bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and Acute Kidney Injury Outcomes in Hospitalized Patients Following SARS-CoV-2 Vaccination: A Case-Control Study
Authors: Martínez-Sánchez Froylan D. , Bastida-Castro Luis A. , Torres-Cuevas José L. , Vasquez-Vasquez Julio A. , Diaz-Jarquin Alejandra , Moreno-Novales Rafael , Balderas-Juarez Joana , Salinas-Ramírez Mauricio A. , Hernández-Castillo Jose L. , Tenorio-Aguirre Erika K.
Published: November 2024

Background:

Acute kidney injury (AKI) is a frequent complication associated with severe COVID-19 and has been linked to increased mortality. While vaccination against SARS-CoV-2 has shown effectiveness in reducing severe COVID-19 outcomes, its impact on the development of AKI among hospitalized patients remains unclear.

Objective:

To evaluate the effect of SARS-CoV-2 vaccination on the incidence and severity of AKI and 28-day mortality among hospitalized patients with severe COVID-19.

Design:

Retrospective case-control study.

Setting:

Conducted at the Internal Medicine Department of Hospital General Dr. Manuel Gea González, Mexico, from April 2020 to December 2021.

Patients:

413 patients over 18 with confirmed severe COVID-19 were included. Patients were categorized based on their vaccination status before COVID-19 infection.

Measurements:

Key outcomes included the incidence of AKI, progression to AKI stage 3, and 28-day mortality. AKI was defined according to the KDIGO criteria.

Methods:

Data were analyzed using univariate and logistic regression models to assess the association between vaccination status and the studied outcomes. Covariates included age, sex, BMI, type 2 diabetes, hypertension, and inflammatory markers.

Results:

Among the 413 patients, 70% developed AKI, with a median hospital stay of 10 days (range 6-17). Vaccinated patients had a significantly lower incidence of AKI compared with nonvaccinated patients (48.7% vs 74.9%; P < .001). After adjusting for confounding factors, vaccination was associated with lower odds of AKI (OR: 0.252, 95% CI: 0.140-0.452), AKI stage 3 (OR: 0.448, 95% CI: 0.205-0.981), and 28-day mortality (OR: 0.187, 95% CI: 0.064-0.544).

Limitations:

As a single-center retrospective study, generalizability is limited. In addition, vaccination data were obtained from medical records, and the completeness of vaccination could not be independently verified.

Conclusions:

SARS-CoV-2 vaccination was independently associated with a reduced risk of AKI, AKI stage 3, and 28-day mortality in hospitalized patients with severe COVID-19. These findings highlight the potential protective effects of vaccination against severe kidney complications in this population.
Adolescents’ perceptions of autonomy-supportive parents and social-emotional health: Serial multiple mediation of positive stress and mental toughness
Authors: Tunca Aslı
Published: November 2024

Adolescence may bring some developmental challenges that affect social-emotional health. However, it is also possible to turn challenges into opportunities. Parental autonomy support, psychological stress, and mental toughness can contribute to adolescents having a healthy period. This study examined the mediating role of positive stress and mental toughness in the relationship between parental autonomy support and social-emotional health. The study included 441 (female 56.46%, male 43.54%) adolescents in Turkey enrolled in a high school. Self-report scales were used in this cross-sectional study. The results showed that positive stress and mental toughness were serial mediators of the relationship between adolescents’ perceptions of parental autonomy support and social-emotional health outcomes (indirect effect = 0.05 [0.03, 0.08]). These results extend the implications of self-determination and positive psychology theories. It guides parents, educators, and school counselors in strengthening adolescents’ social-emotional health. Adolescents’ socio-emotional health can be enhanced through workshops and counseling services that offer parental autonomy support, positive management of stress, and mental toughness.
Examining PTSD Prevalence Among Underserved Populations in the Integrated Community Mental Health Setting 2019 to 2022
Authors: Jones Matthew W. H. , Cook Nicole , McGrath Brenda M. , Crist Rae L. , Larson Annie E , Templeton Anna , Nishiike Yui , Koroukian Siran , Zyzanski Stephen , Stange Kurt C.
Published: November 2024

Background:

The prevalence of Post Traumatic Stress Disorder (PTSD) has been rising since the start of the COVID-19 pandemic, and affects females, sexual and gender minorities, and individuals with social risks at higher rates.

Objective:

This study examines if the prevalence of PTSD increased from 2019 to 2022 among patients who received care in a national network of safety-net, community-based health centers with integrated behavioral health programs that serve patients at high risk for PTSD.

Methods:

We analyzed electronic health record data from patients with 1 or more behavioral health visits during 2019 to 2022 using repeated cross-sectional data to visualize trends. Change in PTSD prevalence based on the diagnoses associated with each visit from 2019 to 2022 was assessed using a general linear mixed model adjusted for patient-level factors.

Results:

Over 4 years, 182 419 distinct patients received care for PTSD, with prevalence increasing from 2019 to 2022 (OR = 1.09, 95% CI = 1.08, 1.10). Females (OR = 1.81, 95% CI = 1.78, 1.84), LGBTQIA individuals (OR = 1.29, 95% CI = 1.26, 1.33), gender diverse individuals (OR = 1.36, 95% CI = 1.29, 1.42), and patients who reported 1 or more social determinants of health needs (OR = 1.52, 95% CI = 1.46, 1.57) were more likely to have a diagnosis of PTSD.

Conclusions:

In a worrying trend, PTSD prevalence has increased among people receiving integrated behavioral health care at community-based health centers, with disparities observed in subpopulations. Continued effort and investment are needed to meet this increasing need in safety-net settings, particularly for those subpopulations observed to have higher prevalence.
Intraconal Left Main Coronary Artery Originating From the Left Sinus of Valsalva
Authors: Bishnoi Arvind , Mainwaring Richard D. , Seehofnerova Anna , Hanley Frank L.
Published: November 2024

Anomalous left main coronary artery (LMCA) with an intraconal course is a relatively rare form of anomalous coronary artery. Intraconal LMCA typically originates from the right sinus of Valsalva. However, this report describes the very unusual circumstance of an intraconal LMCA originating from the left sinus.
Behavioral Activation Therapy for Depression Led by Health Personnel in Older People: A Scoping Review
Authors: Medina-Jiménez Erick A. , Acosta-Quiroz Christian O. , García-Flores Raquel , Aguilar-Navarro Sara G. , Sotelo-Ojeda Jesús E.
Published: November 2024

Behavioral activation therapy is presented as a promising psychological intervention to enhance depression management and related symptoms by increasing engagement in rewarding activities. This study reviews three research endeavors, including randomized controlled trials and a case study. Variability in intervention duration and training approaches is noted, although typically, eight sessions per week were conducted. Therapy components range from participating in pleasurable activities to ongoing support outside sessions. The process of evidence source selection relied on identifying 327 articles across four databases, with three selected for review, utilizing the PRISMA extension for scoping reviews. This ensured rigorous eligibility criteria and a structured methodology for data collection. Overall, these findings support the effectiveness and applicability of behavioral activation therapy in treating depression in older adults. Training non-specialized healthcare personnel would improve the overall quality of medical care and facilitate the dissemination of evidence-based therapies. This, in turn, could be crucial in closing the psychotherapeutic care gap that exists in low and middle-income countries.
Correlation Between Emotional Intelligence and Critical Thinking Disposition Among Undergraduate Saudi Nursing Students
Authors: Hasan Abdalhadi , Noor Hala
Published: November 2024

Introduction

Thinking skills are important concepts that have been discussed by various researchers. Improving and enhancing students’ thinking skills has become a fundamental goal of educational systems. There are several methods used to promote inclusive critical thinking in individuals.

Objectives

This study aimed to assess the correlation between emotional intelligence (EI) and critical thinking disposition skills in undergraduate Saudi nursing students.

Methods

This descriptive correlational study design used a convenience sample of 300 undergraduate nursing students. The respondents were selected from King Khaled University. The study utilized the Schutte Self-Report Emotional Intelligence Test (SSEIT) and the Critical Thinking Disposition Scale (CTDS).

Results

The results demonstrated a positive correlation between the two variables ( r = .60, p < .001). The variables differed among the nursing students depending on their academic year of study ( F = 52.000, p < .001).

Conclusions

In conclusion, higher levels of EI and critical thinking skills in nursing students are associated with improved problem-solving skills and better judgment, which contribute to the future development of EI and critical thinking nursing professionals.
Skin ultrasound for rheumatologists: Technical issues and challenges
Authors: Micu MC , Wortsman X , Naredo E
Published: November 2024

Introduction:

In several rheumatic diseases, the skin is involved and therefore it is an organ of interest which may be investigated by the rheumatologist. Ultrasound imaging has been proposed for assessing multiple skin conditions providing qualitative and quantitative information about different parameters in distinct skin layers. Our aim was to describe with a pictorial essay the main challenges that the ultrasound imaging may encounter when investigating the healthy skin in different body areas.

Subjects and methods:

Fourteen healthy subjects were submitted to skin ultrasound. The body areas that were investigated were decided following the 17 modified Rodnan skin score anatomical areas used in systemic sclerosis. Skin ultrasound was performed with a GE Logiq 10 with two probes (20 and 24 MHz). For an optimal quantification of the skin layers, the dermis interfaces either with the epidermis and hypodermis were investigated.

Results:

The results of the ultrasound analysis are described and summarized in a pictorial essay which shows that some main factors may significantly influence the quality of the images of the skin layers. Specifically, age, scanning position, probe frequency, and the optimal positioning of some anatomical areas, in particular the hands and digits, emerged as factors that may have a relevance in influencing the quality of the imaging of the skin layers. Moreover, some technical suggestions are proposed to help optimizing and standardizing the performance of skin ultrasound assessment in healthy population.

Conclusion:

The pictorial essay we performed shows that the performance of skin ultrasound in healthy subjects still presents several issues that need to be addressed. The definition of the interface in different body areas is the first step which should be standardized before any measurement of the thickness of the skin layers is performed in rheumatic diseases.
Predicting habitat functionality using habitat network models in urban planning
Authors: Kindvall Oskar , Berghauser Pont Meta , Stavroulaki Ioanna , Lanemo Emy , Wigren Lena , Levan Monika
Published: November 2024

Recently, the European Union adopted a Nature restoration law that aims to stop the ongoing decline of biodiversity and even bring back nature to cities. This is challenging as urbanization is an ongoing process that thrives for more land and densification. In this paper we describe a new Open-Source GIS-tool that automates habitat network analyses and simultaneously generates several maps that can be used for assessments, targeting species survival in urban environments. One result of particular interest is the habitat functionality map that combines values of habitat quality and connectivity. We tested the tool’s ability to predict habitat functionality using amphibian occurrence data observed from the city of Gothenburg in Sweden. Our evaluation shows that habitat functionality was generally a good predictor of amphibian distribution. However, the predictability was sensitive to the cartographic representativity of the input biotope map used. Also, predictions of habitat functionality improved when estimating dispersal probabilities using the Cost-distance algorithm, compared to when using Euclidean distance from reproductive habitats. This finding supports the need to use connectivity models that are responsive to variation and changes in roads, traffic volumes and buildings when performing effect analyses on biodiversity in cities. Finally, we demonstrate how the tool can be used to easily identify areas where restoration measures can effectively increase habitat functionality for target species. This can help planners to find efficient solutions for increasing biodiversity within urban areas.
Out of Time and in Place: Housebuilding and Urbanisation in a Mozambican Locality
Authors: Cox Wight Mattie
Published: November 2024

This article examines housebuilding, temporality and small settlement urbanisation in Mozambique. It studies residents who are building next to homes built by their grandparents and parents, on the same or adjacent plots of land, where they grew up. Taking a cue from the residents who claim that they are ‘building their city’, this article explores who is building, how and why. Such building is ‘out of time’ because houses are built out of past attempts to modernise the nation towards shared futures that have never been reached. Inverting this, contemporary housebuilders imaginatively and physically inhabit their own individual futures while producing new modernities. Moreover, such building is ‘out of time’ in the sense of being outside of linear time. Older houses embody material and social fragments from the past that remain in the present, and the way they decay and new ones are produced is anachronistic, reflecting Morten Nielsen’s ‘swelling of time’, in space. Yet, this growth is also happening ‘in place’, led by natives, in the place they grew up, filled with memories and sentimentality. Following this, the article proposes a different analytical framework for thinking about small settlement urbanisation, through the notion of spatial and temporal entanglement.
Making the mos(s)t of nature? Cleantech, smart nature-based solutions, and the ‘rendering investable’ of urban moss
Authors: Ernwein Marion , Palmer James
Published: November 2024

This article examines the ways in which ‘nature-based solutions’ (NBS) to urban environmental problems are contributing to a re-imagining of the forms and roles of vegetal life in cities. Specifically, we examine the versions of nature that are being produced within a subset of nature-based solutions described as ‘smart’ – that is, those involving the enrolment of non-human lifeforms into digital infrastructures comprising sensors, data flows and automated support systems. Whilst NBS are often celebrated for opening up cities to lively ecological processes – thereby contributing to more convivial, ‘more-than-human’ forms of urbanism – their smart incarnations are becoming a playground for entrepreneurial and financial actors seeking new ways to enclose, commodify and derive profit from non-human life in cities. To explicate this argument, we examine the case of a proprietary ‘nature-based solution’ to urban air pollution developed and sold to local authorities and corporate actors by a European cleantech start-up, predicated on optimising the air-filtering capacities of moss. Our analysis proceeds in three stages. First, we draw on scholarship on the bioeconomy to show how the commodification of moss in this case is predicated on discursive arguments which depict moss as at once inherently productive and regenerative, but also fragile and scarce in urban environments. Secondly, we show how this smart NBS is rendered investable through the enrolment of moss into a carefully designed digital apparatus, which purports to stabilise and optimise its air purifying work, thereby making its contributions to urban air quality continuous, consistent and calculable. Finally, building on an assessment of the entanglement of this example with specific urban geographies and modes of urban governance, we critically reflect on the role that smart NBS in general might yet play in either reinforcing or disrupting prevailing dynamics of privatisation, enclosure and green gentrification in cities.
Annivite-(Zn), Cu6(Cu4Zn2)Σ6Bi4S13, from the Jáchymov ore district, Czech Republic: the first Bi-dominant member of the tetrahedrite group
Authors: Sejkora Jiří , Biagioni Cristian , Dolníček Zdeněk , Velebil Dalibor , Škácha Pavel
Published: November 2024

Annivite-(Zn), Cu6(Cu4Zn2)Σ6Bi4S13, is a new IMA-approved mineral species from the Geister vein, Jáchymov ore district, Czech Republic. It occurs as anhedral grains, up to 50 μm in size, and growth zones, up to 100 μm in thickness, hosted by oscillatory zoned annivite-(Zn)/tennantite-(Zn) grains, and associated with Bi-rich tennantite-(Zn), tennantite-(Fe), tetrahedrite-(Zn), the not-yet approved ‘annivite-(Fe)’, bismuth, emplectite, wittichenite and supergene bismite, walpurgite and metazeunerite. In reflected light, annivite-(Zn) is isotropic, pale grey with a brownish shade and very rare pale brown internal reflections. Reflectance data for the four COM wavelengths in air are [λ (nm): R (%)]: 470: 32.3; 546: 32.0; 589: 32.0; 650: 31.6. Electron microprobe analysis gave (in wt.% – average of 5 spot analyses): Cu 36.29, Ag 0.14, Fe 0.08, Zn 7.11, Pb 0.19, As 6.07, Sb 4.50, Bi 21.08, S 23.68, total 99.14. On the basis of ΣMe =16 atoms per formula unit, the empirical formula of annivite-(Zn) is Cu10.13Ag0.02Zn1.93Fe0.03Pb0.02Bi1.79As1.43Sb0.66S13.10. Annivite-(Zn) is cubic, I

$\bar 4$

3m, with unit-cell parameters a = 10.3545(6) Å, V = 1110.16(19) Å3 and Z = 2. Its crystal structure was refined by single-crystal X-ray diffraction data to a final R1 = 0.0493 on the basis of 278 unique reflections with Fo > 4σ(Fo) and 23 refined parameters. Annivite-(Zn) is isotypic with other tetrahedrite-group minerals. Its crystal chemistry is discussed, and previous findings of Bi-rich tetrahedrite-group minerals are briefly reviewed, along with the description of a second finding of annivite-(Zn) from the abandoned Mauritius tin mine, Hřebečná, Krušné hory Mountains, Czech Republic.
Mesenchymal stem cells lineage and their role in disease development
Authors: Xu Qi , Hou Wenrun , Zhao Baorui , Fan Peixin , Wang Sheng , Wang Lei , Gao Jinfang
Published: November 2024

Background

Mesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for different diseases, which are crucial in disease progression. In this study, we describe various lineage analysis methods to explore lineage ontology in vitro and in vivo, elucidate the impact of MSC lineage differentiation on diseases, advance our understanding of the role of MSC differentiation in physiological and pathological states, and explore new targets and ideas associated with disease diagnosis and treatment.
PI3K p85α/HIF-1α accelerates the development of pulmonary arterial hypertension by regulating fatty acid uptake and mitophagy
Authors: Chen Chenyang , Qin Sirun , Song Xiaohua , Wen Juan , Huang Wei , Sheng Zhe , Li Xiaogang , Cao Yu
Published: November 2024

Background

Pulmonary arterial hypertension (PAH) is characterized by lipid accumulation and mitochondrial dysfunction. This study was designed to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) on fatty acid uptake and mitophagy in PAH.

Methods

Peripheral blood samples were obtained from PAH patients. Human pulmonary arterial smooth muscle cells and rat cardiac myoblasts H9c2 were subjected to hypoxia treatment. Male Sprague–Dawley rats were treated with monocrotaline (MCT). Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary artery remodeling, and lipid accumulation were measured. Cell proliferation and ROS accumulation were assessed. Mitochondrial damage and autophagosome formation were observed. Co-immunoprecipitation was performed to verify the interaction between HIF-1α and CD36/PI3K p85α.

Results

HIF-1α, CD36, Parkin, and PINK1 were upregulated in PAH samples. HIF-1α knockdown or PI3K p85α knockdown restricted the expression of HIF-1α, PI3K p85α, Parkin, PINK1, and CD36, inhibited hPASMC proliferation, promoted H9c2 cell proliferation, reduced ROS accumulation, and suppressed mitophagy. CD36 knockdown showed opposite effects to HIF-1α knockdown, which were reversed by palmitic acid. The HIF-1α activator dimethyloxalylglycine reversed the inhibitory effect of Parkin knockdown on mitophagy. In MCT-induced rats, the HIF-1α antagonist 2-methoxyestradiol (2ME) reduced RVSP, RVHI, pulmonary artery remodeling, lipid accumulation, and mitophagy. Recombinant CD36 abolished the therapeutic effect of 2ME but inhibited mitophagy. Activation of Parkin/PINK1 by salidroside (Sal) promoted mitophagy to ameliorate the pathological features of PAH-like rats, and 2ME further enhanced the therapeutic outcome of Sal.

Conclusion

PI3K p85α/HIF-1α induced CD36-mediated fatty acid uptake and Parkin/PINK1-dependent mitophagy to accelerate the progression of experimental PAH.

Graphical Abstract
Serum soluble isoform of receptor for advanced glycation end product is a predictive biomarker for acute exacerbation of idiopathic pulmonary fibrosis: a German and Japanese cohort study
Authors: Kitadai Erika , Yamaguchi Kakuhiro , Ohshimo Shinichiro , Iwamoto Hiroshi , Sakamoto Shinjiro , Horimasu Yasushi , Masuda Takeshi , Nakashima Taku , Hamada Hironobu , Bonella Francesco , Guzman Josune , Costabel Ulrich , Hattori Noboru
Published: November 2024

Background

The receptor for advanced glycation end product (RAGE) is a transmembrane receptor accelerating a pro-inflammatory signal. RAGE signalling is promoted by decreased soluble isoform of RAGE (sRAGE), which is a decoy receptor for RAGE ligands, and RAGE SNP rs2070600 minor allele. In Caucasian and Japanese cohorts, low circulatory sRAGE levels and presence of the minor allele are associated with poor survival of idiopathic pulmonary fibrosis (IPF) and increased disease susceptibility to interstitial lung disease, respectively. However, whether sRAGE and RAGE SNP rs2070600 are associated with acute exacerbation of IPF (AE-IPF) is unclear.

Methods

This retrospective cohort study evaluated the association between the onset of AE-IPF and serum sRAGE levels in 69 German and 102 Japanese patients with IPF. The association of AE-IPF with RAGE SNP rs2070600 in 51 German and 84 Japanese patients, whose DNA samples were stored, was also investigated.

Results

In each cohort, the incidence of AE-IPF was significantly and reproducibly higher in the patients with sRAGE < 467.1 pg/mL. In a pooled exploratory analysis, the incidence of AE-IPF was lowest in the patients with higher sRAGE levels and rs2070600 minor allele, although no significant difference in the incidence was observed between the patients with and without the rs2070600 minor allele.

Conclusions

Low sRAGE levels were associated with increased incidence of AE-IPF in two independent cohorts of different ethnicities. The combination of rs2070600 and sRAGE levels may stratify patients with IPF for the risk of AE.
Harm reduction techniques among cisgender gay, bisexual, and queer men using anabolic androgenic steroids: a qualitative study
Authors: Kutscher Eric , Arshed Arslaan , Greene Richard E. , Kladney Mat
Published: November 2024

Background

Anabolic androgenic steroids (AAS) are synthetic forms of testosterone frequently used as performance enhancing drugs among gay, bisexual, and queer (GBQ) men. Despite widespread use, associated harms, and the likely existence of an AAS use disorder, there is no medical consensus on standards of care for people who use AAS, with most medical providers focusing exclusively on abstinence. Individuals using AAS have developed community-based harm reduction strategies to mitigate these harms.

Methods

This paper is a sub-analysis of qualitative data obtained through semi-structured interviews with GBQ men using AAS for 8 or more weeks recruited through convenience and snowball sampling from clinical sites and LGBTQ + venues in New York City as well as through social media. Interviews were coded with themes developed using reflexive thematic analysis. Data related to harm reduction techniques were then re-analyzed through a prevention strategies framework lens of primary, secondary, and tertiary harm prevention.

Results

Thematic saturation was reached at twelve interviews in the primary analysis, with men reporting frequent use of multiple harm reduction techniques. For primary prevention, men avoided oral steroids and simultaneous substance use, tried to obtain AAS from reputable sources, used “cycling” to dose steroids, and practiced sterile injection techniques. Secondary prevention methods included patient-directed lab testing for hematocrit, liver and kidney function, cholesterol, prostate specific antigen, testosterone, and self-performed blood pressure checks. Tertiary prevention included donating blood and the use of medications without a prescription, including aromatase inhibitors, selective estrogen receptor blockers, aspirin, statins, angiotensin receptor blockers, clomiphene, and human chorionic gonadotropin.

Conclusions

Despite many GBQ men experiencing harms from anabolic androgenic steroids, community members have often sought harm reduction techniques in lieu of abstinence. Though many of these techniques embrace clinical reasoning and may be more broadly applicable, additional research is needed to understand the impact of each intervention on the overall health of individuals using AAS.
The impact of androgen-induced translation in modulating androgen receptor activity
Authors: Israel Justus S. , Marcelin Laura-Maria , Mehralivand Sherif , Scholze Jana , Hofmann Jörg , Stope Matthias B. , Puhr Martin , Thomas Christian , Erb Holger H. H.
Published: November 2024

Introduction

Dysregulated androgen receptor (AR) activity is central to various diseases, particularly prostate cancer (PCa), in which it drives tumour initiation and progression. Consequently, antagonising AR activity via anti-androgens is an indispensable treatment option for metastatic PCa. However, despite initial tumour remission, drug resistance occurs. Therefore, the AR signalling pathway has been intensively investigated. However, the role of AR protein stability in AR signalling and therapy resistance has not yet been deciphered. Therefore, this study aimed to investigate the role of AR protein changes in transactivity and assess its mechanism as a possible target in PCa.

Methods

LNCaP, C4-2, and 22Rv1 cells were treated with R1881, enzalutamide, cycloheximide, and Rocaglamide. Mass spectrometry analyses were performed on LNCaP cells to identify the pathways enriched by the treatments. Western blotting was performed to investigate AR protein levels and localisation changes. Changes in AR transactivity were determined by qPCR.

Results

Mass spectrometry analyses were performed on LNCaP cells to decipher the molecular mechanisms underlying androgen- and antiandrogen-induced alterations in the AR protein. Pathway analysis revealed the enrichment of proteins involved in different pathways that regulate translation. Translational and proteasome inhibitor experiments revealed that these AR protein changes were attributable to modifications in translational activity. Interestingly, the effects on AR protein levels in castration-resistant PCa (CRPC) cells C4-2 or enzalutamide-resistant cells 22Rv1 were less prominent and non-existent. This outcome was similarly observed in the alteration of AR transactivation, which was suppressed in hormone-sensitive prostate cancer (HSPC) LNCaP cells by translational inhibition, akin to the effect of enzalutamide. In contrast, treatment-resistant cell lines showed only a slight change in AR transcription.

Conclusion

This study suggests that in HSPC, AR activation triggers a signalling cascade that increases AR protein levels by enhancing its translation rate, thereby amplifying AR activity. However, this mechanism appears to be dysregulated in castration-resistant PCa cells.
Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
Authors: Adem E. , Cruz Cervera E. , Yizengaw E. , Takele Y. , Shorter S. , Cotton J. A. , Getti G. , Kropf P.
Published: November 2024

Background

In Ethiopia, cutaneous leishmaniasis is mainly caused by Leishmania (L.) aethiopica parasites and presents in three main clinical forms. It is still not clear if the host immune response plays a role in the development of these different presentations. Since neutrophils are likely to be one of the first immune cells present at the site of the sand fly bite, we set up an in vitro model of infection of neutrophils with L. aethiopica and assessed some of the main neutrophil effector functions: association with and internalisation of parasites, apoptosis and ROS production. We used three freshly isolated clinical isolates and one isolate that has been kept in culture for decades.

Results

Our results showed by flow cytometry that all four L. aethiopica isolates had the ability to associate with neutrophils. The three clinical isolates of L. aethiopica associated more efficiently with neutrophils than the long-term cultured L. aethiopica. At 18 h, two distinct populations of neutrophils were identified that associated with L. aethiopica, CD15high and CD15low neutrophils. Confocal microscopy demonstrated that all isolates can be internalised. Our results also showed that all parasites induced apoptosis in L. aethiopica-associated neutrophils. Moreover, our results showed that after 2 h, L. aethiopica-associated neutrophils upregulated their production of ROS, but to a greater extent with the long-term cultured L. aethiopica. After 18 h of incubation, CD15lowparasite+ showed an impaired ability to produce ROS compared to CD15highparasite+.

Conclusions

Using this in vitro model, our results show that different L. aethiopica parasite isolates, most notably long-term cultured parasites, had differential effects on neutrophil effector functions.

Graphical Abstract
Neutrophil and mononuclear leukocyte pathways and upstream regulators revealed by serum proteomics of adult and juvenile dermatomyositis
Authors: Sparling A. Clare , Ward James M. , Sarkar Kakali , Schiffenbauer Adam , Farhadi Payam Noroozi , Smith Michael A. , Rahman Saifur , Zerrouki Kamelia , Miller Frederick W. , Li Jian-Liang , Casey Kerry A. , Rider Lisa G.
Published: November 2024

Objectives

Serum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers.

Methods

Serum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures.

Results

Seventy-eight of 172 proteins were differentially expressed in the sera of DM and JDM patients compared to healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. C-X-C motif chemokine ligand 10 (CXCL10) was the most strongly upregulated protein in both DM and JDM sera. Other highly upregulated proteins in DM included S100 calcium binding protein A12 (S100A12), CXCL9, and nicotinamide phosphoribosyltransferase (NAMPT), while highly upregulated proteins in JDM included matrix metallopeptidase 3 (MMP3), growth differentiation factor 15 (GDF15), and von Willebrand factor (vWF). Pathway analysis indicated that phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), and toll-like receptor 7 (TLR7) signaling were activated in DM and JDM. Additional pathways specific to DM or JDM were identified. A protein cluster associated with neutrophils and mononuclear leukocytes and a cluster of interferon-associated proteins were observed in both DM and JDM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity. Seven proteins correlated with disease activity measures in both DM and JDM sera. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM.

Conclusion

Coordinate analysis of protein expression in DM and JDM patient sera by a multiplex immunoassay validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may further inform the assessment of DM and JDM patients and aid in the identification of potential therapeutic targets.
Glucose chemical exchange saturation transfer MRI for predicting the histological grade of rectal cancer: a comparative study with amide proton transfer-weighted and diffusion-weighted imaging
Authors: Meng Nan , Huang Zhun , Jiang Han , Dai Bo , Shen Lei , Liu Xue , Wu Yaping , Yu Xuan , Fu Fangfang , Li Zheng , Shen Zhiwei , Jiang Baiyan , Wang Meiyun
Published: November 2024

Background

To evaluate the utility of glucose chemical exchange saturation transfer (glucoCEST) MRI with non-contrast injection in predicting the histological grade of rectal cancer.

Methods

This prospective analysis included 60 patients with preoperative rectal cancer who underwent pelvic glucoCEST, amide proton transfer-weighted imaging (APTWI), and diffusion-weighted imaging (DWI). In total, 21 low-grade and 39 high-grade cases were confirmed by postoperative pathology. The MTRasym (1.2 ppm), MTRasym (3.5 ppm), and apparent diffusion coefficient (ADC) values of lesions between the low-grade and high-grade groups were compared. The area under the receiver operating characteristic curve (AUC) was generated to evaluate the diagnostic performance of each technique. Logistic regression (LR) analysis was applied to determine independent predictors and for multi-parameter combined diagnosis.

Results

Elevated MTRasym (1.2 ppm), MTRasym (3.5 ppm) values and lower ADC values were observed in the high-grade group compared with low-grade cases (all p < 0.01). The AUCs of MTRasym (1.2 ppm), MTRasym (3.5 ppm), and ADC for differentiating between low- and high-grade rectal cancer cases were 0.792, 0.839, and 0.855, respectively. The diagnostic performance of the combination of the three indexes was improved (AUC, 0.969; sensitivity, 95.24%; specificity, 87.18%). The good consistency and reliability of the combination of independent predictors were demonstrated by calibration curve analysis and DCA.

Conclusion

The glucoCEST MRI without contrast injection, APTWI, and DWI all facilitate the assessment of histological grade in rectal cancer, and the combination of the three can effectively discriminate between high- and low-grade rectal cancer, which is expected to be a promising imaging marker.

Critical relevance statement

The glucose chemical exchange saturation transfer MRI method facilitates the assessment of histological grade in rectal cancer and offers additional information to improve the diagnostic performance of amide proton transfer-weighted imaging, and diffusion-weighted imaging.

Key Points

Glucose chemical exchange saturation transfer imaging could differentiate histological grade.

Amide proton transfer-weighted and diffusion-weighted were associated with histological grade.

The combination of different parameters showed the best diagnostic performance.

Graphical Abstract
Comparative evaluation of methods for the prediction of protein–ligand binding sites
Authors: Utgés Javier S. , Barton Geoffrey J.
Published: November 2024

The accurate identification of protein–ligand binding sites is of critical importance in understanding and modulating protein function. Accordingly, ligand binding site prediction has remained a research focus for over three decades with over 50 methods developed and a change of paradigm from geometry-based to machine learning. In this work, we collate 13 ligand binding site predictors, spanning 30 years, focusing on the latest machine learning-based methods such as VN-EGNN, IF-SitePred, GrASP, PUResNet, and DeepPocket and compare them to the established P2Rank, PRANK and fpocket and earlier methods like PocketFinder, Ligsite and Surfnet. We benchmark the methods against the human subset of our new curated reference dataset, LIGYSIS. LIGYSIS is a comprehensive protein–ligand complex dataset comprising 30,000 proteins with bound ligands which aggregates biologically relevant unique protein–ligand interfaces across biological units of multiple structures from the same protein. LIGYSIS is an improvement for testing methods over earlier datasets like sc-PDB, PDBbind, binding MOAD, COACH420 and HOLO4K which either include 1:1 protein–ligand complexes or consider asymmetric units. Re-scoring of fpocket predictions by PRANK and DeepPocket display the highest recall (60%) whilst IF-SitePred presents the lowest recall (39%). We demonstrate the detrimental effect that redundant prediction of binding sites has on performance as well as the beneficial impact of stronger pocket scoring schemes, with improvements up to 14% in recall (IF-SitePred) and 30% in precision (Surfnet). Finally, we propose top-N+2 recall as the universal benchmark metric for ligand binding site prediction and urge authors to share not only the source code of their methods, but also of their benchmark.

Scientific contributions

This study conducts the largest benchmark of ligand binding site prediction methods to date, comparing 13 original methods and 15 variants using 10 informative metrics. The LIGYSIS dataset is introduced, which aggregates biologically relevant protein–ligand interfaces across multiple structures of the same protein. The study highlights the detrimental effect of redundant binding site prediction and demonstrates significant improvement in recall and precision through stronger scoring schemes. Finally, top-N+2 recall is proposed as a universal benchmark metric for ligand binding site prediction, with a recommendation for open-source sharing of both methods and benchmarks.
Promoting real-time electricity tariffs for more demand response from German households: a review of four policy options
Authors: Häseler Sönke , Wulf Alexander J.
Published: November 2024

Background

Demand response is an important option for accommodating growing shares of renewable electricity, and therefore, crucial for the success of the energy transition in Germany and elsewhere. In conjunction with smart meters, real-time (or ‘dynamic’) electricity tariffs can facilitate the flexibilization of power consumption and reduce energy bills. Whilst such tariffs are already quite common in several EU member states, Germany lags behind in this respect. The country makes for an interesting case study because of the sheer volume of additional flexibility that its energy transition necessitates.

Main text

This paper discusses how German policymakers can make real-time tariffs more attractive for households and thus entice them to better adapt their consumption to current market conditions. Following an analysis of the current impediments to the adoption of such tariffs, we discuss four policy options: (1) a more ambitious legal definition of real-time tariffs that can promote market transparency and leverage potential savings for consumers, (2) a shift in energy taxation that encourages the uptake of renewable power and increases price spreads, (3) a new model of dynamic network charges which combines grid-serving and market-serving incentives, and (4) a subsidy for users of real-time tariffs that helps internalise the benefits they provide to all electricity consumers. Given the similar regulatory framework, our suggestions should generally also apply to other countries in Europe and beyond.

Conclusions

Overall, we argue that there is considerable scope for policymakers to better exploit market forces to ensure security of electricity supply at lower social cost. Our call for stricter regulation in order to allow the markets to better guide consumer behaviour may seem like a paradox—but it is one well worth embracing.
Temporal patterns and individual characteristics of compulsory treatment orders for mental disorders in Scotland from 2007 to 2020
Authors: Schölin Lisa , Borschmann Rohan , Chopra Arun
Published: November 2024

Background

Compulsory mental health treatment has increased globally. In Scotland, compulsory treatment for >28 days is permitted under hospital- and community-based compulsory treatment orders. Community-based compulsory treatment has not been shown to lead to improved outcomes, and scrutiny of their use is needed.

Aims

To describe the trend, duration and demographic characteristics of compulsory treatment orders in Scotland over a 14-year period.

Method

We conducted a retrospective analysis of order use in Scotland from 1 January 2007 to 31 December 2020, focusing on the (a) number and demographic characteristics of those treated, (b) duration, (c) extensions beyond the 6-month review point and (d) characteristics of new versus continued orders.

Results

The number of individuals on a community-based order increased by 118% (571 v. 1243) from 2007 to 2020, compared with a 16% increase (1316 v. 1532) for hospital-based orders. Of orders starting in 2007, 57.3% were extended, compared with 43.7% in 2020. The median duration was 6 months for first-time orders and 9 months for subsequent orders, which were longest for males (median 11 months); those of African, Caribbean or Black (median 11 months), Asian (median 11 months) and mixed ethnicity (median 10 months); and individuals from the most deprived communities (median 10 months).

Conclusions

There has been a marked rise of community-based compulsory treatment orders in Scotland. If existing trends continue, there will be more people receiving care under community-based orders than hospital-based orders, fundamentally changing the nature of involuntary treatment. Further work needs to explore associations between demographic and diagnostic characteristics on order duration.
Brain Abscess Causes Brain Damage With Long-Lasting Focal Cerebral Hypoactivity that Correlates With Abscess Size: A Cross-Sectional 18F-Fluoro-Deoxyglucose Positron Emission Tomography Study
Authors: Müller Ebba Gløersen , Dahlberg Daniel , Hassel Bjørnar , Revheim Mona-Elisabeth , Connelly James Patrick
Published: November 2024

BACKGROUND AND OBJECTIVES:

Bacterial brain abscesses may have long-term clinical consequences, eg, mental fatigue or epilepsy, but long-term structural consequences to the brain remain underexplored. We asked if brain abscesses damage brain activity long term, if the extent of such damage depends on the size of the abscess, and if the abscess capsule, which is often left in place during neurosurgery, remains a site of inflammation, which could explain long-lasting symptoms in patients with brain abscess.

METHODS:

2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), electroencephalography, and MRI were performed 2 days to 9 years after neurosurgery for bacterial brain abscess.

RESULTS:

FDG-PET/CT revealed hypometabolism in the neocortex or cerebellum overlying the previous bacterial abscess in 38 of 40 patients. The larger the abscess, the greater was the extent of the subsequent hypometabolism (r = 0.63; p = 3 × 10−5). In 9 patients, the extent of subsequent hypometabolism seemed to coincide with the extent of peri-abscess edema in the acute phase. Follow-up MRI after ≥1 year in 9 patients showed focal tissue loss and gliosis. In 13 patients with abnormal electroencephalography recordings, abnormalities extended beyond the cerebral lobe affected by the abscess, indicating damage to wider brain networks. The abscess capsule had an FDG signal indicating inflammation only during the first week after neurosurgical pus drainage.

CONCLUSION:

The bigger a brain abscess is allowed to grow, the more extensive is the long-term focal reduction in brain activity. This finding emphasizes the need for rapid neurosurgical intervention. The abscess capsule does not display long-lasting inflammation and probably does not explain long-term symptoms after brain abscess.
A Phase 2 Sensitivity and Selectivity Study of High-Dose 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent Glioblastoma
Authors: Cozzens Jeffrey W. , Lokaitis Barbara C. , Delfino Kristin , Hoeft Ava , Moore Brian E. , Fifer Amber S. , Amin Devin V. , Espinosa José A. , Jones Breck A. , Acakpo-Satchivi Leslie
Published: November 2024

BACKGROUND AND OBJECTIVES:

The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented, but the problem of false-negative observations remains. This study compares high-grade glioma visualization with low/standard dose 5-ALA (<30 mg/kg) to high-dose 5-ALA (>40 mg/kg) to see if by using this higher dose, it is possible to reduce the rate of false-negative observations without increasing the rate of false-positive (FP) observations and therefore increase the sensitivity.

METHODS:

This is a prospective study of consecutive patients with radiological evidence of presumed high-grade glioma. We reviewed the data from patients who received preoperative low/standard doses and patients who received a preoperative high dose of 5-ALA. Adverse events, dose to observation time, intensity of tumor fluorescence, and results of biopsies in areas of tumor and tumor bed under deep blue light were recorded.

RESULTS:

A total of 22 patients with high-grade glioma received a dose >40 mg/kg (high-dose) and 9 patients received <30 mg/kg (low/standard dose). There were no serious adverse events related to 5-ALA in any subject. There was a very high sensitivity and specificity of 5-ALA for the presence of tumor in both groups. There were no FP observations (fluorescence with no tumor) in either group. The specificity and the positive predictive value were 100% in both groups. The sensitivity and the negative predictive value were 53.3% and 30.0% in the low/standard dose group and 59.5% and 31.8% in the high-dose group, respectively.

CONCLUSION:

High-dose oral 5-aminolevulinic/protoporphyrin fluorescence is a safe and effective aid to the intraoperative detection of high-grade gliomas with high sensitivity and specificity. False-negative observations with a high dose do not seem to be less than that with a low/standard dose. The rate of FP observations with both groups remains very low.