bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated precision medicine approach in major depressive disorder: a study protocol to create a new algorithm for the prediction of treatment response
Authors: Baune Bernhard T. , Minelli Alessandra , Carpiniello Bernardo , Contu Martina , Domínguez Barragán Jorge , Donlo Chus , Ferensztajn-Rochowiak Ewa , Glaser Rosa , Kelch Britta , Kobelska Paulina , Kolasa Grzegorz , Kopeć Dobrochna , Martínez de Lagrán Cabredo María , Martini Paolo , Mayer Miguel-Angel , Menesello Valentina , Paribello Pasquale , Perera Bel Júlia , Perusi Giulia , Pinna Federica , Pinna Marco , Pisanu Claudia , Sierra Cesar , Stonner Inga , Wahner Viktor T. H. , Xicota Laura , Zang Johannes C. S. , Gennarelli Massimo , Manchia Mirko , Squassina Alessio , Potier Marie-Claude , Rybakowski Filip , Sanz Ferran , Dierssen Mara
Published: January 2024

Major depressive disorder (MDD) is the most common psychiatric disease worldwide with a huge socio-economic impact. Pharmacotherapy represents the most common option among the first-line treatment choice; however, only about one third of patients respond to the first trial and about 30% are classified as treatment-resistant depression (TRD). TRD is associated with specific clinical features and genetic/gene expression signatures. To date, single sets of markers have shown limited power in response prediction. Here we describe the methodology of the PROMPT project that aims at the development of a precision medicine algorithm that would help early detection of non-responder patients, who might be more prone to later develop TRD. To address this, the project will be organized in 2 phases. Phase 1 will involve 300 patients with MDD already recruited, comprising 150 TRD and 150 responders, considered as extremes phenotypes of response. A deep clinical stratification will be performed for all patients; moreover, a genomic, transcriptomic and miRNomic profiling will be conducted. The data generated will be exploited to develop an innovative algorithm integrating clinical, omics and sex-related data, in order to predict treatment response and TRD development. In phase 2, a new naturalistic cohort of 300 MDD patients will be recruited to assess, under real-world conditions, the capability of the algorithm to correctly predict the treatment outcomes. Moreover, in this phase we will investigate shared decision making (SDM) in the context of pharmacogenetic testing and evaluate various needs and perspectives of different stakeholders toward the use of predictive tools for MDD treatment to foster active participation and patients’ empowerment. This project represents a proof-of-concept study. The obtained results will provide information about the feasibility and usefulness of the proposed approach, with the perspective of designing future clinical trials in which algorithms could be tested as a predictive tool to drive decision making by clinicians, enabling a better prevention and management of MDD resistance.
Comparing depression, anxiety, and quality of life in individuals with cardiac and non-cardiac chest pain
Authors: Zarean Elham , Samani Zahra Bahrami , Kheiri Soleiman , Torkian Samaneh
Published: January 2024

Background

Psychological factors are often overlooked as potential contributors to cardiovascular disease. This study aimed to investigate the relationship between depression, anxiety, and quality of life with chest pain origin.

Method

This cross-sectional study was performed from 2019 to 2020 and included participants from multiple medical centers across Shahrekord, Iran. Participants were recruited through advertisements in medical centers. Participants were divided into three groups: healthy control (n = 67), chest pain with cardiac origin (CCP) (n = 70), and chest pain with non-cardiac origin (NCCP) (n = 73). Data were collected using the Beck’s Anxiety scale, Beck’s Depression scale, and Short-Form Health Survey questionnaires. The chi-square, exact test, t-test, Kruskal–Wallis, and logistic regression models were used for statistical analysis. All analysis was performed using SPSS 26.

Results

The mean scores of depression and anxiety in the NCCP group (depression = 17.03 ± 11.93, anxiety = 17.18 ± 11.37) were significantly higher than those in the CCP (depression = 9.73 ± 5.76, anxiety = 8.77 ± 5.96) and healthy (depression = 7.00 ± 7.61, anxiety = 6.18 ± 7.63) groups (p < 0.05). The mean score of quality of life in the NCCP group (54.87 ± 12.66) was significantly lower than that in the CCP (76.31 ± 12.49) and healthy (80.94 ± 15.78) groups (p < 0.05). Patients with NCCP had higher odds of having depression (adjusted OR = 4.39, 95% CI: 1.25, 15.35) and lower odds for having mental quality of life scores than the CCP and health groups, respectively (adjusted OR = 0.90, 95% CI: 0.87, 0.94).

Conclusion

Our findings suggest that collaboration between psychiatrists and other specialists may be necessary to improve patients’ health conditions and quality of life.
Internet-based psychoeducation and support programme for relatives of young people with early psychosis: results of the first German-language intervention
Authors: Rus-Calafell Mar , Teismann Tobias , Kullmann Fine , Alatas Dilara , Ballero-Reque Cristina , Holewa Julia , Rüsberg Marilena , Brüne Martin , Paino Mercedes , Schneider Silvia
Published: January 2024

Background

International clinical guidelines recommend Family Interventions (FIs) especially for families of people at early stages of psychosis. The German S3 treatment guideline for schizophrenia gives FIs the highest level of clinical recommendation. However, some family relatives have limited access to these services due to health system constrains. Digital interventions have emerged as a solution to overcome this hindered access to evidence-based family interventions.

Objective

The present pilot study evaluates the feasibility and potential efficacy of the first German moderated online psychoeducation and support programme (ePSP) for relatives of people with early psychosis, with the additional purpose to improve accessibility and reduce waiting times.

Methods

A pre-post study was performed. A brief recruitment period was pre-established (10 weeks) to test potential improvement of regular therapy waiting times in Germany. A total of 25 relatives of people with early psychosis were recruited and received the 12-week moderated online intervention. Assessments were conducted at baseline and at post intervention. Acceptance of the intervention and the user’s experience were also evaluated at post intervention.

Results

Recruitment, retention rates and qualitative data support the feasibility and acceptability of the ePSP. Significant positive effects of the interventions were found on key therapeutic targets, including both primary outcomes (i.e., perceived stress and beliefs about the illness). Twenty-one participants also completed the open-ended questions of the user experience questionnaire, which yielded three main themes: most important modules, difficulties in using the programme and ways to improve ePSP.

Discussion

These results provide preliminary efficacy estimates for a fully powered RCT to investigate superiority (or equipoise) effects of the ePSP in comparison to the routine face-to-face family therapy groups. This future RCT will also allow further exploration of ePSP to improve access to psychological therapy for relatives of young people with psychosis, also in relation to the new ground-breaking Digital Healthcare Act in Germany.
Smartphone-delivered multicomponent lifestyle medicine intervention for improving mental health in a nonclinical population: a randomized controlled trial
Authors: Wong Vincent Wing-Hei , Tong Jessica Tsz-Yan , Shi Nga-Kwan , Ng Chee H. , Sarris Jerome , Ho Fiona Yan-Yee
Published: January 2024

Objective

To prevent the exacerbation of mental health burdens, a growing body of research has recommended a balanced approach that emphasizes both the delivery of mental health treatments to individuals with common mental disorders (CMDs) and the strengthening of protective factors for CMDs among nonclinical populations. This randomized controlled trial (RCT) evaluated the efficacy of a smartphone-delivered multicomponent lifestyle medicine (LM) intervention, Lifestyle Hub, for improving mental health among a nonclinical population of Chinese adults.

Methods

A total of 106 participants with Patient Health Questionnaire-9 total score < 10 and Generalized Anxiety Disorder 7-Item Scale <8 were randomly assigned to either the Lifestyle Hub intervention group (LH, n = 53) or the waitlist control group (WL, n = 53). Lifestyle Hub is an 8-week smartphone-delivered multicomponent LM intervention developed based on the transtheoretical model. The intervention components included lifestyle psychoeducation, physical activity, diet and nutrition, stress management, sleep management, and motivation and goal-setting techniques. Assessments were conducted at baseline, immediate post-intervention, and 1-month follow-up (LH only).

Results

The linear mixed effect model based on the intention-to-treat principle indicated that Lifestyle Hub significantly improved overall mental health, depressive symptoms, anxiety symptoms, stress, insomnia severity, overall health-promoting behaviors, dietary quality, and stress management compared to the WL group at immediate post-intervention (d = 0.13–0.56). No significant between-group differences were observed in terms of functional impairment, health-related quality of life, health responsibility, physical activity level, spiritual growth, and interpersonal relations. The intervention gains in the LH group were maintained at 1-month follow-up. The LH participants indicated that Lifestyle Hub was an acceptable intervention for improving mental health, although a significantly higher level of study attrition was observed in the LH group (20.8%) relative to the WL group (5.7%).

Conclusion

Lifestyle Hub may serve as an efficacious and acceptable intervention for improving mental health in nonclinical adult populations. To extend the benefits of LM interventions at the population level, future studies are warranted to examine a stepped-care approach to delivering LM interventions.

Trial registration: This randomized controlled trial was pre-registered with ClinicalTrials.gov (NCT04295369).
Mortality rates from asbestos-related diseases in Italy during the first year of the COVID-19 pandemic
Authors: Fazzo Lucia , Grande Enrico , Zona Amerigo , Minelli Giada , Crialesi Roberta , Iavarone Ivano , Grippo Francesco
Published: January 2024

Background and aim

Patients with interstitial lung diseases, including asbestosis, showed high susceptibility to the SARS-CoV-2 virus and a high risk of severe COVID-19 symptoms. Italy, highly impacted by asbestos-related diseases, in 2020 was among the European countries with the highest number of COVID-19 cases. The mortality related to malignant mesotheliomas and asbestosis in 2020 and its relationship with COVID-19 in Italy are investigated.

Methods

All death certificates involving malignant mesotheliomas or asbestosis in 2010–2020 and those involving COVID-19 in 2020 were retrieved from the National Registry of Causes of Death. Annual mortality rates and rate ratios (RRs) of 2020 and 2010–2014 compared to 2015–2019 were calculated. The association between malignant pleural mesothelioma (MPM) and asbestosis with COVID-19 in deceased adults ≥80 years old was evaluated through a logistic regression analysis (odds ratios: ORs), using MPM and asbestosis deaths COVID-19-free as the reference group. The hospitalization for asbestosis in 2010–2020, based on National Hospital Discharge Database, was analyzed.

Results

In 2020, 746,343 people died; out of them, 1,348 involved MPM and 286 involved asbestosis. Compared to the period 2015–2019, the mortality involving the two diseases decreased in age groups below 80 years; meanwhile, an increasing trend was observed in subjects aged 80 years and older, with a relative mortality risks of 1.10 for MPM and 1.17 for asbestosis. In subjects aged ≥80 years, deaths with COVID-19 were less likely to have MPM in both genders (men: OR = 0.22; women: OR = 0.44), while no departure was observed for asbestosis. A decrease in hospitalization in 2020 with respect to those in 2010–2019 in all age groups, both considering asbestosis as the primary or secondary diagnosis, was observed.

Conclusions

The increasing mortality involving asbestosis and, even if of slight entity, MPM, observed in people aged over 80 years during the 1st year of the COVID-19 pandemic, aligned in part with the previous temporal trend, could be due to several factors. Although no positive association with COVID-19 mortality was observed, the decrease in hospitalizations for asbestosis among individuals aged over 80 years, coupled with the increase in deaths, highlights the importance of enhancing home-based assistance during the pandemic periods for vulnerable patients with asbestos-related conditions.
Factors affecting the medication literacy of older adults and targeted initiatives for improvement: a cross-sectional study in central China
Authors: Mei Chao , Xu Baoli , Cai Xuefeng , Wan Min , Zhao Zhigang , Lv Yongning , Zhang Yu , You Ruxu
Published: January 2024

Introduction

This study explored the state of rational drug use among older adults in central China, aiming to unveil factors influencing their medication literacy and proposing targeted improvement measures.

Methods

A cross-sectional study involving 454 participants aged 60 and above was conducted in Hubei province between February 1 and May 30, 2023, with data collected through face-to-face interviews by pharmacists. Multiple logistic regression analysis was conducted to determine factors that affected medication literacy.

Results

Of the 412 valid questionnaires, findings revealed inadequate knowledge of rational drug use among older adults in central China. Those who fully understood (105, 25.49%, OR = 9.349, p < 0.001, 95%CI = 3.884–22.502) or partially understood (228, 55.34%, OR = 3.295, p = 0.002, 95%CI = 1.548–7.013) drug instructions exhibited significantly higher medication literacy than those who did not understand (79, 19.17%). Subsequent research revealed a lack of awareness in reading drug instructions or difficulty in understanding them. Most older adults seldom heard of but exhibited high acceptance of medication guidance services.

Discussion

In conclusion, the ability to comprehend drug instructions significantly influenced the medication literacy of older adults. Initiatives such as revising age-appropriate drug instructions could effectively enhance rational drug use among this demographic.
Molecular approaches and challenges for monitoring marine harmful algal blooms in a changing world
Authors: Smith Kirsty F. , Stuart Jacqui , Rhodes Lesley L.
Published: January 2024

Harmful algal blooms (HABs) of marine microalgae are a growing concern globally and many studies predict that their occurrence, range, and toxicity may increase with climate change, highlighting the need for responsive and adaptable monitoring techniques. Monitoring programmes for HABs require appropriate sampling techniques, accurate and quantitative identification of potentially toxic taxa, and the ability to respond to novel species or HAB events. These challenges have made it difficult to move past traditional techniques, but research tools are continuing to be developed to bring new opportunities for both monitoring programmes and fundamental understanding of these globally significant organisms within a changing landscape.
A survey on Bayesian nonparametric learning for time series analysis
Authors: Vélez-Cruz Nayely
Published: January 2024

Time series analysis aims to understand underlying patterns and relationships in data to inform decision-making. As time series data are becoming more widely available across a variety of academic disciplines, time series analysis has become a rapidly growing field. In particular, Bayesian nonparametric (BNP) methods are gaining traction for their power and flexibility in modeling, predicting, and extracting meaningful information from time series data. The utility of BNP methods lies in their ability to encode prior information and represent complex patterns in the data without imposing strong assumptions about the underlying distribution or functional form. BNP methods for time series analysis can be applied to a breadth of problems, including anomaly detection, noise density estimation, and time series clustering. This work presents a comprehensive survey of the existing literature on BNP methods for time series analysis. Various temporal BNP models are discussed along with notable applications and possible approaches for inference. This work also highlights current research trends in the field and potential avenues for further development and exploration.
The Global Ocean Genome: A “Catalog” of Ocean Life
Authors: Laiolo Elisa , Alam Intikhab , Uludag Mahmut , Jamil Tahira , Agusti Susana , Gojobori Takashi , Acinas Silvia G. , Gasol Josep M. , Duarte Carlos M.
Published: January 2024

Life has been evolving in the oceans much longer than it has on land, resulting in highly diverse ocean organisms—particularly microbes like bacteria and archaea. Ocean microbes perform crucial functions that influence the health of the ocean and ultimately impact Earth’s climate. To understand the diversity and functions of marine organisms, scientists have used a powerful technique called metagenomics to study the DNA of all the organisms present in an ocean-water sample at once. In our research, we combined results from multiple ocean metagenomic studies, taken from various locations and depth zones across the world’s oceans, to produce a global ocean genome composed of 317.5 million groups of similar genes—approximately half of which could be categorized by type of organism and function. This unprecedented amount of data has much to teach us about varied ocean habitats and can help scientists answer many questions about ocean organisms and their functions.
Life calendaring as a qualitative strategy to examine human security among queer emerging adult men: a pilot study
Authors: Cleofas Jerome Visperas
Published: January 2024

Emerging adulthood has been characterized as a developmental period of insecurities and instabilities, especially among sexual minorities (i.e., queer people). This brief report proposes the utility of life calendaring as a tool to examine how queer emerging adults make sense of their security. First, this paper reviews the basic principles of human security as an approach to human development among emerging adults and explains how sexuality influences their sense of security in their present and projected lives. Second, this report explains the methodological features of life-calendaring as a qualitative research strategy and describes the process of an ongoing life-calendaring-aided interview research project that examines human security among queer emerging adult men. Finally, this article presents key insights from three life calendaring exemplars to demonstrate queering human security in emerging adulthood.
First record of Alectorobius coniceps (Ixodoidea: Argasidae) and Dermacentor sp. (Ixodoidea: Ixodidae) in Pakistan
Authors: Ali Abid , Khan Mehran , Ullah Zafar , Numan Muhammad , Tsai Kun-Hsien , Alouffi Abdulaziz , Almutairi Mashal M. , Tanaka Tetsuya
Published: January 2024

Alectorobius species are soft ticks primarily infesting birds, such as swallows, while Dermacentor species are hard ticks mainly infesting mammals, such as small ruminants. This study for the first time reported on the morphological and molecular bases of two tick species, namely A. coniceps and a Dermacentor sp. in Pakistan. The former species was examined in swallows’ nests in Khyber Pakhtunkhwa province, while the latter species was examined in small ruminants in Balochistan province. In total, 25 ticks were collected, with 14 ticks morphologically identified as A. coniceps (males = 9 and females = 5) and 11 ticks identified as Dermacentor sp. (males = 7 and females = 4). Following morphological identification, molecular identification was gained by obtaining 16S rDNA and cox1 sequences for these ticks. The BLAST results for the 16S rDNA and cox1 sequences from A. coniceps shared a maximum identity of 97.46% and 96.49% with the same species from Malta. The BLAST analysis of the 16S rDNA and cox1 sequences from Dermacentor sp. showed maximum identities of 98.42% and 97.45% with Dermacentor pavlovskyi from China. The phylogenetic analysis based on 16S rDNA and cox1 of A. coniceps showed a close evolutionary relationship with the same species. The case of Dermacentor sp., based on 16S DNA and cox1, indicated a close evolutionary relationship with Dermacentor pavlovskyi from China.
Evaluation of the Success of Simulation of the Unmanned Aerial Vehicle Precision Landing Provided by a Newly Designed System for Precision Landing in a Mountainous Area
Authors: Kurdel Pavol , Gecejová Natália , Češkovič Marek , Yakovlieva Anna
Published: January 2024

Unmanned aerial vehicle technology is the most advanced and helpful in almost every area of interest in human work. These devices become autonomous and can fulfil a variety of tasks, from simple imaging and obtaining data to search and rescue operations. The most challenging environment for search and rescue operations is the mountainous area. This article is devoted to the theoretical description and simulation tests of a prototype method of landing the light and the medium-weight UAVs used as supplementary devices for SAR (search and rescue) and HEMS (helicopter emergency medical service) in hard-to-reach mountainous terrains. The autonomous flight of a UAV in mountainous terrain has many specifics, and it is usually performed according to predetermined map points (pins) uploaded directly into the control software of the UAV. It is necessary to characterise each point flown on the chosen flight route line in advance and therefore to know its exact geographical coordinates (longitude, latitude and height of the point above the terrain), and the control system of UAV must react to the change in the weather and other conditions in real time. Usually, it is difficult to make this forecast with sufficient time in advance, mainly when UAVs are used as supplementary devices for the needs of HEMS or MRS (mountain rescue service). The most challenging phase is the final approach and landing of the UAV, especially if a loss of GNSS (global navigation satellite system) signal occurs, like in the determined area of the Little Cold Valley in the Slovak High Tatras—which is infamous for the widespread loss of GNSS signals or communication/controlling connection between the UAV and the pilot-operator at the operational station. To solve the loss of guidance, a new method for guiding and controlling the UAV in its final approach and landing in a determined area is tested. An alternative landing navigation system for UAVs in a specific mountainous environment—the authors’ designed frequency Doppler landing system (FDLS)—is briefly described but thoroughly tested with the help of artificial intelligence. An estimation of dynamic stability is used based on the time recording of the current position of the UAV, with the help of a frequency-modulated or amplitude-modulated signal based on the author’s prototype of a precision landing system designed for mountainous terrain. This solution could overcome the problems of GNSS signal loss. The presented research primarily evaluates the success of the simulation flights for the supplementary UAV. The success of navigating the UAV to land in the mountainous environment at an exact landing point using the navigation signals from the FDLS was evaluated at more than 95%.
Auditing the Risk of Financial Fraud Using the Red Flags Technique
Authors: Munteanu Victor , Zuca Marilena-Roxana , Horaicu Adriana , Florea Laura-Andreea , Poenaru Cristina-Elena , Anghel Gabriela
Published: January 2024

Major financial irregularities have contributed significantly to the destabilization of the world economy and the financial environment, by short circuiting investment flows and discrediting financial markets, with significant financial, social, and political consequences. Through the auditor’s key role of providing an independent, objective and professional opinion on the correctness of financial statements, the accounting profession has promoted a new procedure, the anti-fraud audit, which is responsible solely for financial prevention and fraud detection. Fraud detection audits have a methodology and a set of customized tools that help auditors in their mission to ensure the smooth execution of their audits. The purpose of this research is to conduct a comprehensive examination of both theoretical and practical aspects, with the objective of determining the risk profile of financial fraud among auditors. This will aid in preventing, detecting, and correcting such harmful practices. Through an empirical study of a fraudulent corporate entity, the quality of information contained within financial reports will be assessed, as well as the effectiveness of managerial decision-making substantiation. The data processing was carried out using the statistical software SPSS 19.0. when making graphs and interpreting the obtained results.
Calculation of the Differential Breit-Rosenthal Effect in Pb
Authors: Karlsen Martin Kinden , Persson Jonas R.
Published: January 2024

Recent advancements in studying long chains of unstable nuclei have revitalised interest in investigating the hyperfine anomaly. Hyperfine anomaly is particularly relevant for determining nuclear magnetic dipole moments using hyperfine structures where it limits the accuracy. This research paper focuses on the calculation of the differential Breit-Rosenthal effect for the 6p23P1,2, 1D2 and 6p7s3P1 states in Pb, utilising the multi-configurational Dirac-Hartree-Fock code, GRASP2018. The findings show that the differential Breit-Rosenthal effect is typically less than 0.1/fm2, which is often much smaller than the Bohr-Weisskopf effect. The differential Breit-Rosenthal effect for the 6p23P2 state is one order of magnitude smaller than the rest, which is why this state seems to be insensible to the hyperfine anomaly.
RAC1b Collaborates with TAp73α-SMAD4 Signaling to Induce Biglycan Expression and Inhibit Basal and TGF-β-Driven Cell Motility in Human Pancreatic Cancer
Authors: Ungefroren Hendrik , Reimann Julissa , Konukiewitz Björn , Braun Rüdiger , Wellner Ulrich F. , Lehnert Hendrik , Marquardt Jens-Uwe
Published: January 2024

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type characterized by a marked desmoplastic tumor stroma that is formed under the influence of transforming growth factor (TGF)-β. Data from mouse models of pancreatic cancer have revealed that transcriptionally active p73 (TAp73) impacts the TGF-β pathway through activation of Smad4 and secretion of biglycan (Bgn). However, whether this pathway also functions in human PDAC cells has not yet been studied. Here, we show that RNA interference-mediated silencing of TAp73 in PANC-1 cells strongly reduced the stimulatory effect of TGF-β1 on BGN. TAp73-mediated regulation of BGN, and inhibition of TGF-β signaling through a (Smad-independent) ERK pathway, are reminiscent of what we previously observed for the small GTPase, RAC1b, prompting us to hypothesize that in human PDAC cells TAp73 and RAC1b are part of the same tumor-suppressive pathway. Like TAp73, RAC1b induced SMAD4 protein and mRNA expression. Moreover, siRNA-mediated knockdown of RAC1b reduced TAp73 mRNA levels, while ectopic expression of RAC1b increased them. Inhibition of BGN synthesis or depletion of secreted BGN from the culture medium reproduced the promigratory effect of RAC1b or TAp73 silencing and was associated with increased basal and TGF-β1-dependent ERK activation. BGN also phenocopied the effects of RAC1b or TAp73 on the expression of downstream effectors, like the EMT markers E-cadherin, Vimentin and SNAIL, as well as on negative regulation of the ALK2-SMAD1/5 arm of TGF-β signaling. Collectively, we showed that tumor-suppressive TAp73-Smad4-Bgn signaling also operates in human cells and that RAC1b likely acts as an upstream activator of this pathway.
Non-Contrast-Enhanced Multiparametric MRI of the Hypoxic Tumor Microenvironment Allows Molecular Subtyping of Breast Cancer: A Pilot Study
Authors: Bartsch Silvester J. , Brožová Klára , Ehret Viktoria , Friske Joachim , Fürböck Christoph , Kenner Lukas , Laimer-Gruber Daniela , Helbich Thomas H. , Pinker Katja
Published: January 2024

Tumor neoangiogenesis is an important hallmark of cancer progression, triggered by alternating selective pressures from the hypoxic tumor microenvironment. Non-invasive, non-contrast-enhanced multiparametric MRI combining blood-oxygen-level-dependent (BOLD) MRI, which depicts blood oxygen saturation, and intravoxel-incoherent-motion (IVIM) MRI, which captures intravascular and extravascular diffusion, can provide insights into tumor oxygenation and neovascularization simultaneously. Our objective was to identify imaging markers that can predict hypoxia-induced angiogenesis and to validate our findings using multiplexed immunohistochemical analyses. We present an in vivo study involving 36 female athymic nude mice inoculated with luminal A, Her2+, and triple-negative breast cancer cells. We used a high-field 9.4-tesla MRI system for imaging and subsequently analyzed the tumors using multiplex immunohistochemistry for CD-31, PDGFR-β, and Hif1-α. We found that the hyperoxic-BOLD-MRI-derived parameter ΔR2* discriminated luminal A from Her2+ and triple-negative breast cancers, while the IVIM-derived parameter fIVIM discriminated luminal A and Her2+ from triple-negative breast cancers. A comprehensive analysis using principal-component analysis of both multiparametric MRI- and mpIHC-derived data highlighted the differences between triple-negative and luminal A breast cancers. We conclude that multiparametric MRI combining hyperoxic BOLD MRI and IVIM MRI, without the need for contrast agents, offers promising non-invasive markers for evaluating hypoxia-induced angiogenesis.
The Impact of Different Patterns of Residual Disease on Long-Term Oncological Outcomes in Breast Cancer Patients Treated with Neo-Adjuvant Chemotherapy
Authors: Tinterri Corrado , Fernandes Bethania , Zambelli Alberto , Sagona Andrea , Barbieri Erika , Di Maria Grimaldi Simone , Darwish Shadya Sara , Jacobs Flavia , De Carlo Camilla , Iuzzolino Martina , Gentile Damiano
Published: January 2024

Backgrounds: The majority of breast cancer (BC) patients treated with neo-adjuvant chemotherapy (NAC) achieves a pathologic partial response with different patterns of residual disease. No clear correlation between these patterns and oncological results was described. Our aims were to define the predictive factors for different patterns of residual disease and compare the outcomes between the scattered versus the circumscribed pattern. Methods: We reviewed 219 postoperative surgical specimens. Patients were divided into two groups: scattered versus circumscribed. Disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) were analyzed. Results: The scattered and circumscribed patterns were assessed in 111 (50.7%) and 108 (49.3%) patients. Two independent predictive factors for the circumscribed pattern were identified: discontinuation of NAC cycles (p = 0.011), and tumor size post-NAC >18 mm (p = 0.022). No difference was observed in terms of DFS and DDFS. Patients with the scattered pattern exhibited a statistically significant better OS. Discontinuation of NAC cycles, tumor size >18 mm, triple-negative BC, and ypN+ were associated with increased recurrence and poorer survival. Conclusions: Discontinuation of NAC cycles and tumor size are independent factors associated with patterns of residual disease. The scattered pattern presents better survival. Understanding the relationship between NAC, the residual pattern, and differences in survival outcomes offers the potential to optimize the therapeutic approaches.
The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials
Authors: Zhong Xingyu , Sun Jianxuan , Zeng Na , Xiong Yifan , An Ye , Wang Shaogang , Xia Qidong
Published: January 2024

Background: Sex is an important factor influencing the immune system, and the distribution of tumors, including their types and subtypes, is characterized by sexual dichotomy. The aim of this study was to investigate whether there is an association between sex and the treatment effect of immune checkpoint inhibitors (ICI). Methods: Four bibliographic databases were searched. Studies of randomized controlled trials (RCTs) assessing the efficacy of ICI were identified and used, and the primary endpoint was the difference in efficacy of ICI between males and females, presented as overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS). The study calculated the pooled HRs and 95% CIs for OS, PFS and RFS for males and females using a random effects model or a fixed effects model, and thereby assessed the effect of sex on the efficacy of ICI treatment. This study is registered with PROSPERO (CRD42022370939). Results: A total of 103 articles, including a total of 63,755 patients with cancer, were retrieved from the bibliographic database, of which approximately 70% were males. In studies with OS as the outcome, the combined hazard ratio (HR) was 0.77 (95% CI 0.74–0.79) for male patients treated with ICI and 0.81 (95% CI 0.78–0.85) for female patients compared to controls, respectively. The difference in efficacy between males and females was significant. Conclusions: ICI therapy, under suitable conditions for its use, has a positive impact on survival in various types of tumors, and male patients benefit more than females. It may be necessary to develop different tumor immunotherapy strategies for patients of different sexes.
Clinical Diagnosis and Management of Fetal Alcohol Spectrum Disorder and Sensory Processing Disorder in Children
Authors: Breuer Lorel , Greenmyer Jacob R. , Wilson Ted
Published: January 2024

Fetal alcohol spectrum disorder (FASD) is commonly misdiagnosed because of the complexity of presentation and multiple diagnostic criteria. FASD includes four categorical entities (fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol related neurodevelopmental disorder, and alcohol related birth defects). The four FASD diagnostic criteria are facial dysmorphology, growth deficiency, central nervous system dysfunction, and prenatal alcohol exposure. Sensory processing disorders (SPDs) are common in FASD and are observed as inappropriate behavioral responses to environmental stimuli. These can be either a sensory-based motor disorder, sensory discrimination disorder, or sensory modulation disorder. A child with SPD may experience challenges with their fine motor coordination, gross motor coordination, organizational challenges, or behavioral regulation impairments. FASD requires a multidimensional approach to intervention. Although FASD cannot be cured, symptoms can be managed with sleep-based therapies, sensory integration, and cognitive therapies. This paper reviews SPDs in FASD and the interventions that can be used by practitioners to help improve their therapeutic management, although it is unlikely that any single intervention will be the right choice for all patients.
Insights from a Qualitative Exploration of Adolescents’ Opinions on Sex Education
Authors: Díaz-Rodríguez María Victoria , Perelló Vicent Bataller i , Granero-Molina José , Fernández-Medina Isabel María , Ventura-Miranda María Isabel , Jiménez-Lasserrotte María del Mar
Published: January 2024

Background: Adolescence is a crucial time in the development of young people’s identity, and sexuality is a key issue. Comprehensive sex education provides the knowledge and skills to help adolescents protect their sexual and reproductive health and rights. Policies on sex education in secondary schools are highly influential in the development of quality programmes that support comprehensive sex education. The aim of this study was to explore, describe and understand adolescents’ experiences of sex education. Methods: A qualitative study based on Gadamer’s phenomenology was used. Two focus groups and four in-depth interviews were conducted with 12 private school students, followed by inductive data analysis using ATLAS.ti software 9.0. Results: Two main themes were identified in the analysis: (1) sex education is a challenge for secondary schools and (2) student expectations of sex education. Conclusion: It is essential for adolescents to have access to comprehensive sex education that is adapted to the different stages of their development, is provided by specialised teachers, and involves their families in the process.
Impact of a Best Practices Program in Patients with Relapsed/Refractory Multiple Myeloma Receiving Selinexor
Authors: Gordan Lucio N. , Ray David , Ijioma Stephen C. , Dranitsaris George , Warner Amanda , Heritage Trevor , Fink Matthew , Wenk David , Chadwick Paul , Khrystolubova Natasha , Peles Shachar
Published: January 2024

Best practice (BP) in cancer care consists of a multifaceted approach comprising individualized treatment plans, evidence-based medicine, the optimal use of supportive care and patient education. We investigated the impact of a BP program in patients with relapsed/refractory multiple myeloma (RRMM) receiving selinexor. Features of the BP program that were specific to selinexor were initiating selinexor at doses ≤80 mg once weekly and the upfront use of standardized antiemetics. Study endpoints included time to treatment failure (TTF), duration of therapy, dose limiting toxicities and overall survival. Comparative analysis on TTF and duration of therapy was conducted using a log-rank test and multivariate Cox proportional hazard regression. Over the ensuing 12-month post-BP period, 41 patients received selinexor-based therapy compared to 68 patients who received selinexor-based therapy pre-BP implementation. Patients treated in the post-BP period had reductions in TTF (hazard ratio [HR] = 0.50; 95% CI: 0.27 to 0.92). Patients in the pre-BP period were four times more likely to stop therapy than those in the post-period (odds ratio [OR] = 4.0, 95% CI: 1.75 to 9.3). The findings suggest a BP program tailored to selinexor could increase the time to treatment failure, increase treatment duration and lower the incidence of drug limiting toxicities.
Seeking a Hideout: Caves as Refuges for Various Functional Groups of Bryophytes from Terceira Island (Azores, Portugal)
Authors: Cedrés-Perdomo Ruymán David , Polaíno-Martín Clara , Jennings Laura , Gabriel Rosalina
Published: January 2024

Caves represent sites of great geological and biological interest. For most taxonomic groups, caves represent one of the most challenging ecosystems due to their extreme conditions. However, these places are rich in biodiversity, and some groups, such as bryophytes, can take advantage of these conditions. Bryophytes from twelve caves on Terceira Island (Azores archipelago) were sampled and compared in terms of species richness, abundance, and composition. The results revealed a high species richness of bryophytes, with one-fifth of the species being threatened and one-third endemic. Moreover, the dominance of bryophyte species, as determined by different functional groups, varies depending on the sampled cave and, consequently, the environmental variables. This is evident from the high β-diversity values obtained, demonstrating significant dissimilarities in species composition among the surveyed caves. Both macro- and microclimatic variables significantly influenced the richness and abundance of bryophyte species in different ways, depending on the functional group studied. Highlighting bryophyte diversity in cave environments, this study points to the need for effective management strategies to preserve and protect these unique and ecologically significant communities. These places can serve as refuges for some species, even for bryophytes, a taxonomic group with a long-distance dispersal strategy.
The Education Component and the Inclusion of the Enrolment Survival Measure: Provincial Equitable Share (PES)
Authors: Mthimkhulu Sithembiso Felix , Tewari Dev
Published: January 2024

This paper investigates the intergovernmental transfer systems in South Africa, more specifically, the underlying determinants and formula of the unconditional grants of the education component of the Provincial Equitable Share (PES). The PES formula is a weighted shares formula that depends on the demographic shares of the provinces (population) to determine the equitable share outcomes to be transferred to individual provinces. We find that the variables used have two main weaknesses: Firstly, the enrolment variable, which could be contaminated with school repeats and dropouts, is too broad to be an effective measure for representing the real beneficiaries of the transfers. Secondly, infrequent updates about the school-age cohort population variables render the desired PES grant transfers for education outdated as well as serially inconsistent. The paper also provides an analysis of the PES formula’s mathematical construct, followed by a few suggested variables to improve the relevance and accuracy of the formula of the revenue transfer. One such improvement is demonstrated by the inclusion of the Enrolment Survival Measure (ESR). More research and data are required to extrapolate nuanced results and to understand the socio-economic impacts of adopting these new variables in the PES formula going forward.
Thermodynamic, Economic and Maturity Analysis of a Carnot Battery with a Two-Zone Water Thermal Energy Storage for Different Working Fluids
Authors: Koksharov Josefine , Zendel Lauritz , Dammel Frank , Stephan Peter
Published: January 2024

The rising share of renewable energies leads to increased fluctuations in electrical power supply. One possibility to shift the surplus energy based on demand is a Carnot battery (CB). A CB uses a heat pump or resistance heater to convert and store thermal energy into electrical energy. Later, the stored thermal energy is converted back into electrical energy using a heat engine. This study investigates a CB with a two-zone tank for thermal energy storage. A transcritical process with CO2 is applied for charging, while discharging employs a transcritical process with CO2 and six refrigerants operating in a subcritical process. The transcritical process with CO2 and the four most promising subcritical processes are compared regarding round trip efficiency and levelized cost of electricity (LCOE) depending on the pinch points 5 K and 1 K in the heat exchangers. Additionally, the technology readiness level (TRL) is determined for these configurations. The results show round-trip efficiencies between 11.3% and 33.5% and LCOEs ranging from EUR 0.95 (kWh)−1 to EUR 2.09 (kWh)−1 for the considered concepts with TRLs of up to six.
Electric Water Boiler Energy Prediction: State-of-the-Art Review of Influencing Factors, Techniques, and Future Directions
Authors: Kachalla Ibrahim Ali , Ghiaus Christian
Published: January 2024

Accurate and efficient prediction of electric water boiler (EWB) energy consumption is significant for energy management, effective demand response, cost minimisation, and robust control strategies. Adequate tracking and prediction of user behaviour can enhance renewable energy mini-grid (REMD) management. Fulfilling these demands for predicting the energy consumption of electric water boilers (EWB) would facilitate the establishment of a new framework that can enhance precise predictions of energy consumption trends for energy efficiency and demand management, which necessitates this state-of-the-art review. This article first reviews the factors influencing the prediction of energy consumption of electric water boilers (EWB); subsequently, it conducts a critical review of the current approaches and methods for predicting electric water boiler (EWB) energy consumption for residential building applications; after that, the performance evaluation methods are discussed. Finally, research gaps are ascertained, and recommendations for future work are summarised.
Enhancing Efficiency in Alkaline Electrolysis Cells: Optimizing Flow Channels through Multiphase Computational Fluid Dynamics Modeling
Authors: Xue Longchang , Song Shuaishuai , Chen Wei , Liu Bin , Wang Xin
Published: January 2024

The efficient operation of alkaline water electrolysis cells hinges upon understanding and optimizing gas–liquid flow dynamics. Achieving uniform flow patterns is crucial to minimize stagnant regions, prevent gas bubble accumulation, and establish optimal conditions for electrochemical reactions. This study employed a comprehensive, three-dimensional computational fluid dynamics Euler–Euler multiphase model, based on a geometric representation of an alkaline electrolytic cell. The electrochemical model, responsible for producing hydrogen and oxygen at the cathode and anode during water electrolysis, is integrated into the flow model by introducing mass source terms within the user-defined function. The membrane positioned between the flow channels employs a porous medium model to selectively permit specific components to pass through while restricting others. To validate the accuracy of the model, comparisons were made with measured data available in the literature. We obtained an optimization design method for the channel structure; the three-inlet model demonstrated improved speed and temperature uniformity, with a 22% reduction in the hydrogen concentration at the outlet compared to the single-inlet model. This resulted in the optimization of gas emission efficiency. As the radius of the spherical convex structure increased, the influence of the spherical convex structure on the electrolyte intensified, resulting in enhanced flow uniformity within the flow field. This study may help provide recommendations for designing and optimizing flow channels to enhance the efficiency of alkaline water electrolysis cells.
The Fluid–Solid Interaction in the Nonlinear Pressure–Flux Relationship of Bordered Pits in Oriental Arborvitae (Platycladus orientalis)
Authors: Xia Peng , Wu Yunjie , Song Wenlong , Xie Li , Jia Ziyi , Wang Xin , Li Qionglin
Published: January 2024

The nonlinear pressure–flux relationship in the xylem of a conifer is attributed to the fluid–solid interaction within the bordered pits. However, the fluid–solid interactions between the torus–margo structure and the water flow within the pit lack comprehensive understanding. Herein, a fluid–solid interaction model was developed including the deformation of the torus–margo and the flow of water transportation. Nine pit samples were reconstructed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) pictures. Fluid–solid coupling models for pits in the stems of oriental arborvitae (Platycladus orientalis) were developed. The deflection of the torus was roughly proportional to the pressure difference between adjacent tracheids, while the pit resistance exhibited a considerable nonlinear increase. From 250 to 1750 Pa, the pit resistance increased from 4.1466 × 1016 Pa·s/m3 to 8.8344 × 1016 Pa·s/m3. The pit resistance decreased, and the pit’s ability to regulate water flow enhanced when the pit diameter increased. Both the pit resistance and the pit’s ability to regulate water decreased when the pit depth increased. The decrease in Young’s modulus for the margo promoted the nonlinear pressure–flux relationship in bordered pits. The findings provide theoretical evidence for the nonlinear relationship between pressure and flux in bordered pits, as well as for the prevention of gas bubble transit through a bordered pit during tracheid cavitation. The passive hydraulic regulation of bordered pits could increase flow resistance and reduce the water flow rate in the xylem, inhibiting tree transpiration.