bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual-energy CT in head and neck applications
Authors: Tunlayadechanont Padcha , Sananmuang Thiparom
Published: January 2025

Dual-energy CT (DECT), also known as spectral CT, has advanced diagnostic capabilities in head and neck pathologies beyond those of conventional single-energy CT (SECT). By having images at two distinct energy levels, DECT generates virtual monoenergetic images (VMIs), iodine maps, and quantitative features such as iodine concentration (IC) and spectral Hounsfield unit attenuation curves (SHUAC), which leads to enhancing tissue characterization, reducing artifacts, and differentiating head and neck pathologies. This review highlights DECT’s applications in evaluating head and neck squamous cell carcinoma (SCC), thyroid cartilage invasion, cervical lymph node metastasis, radiation therapy planning, post-treatment assessment, and role in other head and neck conditions, such as infection and sialolithiasis. Additionally, it explores emerging applications of DECT in radiomics and artificial intelligence. The review also discusses about integrating DECT into clinical practice requires overcoming workflow challenges and ensuring radiologist proficiency with its diverse image reconstructions. As DECT technology evolves, its integration promises to further enhance the efficacy of managing head and neck pathologies.
Dental implant in esthetic zone: A case report
Authors: Jundaeng Jarupat , Chamchong Rapeeporn , Nithikathkul Choosak
Published: January 2025

This case report emphasizes the complexities involved in dental implant placement within the anterior esthetic zone, focusing on the integration of advanced surgical techniques and meticulous prosthetic design for optimal esthetic and functional results. A 28-year-old male presented with the absence of the upper left central incisor, which had been extracted 5 years prior due to fracture. Clinical and radiographic assessments indicated normal alveolar bone levels; however, the esthetic demands required a specialized approach. The surgical procedure included a papilla preservation flap, immediate implant placement, and bone grafting to prevent peri-implant resorption and achieve an optimal emergence profile. An Osstem implant and resorbable Xenograft were utilized to address the thin labial bone. Over 4 months, successful osseointegration occurred, followed by the placement of a permanent crown. This case illustrates that dental implant restoration in the anterior esthetic zone can effectively address functional and esthetic challenges, leading to high patient satisfaction with the final restoration’s natural appearance.
Study on Impact of COVID-19 Pandemic on Implementation of Agile Project Management
Authors: Shetty1 Samruddhi , Joshi1 Nirmala
Published: January 2025

The COVID-19 pandemic significantly disrupted all aspects of human life during 2020 and 2021, leading to widespread remote work due to strict restrictions aimed at controlling the virus’s spread. This shift affected various industries, including software development, where many teams transitioned to remote work and adopted hybrid project management methodologies. Combining Agile with waterfall approaches helped address the new challenges posed by remote collaboration and communication barriers. The research article concentrates on the impact of COVID on Agile values.
Resolving an Enigma of FinTech, Digital Assets and Electronic Commerce: Insight to Time-varying Dynamic Connectedness
Authors: Yadav Miklesh Prasad , Al-Qudah Anas Ali , Sandhu Kamaljeet , Gupta Neha
Published: January 2025

This study investigates the interconnectedness among FinTech, digital assets and e-commerce stocks, offering profound insights into the complex financial ecosystem. Utilizing the advanced Time-Varying Parameter Vector Autoregression and Baruník–Krehlik (2018) models, the research uncovers the relationships and interconnected dynamics amongst these innovative asset classes. The results highlight Mastercard’s pivotal role as both a significant receiver and transmitter of shocks within the market, contrasting with Tencent’s demonstrated resilience and diversification capabilities across various frequencies. These fundamental discoveries aid investors, portfolio managers and policy analysts in navigating the financial markets more strategically, fostering informed investment decisions and robust risk mitigation strategies in volatile environments.
I’m Not the Doctor for You: Cognitive Bias, Complex Illness, and a Moral Imperative
Authors: Kuon Carla P.
Published: January 2025

Cognitive Bias and the Treatment of Complex Illnesses: A Reflection on Substance Use Disorder and Long COVID. Physicians use anchoring and confirmation bias every day to make snap decisions about patient care. However, in the case of poorly understood complex illness, cognitive bias can lead to poor outcomes for the patient. This article explores how recognizing and overcoming cognitive bias leads to increased personal career satisfaction, and improved patient outcomes. In an era where health disparities are increasingly recognized, and in the post-COVID era in particular, there's a need to recognize cognitive bias against complex illnesses such as Long COVID and Chronic Fatigue Syndrome. It may even be a moral imperative.
Integrative application of licorice root extract and melatonin improves faba bean growth and production in Cd-contaminated saline soil
Authors: Abd El Mageed Shimaa A. , Sayed Ali A. S. , Shaaban Ahmed , Hemida Khaulood A. , Abdelkhalik Abdelsattar , Semida Wael M. , Mohamed Ibrahim A. A. , Gyushi Mohammed A. H. , Elmohsen Yasmine H. Abd , Abd El Mageed Taia A.
Published: January 2025

Background

Globally, salinity poses a threat to crop productivity by hindering plant growth and development via osmotic stress and ionic cytotoxicity. Plant extracts have lately been employed as exogenous adjuvants to improve endogenous plant defense mechanisms when grown under various environmental stresses, such as salinity. This study investigated the potential of melatonin (Mt; 0, 50, and 100 mM) as an antioxidant and licorice root extract (LRE; 0.0 and 3%) as an organic biostimulant applied sequentially as a foliar spray on faba bean (Vicia faba L.) grown in cadmium (Cd)-contaminated saline soil conditions [Cd = 4.71 (mg kg− 1 soil) and ECe = 7.84 (dS m− 1)]. Plants not receive any treatment and sprayed with H2O were considered controls. The experimental treatments were laid out in strip plot in a randomized complete block design replicated thrice, where the LRE and Mt were considered as vertical and horizontal strips, respectively. Growth characteristics, photosynthetic pigments, nutrient uptake, physiology and metabolic responses, anatomical features, and yield were assessed.

Results

Cadmium (Cd) and salinity-induced stress significantly altered leaf integrity, photosynthetic efficiency, total soluble sugars (TSS), free proline (FPro), total phenolic, DPPH, and total soluble proteins (TSP), non-enzymatic and enzymatic antioxidants, growth characteristics and yield-related traits. However, the application of LRE + Mt considerably improved these negative effects, with higher improvements were observed due to application of LRE + Mt100. Application of LRE + Mt significantly reduced hydrogen peroxide (H2O2) accumulation, lipid peroxidation and Cd content in leaves and seeds, all of which had increased due to Cd stress. Application of LRE + Mt significantly mitigated the Cd-induced oxidative damage by increasing the activity of reactive oxygen species (ROS) scavenging enzymes such as superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, in parallel with enhanced ascorbate and reducing glutathione content. Exogenous application of LRE + Mt significantly increased osmolyte content, including FPro, TSS, and total phenols and mitigated Cd-induced reduction to considerable levels.

Conclusions

Our findings showed that LRE + Mt increased V. faba plants’ morphological, physiological, and biochemical properties, reducing Cd stress toxicity, and promoting sustainable agricultural practices.

Clinical trial number

Not applicable.
Outcomes of an Emergency Department opioid alternatives Program implemented within a safety-net hospital system
Authors: Montague Magda , Hopson Charlotte , Layton Claire , Fishe Jennifer , Norse Ashley , Webb L. Kendall , Duran-Gehring Petra , Bertrand Andrew , Brailsford Jennifer , Munson Taylor , Wang Rui , Menze Nolan , Perl Katelyn , Hendry Phyllis , Sheikh Sophia
Published: January 2025

Background

The ongoing opioid epidemic in the United States has reinforced the need to provide multimodal and non-opioid pain management interventions. The PAMI-ED ALT program employed a multifaceted approach in the Emergency Department (ED) developing electronic health record (EHR) pain management order panels and discharge panels, as well as educating patients, clinicians, and ED staff on opioid alternatives, including non-pharmacologic interventions. The primary objective of this analysis was to compare changes in opioid and non-opioid analgesic administrations and prescribing in ED patients with select pain conditions (renal colic, headache, low back, and non-low back musculoskeletal pain) before and after implementation of PAMI ED-ALT. Secondary outcomes included characterizing changes in 30-day ED all-cause recidivism and hospital all-cause admissions within these pain populations.

Methods

Demographics, opioid and opioid alternative utilization, hospital admission, 30-day ED returns and change in pain intensity score were collected from January 2019-March 2020 (pre-program implementation) and January 2021-March 2023 (post-program implementation) for both the ED aggregate and program target pain populations.

Results

Pain management order panel utilization increased throughout the post-implementation period. When comparing pre to post program data, there was a reduction in opioid administrations and prescriptions for most of the target pain conditions, as well as within the ED aggregate population. Opioid alternative administrations and prescriptions increased for all pain conditions except renal colic. Hospital admissions decreased significantly amongst those with low back pain and headache/migraine and 30-day ED returns significantly declined in those with musculoskeletal pain.

Conclusion

Our findings demonstrate an opioid-alternatives program implemented within a safety-net hospital system serving a predominantly socially disadvantaged patient population can lead to changes in ED pain management and potentially reduce 30-day ED recidivism and hospitalizations.
Psychological interventions for refugees with depression: a systematic literature review
Authors: Uhr Cornelia , Pawils Silke , Morina Nexhmedin , Alkailani Heba , Metzner Franka
Published: January 2025

Background

Ongoing global crises are forcing an increasing number of people to seek refuge in other countries. Refugees have often experienced multiple potentially traumatic events before and during their flight and are burdened by psychosocial problems in exile. Epidemiological research suggests that many refugees suffer from depression and need psychological care. Yet, a systematic review of psychological interventions for refugees with depression is lacking.

Method

After registering in the International Prospective Register of Systematic Reviews (PROSPERO), a systematic search for trials of psychological interventions for adult refugees with depression was conducted across three electronic databases (MEDLINE, Web of Science, & PsycINFO). Relevant data reported in original journal publications were extracted, synthesized and assessed qualitatively by two independent raters. The methodological quality of included trials was assessed.

Results

Of 1316 publications, a total of 20 studies met eligibility criteria. Nine of these trials were carried out in an individual setting and ten in a group setting, with one of the trials being conducted digitally. Nine studies were designed as a randomized controlled trial (RCT), with only one of them using an active control group. In nine trials, the use of an interpreter was reported. Three of the trials applied multimodal treatments, and a total of sixteen studies applied manualized treatments. Seventeen interventions were adaptations of treatment programs developed in high income countries within a western context. Overall, nineteen out of twenty trials reported a significant improvement in depressive symptoms. Culturally adapted cognitive behavioural therapy (CA-CBT) was most frequently used (4 RCTs) and produced large effect sizes. Overall, all trials had limitations in study design.

Conclusions

Our current review suggests that psychological interventions, and in particular CA-CBT interventions, can significantly improve depressive symptoms in refugees. However, the small number of trials and limitations in study design underscore the need for more research in this field.

The protocol for this review was registered in PROSPERO; registration number: CRD42021251943.
Indigenous university students' perceptions regarding nature, their daily lives and climate change: a photovoice study
Authors: Dias Ieda M. A. V. , Grande Antonio Jose , Jardim Paulo T. C. , Machado Alessandra Aparecida Vieira , Soratto Jacks , da Rosa Maria Inês , Ceretta Luciane Bisognin , Roever Leonardo , Zourntos Xanthi , Harding Seeromanie
Published: January 2025

Background

Climate change has severe health impacts, particularly for populations living in environmentally sensitive areas such as riversides, slopes, and forests. These challenges are exacerbated for Indigenous communities, who often face marginalisation and rely heavily on the land for their livelihoods. Despite their vulnerability, the perspectives of Indigenous populations on climate change and its impacts remain underexplored, creating a critical gap in the literature. This study explored the perceptions of Indigenous Brazilian university students on how climate change affects their daily lives and gathered their insights on potential adaptations to mitigate climate change-related impacts.

Methods

Using a participatory arts-based approach, participants captured photographs reflecting their lived experiences with climate change. Follow-up interviews provided a narrative framework for qualitative analysis, enabling participants to articulate the strengths and concerns of their communities while transcending cultural and linguistic barriers.

Results

The study revealed key themes, including (1) the fragility of ecosystems critical to Indigenous livelihoods, (2) the erosion of traditional knowledge systems due to environmental and social disruptions, and (3) the need for community-driven strategies to protect territories and preserve cultural identities. Participants highlighted the interconnectedness of their cultural values with environmental stewardship, emphasising the importance of maintaining these relationships as a form of resilience.

Conclusion

This study underscores the importance of protecting Indigenous territories and respecting their cultural identities to safeguard their survival and traditions. The voices of Indigenous university students provided valuable insights into community-based adaptations and strategies for mitigating the impacts of climate change.
Effects of home bleaching agents on hybrid ceramics: mechanical properties and color change
Authors: Hafny Waleed M. , Ibrahim Imam M. , El-Demellawy Mohamed , Abdel Sadek Hoda M.
Published: January 2025

Background

Home bleaching is a promising option for addressing discolored teeth conservatively. However, its impact on the physical and mechanical properties of indirect restorations remains unknown. This study provides comparative insights into the material responses to aesthetic treatments by assessing the effects of home bleaching agents on two hybrid ceramics: VITA ENAMIC® and Grandio Blocs. The focus is on evaluating color stability and biaxial flexural strength.

Methods

60 discs (12 × 1 mm) were prepared from hybrid ceramics. Specimens were divided into two groups according to type of hybrid ceramic (30 specimens in each group); group A: VITA ENAMIC®, group B: Grandio Blocs. Each group was further subdivided into 3 subgroups according to the concentration of home bleaching agents used (10 specimens in each subgroup); subgroup C: unbleached control group, subgroup C10%: carbamide peroxide 10% bleaching agent, and subgroup C35%: carbamide peroxide 35% bleaching agent. Samples of subgroup C10% were bleached with Home Bleaching Opalescence PF (10%) for 8 h per day for 14 days, as directed by the manufacturer. Samples of subgroup C35% were bleached using WHITEsmile Carbamide Peroxide (35%), following the manufacturer’s directions for 30 min every day for 14 days. Color change (ΔE) was assessed using of the CIE L*a*b* system. Then, the biaxial flexural strength test was done. The data were analyzed using two-way ANOVA tests and Weibull analysis.

Results

VITA ENAMIC samples exhibited significantly higher color change than Grandio Blocs (p < 0.001), while Grandio Blocs showed significantly higher biaxial flexural strength (p < 0.001). The concentration of the bleaching agent had no significant effect on color change (p = 0.086). However, regardless of its concentration, bleaching significantly reduced biaxial flexural strength in both materials (p < 0.001). Weibull analysis showed that Grandio Blocs had higher characteristic strength, while VITA ENAMIC demonstrated more reliable failure behavior.

Conclusions

Compared to Grandio Blocs, VITA ENAMIC® exhibited a greater color change with both 10% and 35% carbamide peroxide home bleaching agents. Additionally, both concentrations of carbamide peroxide reduced the biaxial flexural strength of hybrid ceramics. These findings can guide clinicians in selecting hybrid ceramics based on clinical demands for aesthetics and durability. VITA ENAMIC® offers greater structural reliability and predictability for aesthetic restorations, while Grandio Blocs provide superior durability and stress resistance for high-stress clinical applications.
Investigation of the causal relationship between patient portal utilization and patient’s self-care self-efficacy and satisfaction in care among patients with cancer
Authors: Park Jaeyoung , Guo Shilin , Liang Muxuan , Zhong Xiang
Published: January 2025

Objective

The objective of this study was to examine the causal relationship between the usage of patient portals and patients’ self-care self-efficacy and satisfaction in care outcomes in the context of cancer care.

Methods

The National Institute’s HINTS 5 Cycle 1–4 (2017–2020) data were used to perform a secondary data analysis. Patients who reported being ever diagnosed with cancer were included in the study population. Their portal usage frequency was considered as an intervention. Patient’s self-care self-efficacy and satisfaction in care were the primary outcomes considered and they were measured by survey respondents’ self-reported information. A set of conditional independence tests based on the causal diagram was developed to examine the causal relationship between patient portal usage and the targeted outcomes.

Results

A total of 2579 were identified as patients with cancer or cancer survivors. We identified patient portals’ impact on strengthening patients’ ability to take care of their own health (P = .02, for the test rejecting which is necessary for the expected causal relationship, ie, the portal usage impacts the target outcome; P = .06, for the test rejecting which is necessary for the reverse causal relationship), and we identified heterogenous causal relationships between frequent patient portal usage and patients’ perceived quality of care (P = .04 and P = .001, for the tests rejecting both suggests heterogeneous causal relationships). We could not conclusively determine the causal relationship between patient portal usage and patients’ confidence in getting advice or information about health or cancer care related topics (P > .05 for both tests, suggesting inconclusive causal directions).

Conclusions

The results advocate patient portals and promote the need to provide better support and education to patients. The proposed statistical method exploits the potential of national survey data for causal inference studies.
Families’ opinions about their involvement in care during hospitalization: a mixed-methods study
Authors: Woldring Josien M. , Paans Wolter , Gans Reinold O. B. , van der Werf Hinke M. , Luttik Marie Louise
Published: January 2025

Background

Healthcare professionals in the hospital setting frequently assume primary caregiving responsibilities, which often leads family members to perceive this as standard practice during hospitalization. This dynamic may create a gap between actual and desired levels of family involvement. The aim of this study is to explore the opinions of families about their involvement in care during the hospitalization of a relative.

Methods

A sequential explanatory mixed-method study design was used, where quantitative data collection is followed by qualitative data collection for a deeper understanding of the quantitative findings. Data were collected between November 2023 and April 2024 across 15 wards in a university hospital in the north of the Netherlands. 153 family members of hospitalized patients completed the adapted Families’ Importance in Nursing Care–Families’ Opinions questionnaire, providing valuable quantitative data. Twenty-three of these family members were subsequently interviewed to gather qualitative insights. Data were analyzed sequentially, with the quantitative results guiding qualitative data collection. The two types of data were integrated to draw comprehensive conclusions about the significance of family involvement during hospitalization. The study adhered to the guidelines of the Good Reporting of A Mixed Method Study (GRAMMS).

Results

The questionnaire scores indicate a high willingness for involvement in care during hospitalization. Subsequent in-depth interviews led to the development of a model demonstrating that this involvement is sequentially related to the themes of acknowledgement, alignment, and collaboration.

Conclusions

Family members expressed a need to be acknowledged by healthcare professionals as partners in care. Role agreements and information sharing during hospital care should be aligned to achieve effective collaboration between family members and healthcare professionals.
Shift work schedules alter immune cell regulation and accelerate cognitive impairment during aging
Authors: de Souza Karienn A. , Jackson Morgan , Chen Justin , Reyes Jocelin , Muayad Judy , Tran Emma , Jackson William , Newell-Rogers M. Karen , Earnest David J.
Published: January 2025

Background

Disturbances of the sleep-wake cycle and other circadian rhythms typically precede the age-related deficits in learning and memory, suggesting that these alterations in circadian timekeeping may contribute to the progressive cognitive decline during aging. The present study examined the role of immune cell activation and inflammation in the link between circadian rhythm dysregulation and cognitive impairment in aging.

Methods

C57Bl/6J mice were exposed to shifted light-dark (LD) cycles (12 h advance/5d) during early adulthood (from ≈ 4-6mo) or continuously to a “fixed” LD12:12 schedule. At middle age (13-14mo), the long-term effects of circadian rhythm dysregulation on cognitive performance, immune cell regulation and hippocampal microglia were analyzed using behavioral, flow cytometry and immunohistochemical assays.

Results

Entrainment of the activity rhythm was stable in all mice on a fixed LD 12:12 cycle but was fully compromised during exposure to shifted LD cycles. Even during “post-treatment” exposure to standard LD 12:12 conditions, re-entrainment in shifted LD mice was marked by altered patterns of entrainment and increased day-to-day variability in activity onset times that persisted into middle-age. These alterations in light-dark entrainment were closely associated with dramatic impairment in the Barnes maze test for the entire group of shifted LD mice at middle age, well before cognitive decline was first observed in aged (18-22mo) animals maintained on fixed LD cycles. In conjunction with the effects of circadian dysregulation on cognition, shifted LD mice at middle age were distinguished by significant expansion of splenic B cells and B cell subtypes expressing the activation marker CD69 or inflammatory marker MHC Class II Invariant peptide (CLIP), differential increases in CLIP+, 41BB-Ligand+, and CD74 + B cells in the meningeal lymphatics, alterations in splenic T cell subtypes, and increased number and altered functional state of microglia in the dentate gyrus. In shifted LD mice, the expansion in splenic B cells was negatively correlated with cognitive performance; when B cell numbers were higher, performance was worse in the Barnes maze. These results indicate that disordered circadian timekeeping associated with early exposure to shift work-like schedules alone accelerates cognitive decline during aging in conjunction with altered regulation of immune cells and microglia in the brain.
Identification of genetic mechanisms of non-isolated auditory neuropathy with various phenotypes in Chinese families
Authors: Cao Yang , Zhang Xiaolong , Lan Lan , Li Danyang , Li Jin , Xie Linyi , Xiong Fen , Yu Lan , Wu Xiaonan , Wang Hongyang , Wang Qiuju
Published: January 2025

Background

Non-isolated auditory neuropathy (AN), or syndromic AN, is marked by AN along with additional systemic manifestations. The diagnostic process is challenging due to its varied symptoms and overlap with other syndromes. This study focuses on two mitochondrial function-related genes which result in non-isolated AN, FDXR and TWNK, providing a summary and enrichment analysis of genes associated with non-isolated AN to elucidate the genotype-phenotype correlation and underlying mechanisms.

Methods

Seven independent Chinese Han patients with mutations in FDXR and TWNK underwent comprehensive clinical evaluations, genetic testing, and bioinformatics analyses. Diagnostic assessments included auditory brainstem response and distortion product otoacoustic emissions, supplemented by other examinations. Whole exome sequencing and Sanger sequencing validated genetic findings. Pathogenicity was assessed following American College of Medical Genetics and Genomics guidelines. Genes associated with non-isolated AN were summarized from prior reports, and functional enrichment analysis was conducted using Gene Ontology databases.

Results

A total of 11 variants linked to non-isolated AN were identified in this study, eight of which were novel. Patients’ age of hearing loss onset ranged from 2 to 25 years, averaging 11 years. Hearing loss varied from mild to profound, with 57.1%(4/7) of patients having risk factors and 71.4%(5/7) exhibiting additional systemic symptoms such as muscle weakness, ataxia, and high arches. Functional enrichment analysis revealed that genes associated with non-isolated AN predominantly involve mitochondrial processes, affecting the central and peripheral nervous, musculoskeletal, and visual systems.

Conclusion

This study identifies novel mutations in FDXR and TWNK that contribute to non-isolated AN through mitochondrial dysfunction. The findings highlight the role of mitochondrial processes in non-isolated AN, suggesting potential relevance as biomarkers for neurodegenerative diseases. Further research is required to explore these mechanisms and potential therapies.

Graphical Abstract
Protective effects of resveratrol and naringenin against nonylphenol-induced oxidative stress in rats
Authors: Elewa Haitham S. , Salama Dawlat A. , Hikal Mohamed S. , El hamid Mohamed F. Abd , Eid Mohamed H. , Khalil Fatma M. A. , Albadrani Muayad S. , Abdelaal Khaled , El-Tokhy Ahmed I.
Published: January 2025

Nonylphenol (NP) is a ubiquitous environmental endocrine disrupting chemical and oxidative stress inducer in biological systems. Resveratrol (RES) and Naringenin (NG) are phytochemicals possessing antioxidant properties and estrogenic activity. This study was conducted to investigate the toxicity of NP and the mitigating effects of RES and NG on NP toxicity in rats. Thirty male rats were classified into 5 groups as follows: 1- Normal control (NC), 2- Dimethyl sulfoxide (DMSO) group, 3- NP group, 4- NP + RES and 5- NP + NG. Results revealed that NP treatment significantly decreased the activities of superoxide dismutase, Catalase, Glutathione peroxidase and Glutathione content in blood, liver and kidney compared to NC and DMSO groups. Conversely, activity of Glutathione-s-transferase was significantly elevated in blood and decreased in liver and kidney. Moreover, significant escalation was observed in the levels of Malondialdehyde. Also, NP treatment led to a significant decrease in serum total testosterone and testis weight, accompanied with concurrent elevation in estradiol level compared to NC and DMSO groups. All the recorded effects induced by NP treatment were effectively countered by co-treatment with RES or NG. In addition, molecular docking studies were carried out to reveal the interactions between NP, RES, NG and estrogen receptor beta which provide a possible mechanism for their potential estrogenic activity. Overall, our study gives a deeper understanding of the toxic effect of NP on antioxidant capacity and endocrine functions as well as the potential therapeutic utility of RES and NG in alleviating these adverse effects.
Neuroligin-3 R451C induces gain-of-function gene expression in astroglia in an astroglia-enriched brain organoid model
Authors: Dang Rui , Dalmia Mridul , Ma Ziyuan , Jin Mengmeng , Aluru Kushal , Mirabella Vincent R. , Papetti Ava V. , Cai Li , Jiang Peng
Published: January 2025

Astroglia are integral to brain development and the emergence of neurodevelopmental disorders. However, studying the pathophysiology of human astroglia using brain organoid models has been hindered by inefficient astrogliogenesis. In this study, we introduce a robust method for generating astroglia-enriched organoids through BMP4 treatment during the neural differentiation phase of organoid development. Our RNA sequencing analysis reveals that astroglia developed within these organoids exhibit advanced developmental characteristics and enhanced synaptic functions compared to those grown under traditional two-dimensional conditions, particularly highlighted by increased neurexin (NRXN)-neuroligin (NLGN) signaling. Cell adhesion molecules, such as NRXN and NLGN, are essential in regulating interactions between astroglia and neurons. We further discovered that brain organoids derived from human embryonic stem cells (hESCs) harboring the autism-associated NLGN3 R451C mutation exhibit increased astrogliogenesis. Notably, the NLGN3 R451C astroglia demonstrate enhanced branching, indicating a more intricate morphology. Interestingly, our RNA sequencing data suggest that these mutant astroglia significantly upregulate pathways that support neural functions when compared to isogenic wild-type astroglia. Our findings establish a novel astroglia-enriched organoid model, offering a valuable platform for probing the roles of human astroglia in brain development and related disorders.
Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays
Authors: Fortuno Cristina , Llinares-Burguet Inés , Canson Daffodil M. , de la Hoya Miguel , Bueno-Martínez Elena , Sanoguera-Miralles Lara , Caldes Sonsoles , James Paul A. , Velasco-Sampedro Eladio A. , Spurdle Amanda B.
Published: January 2025

Background

TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.

Methods

We conducted splicing analyses using a minigene construct containing TP53 exons 2 to 9 transfected into human breast cancer SKBR3 cells, and compared results against different splice prediction methods, including correlation with the SpliceAI-10k calculator. We additionally applied the splicing results for TP53 variant classification using an approach consistent with the ClinGen Sequence Variant Interpretation Splicing Subgroup recommendations.

Results

Aberrant transcript profile consistent with loss of function, and for which a PVS1 (RNA) code would be assigned, was observed for 42 (71%) of prioritised variants, of which aberrant transcript expression was over 50% for 26 variants, and over 80% for 15 variants. Data supported the use of SpliceAI ≥ 0.2 cutoff for predicted splicing impact of TP53 variants. Prediction of aberration types using SpliceAI-10k calculator generally aligned with the corresponding assay results, though maximum SpliceAI score did not accurately predict level of aberrant expression. Application of the observed splicing results was used to reclassify 27/59 (46%) test variants as (likely) pathogenic or (likely) benign.

Conclusions

In conclusion, this study enhances the integration of splicing predictions and provides splicing assay data for exonic variants to support TP53 germline classification.

Graphical abstract
Fasciola cinereum: a novel choke point for epilepsy treatment
Authors: Yu Lilong , Jiang Dongxiao , Wang Yi , Chen Zhong , Yang Lin
Published: January 2025

Ablation of seizure foci represents a crucial therapeutic approach for epilepsy. Traditionally, the seizure foci are predominantly located in the anterior hippocampus and amygdala. However, recent research by Ivan Soltesz and his colleagues described the posterior hippocampal fasciola cinereum (FC) as a region activated during seizures. Their findings demonstrate that inhibition and ablation of FC reduce seizures frequency. Therefore, FC emerges as a critical seizure node within the posterior hippocampus, playing an important role in epilepsy treatment.
Comparison of three cryotherapy techniques for early post-TKA pain control in terms of efficacy and patient satisfaction: a randomized controlled trial
Authors: Chareancholvanich Keerati , Keesukpunt Worawut , Pornrattanamaneewong Chaturong , Narkbunnam Rapeepat , Jarusriwanna Atthakorn
Published: January 2025

Background

Cryotherapy is a non-pharmacological option that complements drug therapy to achieve the most comprehensive multimodal analgesia. Various techniques are currently available, including the conventional gel cold pack, the cryo-cuff, and a novel mobile cold compression device (MCCD). This study aimed to evaluate and compare three cryotherapy techniques in terms of efficacy and patient satisfaction in patients undergoing total knee arthroplasty (TKA).

Methods

This prospective randomized study included 108 patients who were scheduled for primary unilateral TKA. The patients were allocated to 3 groups for postoperative cryotherapy techniques: gel cold pack, cryo-cuff, and MCCD. Scores on the visual analog scale (VAS) for pain intensity, morphine consumption, knee range of motion (ROM), knee swelling, length of hospital stay, and patient satisfaction were collected.

Results

Postoperative VAS scores showed a significant difference among the groups at 8 and 72 h after surgery (P = 0.002 and 0.026, respectively). At the earliest postoperative time point, post hoc analysis demonstrated that patients in the MCCD group had lower pain scores than those in the gel cold pack (P < 0.001) and the cryo-cuff group (P = 0.030). However, cryo-cuff reduced knee swelling significantly compared to gel cold pack (P = 0.028) and MCCD (P = 0.011) at postoperative 72 h. The total satisfaction score was 86.8, 82.8, and 89.1 with gel cold pack, cryo-cuff, and MCCD, respectively.

Conclusions

Cryotherapy is an adjunct to post-TKA pain control at the surgical site. MCCD has shown superior efficacy in pain reduction during the earliest postoperative period, and achieved high patient satisfaction.

Trial registration

This study was registered in the Thai Clinical Trials Registry database (no. TCTR20200517002).
Data-driven joint routing, topology, and mobility design for FANET systems using a digital twin approach
Authors: Mohammad El-Basioni Basma M.
Published: January 2025

The drones industry has witnessed great progress, and its systems have many important applications. The free autonomous movement of drones is considered a double-edged sword; it enables a tremendous use cases, at the same time, it makes the design of the communication network among drones, especially the routing protocol, a very delicate matter. Therefore, the research is heading toward achieving joint design that controls the movement in favor of communication. The current work is based on the idea of exploiting the use of drones in conveying data for building digital twin in building digital twin of the drones system itself such that the joint design can be realized. The decision support of the network digital twin is provided by model-based reinforcement learning using dynamic programming and policy iteration algorithm. The digital twin model allows the reinforcement learning model to learn, offline plan, and online re-plan through observing the outcomes of the real environment. This paper describes and implements the proposed solution and compares it to a standard Ad-hoc routing protocol and a model-free reinforcement learning-based routing protocol. The simulation results showed that the proposed solution greatly improves the overall network Quality of Service (QoS).
Investigating the relationship of hydration status on the clinical outcomes of COVID-19 patients
Authors: Rezaei Mahdiye , Salari Nader , Naghibzadeh Amirhossein , Mohammadi Mohammad , Abdi Alireza
Published: January 2025

Background

Existing evidence suggests that the hydration status of COVID-19 patients may influence clinical indicators and outcomes of the disease. However, there is a lack of research specifically investigating this aspect. Therefore, this study aimed to ascertain the correlation between hydration status and clinical outcomes among COVID-19 patients.

Method

This descriptive-analytical study included 110 patients hospitalized with COVID-19 at hospitals affiliated with Kermanshah University of Medical Sciences. Hydration status was assessed using the Free Water Deficit tool, mortality was evaluated using the Sequential Organ Failure Assessment (SOFA) tool, and the severity of COVID-19 was determined using the COVID-GRAM Risk Score tool. Data were obtained from clinical examinations and patient records and analyzed using SPSS software, version 24.

Results

The study included 110 participants with an average age of 58.2 ± 17.9 years. Females constituted 52.3% of the patient population. Additionally, 54% of patients had a history of underlying diseases, and 24.5% exhibited fluid deficiency. Data analysis revealed no statistically significant difference in average hydration scores when considering the main variables of SOFA and COVID-GRAM risk score results, and other variables such as gender, age, underlying diseases, place of residence, tobacco and drug use, respiratory distress, and PCR test results. Furthermore, the Pearson correlation test revealed no significant relationship between the Free Water Deficit tool results and levels of sodium, potassium, urea, creatinine, blood osmolality, total and direct bilirubin, blood lactate, PaO2, FiO2, platelet counts, mean arterial pressure and patient weight.

Conclusion

The findings of this study did not support the initial research objectives and hypotheses, as no significant relationship was found between hydration status and clinical outcomes in COVID-19 patients. Additionally, 24.5% of the subjects exhibited a fluid deficit. Given that this study is the first to explore this specific aspect, further research is recommended to investigate the hydration status of critically ill patients.
Lupus activity in lupus nephritis patients with end-stage renal disease treated with hemodialysis
Authors: Morad Caroline Samy , Zaiema Shams ElDoha Galal , Hafez Eman Ahmed , Mansour Mohammed Maher Mohammed Mohammed , Khalil Amr Elsayed Mohammed Abd-Allah , Hassan Shaymaa Gamal Arafa
Published: January 2025

Background

Lupus nephritis is one of the major causes of ESRD, which may necessitate renal replacement therapy, especially hemodialysis. Evaluating post-HD lupus flares in LN patients is pivotal in improving their outcomes. This issue is still under consideration by researchers. This research analyzed lupus activity in LN patients with ESRD treated with HD.

Methods

A number of 70 LN patients diagnosed by renal biopsy were divided into age- and sex-matched two groups: They were divided into two groups: the HD Group, which were LN patients who progressed to ESRD treated with HD (n = 35), and the CKD Group, which contains LN patients’ stage III, IV by renal biopsies and HD free (n = 35). The non-renal systemic lupus erythematosus (SLE) disease activity index (nrSLEDAI) score was used to estimate lupus flares in both groups regardless of the stage of renal affection.

Results

The HD group exhibited considerably declined lupus activity compared to the CKD group, irrespective of the progression of renal pathology. With long-term period maintenance on HD, there was an obvious remission in both clinical and serological parameters of SLE recorded by the nrSLEDAI scoring system. Current doses of oral corticosteroids were less in the HD group than in the CKD group.

Conclusion

Using the nrSLEDAI score, our current research provides evidence of a reverse association between the longevity of hemodialysis (HD) and lupus activity, a "Cut-down phenomenon.” We believe that performing clinical trials and developing new post-HD evidence-based treat-to-target management guidelines for LN patients is now mandatory to improve their clinical outcomes and quality of life.
EFFICIENT MAPPING OF COMPLEX GROUNDWATER SYSTEMS ASSOCIATED WITH BRAIDED RIVERS USING SMALL COIL SURFACE NUCLEAR MAGNETIC RESONANCE
Authors: Vang Mathias Østbjerg , Grombacher Denys , Larsen Jakob Juul , Wilson Scott
Published: January 2025

Braided river systems are a substantial source of groundwater recharge in New Zealand. These rivers flow from high relief towards the sea across alluvial plain aquifers, across which the primary groundwater recharge occurs. These aquifers are often used for agricultural irrigation, and overexploitation can occur if there is limited knowledge on aquifer recharge mechanisms. To understand these complex recharge patterns a more detailed knowledge of the lithological controls on surface water-groundwater exchange is necessary. Here we present a case study, where surface nuclear magnetic resonance (SNMR) was employed in braided river systems to identify subsurface structures. We found the method to be efficient in identifying permeability contrasts beneath riverbeds and river berms in multiple river settings. We calibrated a local archetype by coincident borehole lithology and SNMR derived water contents, to find the SNMR signature related to lithological changes. The resulting archetypes were extrapolated to SNMR sites where there is no coinciding borehole information to identify these lithological transitions at multiple sites. We show that a combined borehole and SNMR survey can map transitions from aquifers to low permeability-layers efficiently in three case studies. The small 20 m x 20 m SNMR coil enabled acquisition on small bars within the river while resolving the thin saturated units, previously not resolvable with a larger coil size. The lateral constrained inversion (LCI) improved lateral consistency and the ability to track the features of the braidplain aquifer in all three rivers within the top 10 m. These results demonstrate SNMR as a multisite geophysical method capable of mapping important hydrogeological layers to provide valuable information on recharge to vulnerable aquifers.
Elastic wavefield separation of DAS-VSP data based on non-stationary polarization projection
Authors: Wang Tengfei , Cheng Jiubing , Cao Zhonglin , Wang Tengyu , Duan Pengfei
Published: January 2025

Distributed acoustic sensing (DAS) generally records the seismic signals by detecting the axial strain or strain rate that is stimulated by the impinging elastic wavefields along the optical fibers. It has become an important seismic observation technology, especially in vertical seismic profiling (VSP) applications, due to its low cost, easy deployment and high-density spatial sampling. Although current DAS-VSP acquisitions typically offer only a single-component observation, they still provide valuable elastic information about the subsurface. Separating P and S waves from the DAS-VSP data and leveraging these wavefield information is very important for the inversion of elastic parameters and seismic imaging. Therefore, a polarization projection method is introduced to deal with the P/S separation of walkaway DAS-VSP data. Firstly, the polarization directions of P and S waves are estimated using the dispersion relation derived from elastodynamic wave equations. Then, the P/S wave separation is achieved through a non-stationary polarization projection that can take into account the effects of spatially varying wave velocities. Finally, a two-step workflow is proposed to successively separate the P and S waves in common-shot and common-receiver gathers. The results of synthetic and real walkaway DAS-VSP data demonstrate that this method can effectively separate P- and S-wave signals from DAS-VSP data, and provide effective data preconditioning for subsequent velocity model building and seismic imaging.
Melanoma Among Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Rotz Seth J. , Stratton Kayla , Leisenring Wendy M. , Smith Susan A. , Howell Rebecca M. , Bates James E. , Pappo Alberto S. , Neglia Joseph P. , Armstrong Gregory T. , Turcotte Lucie M.
Published: January 2025

PURPOSE

Melanoma as a subsequent malignant neoplasm has been described among childhood cancer survivors; however, the risk factors and long-term survival are not well understood.

METHODS

We assessed incidence, risk factors, and outcomes for melanoma among participants in the Childhood Cancer Survivor Study cohort. Cumulative incidence and standardized incidence ratios (SIRs) were calculated, and multivariable Cox models were used to determine hazard ratios (HRs) and associated 95% CI for melanoma risk factors. Radiation exposure to seven body regions and melanoma status for each of eight regions per survivor were integrated into the Cox model.

RESULTS

Among 25,716 participants, 177 melanomas developed in 160 survivors (110 invasive, 62 in situ cutaneous, five ocular). The 40-year melanoma cumulative incidence was 1.1% (95% CI, 0.9 to 1.4) for all participants and 1.5% (95% CI, 1.0 to 2.1) among those receiving a cumulative radiation dose of ≥40 Gy. Compared with the general population, the SIR for invasive skin or ocular melanoma was 2.0 (95% CI, 1.6 to 2.4). A cumulative radiation dose of ≥40 Gy to the corresponding body region(s) of the melanoma (HR, 2.0 [95% CI, 1.1 to 3.7]), a cumulative cyclophosphamide equivalent dose of ≥20,000 mg/m
2
(HR, 1.9 [95% CI, 1.1 to 3.6]), and bleomycin exposure (HR, 2.2 [95% CI, 1.2 to 4.1]) were associated with increased cutaneous melanoma. Invasive melanoma at any site was associated with an increased risk of death (HR, 2.4 [95% CI, 1.7 to 3.3]).

CONCLUSION

Childhood cancer survivors have more than a two-fold increased risk of melanoma compared with the general population, and those with an invasive melanoma have more than a two-fold risk of death. High-dose radiation and alkylating agent exposure, and bleomycin are important risk factors for melanoma and should be considered in future patient guidance and screening.