivianite from a commercial company (ComViv). Potassium dihydrogen phosphate (KH2PO4) was used as a reference fertilizer in the P experiment, and Fe-EDDHA and Fe(II)-sulfate (FeSO4.7H2O) were used in the Fe experiment. Total P uptake by wheat plants from the product dominated by vivianite and phosphate-green rust (VivSol) was not significantly different from KH2PO4. The relative P use efficiency, i.e., the equivalence in terms of P recovery of VivSol was 74% of KH2PO4, making VivSol the effective P source for durum wheat among the products tested (aside from KH2PO4). For Fe uptake, product dominated by vivianite and metavivianite (VivInsol7.0), was the most effective Fe source for white lupin followed by Fe-EDDHA, ComViv, and VivSol with VivInsol6.5 as the least effective but without significant differences with Fe(II)-sulfate. The average crystallite sizes of the biovivianite were 59 nm, 63 nm, and 66 nm for VivSol, VivInsol7.0, and VivInsol6.5, respectively.

Conclusions

The mineral constituents of the biovivianite coupled with their nano-crystallite sizes explained its effectiveness as P and Fe fertilizers. The results reveal that biovivianite production is a novel way of producing efficient P and Fe fertilizers from P-enriched Fe sludge or P-rich water. Thus, it can be used for producing fertilizers with high P and Fe concentrations from water purification, providing new tools for a circular economy approach in the use of a non-renewable resource such as P.

Graphical Abstract
Fungal and bacterial communities and their associations in snow-free and snow covered (sub-)alpine Pinus cembra forest soils
Authors: Probst Maraike , Telagathoti Anusha , Mandolini Edoardo , Peintner Ursula
Published: April 2024

Background

In Europe,Pinus cembraforests cover subalpine and alpine areas and they are of high conservational and ecological relevance. These forests experience strong seasonality with alternating snow-free and snow covered periods. AlthoughP. cembrais known for mycorrhization and mycorrhizae usually involve fungi, plants and bacteria, the community compositions of fungi and bacteria and their associations in (sub-)alpineP. cembraforests remain vastly understudied. Here, we studied the fungal and bacterial community compositions in three independent (sub-)alpineP. cembraforests and inferred their microbial associations using marker gene sequencing and network analysis. We asked about the effect of snow cover on microbial compositions and associations. In addition, we propose inferring microbial associations across a range of filtering criteria, based on which we infer well justified, concrete microbial associations with high potential for ecological relevance that are typical forP. cembraforests and depending on snow cover.

Results

The overall fungal and bacterial community structure was comparable with regards to both forest locations and snow cover. However, occurrence, abundance, and diversity patterns of several microbial taxa typical forP. cembraforests differed among snow-free and snow covered soils, e.g.Russula, TetracladiumandPhenoliphera.Moreover, network properties and microbial associations were influenced by snow cover. Here, we present concrete microbial associations on genus and species level that were repeatedly found across microbial networks, thereby confirming their ecological relevance. Most importantly, ectomycorrhizal fungi, such asBasidioascus, PseudotomentellaandRhizopogon,as well as saprobicMortierellachanged their bacterial association partners depending on snow cover.

Conclusion

This is the first study researching fungal-bacterial associations across several (sub-)alpineP. cembraforests. The poorly investigated influence of snow cover on soil fungi and bacteria, especially those mycorrhizingP. cembraroots, but also saprobic soil organisms, underlines the relevance of forest seasonality. Our findings highlight that the seasonal impact of snow cover has significant consequences for the ecology of the ecosystem, particularly in relation to mycorrhization and nutrient cycling. It is imperative to consider such effects for a comprehensive understanding of the functioning resilience and responsiveness of an ecosystem.
A combination of suprachoroidal injection of triamcinolone using a custom-made needle and intravitreal Ziv-aflibercept every eight weeks to manage naïve/denovo central DME: a single-center retrospective case series
Authors: Marashi Ameen , Baba Marwa , Abu Ghedda Sedra , Kitaz Mohammad Nour , Zazo Aya
Published: April 2024

Background

Previous studies have shown promising effects of combining intravitreal bevacizumab and suprachoroidal injection of triamcinolone acetonide in treating DME. However, further research is needed.

Objective

To assess the efficacy and safety of combining both intravitreal Ziv-aflibercept and suprachoroidal injection of triamcinolone acetonide using a custom-made needle in naïve and de novo central diabetic macular edema (DME) patients every eight weeks for 24 weeks.

Methods

Central macular thickness was measured via spectral domain-optical coherence tomography, and best-corrected visual acuity was measured via a Snellen chart at baseline and at 4, 8, 12, 16, and 24 weeks postinjection. Additionally, cataract progression, intraocular pressure (IOP), and ocular safety were analyzed.

Results

A total of 10 eyes of 6 patients were treated with suprachoroidal injections of triamcinolone acteonid combined with an intravitreal injection of Ziv-aflibercept. Vision improved from 0.69 log minimum angle of resolution (MAR) at baseline to 0.39 log MAR after treatment. Central macular thickness significantly decreased from 462.3 ± 166 μm at baseline to 362.7 ± 77.6 μm at 24 weeks postinjection.

Conclusion

Suprachoroidal injection of triamcinolone using a custom-made needle with the intravitreal agent Ziv-aflibercept to treat de novo/naïve central DME has favorable outcomes and adequate safety results. Moreover, this study demonstrated the benefit of adapting the previous treatment combination for extending the interval between anti-VEGF treatments from 4 to 8 weeks, which could prevent further expenses, especially in low-income countries.However, large multicenter randomized clinical trials with longer follow-up periods are needed to assess this treatment route, especially in low-income and resourced countries.
Improved automated one-pot two-step radiosynthesis of (S)-[18F]FETrp, a radiotracer for PET imaging of indoleamine 2,3-dioxygenase 1 (IDO1)
Authors: Maisonial-Besset Aurélie , Kryza David , Kopka Klaus , Levesque Sophie , Moreau Emmanuel , Wenzel Barbara , Chezal Jean-Michel
Published: April 2024

Background

(S)-[18F]FETrp is a promising PET radiotracer for imaging IDO1 activity, one of the main enzymes involved in the tryptophan metabolism that plays a key role in several diseases including cancers. To date, the radiosynthesis of this tryptophan analogue remains highly challenging due to partial racemization occurring during the nucleophilic radiofluorination step. This work aims to develop a short, epimerization-free and efficient automated procedure of (S)-[18F]FETrp from a corresponding enantiopure tosylate precursor.

Results

Enantiomerically pure (S)- and (R)-FETrp references as well as tosylate precursors (S)- and (R)-3 were obtained from corresponding Na-Boc-(L and D)-tryptophan in 2 and 4 steps, respectively. Manual optimisation of the radiolabelling conditions resulted in > 90% radiochemical conversion with more than 99% enantiomeric purity. Based on these results, the (S)-[18F]FETrp radiosynthesis was fully automated on a SynChrom R&D EVOI module to produce the radiotracer in 55.2 ± 7.5% radiochemical yield, 99.9% radiochemical purity, 99.1 ± 0.5% enantiomeric excess, and molar activity of 53.2 ± 9.3 GBq/µmol (n = 3).

Conclusions

To avoid racemisation and complicated purification processes, currently encountered for the radiosynthesis of (S)-[18F]FETrp, we report herein significant improvements, including a versatile synthesis of enantiomerically pure tosylate precursor and reference compound and a convenient one-pot two-step automated procedure for the radiosynthesis of (S)-[18F]FETrp. This optimised and robust production method could facilitate further investigations of this relevant PET radiotracer for imaging IDO1 activity.
Diffusion tensor imaging in anisotropic tissues: application of reduced gradient vector schemes in peripheral nerves
Authors: Foesleitner Olivia , Sulaj Alba , Sturm Volker , Kronlage Moritz , Preisner Fabian , Kender Zoltan , Bendszus Martin , Szendroedi Julia , Heiland Sabine , Schwarz Daniel
Published: April 2024

Background

In contrast to the brain, fibers within peripheral nerves have distinct monodirectional structure questioning the necessity of complex multidirectional gradient vector schemes for DTI. This proof-of-concept study investigated the diagnostic utility of reduced gradient vector schemes in peripheral nerve DTI.

Methods

Three-Tesla magnetic resonance neurography of the tibial nerve using 20-vector DTI (DTI20) was performed in 10 healthy volunteers, 12 patients with type 2 diabetes, and 12 age-matched healthy controls. From the full DTI20 dataset, three reduced datasets including only two or three vectors along the x- and/or y- and z-axes were built to calculate major parameters. The influence of nerve angulation and intraneural connective tissue was assessed. The area under the receiver operating characteristics curve (ROC-AUC) was used for analysis.

Results

Simplified datasets achieved excellent diagnostic accuracy equal to DTI20 (ROC-AUC 0.847–0.868, p ≤ 0.005), but compared to DTI20, the reduced models yielded mostly lower absolute values of DTI scalars: median fractional anisotropy (FA) ≤ 0.12; apparent diffusion coefficient (ADC) ≤ 0.25; axial diffusivity ≤ 0.96, radial diffusivity ≤ 0.07). The precision of FA and ADC with the three-vector model was closest to DTI20. Intraneural connective tissue was negatively correlated with FA and ADC (r ≥ -0.49, p < 0.001). Small deviations of nerve angulation had little effect on FA accuracy.

Conclusions

In peripheral nerves, bulk tissue DTI metrics can be approximated with only three predefined gradient vectors along the scanner’s main axes, yielding similar diagnostic accuracy as a 20-vector DTI, resulting in substantial scan time reduction.

Relevance statement

DTI bulk tissue parameters of peripheral nerves can be calculated with only three predefined gradient vectors at similar diagnostic performance as a standard DTI but providing a substantial scan time reduction.

Key points

• In peripheral nerves, DTI parameters can be approximated using only three gradient vectors.

• The simplified model achieves a similar diagnostic performance as a standard DTI.

• The simplified model allows for a significant acceleration of image acquisition.

• This can help to introduce multi-b-value DTI techniques into clinical practice.

Graphical Abstract
Surgical management of spontaneous posterior fossa hematoma: predictors of the neurological outcome
Authors: Saad Mahmoud , Ali Hanee , Mowafy Ali A. , Badran Mohamed , Taha Ahmed Naguib , Amen Mohamed Mohsen
Published: April 2024

Objective

To detect demographic, clinical, and radiological predictors of patient outcomes and prognosis in spontaneous cerebellar hematoma patients that may guide accurate decision making.

Methods

This retrospective study was conducted on 45 patients with spontaneous cerebellar hematoma who underwent surgical treatment. The patient data including demographics (age, gender), preoperative consciousness at the time of admission, medical comorbidities (HTN, DM), radiological findings (location, volume, and diameter of the cerebellar hematoma, hydrocephalus, compression of the fourth ventricle, effacement of the quadrigeminal cistern, intraventricular hematoma, tight posterior fossa, and brain stem compression), and treatment methods were collected and correlated with prognosis. Outcome assessment was done using the Glasgow Outcome Scale (GOS), classified into good outcome (favorable result; GOS > 4) and poor outcome (unfavorable result; GOS < 4).

Results

There was a statistically significant correlation (p = 0.030) between the time to surgery and GOS, with more favorable outcomes in patients who underwent early surgery compared to late surgery. Unfavorable outcomes were detected in patients with higher Taneda grade and Kirollos grade, and both were statistically significant (p = 0.001). The presence of hydrocephalus and/or brainstem compression had a statistically significant (p < 0.001) negative impact on outcomes. Patients with extensive IVH had an unfavorable outcome compared to other patients (p = 0.016). The mortality rate in our study was 28.9%.

Conclusions

Surgical management of spontaneous cerebellar hematoma is challenging. Many factors influence the appropriate decision making and surgical outcome. Predictors of an unfavorable outcome include the level of consciousness at admission, delayed time to surgery, a higher grade of 4th ventricular effacement (Kirollos) and quadrigeminal cistern effacement (Taneda), extensive IVH, hydrocephalus, and brainstem compression (statistically significant). There was no statistical significance regarding gender, age, hematoma volume, or hematoma diameter in relation to an unfavorable outcome.
3T multiparametric MRI’s accuracy in detecting prostate cancer using Prostate Imaging Reporting and Data System (PIRADS) version 2.1 with prostate biopsy as a reference
Authors: Dhulaimi Mohammad Abdullah , Aldarmasi Moroj Ahmad , Almasri Areen Ghazi , Mosharraf Syed Mohammad
Published: April 2024

Background

Multiparametric magnetic resonance imaging (MRI) is valuable in detecting prostate cancer due to its high sensitivity to malignant lesions. It is commonly utilized to improve the identification of clinically significant cancers within the prostate. This study aimed to correlate the findings from 3T multiparametric MRI of the prostate using the updated Prostate Imaging Reporting and Data System version 2.1 (PIRADSv2.1) from 2019 with reference to prostate biopsy results. Additionally, PIRADSv2.1 was used to calculate the sensitivity, specificity, positive predictive value, and negative predictive value of the 3T multiparametric MRI of the prostate.

Methods and materials

A retrospective study was conducted at a tertiary center, wherein we identified patients who underwent a prostate biopsy between June 2019 and June 2021 and had a corresponding MRI of the prostate performed at the same institution, evaluated with PIRADSv2.1 criteria.

Results

A total of 50 patients were eligible for final analysis. The prevalence of prostate cancer was 69% (95% confidence interval (CI) 54–81%). Receiver operating characteristic (ROC) curves were generated for 3T multiparametric MRI of the prostate using PIRADSv2.1 to diagnose prostate cancer; the area under the ROC curve was 0.81 (95% CI 0.68–0.95, p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of the 3T multiparametric prostate MRI using PIRADSv2.1 were 74.0%, 87.0%, 92.9%, and 59.1%, respectively.

Conclusions

PIRADSv2.1 exhibited good overall performance in the diagnosis of prostate cancer.
Modeling life expectancy and cost effectiveness for UHPC bridge retrofitting techniques
Authors: Hossain Abid , Chang Carlos M.
Published: April 2024

Bridge components are subject to both structural loads and environmental stressors, rendering them susceptible to accelerated deterioration and potential collapse in the absence of effective maintenance and rehabilitation strategies. Moreover, the phenomenon of wet-dry cycling, coupled with elevated chloride concentrations prevalent in coastal regions, further expedites the degradation process of bridges, thereby escalating maintenance frequency and repair costs. In response to this challenge, the integration of innovative materials such as Ultra High-Performance Concrete (UHPC) is being explored for the development and implementation of maintenance and rehabilitation strategies. This study presents a comparative analysis between conventional methods and UHPC applications for bridge repairs, utilizing Life Cycle Cost Analysis (LCCA) to encompass both agency and user costs, and applies Monte Carlo simulation to account for the variability of the modeling factors. A practical case study illustrates the applicability of the LCCA methodology, revealing that the utilization of UHPC contributes to a reduction in the total life cycle cost for bridge maintenance and rehabilitation. Life expectancy, Average Daily Traffic (ADT), and the duration of construction activities during rehabilitation emerge as the most influential factors affecting life cycle costs. The main contributions of the study are the development of the life-expectancy model and step-by-step Life-Cycle Cost Analysis (LCCA) methodology. Findings from this study aim to identify cost-effective retrofitting techniques for maintaining bridges in a “State of Good Repair.”
Adjuvant Chemotherapy in Premenopausal Patients With Hormone-Positive Breast Cancer With a Recurrence Score of 16-25: A Retrospective Analysis Using the National Cancer Database
Authors: Ashok Kumar Prashanth , Wang Dongliang , Huang Danning , Sivapiragasam Abirami
Published: April 2024

PURPOSE

Results from the TAILORx trial revealed that the use of adjuvant chemotherapy along with endocrine therapy had no survival advantage in patients with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2–negative (HER2–), node-negative (N0) breast cancer (BC) with an intermediate (11-25) 21-gene recurrence score (RS) in the overall population. However, in patients under age 50 years, adjuvant chemotherapy demonstrated a progression-free survival benefit when the RS ranged from 16-25. We studied this cohort with the population-based national database.

METHODS

The 2010-2018 National Cancer Database was used to include patients with BC age 18-50 years, N0, M0, RS 16-25, ER+/progesterone receptor±, and HER2–. Patients were divided into two groups on the basis of adjuvant chemotherapy use, and the survival between them was compared.

RESULTS

Adjuvant chemotherapy use was noted in 4,808/15,792 (30.45%) patients. Median RS was 18 and 21 in patients without and with adjuvant chemotherapy, respectively. Factors associated with adjuvant chemotherapy use were higher T stage, poor and moderately differentiated tumors, age <40 years, care at an academic center, Caucasian race, patients undergoing mastectomy, regional lymph node surgery, and radiation therapy. Kaplan-Meier survival at 10 years was better with adjuvant chemotherapy (96.2% v 91.6%). Patients without adjuvant chemotherapy had more adverse outcomes (hazard ratio [HR], 1.683 [95% CI, 1.392 to 2.036]; P < .0001). Subgroup analysis showed that the benefit was significant in patients with RS scores 21-25 (HR, 1.953 [95% CI, 1.295 to 2.945]), ductal histology (HR, 1.521 [95% CI, 1.092 to 2.118]), Caucasian race (HR, 1.655 [95% CI, 1.180 to 2.322]), and 41-50 years age group (HR, 1.732 [95% CI, 1.244 to 2.411]).

CONCLUSION

Our study showed an overall survival benefit for adjuvant chemotherapy use in patients with ER-positive, N0 premenopausal BC patients, age less than 50 years, with an intermediate RS score, particularly 21-25.
Topological defects and boundary states in four-dimensional topological insulator
Authors: Chang Zhi-Wen , Hao Wei-Chang , Liu Xin
Published: April 2024

We show the connection between the second Chern number and topological defects, in a (4+1)-dimensional time-reversal invariant Dirac lattice model. It is discovered that two types of topological defects, the five-dimensional (5D) and four-dimensional (4D) point defects arise from the singular points of wave functions together with the geometric meaning of the second Chern number. We demonstrated that the 5D point defects appear at the band crossing positions with a topological transition, leading to a jump of the second Chern number. The 4D point defects exist in an insulating bulk, whose topological charges can give the evaluations of the second Chern number of energy bands. Finally, we discussed the possible structures of the boundary states in the light of the realization way of the 4D model. Our theory provides not only a new perspective to grasp the second Chern number, but also a simple approach to derive its values without calculating any integrals.
The influence patterns of carbon flux in different climatic zones in China —Based on the complex network approach
Authors: Qing Ting , Wang Fan , Du Ruijin , Dong Gaogao , Tian Lixin
Published: April 2024

Research on ecosystem carbon flux can provide important methodological and strategic support for climate change mitigation. The existing studies focus on the calculation of carbon flux, ignoring the intertwined effects between regions. The quantification and analysis of the interaction patterns of carbon flux is crucial for understanding the global carbon cycle process, forecasting and coping with climate change. In this study, carbon flux network model sequences are established based on complex network theory using carbon flux data spanning from December 1, 2005, to November 30, 2020. The time delay effect is introduced to accurately quantify the influence patterns of carbon flux within climate zones across China. The findings indicate that the probability distribution function of the link weights during the various seasons of each year exhibits a bimodal distribution with distinct positive and negative components. The delay probability distribution function reveals the significant impact of delay effects, which are especially pronounced and mostly significant long-term lag effects in nodes with negative weights. Further, the results of the interactions of carbon flux among climate zones demonstrate that changes in carbon flux in the plateau and southern temperate regions have either positive or negative impacts on other climate zones. Therefore, controlling carbon flux changes in these climatic zones can effectively optimize the distribution of carbon flux. The modeling framework and results presented in this paper provide useful insights for the regulation and distribution optimization of carbon flux in China.
Dietary restriction and life-history trade-offs: insights into mTOR pathway regulation and reproductive investment in Japanese quail
Authors: Reda Gebrehaweria K. , Ndunguru Sawadi F. , Csernus Brigitta , Gulyás Gabriella , Knop Renáta , Szabó Csaba , Czeglédi Levente , Lendvai Ádám Z.
Published: April 2024

Resources are needed for growth, reproduction and survival, and organisms must trade off limited resources among competing processes. Nutritional availability in organisms is sensed and monitored by nutrient-sensing pathways that can trigger physiological changes or alter gene expression. Previous studies have proposed that one such signalling pathway, the mechanistic target of rapamycin (mTOR), underpins a form of adaptive plasticity when individuals encounter constraints in their energy budget. Despite the fundamental importance of this process in evolutionary biology, how nutritional limitation is regulated through the expression of genes governing this pathway and its consequential effects on fitness remain understudied, particularly in birds. We used dietary restriction to simulate resource depletion and examined its effects on body mass, reproduction and gene expression in Japanese quails (Coturnix japonica). Quails were subjected to feeding at 20%, 30% and 40% restriction levels or ad libitum for 2 weeks. All restricted groups exhibited reduced body mass, whereas reductions in the number and mass of eggs were observed only under more severe restrictions. Additionally, dietary restriction led to decreased expression of mTOR and insulin-like growth factor 1 (IGF1), whereas the ribosomal protein S6 kinase 1 (RPS6K1) and autophagy-related genes (ATG9A and ATG5) were upregulated. The pattern in which mTOR responded to restriction was similar to that for body mass. Regardless of the treatment, proportionally higher reproductive investment was associated with individual variation in mTOR expression. These findings reveal the connection between dietary intake and the expression of mTOR and related genes in this pathway.
Robo-Therm, a pipeline to RNA Thermometer discovery and validation
Authors: Sharts Davis M , Almanza Maria T. , Banks Andrea Victoria , Castellanos Alyssa M , O. Hernandez Catherine G , Lopez Monica L , Rodriguez Daniela , Tong Alina Y , Segeberg Maximilian R , M. Passalacqua Luiz F. , Abdelsayed Michael M
Published: April 2024

RNA thermometers are highly structured noncoding RNAs located in the 5′ untranslated regions (UTR) of genes that regulate expression by undergoing conformational changes in response to temperature. The discovery of RNA thermometers through bioinformatics is difficult because there is little sequence conservation among their structural elements. Thus, the abundance of these thermo-sensitive regulatory structures remains unclear. Herein, to advance the discovery and validation of RNA thermometers, we developed Robo-Therm, a pipeline that combines an adaptive and user-friendly in silico motif search with a well-established reporter system. Through our application of Robo-Therm, we discovered two novel RNA thermometers in bacterial and bacteriophage genomes found in the human gut. One of these thermometers is present in 5′-UTR of a gene that codes for σ70 RNA polymerase subunit in the bacteria Mediterraneibacter gnavus and Bacteroides pectinophilus, and in the bacteriophage Caudoviricetes, which infects Bacteroides pectinophilus. The other thermometer is in the 5′-UTR of a tetracycline resistance gene (tetR) in the intestinal bacteria Escherichia coli and Shigella flexneri. Our Robo-Therm pipeline can be applied to discover multiple RNA thermometers across various genomes.