bluuebunny/crossref_metadata_2025 huggingface dataset:
EL RESCATE BANCARIO: IMPORTANCIA Y EFECTOS SOBRE ALGUNOS SISTEMAS FINANCIEROS AFECTADOS
Authors: Calvo Bernardino Antonio , Martín de Vidales Carrasco Irene
Published: January 2024

El objetivo de este artículo es realizar un análisis del impacto que ha tenido la grave crisis financiera que, desde finales de 2008, hace estragos sobre los sistemas crediticios de algunos de los países que han precisado un rescate para sus sistemas bancarios; en concreto, para España, Alemania, Irlanda, Islandia y Estados Unidos. Para ello, y después de exponer los principales mecanismos de ayuda utilizados en cada uno de ellos, así como su importancia en el conjunto de sus economías, se presentarán los principales cambios que han sufrido sus sistemas bancarios, para lo cual se ha realizado un análisis de la evolución de algunos de sus datos económico-financieros más relevantes y de diversos indicadores de servicio bancario.
Närhet på distans: En guide för ledarskap på distansmed stöd av digitala arbetssätt
Authors: Martin Jason , Wallo Andreas , Gremyr Ida , Wiger Malin , Braf Ewa , Melin Ulf , Elg Mattias
Published: January 2024

Det du nu läser är en guide tänkt att användas som ett stöd och en vägledning till dig som i arbetet leder eller deltar i aktiviteter på distans med stöd av digitala arbetssätt. Guiden är utvecklad av forskare och organisationer i flera forskningsprojekt som studerar möjligheter och ut­maningar i ledarskap på distans med stöd av digitala ar­betssätt. Guiden vänder sig i första hand till er som är chefer och ledare med ansvar för att planera och genomföra aktivite­ter på distans med stöd av digitala arbetssätt, men den kan även läsas av medarbetare och andra funktioner i era orga­nisationer. En central del i guiden är ”verktygslådan” där vi, utifrån våra egna forskningsresultat samt med stöd av tidigare forskning, har satt ihop ett urval av praktiska verktyg som kan användas för att möjliggöra ett effektivare ledarskap på distans. Guiden och verktygen i verktygslådan tar avstamp i var­dagsnära situationer och aktiviteter som vi i våra forsk­ningsprojekt sett innehåller stor potential att förbättra hur arbete på distans med stöd av digitala arbetssätt kan orga­niseras och ledas. Vi visar vanligt förekommande arbetssätt och verktyg och ger konkreta och praktiska tips på hur ni kan arbeta tillsammans för att kunna uppnå bättre resultat, lära och utveckla både för individer och för organisationen samt bidra till bättre hälsa och välbefinnande. Guiden kan ses som en palett av arbetssätt och verktyg som ni antingen kan pröva direkt och/eller ha som under­lag för diskussion i syfte att ta fram egna, skräddarsydda arbetssätt. Använd den som inspiration och hjälpmedel för att utveckla ditt ledarskap och medarbetarskap samt ditt sätt att leda och möjliggöra digitala aktiviteter på distans. Om du vill testa någon eller några av de verktyg och ar­betssätt som presenteras i guiden tillsammans forskare så hör av dig till Jason Martin (jason.martin@liu.se) eller Andreas Wallo (andreas.wallo@liu.se) på Linköpings universitet.
Duplex droplet digital PCR detection of Streptococcus uberis and Streptococcus dysgalactiae, major etiological agents of bovine mastitis
Authors: Diana Leticia , Traglia German , Diana Virginia , Calvinho Luis , Laporta Jimena , Iriarte Andrés , Puentes Rodrigo
Published: January 2024

Bovine mastitis is one of the most important diseases affecting dairy cattle worldwide, resulting in significant economic losses due to high costs mainly associated with decreased production, antimicrobial treatment, and early culling of animals. The genus Streptococcus is among the primary bacterial pathogens causing bovine mastitis worldwide. The correct and timely diagnosis of mastitis is critical for the dairy industry, not only from the point of view of milk hygiene but also for economic, public health, and animal welfare reasons. Herein, we developed a diagnostic test of bovine intramammary infection employing a duplex droplet digital PCR (dddPCR) to detect and quantify Streptococcus uberis and Streptococcus dysgalactiae in milk, which outperforms the gold standard culture-based technique and the endpoint PCR. Indeed the detection limit for cultures and mock samples for dddPCR was a hundred times lower than the endpoint PCR. Additionally, the CFU/mL estimated based on the number of copies/uL obtained through dddPCR exhibited a strong correlation with the observed CFU/mL from the culture (r^2 > 0.99, p-value < 0.001), indicating that dddPCR provides a dependable estimate of this parameter. Moreover, the sensitivity of endpoint PCR, determined from artificial samples, was 40% for S. uberis and 55.4% for S. dysgalactiae meanwhile, the sensitivity of dddPCR was 80% and 100% for S. uberis and S. dysgalactiae, respectively, while the specificity was 100% for both techniques and pathogens. In conclusion, we propose a robust and reliable technique standardized for detecting and quantifying two of the most important bacteria that cause bovine mastitis. This dddPCR method may be particularly suitable to detect pathogens in milk samples with low bacterial loads or intermittently shedding and should be further tested with a larger sample size in future research.
Gradually decreasing daylength after smoltification induced by “winter signal“ reduced sexual maturation in male Atlantic salmon
Authors: Skjold Vetle , Rørvik Kjell-Arne , Sveen Lene , Burgerhout Erik , Mota Vasco C. , Weihe Rúni , Ytrestøyl Trine , Bou Marta , Jacobsen Hans Jákup , Allaoui Giovanni , Fuskevåg Ole-Martin , Dessen Jens-Erik
Published: January 2024

Introduction

Maturation in seawater-adapted (smoltified) male Atlantic salmon is undesirable yet frequently reported in fish weighing up to 1 kg reared under intensive conditions in land-based facilities. Although the photoperiod regulates both smoltification and maturation, the optimal post-smoltification regimen for the prevention of maturation is unclear.

Methods

In this study, mixed-sex Atlantic salmon weighing 95 g were exposed to three different photoperiod regimes: continuous daylength, gradually decreasing daylength, and short-to-long daylength after the induction of smoltification by the “winter signal” (12 h:12 h light:dark). Fish were maintained under these conditions in triplicate for 18 weeks in a brackish water flow-through system at 12°C and with a salinity of 20 ppt. This initial phase was followed by a grow-out period (1 kg–2.5 kg) in seawater (32-ppt salinity) at 13°C for 11 weeks, with exposure to decreasing daylength. Throughout the 29-week study, body condition, gonad development, and morphological traits were assessed. Additionally, during exposure to brackish water, serum 11-ketotestosterone (11-KT) levels were quantified, and the testes were examined histologically. Upon termination of the study, the maturation rate was determined.

Results

This study exclusively detected maturation among male salmon. Under continuous light exposure, the number of fish initiating maturity steadily increased from week 8 and continued to increase in the subsequent samplings. In the short-to-long daylength group, a subset of male fish showed elevated 11-KT levels at week 14, although their gonadal development and morphological changes were not evident until week 18. Male fish exposed to decreasing daylength showed no substantial increase in 11-KT levels, although a few fish exhibited advanced gonad development by week 18. At the end of the trial, markedly lower percentages of maturing and fully mature male fish were observed among those fish previously exposed to decreasing daylength. The maturation rates at study termination were 44.4% for the short-to-long daylength group, 29.4% for the continuous daylength group, and 4.3% for the decreasing daylength group.

Discussion

These results show that photoperiod can be utilized to regulate maturation in male Atlantic salmon. In addition, decreasing the photoperiod after smoltification seems to limit early sexual maturation without compromising body size development. Thus, decreasing the photoperiod could be utilized to limit maturation in the production of post-smolt salmon or salmon in land-based facilities.
Whole genome sequencing and annotation of Daedaleopsis sinensis, a wood-decaying fungus significantly degrading lignocellulose
Authors: Ma Jin-Xin , Wang Hao , Jin Can , Ye Yi-Fan , Tang Lu-Xin , Si Jing , Song Jie
Published: January 2024

Daedaleopsis sinensis is a fungus that grows on wood and secretes a series of enzymes to degrade cellulose, hemicellulose, and lignin and cause wood rot decay. Wood-decaying fungi have ecological, economic, edible, and medicinal functions. Furthermore, the use of microorganisms to biodegrade lignocellulose has high application value. Genome sequencing has allowed microorganisms to be analyzed from the aspects of genome characteristics, genome function annotation, metabolic pathways, and comparative genomics. Subsequently, the relevant information regarding lignocellulosic degradation has been mined by bioinformatics. Here, we sequenced and analyzed the genome of D. sinensis for the first time. A 51.67-Mb genome sequence was assembled to 24 contigs, which led to the prediction of 12,153 protein-coding genes. Kyoto Encyclopedia of Genes and Genomes database analysis of the D. sinensis data revealed that 3,831 genes are involved in almost 120 metabolic pathways. According to the Carbohydrate-Active Enzyme database, 481 enzymes are found in D. sinensis, of which glycoside hydrolases are the most abundant. The genome sequence of D. sinensis provides insights into its lignocellulosic degradation and subsequent applications.
Near-infrared light-heatable platinum nanozyme for synergistic bacterial inhibition
Authors: Li Xue , Zhu Weisheng , Zhou Yuan , Wang Nan , Gao Xiangfan , Sun Suling , Cao Mengting , Zhang Zhijun , Hu Guixian
Published: January 2024

The development of non-antibiotic strategies for bacterial disinfection is of great clinical importance. Among recently developed different antimicrobial strategies, nanomaterial-mediated approaches, especially the photothermal way and reactive oxygen species (ROS)-generating method, show many significant advantages. Although promising, the clinical application of nanomaterials is still limited, owing to the potential biosafety issues. Further improvement of the antimicrobial activity to reduce the usage, and thus reduce the potential risk, is an important way to increase the clinical applicability of antibacterial nanomaterials. In this paper, an antimicrobial nanostructure with both an excellent photothermal effect and peroxidase-like activity was constructed to achieve efficient synergistic antimicrobial activity. The obtained nano-antimicrobial agent (ZIF-8@PDA@Pt) can not only efficiently catalyze the production of ROS from H2O2 to cause damage to bacteria but also convert the photon energy of near-infrared light into thermal energy to kill bacteria, and the two synergistic effects induced in a highly efficient antimicrobial activity. This study not only offers a new nanomaterial with efficient antibacterial activity but also proposes a new idea for constructing synergistic antibacterial properties.
The role of microRNA-325-3p as a critical player in cell death in NSCs and astrocytes
Authors: Lee Yukyeong , Lee Seung-Won , Jeong Dahee , Lee Hye Jeong , Ko Kinarm
Published: January 2024

Neural stem cells (NSCs) are defined by their ability to self-renew and generate various cell types within the nervous system. Understanding the underlying mechanism by which NSCs proliferate and differentiate is crucial for the efficient modulation of in vivo neurogenesis. MicroRNAs are small non-coding RNAs controlling gene expression concerned in post-transcriptional control by blocking messenger RNA (mRNA) translation or degrading mRNA. MicroRNAs play a role as modulators by matching target mRNAs. Recent studies have discussed the biological mechanism of microRNA regulation in neurogenesis. To investigate the role of microRNAs in NSCs and NSC-derived glial cells, we screened out NSC-specific microRNAs by using miRNome-wide screening. Then, we induced downregulation by the sponge against the specific microRNA to evaluate the functional role of the microRNA in proliferation, differentiation, and apoptosis in NSCs and NSC-derived astrocytes. We found that microRNA-325-3p is highly expressed in NSCs and astrocytes. Furthermore, we showed that microRNA-325-3p is a regulator of apoptosis by targeting brain-specific angiogenesis inhibitor (BAI1), which is a receptor for apoptotic cells and expressed in the brain and cultured astrocytes. Downregulation of microRNA-325-3p using an inducible sponge system induced cell death by regulating BAI1 in NSCs and NSC-derived astrocytes. Overall, our findings can provide an insight into the potential roles of NSC-specific microRNAs in brain neurogenesis and suggest the possible usage of the microRNAs as biomarkers of neurodegenerative disease.
Bridging the gap: glucose transporters, Alzheimer’s, and future therapeutic prospects
Authors: Albaik Mai , Sheikh Saleh Dalaa , Kauther Dana , Mohammed Hajira , Alfarra Shurouq , Alghamdi Adel , Ghaboura Nehmat , Sindi Ikhlas A.
Published: January 2024

Glucose is the major source of chemical energy for cell functions in living organisms. The aim of this mini-review is to provide a clearer and simpler picture of the fundamentals of glucose transporters as well as the relationship of these transporters to Alzheimer’s disease. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic databases (PubMed and ScienceDirect) were used to search for relevant studies mainly published during the period 2018–2023. This mini-review covers the two main types of glucose transporters, facilitated glucose transporters (GLUTs) and sodium-glucose linked transporters (SGLTs). The main difference between these two types is that the first type works through passive transport across the glucose concentration gradient. The second type works through active co-transportation to transport glucose against its chemical gradient. Fluctuation in glucose transporters translates into a disturbance of normal functioning, such as Alzheimer’s disease, which may be caused by a significant downregulation of GLUTs most closely associated with insulin resistance in the brain. The first sign of Alzheimer’s is a lack of GLUT4 translocation. The second sign is tau hyperphosphorylation, which is caused by GLUT1 and 3 being strongly upregulated. The current study focuses on the use of glucose transporters in treating diseases because of their proven therapeutic potential. Despite this, studies remain insufficient and inconclusive due to the complex and intertwined nature of glucose transport processes. This study recommends further understanding of the mechanisms related to these vectors for promising future therapies.
Clinical cure induced by pegylated interferon α-2b in the advantaged population of chronic hepatitis B virus infection: a retrospective cohort study
Authors: Wen Chaojing , Wang Yixuan , Tian Haoyue , Lei Yu , Wang Zhiyi , Cai Dachuan , Zhou Zhi , Shi Xiaofeng
Published: January 2024

Background

Among the advantaged population with clinical cure of chronic hepatitis B, chronic inactive hepatitis B virus carriers (IHCs) and nucleoside analog-experienced patients have similar serological manifestations. This study established non-interferon-treated groups as controls to compare the efficacy of pegylated interferon α-2b (Peg-IFNα-2b) in achieving clinical cure between IHCs and nucleoside analog (NA)-experienced patients.

Method

A total of 270 patients were enrolled in this observational study. The IHC cohort comprised 55 patients who received Peg-IFNα-2b (Peg-IFN group), and the other 70 patients did not receive any antiviral treatment (untreated group). Patients treated with NAs were divided into two groups: one group (70 patients) receiving NA add-on Peg-IFNα-2b therapy regimen (NA add-on Peg-IFN group) and another group (75 patients) receiving continuous NA monotherapy (NA group). The primary endpoints were hepatitis B surface antigen (HBsAg) clearance and HBsAg seroconversion at 48 weeks and 72 weeks.

Results

At 48 weeks, 65.5% (36/55) and 52.9% (37/70) patients achieved HBsAg clearance in the Peg-IFN group and NA add-on Peg-IFN group, respectively (p = 0.156). HBsAg seroconversion was achieved in 47.3% (26/55) of the Peg-IFN group and 34.3% (24/70) of the NA add-on Peg-IFN group (p = 0.141). At the follow-up of 72 weeks, 36 patients in the Peg-IFN group achieved HBsAg loss (65.5%, 36/55), and 33 patients in the NA add-on Peg-IFN group achieved HBsAg clearance (47.1%, 33/70), which were significantly higher than in the Peg-IFN group (p = 0.041). The HBsAg seroconversion rates in the Peg-IFN group and NA add-on Peg-IFN group at 72 weeks were 45.5% (25/55) and 32.9% (23/70), respectively (p = 0.151). No patient achieved HBsAg clearance or seroconversion in the NA group and untreated group. Furthermore, the receiver operating characteristic curve showed baseline HBsAg< 72 IU/mL, and the decline of HBsAg of more than 80% and 98% from baseline to 12 and 24 weeks provided good predictions for HBsAg clearance. Meanwhile, 77% of patients with baseline HBsAg< 100 IU/mL achieved a clinical cure at 48 weeks.

Conclusion

Peg-IFNα-2b results in a high rate of HBsAg clearance and seroconversion in both IHCs and NA-experienced patients, especially for those patients who have HBsAg below 100 IU/mL.
No role of working memory in the relation between mental rotation and postural stability
Authors: Hofmann Philipp , Siebertz Markus , Jansen Petra
Published: January 2024

This study investigated the relationship between mental rotation ability and postural stability, with a focus on the role of the visuospatial sketchpad of working memory, as it has been found to be correlated with both concepts. A total of 87 healthy young adults completed a postural stability task on a force plate, a mental rotation task, and both spatial and object working memory tasks in a counterbalanced order. Bayesian correlations revealed weak positive correlations between mental rotation and postural stability, as well as a correlation between mental rotation and spatial working memory. A weak association was also observed between mental rotation and object working memory. No correlation was found between the working memory components and postural stability. Furthermore, the results showed that spatial working memory did not play a crucial role in predicting postural stability. We conclude that the visuospatial sketchpad, particularly the spatial working memory component, cannot explain the relationship between mental rotation and postural stability.
Cardiovascular health of offspring conceived by assisted reproduction technology: a comprehensive review
Authors: Li Jie , Liu Yang , Huang Hefeng , Jin Li
Published: January 2024

Recently, the use of assisted reproductive technology (ART) has rapidly increased. As a result, an increasing number of people are concerned about the safety of offspring produced through ART. Moreover, emerging evidence suggests an increased risk of cardiovascular disease (CVD) in offspring conceived using ART. In this review, we discuss the epigenetic mechanisms involved in altered DNA methylation, histone modification, and microRNA expression, as well as imprinting disorders. We also summarize studies on cardiovascular changes and other risk factors for cardiovascular disease, such as adverse intrauterine environments, perinatal complications, and altered metabolism following assisted reproductive technology (ART). Finally, we emphasize the epigenetic mechanisms underlying the increased risk of CVD in offspring conceived through ART, which could contribute to the early diagnosis and prevention of CVD in the ART population.
Associations of gestational diabetes and proton density fat fraction of vertebral bone marrow and paraspinal musculature in premenopausal women
Authors: Harada Saori , Gersing Alexandra S. , Stohldreier Yannick , Dietrich Olaf , Lechner Andreas , Seissler Jochen , Ferrari Uta , Pappa Eleni , Hesse Nina
Published: January 2024

Background and objective

Fat content in bones and muscles, quantified by magnetic resonance imaging (MRI) as a proton density fat fraction (PDFF) value, is an emerging non-invasive biomarker. PDFF has been proposed to indicate bone and metabolic health among postmenopausal women. Premenopausal women with a history of gestational diabetes (GDM) carry an increased risk of developing type 2 diabetes and an increased risk of fractures. However, no studies have investigated the associations between a history of GDM and PDFF of bone or of paraspinal musculature (PSM), composed of autochthonous muscle (AM) and psoas muscle, which are responsible for moving and stabilizing the spine. This study aims to investigate whether PDFF of vertebral bone marrow and of PSM are associated with a history of GDM in premenopausal women.

Methods

A total of 37 women (mean age 36.3 ± 3.8 years) who were 6 to 15 months postpartum with (n=19) and without (n=18) a history of GDM underwent whole-body 3T MRI, including a chemical shift encoding-based water-fat separation. The PDFF maps were calculated for the vertebral bodies and PSM. The cross-sectional area (CSA) of PSM was obtained. Associations between a history of GDM and PDFF were assessed using multivariable linear and logistic regression models.

Results

The PDFF of the vertebral bodies was significantly higher in women with a history of GDM (GDM group) than in women without (thoracic: median 41.55 (interquartile range 32.21-49.48)% vs. 31.75 (30.03-34.97)%; p=0.02, lumbar: 47.84 (39.19-57.58)% vs. 36.93 (33.36-41.31)%; p=0.02). The results remained significant after adjustment for age and body mass index (BMI) (p=0.01-0.02). The receiver operating characteristic curves showed optimal thoracic and lumbar vertebral PDFF cutoffs at 38.10% and 44.18%, respectively, to differentiate GDM (AUC 0.72 and 0.73, respectively, sensitivity 0.58, specificity 0.89). The PDFF of the AM was significantly higher in the GDM group (12.99 (12.18-15.90)% vs. 10.83 (9.39-14.71)%; p=0.04) without adjustments, while the CSA was similar between the groups (p=0.34).

Conclusion

A history of GDM is significantly associated with a higher PDFF of the vertebral bone marrow, independent of age and BMI. This statistical association between GDM and increased PDFF highlights vertebral bone marrow PDFF as a potential biomarker for the assessment of bone health in premenopausal women at risk of diabetes.
Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata
Authors: Zheng Xue-Yong , Ma Yan-Ping , Zhang Bo , Chen Yan-Xin , Tang Lei , Tai Xiao-Hua , Cao Jia-Hao
Published: January 2024

Background

Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.

Objectives

This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata.

Methods

genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein–protein interaction networks.

Result

Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12–1.75, p = 3.03×10−3) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein–protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3.

Conclusion

This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.
Sister haplotypes and recombination disequilibrium: a new approach to identify associations of haplotypes with complex diseases
Authors: Liao Shun-Yao , Tan Yuan-De
Published: January 2024

Haplotype-based association analysis has several advantages over single-SNP association analysis. However, to date all haplotype-disease associations have not excluded recombination interference among multiple loci and hence some results might be confounded by recombination interference. Association of sister haplotypes with a complex disease, based on recombination disequilibrium (RD) was presented. Sister haplotypes can be determined by translating notation of DNA base haplotypes to notation of genetic genotypes. Sister haplotypes provide haplotype pairs available for haplotype-disease association analysis. After performing RD tests in control and case cohorts, a two-by-two contingency table can be constructed using sister haplotype pair and case-control pair. With this standard two-by-two table, one can perform classical Chi-square test to find statistical haplotype-disease association. Applying this method to a haplotype dataset of Alzheimer disease (AD), association of sister haplotypes containing ApoE3/4 with risk for AD was identified under no RD. Haplotypes within gene IL-13 were not associated with risk for breast cancer in the case of no RD and no association of haplotypes in gene IL-17A with risk for coronary artery disease were detected without RD. The previously reported associations of haplotypes within these genes with risk for these diseases might be due to strong RD and/or inappropriate haplotype pairs.
Osteo-immunological impact of radon spa treatment: due to radon or spa alone? Results from the prospective, thermal bath placebo-controlled RAD-ON02 trial
Authors: Eckert Denise , Evic Megi , Schang Jasmin , Isbruch Maike , Er Melissa , Dörrschuck Lea , Rapp Felicitas , Donaubauer Anna-Jasmina , Gaipl Udo S. , Frey Benjamin , Fournier Claudia
Published: January 2024

Musculoskeletal disorders (MSDs) are associated with pain and lead to reduced mobility and quality of life for patients. Radon therapy is used as alternative or complementary to pharmaceutical treatments. According to previous reports, radon spa leads to analgesic and anti-inflammatory effects, but the cellular and molecular mechanisms are widely unknown. A previous study (RAD-ON01) revealed, that bone erosion markers like collagen fragments (C-terminal telopeptide, CTX) are reduced after radon spa treatment in serum of patients with degenerative MSDs. Within the scope of the prospective, placebo-controlled RAD-ON02 trial presented here, we analyzed the influence of radon and thermal spa treatment on osteoclastogenesis. From patient blood, we isolate monocytes, seeded them on bone slices and differentiated them in the presence of growth factors into mature osteoclasts (mOCs). Subsequent analysis showed a smaller fraction of mOCs after both treatments, which was even smaller after radon spa treatment. A significantly reduced resorbed area on bone slices reflects this result. Only after radon spa treatment, we detected in the serum of patients a significant decrease of receptor activator of NF-κB ligand (RANKL), which indicates reduced differentiation of OCs. However, other markers for bone resorption (CTX) and bone formation (OPG, OCN) were not altered after both treatments. Adipokines, such as visfatin and leptin that play a role in some MSD-types by affecting osteoclastogenesis, were not changed after both treatments. Further, also immune cells have an influence on osteoclastogenesis, by inhibiting and promoting terminal differentiation and activation of OCs, respectively. After radon treatment, the fraction of Treg cells was significantly increased, whereas Th17 cells were not altered. Overall, we observed that both treatments had an influence on osteoclastogenesis and bone resorption. Moreover, radon spa treatment affected the Treg cell population as well as the Th17/Treg ratio were affected, pointing toward a contribution of the immune system after radon spa. These data obtained from patients enrolled in the RAD-ON02 trial indicate that radon is not alone responsible for the effects on bone metabolism, even though they are more pronounced after radon compared to thermal spa treatment.
Beyond mere respect: new perspectives on dignity for healthcare workplace learning
Authors: Klinner Christiane , Dario Amabile Borges , Bell Amani , Nisbet Gillian , Penman Merrolee , Monrouxe Lynn V.
Published: January 2024

Introduction

Although dignity in workplace learning in healthcare is gathering interest, we know little about stakeholders’ conceptualizations in this area across professional groups. Dignity breaches in workplace learning are common, often with serious and long-lasting consequences for the affected. Conceptualizations shape behaviours and experiences. To prevent dignity violations in students’ learning, it is thus important to understand stakeholders’ understandings of the topic. This study therefore explores the dignity conceptualizations around workplace learning that students, placement educators and university staff hold across seven allied health professional groups.

Methods

Using a social constructionist perspective, we conducted individual and group narrative interviews (n = 51) with students, placement educators and university workplace learning staff from seven allied health professional groups. We used the 5-step Framework Analysis to explore and develop themes, identifying differences and similarities across stakeholder groups.

Results

We identified eight distinct, yet interrelated, dimensions of dignity from participants’ narratives: dignity as respect, dignity as self-x (the various relationships we have with ourselves), dignity as feeling safe, dignity as understanding otherness, dignity as supporting others, dignity as equality, dignity as professionalism, and dignity as belonging. Dignity as respect was identified across all participants, although mutual respect and a culture of respect were only present in academic participants’ talk. The remaining seven dimensions all present important factors extending our understanding of the construct of dignity.

Discussion

In line with existing research, our study identifies the absence of an unambiguous, positive conceptualization of dignity in workplace learning among stakeholders. It adds novelty in two ways: by identifying dignity dimensions that require informed action beyond respecting others, and by revealing a tension between dignity as professionalism and dignity as equality. We suggest revising existing dignity concepts in workplace learning to address this tension and to reinforce that active care, team integration and skilled support are all non-negotiable elements of dignified behaviour within workplace learning.
Case report: abemaciclib-induced syndrome of inappropriate antidiuretic hormone (SIADH) without underlying kidney injury in a patient with early-stage estrogen receptor (ER)+ breast cancer
Authors: Carleton Neil , Foldi Julia
Published: January 2024

The CDK4/6 inhibitor, abemaciclib, is now the standard of care adjuvant therapy for patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) tumors at high risk of recurrence. Real-world usage uncovers emerging side effects that may have been previously unreported in clinical trials. Here, we present the clinical course of a patient who developed a syndrome of inappropriate antidiuretic hormone (SIADH) without underlying kidney injury due to abemaciclib use.
Lactobacillus acidophilus and its metabolite ursodeoxycholic acid ameliorate ulcerative colitis by promoting Treg differentiation and inhibiting M1 macrophage polarization
Authors: Deng Song , Pei Chaoying , Cai Kaiwei , Huang Wenyi , Xiao Xiaoyi , Zhang Xingyuan , Liang Rongyao , Chen Yanlong , Xie Zhiyong , Li Pei , Liao Qiongfeng
Published: January 2024

Lactobacillus acidophilus (LA) is a common clinical probiotic that improves ulcerative colitis (UC) by restoring intestinal immune balance. However, the interaction of LA with the gut microbiota and its metabolites in the treatment of UC remains unknown. Therefore, this study seeks to elucidate whether the gut microbiota and its metabolites act as pivotal effectors in LA’s therapeutic mechanisms and how precisely they modulate intestinal immunity. In this study, we verified that LA can obviously ameliorate the disease severity, and regulate intestinal immune disorders in UC mice. Subsequently, antibiotic (ABX)-mediated depletion of the gut microflora demonstrated that the therapeutic efficiency of LA was closely associated with gut microbiota. In addition, the results of metabolomics revealed that ursodeoxycholic acid (UDCA), a metabolite of intestinal flora, may be a potential effector molecule mediating therapeutic effects of LA. Indeed, we found that UDCA can improve the macro pathological characteristics of UC mice, and through a comprehensive set of in vivo and in vitro experiments, we discovered that UDCA exerts dual effects on immune regulation. Firstly, it promotes the differentiation of Treg cells, resulting in increased secretion of anti-inflammatory cytokines. Secondly, UDCA inhibits the polarization of M1 macrophages, effectively reducing the secretion of pro-inflammatory cytokines. Moreover, we found that UDCA regulation of immune response is directly related to the RapGap/PI3K-AKT/NF-κB signaling pathway. In conclusion, LA and its metabolite, UDCA, may treat UC by activating the RapGap/PI3K-AKT/NF-κB signaling pathway and modulating Treg cells and M1 macrophages. All in all, our findings highlight the potential of microbial metabolites in enhancing probiotic for UC treatment.
Effects of STN-DBS on cognition and mood in young-onset Parkinson’s disease: a two-year follow-up
Authors: Hong Jun , Xie Huimin , Chen Yuhua , Liu Di , Wang Tianyu , Xiong Kun , Mao Zhiqi
Published: January 2024

Background

The effects of subthalamic nucleus deep brain stimulation (STN-DBS) on the cognition and mood of patients with PD are still not uniformly concluded, and young-onset Parkinson’s disease (YOPD) is even less explored.

Objective

To observe the effectiveness of STN-DBS on the cognition and mood of YOPD patients.

Methods

A total of 27 subjects, with a mean age at onset of 39.48 ± 6.24 and age at surgery for STN-DBS of 48.44 ± 4.85, were followed up preoperatively and for 2 years postoperatively. Using the Unified Parkinson disease rating scale (UPDRS), H&Y(Hoehn and Yahr stage), 39-Item Parkinson’s Disease Questionnaire (PDQ-39), Mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) to assess motor, cognition, and mood.

Results

At the 2-year follow-up after STN-DBS, YOPD patients showed significant improvements in motor and quality of life (UPDRS III: p < 0.001, PDQ-39: p < 0.001); overall cognition was not significantly different from preoperative (MMSE: p = 0.275, MoCA: p = 0.913), although language function was significantly impaired compared to preoperative (MMSE: p = 0.004, MoCA: p = 0.009); depression and anxiety symptoms also improved significantly (HAMD: p < 0.001, HAMA: p < 0.001) and the depression score correlated significantly with motor (preoperative: r = 0.493, p = 0.009), disease duration (preoperative: r = 0.519, p = 0.006; postoperative: r = 0.406, p = 0.036) and H&Y (preoperative: r = 0.430, p = 0.025; postoperative: r = 0.387, p = 0.046); total anxiety scores were also significantly correlated with motor (preoperative: r = 0.553, p = 0.003; postoperative: r = 0.444, p = 0.020), disease duration (preoperative: r = 0.417, p = 0.031), PDQ-39 (preoperative: r = 0.464, p = 0.015) and H&Y (preoperative: r = 0.440, p = 0.022; postoperative: r = 0.526, p = 0.005).

Conclusion

STN-DBS is a safe and effective treatment for YOPD. The mood improved significantly, and overall cognition was not impaired, were only verbal fluency decreased but did not affect the improvement in quality of life.
Estradiol reduction through aromatase inhibition impairs cocaine seeking in male rats
Authors: Alvarado-Torres John K. , Morales-Silva Roberto , Sanabria Ponce de Leon Alexia , Rodriguez-Torres Genesis , Perez-Torres Joshua , Perez-Perez Yobet , Mueller Devin , Sepulveda-Orengo Marian T.
Published: January 2024

Introduction

Clinical and preclinical research on cocaine use disorder (CUD) has shown that sex differences in drug seeking are influenced by hormonal fluctuations. Estradiol (E2), a sex steroid hormone, has been linked to female drug effects, vulnerability to use/abuse, and psychosocial factors. Preclinical studies show that estradiol in females facilitates the extinction of cocaine-seeking behavior indicating a possible role in regulating extinction learning. Similar to females, males’ brains contain the aromatase enzyme which converts testosterone to estradiol. However, it is unclear whether estradiol plays a role in male extinction learning as it does in females. Furthermore, how endogenously aromatized estradiol affects drug addiction in males is unknown. Therefore, this study investigated whether endogenous estradiol regulates cocaine seeking in male rats. We hypothesized that decreased aromatase enzyme activity, resulting in decreased estradiol synthesis in male brains, will impair extinction learning leading to increased cocaine-seeking behavior.

Methods

This hypothesis was tested using cocaine-conditioned place preference (CPP), and short access self-administration (SA), followed by extinction and reinstatement. Before each extinction session for CPP or SA, male rats received an injection of either 1 (low dose) or 2.5 mg/kg (high dose) of the aromatase inhibitor Fadrozole (FAD), or vehicle.

Results

FAD groups showed dose-dependent effects on cocaine-seeking behavior compared to the vehicle group during CPP extinction. Specifically, low dose FAD facilitated extinction of cocaine CPP, whereas high dose FAD impaired it. In contrast, neither dose of FAD had any effects on the extinction of cocaine SA. Interestingly, only the low dose FAD group had decreased active lever pressing during cue- and cocaine-primed reinstatement compared to the vehicle group. Neither dose of FAD had an effect on sucrose extinction or reinstatement of sucrose seeking.

Discussion

These results from CPP experiments suggest that estradiol may impact extinction learning, as a low dose of FAD may strengthen the formation of cocaine extinction memory. Additionally, in male rats undergoing cocaine SA, the same low dose of aromatase inhibitor effectively reduced reinstatement of cocaine-seeking behavior. Thus, estradiol impacts cocaine seeking and extinction in both males and females, and it may also influence the development of sex-specific treatment strategies for CUD.
Serum GFAP, NfL, and tau concentrations are associated with worse neurobehavioral functioning following mild, moderate, and severe TBI: a cross-sectional multiple-cohort study
Authors: Edwards Katie A. , Lange Rael T. , Lippa Sara M. , Brickell Tracey A. , Gill Jessica M. , French Louis M.
Published: January 2024

Introduction

The purpose of this study was to examine whether blood-based biomarkers associate with neurobehavioral functioning at three time points following traumatic brain injury (TBI).

Materials and methods

Participants were 328 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence (DVBIC-TBICoE) 15-Year Longitudinal TBI Study, recruited into three groups: uncomplicated mild TBI (MTBI, n = 155); complicated mild, moderate, severe TBI combined (STBI, n = 97); non-injured controls (NIC, n = 76). Participants were further divided into three cohorts based on time since injury (≤12 months, 3–5 years, and 8–10 years). Participants completed the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF) and underwent blood draw to measure serum concentrations of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau. A total of 11 MMPI-2-RF scales were examined (e.g., depression, anxiety, anger, somatic, cognitive symptoms). Stepwise hierarchical regression models were conducted within each group.

Results

Significant associations were found between biomarkers and MMPI-2-RF scales (all p < 0.05; R2Δ > 0.10). GFAP was inversely related to (a) neurological complaints in the MTBI group at ≤12 months, (b) demoralization, anger proneness in the STBI group at ≤12 months, and (c) head pain complaints in the STBI group at 8–10 years. NfL was (a) related to low positive emotions in the NIC group; and inversely related to (b) demoralization, somatic complaints, neurological complaints, cognitive complaints in the MTBI group at ≤12 months, (c) demoralization in the STBI group at ≤12 months, and (d) demoralization, head pain complaints, stress/worry in the STBI group at 3–5 years. In the STBI group, there were meaningful findings (R2Δ > 0.10) for tau, NFL, and GFAP that did not reach statistical significance.

Discussion

Results indicate worse scores on some MMPI-2-RF scales (e.g., depression, stress/worry, neurological and head pain complaints) were associated with lower concentrations of serum GFAP, NfL, and tau in the sub-acute and chronic phase of the recovery trajectory up to 5 years post-injury, with a reverse trend observed at 8–10 years. Longitudinal studies are needed to help elucidate any patterns of association between blood-based biomarkers and neurobehavioral outcome over the recovery trajectory following TBI.
Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis
Authors: Howard James F. , Bril Vera , Vu Tuan , Karam Chafic , Peric Stojan , De Bleecker Jan L. , Murai Hiroyuki , Meisel Andreas , Beydoun Said R. , Pasnoor Mamatha , Guglietta Antonio , Van Hoorick Benjamin , Steeland Sophie , T’joen Caroline , Utsugisawa Kimiaki , Verschuuren Jan , Mantegazza Renato ,   the ADAPT+ Study Group
Published: January 2024

Objective

ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).

Methods

ADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.

Results

As of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab−. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab− participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5–7.6]).

Conclusion

Results of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG.

Clinical trial registration

https://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403.
Case report: Significance of the large rhomboid lip in microvascular decompression: insights from two clinical cases
Authors: Ding Feiyu , Li Pan , Zuo Xiaozhou , Song Wenxiong , Xiao Yong , Wang Dong , Geng Liangyuan , Hu Xinhua , Yang Kun , Liu Yong , Zou Yuanjie
Published: January 2024

The rhomboid lip (RL) is a layer of neural tissue that extends outside the fourth ventricle and is connected to the lateral recess of the fourth ventricle. Although this anatomical structure has been rigorously studied, it is often overlooked in microvascular decompression (MVD) surgery. In this report, we present two cases, one of hemifacial spasm (HFS) and one of glossopharyngeal neuralgia (GPN), in which a large RL was observed during surgery. We found that a large RL is easily confused with arachnoid cysts, and accurate identification and dissection are important to protect the lower cranial nerves.