bluuebunny/crossref_metadata_2025_split huggingface dataset:
Other‐cause mortality in incidental prostate cancer
Authors: Di Bello Francesco , Baudo Andrea , de Angelis Mario , Jannello Letizia Maria Ippolita , Siech Carolin , Tian Zhe , Goyal Jordan A. , Collà Ruvolo Claudia , Califano Gianluigi , La Rocca Roberto , Morra Simone , Acquati Pietro , Saad Fred , Shariat Shahrokh F. , Carmignani Luca , de Cobelli Ottavio , Briganti Alberto , Chun Felix K. H. , Longo Nicola , Karakiewicz Pierre I. 
Published: March 2024

AbstractBackgroundIn incidental prostate cancer (IPCa), elevated other‐cause mortality (OCM) may obviate the need for active treatment. We tested OCM rates in IPCa according to treatment type and cancer grade and we hypothesized that OCM is significantly higher in not‐actively‐treated patients.MethodsWithin the Surveillance, Epidemiology, and End Results database (2004−2015), IPCa patients were identified. Smoothed cumulative incidence plots as well as multivariable competing risks regression models were fitted to address OCM after adjustment for cancer‐specific mortality (CSM).ResultsOf 5121 IPCa patients, 3655 (71%) were not‐actively‐treated while 1466 (29%) were actively‐treated. Incidental PCa not‐actively‐treated patients were older and exhibited higher proportion of Gleason sum (GS) 6 and clinical T1a stage. In smoothed cumulative incidence plots, 5‐year OCM was 20% for not‐actively‐treated versus 8% for actively‐treated patients. Conversely, 5‐year CSM was 5% for not‐actively‐treated versus 4% for actively‐treated patients. No active treatment was associated with 1.4‐fold higher OCM, even after adjustment for age, cancer characteristics, and CSM. According to GS, OCM reached 16%, 27%, and 35% in GS 6, 7, and 8−10 not‐actively‐treated IPCa patients, respectively and exceeded CSM recorded for the same three groups (2%, 6%, and 28%, respectively).ConclusionOur results quantified OCM rates, confirming that in not‐actively‐treated IPCa patients OCM is indeed significantly higher than in their actively‐treated counterparts (HR: 1.4). These observations validate the use of no active treatment in IPCa patients, in whom OCM greatly surpasses CSM (20% vs. 5%).
The use of prodrugs as drugs of abuse
Authors: Ponce Julio de Carvalho 
Published: March 2024

AbstractProdrugs are an important strategy for the development and design of therapeutic drugs. They involve the addition of an easily removable group (such as an ester) to a molecule in order to chemically protect it from metabolism, hydrolysis, or interaction with tissues. In the therapeutic drug market, prodrugs may reduce adverse effects, lead to more accurate tissue delivery, increase bioavailability and duration of effects. The same strategy has, however, been used in the illicit drug market. Internationally controlled drugs such as LSD, MDMA and benzodiazepines have been detected in the market with the addition of alkyl chain that can be removed in physiological conditions. Cyclical analogues may also be used, as is the case for 1cP‐LSD and GBL (a prodrug of GHB). Adequate detection requires increased care with extraction and analytical conditions—as the parent drugs may be formed as artifacts during these processes—and an in‐depth knowledge of metabolic pathways to avoid erroneous detection and allow for adequate identification of the drug used. Legislative updates may also be necessary to ensure prodrugs can be controlled at the same level as other illicit drugs.This article is categorized under:
Toxicology > New Psychoactive Substances
Toxicology > Drug Analysis
Toxicology > Analytical
Correlates of mental disorder and harmful substance use in an indigenous Australian urban sample: an analysis of data from the Queensland Urban Indigenous Mental Health Survey
Authors: Basit Tabinda , Toombs Maree , Santomauro Damian , Whiteford Harvey , Ferrari Alize 
Published: March 2024

Abstract

Purpose
Limited data exists on the relationship between sociodemographic and cultural variables and the prevalence of specific mental and substance use disorders (MSDs) among Indigenous Australians, using diagnostic prevalence data. This paper utilises data from the Queensland Urban Indigenous Mental Health Survey (QUIMHS), a population-level diagnostic mental health survey, to identify socioeconomic and cultural correlates of psychological distress and specific MSDs in an urban Indigenous Australian sample.

Methods
Using a mixture of household sampling (door-knocking) and snowball sampling (promotion of the survey in the community), 406 participants aged 18 to 89 were recruited across key locations in Southeast Queensland. The study investigated various demographic, socioeconomic, and cultural factors as predictors of psychological distress (measured by the Kessler-5) and MSD diagnoses (utilising the Composite International Diagnostic Interview, CIDI 3.0) using a series of univariate logistic regressions.

Results
Individuals in unstable housing (homeless, sleeping rough) and those reporting financial distress were more likely to experience an MSD in the past 12 months and throughout their lifetime. Individuals reporting lower levels of connection and belonging, limited participation in cultural events, and lower empowerment were more likely to have a lifetime mental disorder.

Conclusion
This data emphasises the importance of addressing systemic and social determinants of health when designing and delivering community mental health services and underscores the need for holistic approaches when working with Indigenous communities.
Algebraic Conditions for Conformal Superintegrability in Arbitrary Dimension
Authors: Kress Jonathan , Schöbel Konrad , Vollmer Andreas 
Published: March 2024

AbstractWe consider second order (maximally) conformally superintegrable systems and explain how the definition of such a system on a (pseudo-)Riemannian manifold gives rise to a conformally invariant interpretation of superintegrability. Conformal equivalence in this context is a natural extension of the classical (linear) Stäckel transform, originating from the Maupertuis-Jacobi principle. We extend our recently developed algebraic geometric approach for the classification of second order superintegrable systems in arbitrarily high dimension to conformally superintegrable systems, which are presented via conformal scale choices of second order superintegrable systems defined within a conformal geometry. For superintegrable systems on constant curvature spaces, we find that the conformal scales of Stäckel equivalent systems arise from eigenfunctions of the Laplacian and that their equivalence is characterised by a conformal density of weight two. Our approach yields an algebraic equation that governs the classification under conformal equivalence for a prolific class of second order conformally superintegrable systems. This class contains all non-degenerate examples known to date, and is given by a simple algebraic constraint of degree two on a general harmonic cubic form. In this way the yet unsolved classification problem is put into the reach of algebraic geometry and geometric invariant theory. In particular, no obstruction exists in dimension three, and thus the known classification of conformally superintegrable systems is reobtained in the guise of an unrestricted univariate sextic. In higher dimensions, the obstruction is new and has never been revealed by traditional approaches.
Pre-proenkephalin 1 is Downregulated Under Unloading and is Involved in Osteoblast Biology
Authors: Puri Chiara , Dannenberg Charlotte , Ucci Argia , Ponzetti Marco , Pucci Elisa , Silvestri Luciana , Lau Patrick , Frings-Meuthen Petra , Heer Martina , Rucci Nadia , Teti Anna , Maurizi Antonio 
Published: March 2024

AbstractPre-proenkephalin 1 (Penk1) is a pro-neuropeptide that belongs to the typical opioid peptide’s family, having analgesic properties. We previously found Penk1 to be the most downregulated gene in a whole gene profiling analysis performed in osteoblasts subjected to microgravity as a model of mechanical unloading. In this work, Penk1 downregulation was confirmed in the bones of two in vivo models of mechanical unloading: tail-suspended and botulinum toxin A (botox)-injected mice. Consistently, in the sera from healthy volunteers subjected to bed rest, we observed an inverse correlation between PENK1 and bed rest duration. These results prompted us to investigate a role for this factor in bone. Penk1 was highly expressed in mouse bone, but its global deletion failed to impact bone metabolism in vivo. Indeed, Penk1 knock out (Penk1−/−) mice did not show an overt bone phenotype compared to the WT littermates. Conversely, in vitro Penk1 gene expression progressively increased during osteoblast differentiation and its transient silencing in mature osteoblasts by siRNAs upregulated the transcription of the Sost1 gene encoding sclerostin, and decreased Wnt3a and Col1a1 mRNAs, suggesting an altered osteoblast activity due to an impairment of the Wnt pathway. In line with this, osteoblasts treated with the Penk1 encoded peptide, Met-enkephalin, showed an increase of Osx and Col1a1 mRNAs and enhanced nodule mineralization. Interestingly, primary osteoblasts isolated from Penk1−/− mice showed lower metabolic activity, ALP activity, and nodule mineralization, as well as a lower number of CFU-F compared to osteoblasts isolated from WT mice, suggesting that, unlike the transient inhibition, the chronic Penk1 deletion affects both osteoblast differentiation and activity. Taken together, these results highlight a role for Penk1 in the regulation of the response of the bone to mechanical unloading, potentially acting on osteoblast differentiation and activity in a cell-autonomous manner.
A Second Fungal Outbreak in Castañar Cave, Spain, Discloses the Fragility of Subsurface Ecosystems
Authors: Martin-Pozas Tamara , Nováková Alena , Jurado Valme , Cuezva Soledad , Fernandez-Cortes Angel , Saiz-Jimenez Cesareo , Sanchez-Moral Sergio 
Published: March 2024

AbstractCastañar is a cave with strict visitor control measures since it was open to public visits in 2003. However, in recent years, the cave suffered two fungal outbreaks, the first in 2008 and controlled by cleaning the contaminated sediments and subsequent closure of the cave until 2014. The cave was reopened but limited to a maximum of 450 visitors/year. Despite these restrictions on visit, the cave experienced a second outbreak in 2021, originating from the installation of a steel grating walkway, aiming at protecting the ground sediments from the visitors’ footsteps. Here, we conducted an analysis using Next-Generation Sequencing and culture-dependent techniques to investigate the fungal communities related to the second outbreak and compare with those present before the cave suffered the outbreak. The results show that the most abundant fungi involved in the 2021 outbreak were already detected in 2020, and even in 2008 and 2009, although the main species that originating both outbreaks were different, likely due to the different carbon sources introduced into the cave.
Incidence of complications and urinary incontinence following endoscopic enucleation of the prostate in men with a prostate volume of 80 ml and above: results from a multicenter, real-world experience of 2512 patients
Authors: Gauhar Vineet , Castellani Daniele , Herrmann Thomas R. W. , Gökce Mehmet Ilker , Fong Khi Yung , Gadzhiev Nariman , Malkhasyan Vigen , Pirola Giacomo Maria , Naselli Angelo , Mahajan Abhay , Maheshwari Pankaj Nandkishore , Biligere Sarvajit , Tursunkulov Azimdjon N. , Nasirov Furkat , Petov Vladislav , Dellabella Marco , Lim Ee Jean , Socarrás Moisés Rodríguez , Zawadzki Marek , Cormio Luigi , Busetto Gian Maria , Teoh Jeremy Yuen-Chun , Somani Bhaskar Kumar , Enikeev Dmitry , Sofer Mario , Gómez Sancha Fernando 
Published: March 2024

Abstract
Purpose
To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV).

Methods
We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019–January 2023). Inclusion criteria: prostate volume ≥ 80 ml. Exclusion criteria: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy.
Primary outcome: complication rate. Secondary outcomes: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80–100 ml; Group 2 PV = 101–200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence.

Results
There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003–1.035) was the only factor significantly associated with higher odds of incontinence.

Conclusions
PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI.
Implantation and reimplantation: epidemiology, etiology and pathogenesis over the last 30 years
Authors: Ketterer M. C. , Shiraliyev K. , Arndt S. , Aschendorff A. , Beck R. 
Published: March 2024

Abstract
Introduction
Due to the increasing number of cochlear implant (CI) recipients, growing indications, and the aging population, the reimplantation of CI recipients has become a focus of attention. The aim of this study is to examine the causes, timing, and postoperative speech understanding in a large cohort over the past 30 years.

Methods
A retrospective data analysis was conducted on over 4000 CI recipients and 214 reimplanted children and adults from 1993 to 2020. This involved collecting and comparing data on causes, manufacturer information, and demographic data. In addition, a comparison of speech understanding in Freiburg monosyllables and numbers before and after reimplantation was carried out.

Results
Children did not exhibit elevated rates of reimplantation. The overall reimplantation rate in the entire cohort was 5%. The CI overall survival rate after 10 years in the entire cohort was 95.2%. Device failure was the most common reason for reimplantation, with 48% occurring within the first 5 years after implantation. The second most common reason was medical complications, with the risk of reimplantation decreasing as more time passed since the initial implantation. There were no significant differences in Freiburg numbers and monosyllable comprehension before and after reimplantation, both in the overall cohort and in the subcohorts based on indications. Even a technical upgrade did not result in a significant improvement in speech understanding.

Discussion
There was no significant difference in the frequency of reimplantation based on patient age, especially when comparing children and adults. Device failure is by far the most common indication for reimplantation, with no significant difference in implant survival between manufacturers. Patients most often choose the same manufacturer for reimplantation. The likelihood of reimplantation decreases with increasing time since the initial implantation. The indication for reimplantation should be carefully considered, as on average, no improved speech understanding is achieved, regardless of the cause, even with a technical upgrade.
Deciphering the interplay between psychopathological symptoms, sensorimotor, cognitive and global functioning: a transdiagnostic network analysis
Authors: Fritze Stefan , Brandt Geva A. , Volkmer Sebastian , Daub Jonas , Krayem Maria , Kukovic Jacqueline , Schwarz Emanuel , Braun Urs , Northoff Georg , Wolf Robert Christian , Kubera Katharina M. , Meyer-Lindenberg Andreas , Hirjak Dusan 
Published: March 2024

Abstract
Background
Understanding the relationship between psychopathology and major domains of human neurobehavioral functioning may identify new transdiagnostic treatment targets. However, studies examining the interrelationship between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample are lacking. We hypothesized a close relationship between sensorimotor and cognitive functioning in a transdiagnostic patient sample.

Methods
We applied network analysis and community detection methods to examine the interplay and centrality [expected influence (EI) and strength] between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample consisting of 174 schizophrenia spectrum (SSD) and 38 mood disorder (MOD) patients. All patients (n = 212) were examined with the Positive and Negative Syndrome Scale (PANSS), the Heidelberg Neurological Soft Signs Scale (NSS), the Global Assessment of Functioning (GAF), and the Brief Cognitive Assessment Tool for Schizophrenia consisted of trail making test B (TMT-B), category fluency (CF) and digit symbol substitution test (DSST).

Results
NSS showed closer connections with TMT-B, CF, and DSST than with GAF and PANSS. DSST, PANSS general, and NSS motor coordination scores showed the highest EI. Sensory integration, DSST, and CF showed the highest strength.

Conclusions
The close connection between sensorimotor and cognitive impairment as well as the high centrality of sensorimotor symptoms suggests that both domains share aspects of SSD and MOD pathophysiology. But, because the majority of the study population was diagnosed with SSD, the question as to whether sensorimotor symptoms are really a transdiagnostic therapeutic target needs to be examined in future studies including more balanced diagnostic groups.
Pan-cancer analysis of DDIT4 identifying its prognostic value and function in acute myeloid leukemia
Authors: Li Fangmei , Miao Jiyu , Liu Rui , Zhang Ru , He Aili 
Published: March 2024

Abstract
Background
Acute myeloid leukemia (AML) is a hematological malignancy derived from the accumulation of abnormal proliferation of infantile leukocytes in the hematopoietic system. DNA-damage-inducible transcript 4 (DDIT4) acting as a negative regulator of rapamycin inhibitor is involved in various cellular functions. Many studies have suggested that DDIT4 plays a key role in tumorigenesis. However, the role of DDIT4 in AML has been poorly studied.

Method
In this study, we analyzed the expression of DDIT4 in AML patients using The Cancer Genome Atlas and real-time polymerase chain reaction. The Chi-square test was used to assess the correlation between DDIT4 and clinical characters in AML patients. Loss-of-function experiments were implemented to investigate the role of DDIT4 in AML carcinogenesis. The R package was applied to evaluate the correlation between DDIT4 expression and immune cells.

Results
Results showed that the expression of DDIT4 was associated with Age, Cytogenetic risk, Cytogenetics and OS event. Moreover, high expression of DDIT4 led to a terrible prognosis. KEGG analysis showed that differently expressed genes (DEGs) were involved in the PI3-Akt signaling pathway. GSEA enrichment analysis displayed DEGs were correlated with apoptosis. Functional experiments presented that knocking down DDIT4 suppressed cell cycle transition/proliferation and facilitated apoptosis. In addition, DDIT4 is associated with immune infiltration.

Conclusion
Our research verified that DDIT4 can be used as a prognostic marker and a potential therapeutic target for AML.
Year-round dynamics of arbuscular mycorrhizal fungi communities in the roots and surrounding soils of Cryptomeria japonica
Authors: Djotan Akotchiffor Kevin Geoffroy , Matsushita Norihisa , Fukuda Kenji 
Published: March 2024

AbstractArbuscular mycorrhizal fungi (AMF) live simultaneously inside and outside of host plant roots for a functional mycorrhizal symbiosis. Still, the year-round dynamics and relationships between soil properties and AMF communities of trees in forest ecosystems remain unclear. We collected paired root and soil samples of the same Cryptomeria japonica trees at two forest sites (five trees at each site) every 2 months over a year. Total DNA was extracted from roots and soil separately and soil physicochemical properties were measured. With Illumina’s next-generation amplicon sequencing targeting the small subunit of fungal ribosomal DNA, we clarified seasonal dynamics of soil properties and AMF communities. Soil pH and total phosphorus showed significant seasonality while total carbon, nitrogen, and C/N did not. Only pH was a good predictor of the composition and dynamics of the AMF community. The total AMF community (roots + soil) showed significant seasonality because of variation from May to September. Root and soil AMF communities were steady year-round, however, with similar species richness but contained significantly different AMF assemblages in any sampling month. Despite the weak seasonality in the communities, the top two dominant OTUs showed significant but different shifts between roots and soils across seasons with strong antagonistic relationships. In conclusion, few dominant AMF taxa are dynamically shifting between the roots and soils of C. japonica to respond to seasonal and phenological variations in their microhabitats. AMF inhabiting forest ecosystems may have high environmental plasticity to sustain a functional symbiosis regardless of seasonal variations that occur in the soil.
An insight into role of amino acids as antioxidants via NRF2 activation
Authors: Egbujor Melford C. , Olaniyan Olugbemi T. , Emeruwa Chigbundu N. , Saha Sarmistha , Saso Luciano , Tucci Paolo 
Published: March 2024

AbstractOxidative stress can affect the protein, lipids, and DNA of the cells and thus, play a crucial role in several pathophysiological conditions. It has already been established that oxidative stress has a close association with inflammation via nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Amino acids are notably the building block of proteins and constitute the major class of nitrogen-containing natural products of medicinal importance. They exhibit a broad spectrum of biological activities, including the ability to activate NRF2, a transcription factor that regulates endogenous antioxidant responses. Moreover, amino acids may act as synergistic antioxidants as part of our dietary supplementations. This has aroused research interest in the NRF2-inducing activity of amino acids. Interestingly, amino acids' activation of NRF2-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway exerts therapeutic effects in several diseases. Therefore, the present review will discuss the relationship between different amino acids and activation of NRF2–KEAP1 signaling pathway pinning their anti-inflammatory and antioxidant properties. We also discussed amino acids formulations and their applications as therapeutics. This will broaden the prospect of the therapeutic applications of amino acids in a myriad of inflammation and oxidative stress-related diseases. This will provide an insight for designing and developing new chemical entities as NRF2 activators.