bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting pain and its association with mortality in patients with stroke
Authors: Viktorisson Adam , Hashem Aref Haj , S Sunnerhagen Katharina , Abzhandadze Tamar
Published: January 2025

Background and objectives

Poststroke pain (PSP) is a prevalent and severe consequence of stroke, encompassing central, neuropathic, and nonneuropathic pain. In this study, we aimed to investigate clinical factors associated with PSP three months after stroke and concurrently explore the association between PSP and one-year mortality.

Methods

This registry-based study comprised data from stroke patients admitted to three hospitals in Sweden between November 2014 and June 2019. The outcome was PSP three months after stroke. Twelve (out of 28) predictor variables were selected by three machine learning methods, and a multivariable binary logistic regression model was fitted for predicting PSP. The association between PSP and one-year poststroke mortality was examined using Cox proportional hazards models.

Results

Among 4,160 stroke patients participating in the three-month follow-up, 54.7% reported PSP. Antiplatelet use, diabetes, hemiparesis, sensory deficits, and need for assistance before stroke were significant predictors of PSP. Male sex, being born in Sweden, higher income, and regular prestroke physical activity predicted the absence of PSP. After adjustment for age, sex, region of birth, and stroke severity, patients experiencing PSP had a significantly higher one-year mortality rate than those without pain, and the most severe level of pain (constant pain) was associated with the highest cumulative mortality.

Conclusion

The study findings indicate treatable factors associated with PSP, which highlight areas of improvement in management strategies. Clinicians should recognize that PSP is associated with increased one-year mortality, emphasizing the importance of pain prevention and treatment for enhanced poststroke outcomes.
Environmental burden of disease resulting from long-term nitrogen dioxide exposure in Germany
Authors: Sell Paulina , Plass Dietrich , Kienzler Sarah , Zeeb Hajo
Published: January 2025

Background

Exposure to nitrogen dioxide (NO2) is associated with an increased risk of cardiovascular, respiratory, and other diseases and health outcomes. Although NO2 emissions have decreased in Germany, concentrations currently observed still pose a threat to population health. The aim of this study is to estimate the environmental burden of disease (EBD) resulting from long-term NO2 exposure in Germany from 2010 to 2021.

Methods

To estimate the attributable disease burden, World Health Organization’s EBD approach was used. We first conducted a systematic literature review to identify exposure–response functions (ERFs) which mathematically represent the association between NO2 exposure and the health outcomes: asthma, chronic obstructive pulmonary disease (COPD), type 2 diabetes mellitus (T2DM), ischemic heart disease, lung cancer, stroke, and cardiovascular and respiratory mortality. Then, we estimated the years of life lost (YLL), years lived with disability (YLD) and, where possible, disability-adjusted life years (DALYs) due to these health outcomes in Germany, using mostly publicly available data. In a third step, using the ERFs and modelled ambient NO2 exposure data, the fraction of the disease burden attributable to NO2 exposure was estimated for each health outcome and year, stratified by sex.

Results

The systematic review yielded recent ERFs for some exposure-outcome pairs, but not always for both mortality and morbidity outcomes. A full DALY calculation was possible for COPD and T2DM. For the other outcomes, either only YLL or YLD were calculated. Summing up the estimated YLD and YLL of all outcomes, the burden of disease due to NO2 exposure in Germany decreased from 261,503 (95% UI 69,290–489,273) lost healthy years in 2010 to 100,032 (95% UI 24,558–191,715) in 2021.

Conclusions

Although the burden of disease attributable to NO2 exposure decreased from 2010 to 2021, NO2 still poses a threat to population health in Germany. While the current legal concentration limit was generally not exceeded in Germany in 2021, stricter new values proposed by WHO were frequently surpassed. When comparing the results to a previous assessment, it was obvious how strongly different input data impact the results. Transparent reporting of input data and discussing potential challenges when interpreting EBD results are critical.
Examining associations between oral cancer mortality and economic development of 13 European countries: an ecological and correlational study
Authors: Boruzs Klára , Bán Eszter Barbara , Dombrádi Viktor , Bányai Gábor , Szőllősi Gergő József , Bíró Klára
Published: January 2025

Background

Cancer is a significant public health issue all over the world. The diagnosis, treatment and follow-up of cancer patients are a huge health, economic and social burden for societies. The link between the state of health of a country and its economic performance has been proven by numerous studies. The aim of this study was to examine the age-standardized death rate of oral cancer in relation to the economic development of 13 European countries.

Methods

Aggregated data were collected from the European Health for All (HFA-DB) database until 2019 and analysed using second degree polynomial functions and correlation analyses, followed by time-series analysis involving vector autoregressive models.

Results

We found that in 10 of the 13 surveyed countries, the age-standardized death rate of oral cancer initially increased with GDP growth and then showed a downward trend above a certain level of economic development. Austria had a weak but significant positive effect with the second lag of GDP, Hungary had a significant negative effect with the first lag of GDP, and Italy had a significant negative effect with the second lag of GDP. In most cases, both the first and second lags of GDP changes were not statistically significant, indicating that short-term fluctuations in GDP do not directly influence changes in oral cancer mortality rates. Overall, while there are clear long-term associations between GDP and oral cancer mortality rates, the immediate causal effects of GDP changes on mortality rates are limited, suggesting that other factors and longer-term dynamics could play a more crucial role in this relationship.

Conclusions

An increase in a country’s economic development alone does not guarantee a decrease in the number of oral cancer patients. Therefore, in order to reduce the number of cases of oral cancer, strengthening education and prevention are essential.
Navigating the fear: assessing nursing students’ concerns and preventive practices in response to Monkeypox in Egypt
Authors: Amin Shaimaa Mohamed , Demerdash Doaa El , El-Sayed Mona Metwally , Salama Tasneem Ragab Ahmed , Elsehrawy Mohamed Gamal , Atta Mohamed Hussein Ramadan
Published: January 2025

Background

Monkeypox has emerged as a global health concern, necessitating preventive measures and awareness among healthcare students. Understanding nursing students’ fears, concerns, and preventive practices regarding Monkeypox can help improve preparedness and response strategies.

Aim

This study aimed to assess the levels of fear, concerns, and preventive practices related to monkeypox among nursing students at Beni Suef University, Egypt, during the 2024–2025 academic year.

Methods

A cross-sectional descriptive design was employed, involving 505 nursing students systematically randomized recruited. Data collection utilized three validated tools: the Monkeypox Fear Scale, Monkeypox Concern Scale, and Monkeypox Preventive Practices Scale. Reliability was confirmed with Cronbach’s alpha values ranging from 0.87 to 0.94. Data analysis included descriptive statistics, Spearman correlation, and multiple linear regression using SPSS Version 23.

Results

Most (56.2%) students rarely worried about Monkeypox infection, though 49.2% reported anxiety influenced by media coverage. High preventive practices were noted, with 60.6% frequently practicing hygiene measures. A strong positive correlation between Monkeypox concern and fear (r = 0.646, p < 0.001) and a moderate positive correlation between Monkeypox concern and preventive practices (r = 0.229, p = 0.001). Fear was also significantly correlated with preventive practices (r = 0.432, p < 0.001). Multiple linear regression analysis (R² = 0.216, F = 22.633, p < 0.001) revealed that fear was a strong positive predictor of preventive practices, while Monkeypox concern had a positive but non-significant effect (B = 0.138, p = 0.156). Age was not a significant predictor (B = 0.251, p = 0.637), whereas family income showed a significant negative association (B = -1.885, p = 0.010).

Conclusion

The study revealed moderate fear and concerns among nursing students, with generally high adherence to preventive practices.

Implication

Findings suggest the need for targeted health education programs to address monkeypox-related concerns and enhance preventive measures, thus improving nursing students’ readiness to respond to emerging health threats.
Knowledge, attitude and practice of family caregivers on pressure injury prevention for community-dwelling older adults: a cross-sectional study in an Indonesia City
Authors: Sari Sheizi Prista , Everink Irma H. J. , Lohrmann Christa , Amir Yufitriana , Sari Eka Afrima , Halfens Ruud J. G. , Schols Jos M. G. A.
Published: January 2025

Background

Older adults in Indonesia are mostly living at home with their families. Informal care provided by family caregivers is essential to prevent older adults from getting pressure injuries (PIs). The objectives of this study were to examine the knowledge, attitude and practice of family caregivers regarding PI prevention among community-dwelling older adults in Indonesia.

Methods

A cross-sectional survey was conducted involving 267 family caregivers randomly selected from a population list provided by municipalities in Bandung, West Java, Indonesia. The study utilized the paper-based Knowledge, Attitude, and Practice on Pressure Injury (KAP-PI) questionnaire. Descriptive analyses (i.e. percentage, mean and standard deviation) were used to present participants’ scores in each domain based on their characteristics or categories and scores in every single item of questions or statements. Bivariate comparison analyses were conducted using independent t-test or ANOVA test to compare scores and a Chi-square was run to check correlations between knowledge, attitude and practice domains.

Results

This study show that more than half of the participants (61.0%) had insufficient knowledge about PI prevention, but nearly all participants (94.4%) had a positive attitude toward PI prevention for their older relatives. Still, 41.2% of the participants had inadequate practice on PI prevention. A correlation analysis revealed that having sufficient knowledge and a positive attitude towards PI prevention were positively correlated with practice (p < .05).

Conclusion

This study highlights a significant gap in family caregivers’ knowledge and practice regarding pressure injury (PI) prevention, despite their generally positive attitudes toward the care of older relatives. The findings are the initial diagnosis to guide educational strategies. Research should be performed to explore effective educational materials and an education program and also the necessary professional support to strengthen family caregivers’ role in PI prevention.
Reversal gene expression assessment for drug repurposing, a case study of glioblastoma
Authors: Sun Shixue , Shyr Zeenat , McDaniel Kathleen , Fang Yuhong , Tao Dingyin , Chen Catherine Z. , Zheng Wei , Zhu Qian
Published: January 2025

Background

Glioblastoma (GBM) is a rare brain cancer with an exceptionally high mortality rate, which illustrates the pressing demand for more effective therapeutic options. Despite considerable research efforts on GBM, its underlying biological mechanisms remain unclear. Furthermore, none of the United States Food and Drug Administration (FDA) approved drugs used for GBM deliver satisfactory survival improvement.

Methods

This study presents a novel computational pipeline by utilizing gene expression data analysis for GBM for drug repurposing to address the challenges in rare disease drug development, particularly focusing on GBM. The GBM Gene Expression Profile (GGEP) was constructed with multi-omics data to identify drugs with reversal gene expression to GGEP from the Integrated Network-Based Cellular Signatures (iLINCS) database.

Results

We prioritized the candidates via hierarchical clustering of their expression signatures and quantification of their reversal strength by calculating two self-defined indices based on the GGEP genes’ log2 foldchange (LFC) that the drug candidates could induce. Among five prioritized candidates, in-vitro experiments validated Clofarabine and Ciclopirox as highly efficacious in selectively targeting GBM cancer cells.

Conclusions

The success of this study illustrated a promising avenue for accelerating drug development by uncovering underlying gene expression effect between drugs and diseases, which can be extended to other rare diseases and non-rare diseases.
Evaluation of the impact of continuous nursing and cluster nursing on carpal tunnel syndrome release surgery
Authors: Chen Yang , Li Ruihua , Zhu Yongqiang , Chen Ran
Published: January 2025

Background

This study aimed to estimate the influence of continuous and cluster nursing on carpal tunnel syndrome (CTS) release surgery.

Methods

Ninety-six patients with CTS were treated in our hospital from November 2019 to December 2021. These patients were randomly divided into two groups of 48 patients. Both groups underwent open carpal tunnel release surgery. The control group received routine nursing care, while the study group received a combination of continuous and cluster nursing interventions. The Boston carpal tunnel question, the Visual Analogue Scale (VAS), the Numerical Rating Scale (NRS), the Pittsburgh Sleep Quality Index (PSQI), Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Barthel index were used to compare hand function recovery, hand pain, sleep quality, and quality of life between the two groups before and 3 months after surgery.

Results

Both groups experienced improvements in hand function and pain 3 months after surgery. However, the study group demonstrated lower scores in symptom and dysfunction, as well as lower VAS and NRS scores compared to the control group (P < 0.05). Additionally, both groups showed an increase in the Barthel and PSQI scores 3 months after surgery. Notably, the study group exhibited higher Barthel scores and lower PSQI scores than the control group (P < 0.05).

Conclusion

The use of continuous and cluster nursing in patients undergoing CTS release surgery proves to be advantageous in alleviating hand pain, facilitating hand function recovery, and effectively enhancing sleep quality and overall quality of life for patients.
The ameliorative effect of selenium-loaded chitosan nanoparticles against silver nanoparticles-induced ovarian toxicity in female albino rats
Authors: Shalaby Omnia E. , Ahmed Yasmine H. , Mekkawy Aya M. , Mahmoud Mohamed Y. , Elbargeesy G. A.
Published: January 2025

Background

Recently, silver nanoparticles (Ag-NPs) were shown to provoke oxidative stress through the release of reactive oxygen species and consequently induce cell damage. Selenium-loaded chitosan nanoparticles (CS-SeNPs) have anti-inflammatory and antioxidant effects, indicating that they ameliorate Ag-NPs-induced ovarian toxicity.

Objective

This study aimed to assess how well CS-SeNPs counteract the damaging effects of Ag-NPs on the ovarian tissue of adult female albino rats.

Methods

Forty mature female albino rats were divided into four equal groups: for 60 days, Group I (control) was given 0.5 ml/kg of distilled water; Group II was given Ag-NPs orally (100 mg/kg); Group III was given Ag-NPs orally (100 mg/kg/d) plus CS-SeNPs (0.5 mg/kg/d); and Group IV was given only CS-SeNPs orally (0.5 mg/kg/d). All the ovarian tissues were removed and underwent immunohistochemical, histological, and biochemical analyses.

Results

Ag-NPs-exposed rats revealed a marked reduction in reduced glutathione (GSH) and superoxide dismutase (SOD). Numerous histopathological alterations were found along with a significant increase in PCNA- and Caspase-3-immunoreactive cells. Most of these alterations were successfully ameliorated by CS-SeNPs, as indicated by marked increases in GSH and SOD.

Conclusion

CS-SeNPs ameliorate the toxic effects of Ag-NPs on the ovarian tissue of adult female albino rats.
DPV pUL15 possesses a potential NLS, which is important for the location of the terminase complex and for viral proliferation and genome cleavage
Authors: Yang Qiao , Feng Yaya , Liu Lizhen , Yang Linlin , Wang Mingshu , Wu Ying , Tian Bin , Ou Xumin , Jia Renyong , Zhu Dekang , Chen Shun , Liu Mafeng , Zhao Xinxin , Zhang Shaqiu , Huang Juan , Sun Di , He Yu , Wu Zhen , Zhang Ling , Yu Yanling , Cheng Anchun
Published: January 2025

In herpesvirus, the terminase subunit pUL15 is involved in cleavage of the viral genome concatemers in the nucleus. Previous studies have shown that herpes simplex virus 1 (HSV-1) pUL15 can enter the nucleus without other viral proteins and help other terminase subunits enter the nucleus. However, this study revealed that duck plague virus (DPV) pUL15 cannot localize independently to the nucleus and can only be localized in the nucleus in the presence of pUL28 and pUL33. However, the data suggested the presence of a potential nuclear localization signal (NLS) in DPV pUL15, which is important for the localization of the terminase subunits. Subsequently, several single-point mutants were constructed to identify the vital amino acids within the NLS. The conserved amino acids K187, R188, and K190 are critical for the nuclear localization of pUL15, pUL28, and pUL33 but not for their interaction. Furthermore, corresponding recombinant viruses were constructed. The results revealed that the mutations rUL15K187Q, rUL15K188Q and rUL15K190Q had an obvious influence on concatemeric genome cleavage, but only K190Q significantly affected the production of progeny virions. These findings indicate that the NLS is important for the functions of DPV pUL15. Overall, a potential NLS and the key amino acids in DPV pUL15 were identified. Mutations in K187, K188 and K190 affected the cleavage of the concatemeric genome, but only mutations in K190 had an obvious effect on viral proliferation.
Analyzing environmental delivery of industrial technology and energy use-loss in China
Authors: Naimoğlu Mustafa , Alola Andrew Adewale
Published: January 2025

This study examines key indicators impacting China’s industrial sector: carbon dioxide (CO2) emissions by industry, industrial value added per worker, technology advancement in industrial design, fossil fuel usage, and energy losses in production and transmission. China’s industrial sector, heavily reliant on fossil fuels, has significant implications for environmental quality, establishing the country as the leading global carbon emitter. Rising energy losses compound economic challenges by driving up energy demand, increasing external dependencies, and straining foreign exchange reserves. In this context, we analyze how China’s industrial environment responds to technology adoption, energy losses, and fossil fuel usage. Using Fourier extensions enriched with time-series analyses, we assess the direction and magnitude of these responses, alongside testing the Environmental Kuznets Curve (EKC) hypothesis using Fully Modified Ordinary Least Squares, Canonical Cointegrating Regressions, and Dynamic Ordinary Least Squares methods. Our findings affirm the EKC hypothesis for China’s industrial sector, revealing that while fossil fuel usage and energy losses drive up CO2 emissions, advancements in industrial technology can offset some of these environmental impacts by reducing carbon emissions. Based on these findings, policymakers should focus on technological innovations that help decrease energy losses and fossil fuel consumption within the industrial sector.
Efficiency and heat transport processes of low-temperature aquifer thermal energy storage systems: new insights from global sensitivity analyses
Authors: Tas Luka , Hartog Niels , Bloemendal Martin , Simpson David , Robert Tanguy , Thibaut Robin , Zhang Le , Hermans Thomas
Published: January 2025

Aquifer thermal energy storage (ATES) has great potential to mitigate CO2 emissions associated with the heating and cooling of buildings and offers wide applicability. Thick productive aquifer layers have been targeted first, as these are the most promising hydrogeological context for ATES. Regardless, there is currently an increasing trend to target more complex aquifers such as low-transmissivity and alluvial aquifers or fractured rock formations. There, the uncertainty of subsurface characteristics and, with that, the risk of poorly performing systems is considerably higher. Commonly applied strategies to decide upon the ATES feasibility and well design standards for optimization need to be adapted. To further promote the use of ATES in such less favorable aquifers an efficient and systematic methodology evaluating the optimal conditions, while not neglecting uncertainty, is crucial. In this context, the distance-based global sensitivity analysis (DGSA) method is proposed. The analysis focuses on one promising thick productive aquifer, first used to validate the methodology, as well as a complex shallow alluvial aquifer. Through this method, multiple random model realizations are generated by sampling each parameter from a predetermined range of uncertainty. The DGSA methodology validates that the hydraulic conductivity, the natural hydraulic gradient and the annual storage volume dominate the functioning of an ATES system in both hydrogeological settings. The method also advances the state of the art in both settings. It efficiently identifies most informative field data ahead of carrying out the field work itself. In the studied settings, Darcy flux measurements can provide a first estimate of the relative ATES efficiency. It further offers a substantiated basis to streamline models in the future. Insensitive parameters can be fixed to average values without compromising on prediction accuracy. It also demonstrates the insignificance of seasonal soil temperature fluctuations on storage in unconfined shallow aquifers and it clarifies the thermal energy exchange dynamics directly above the storage volume. Finally, it creates the opportunity to explore different storage conditions in a particular setting, allowing to propose cutoff criteria for the investment in ATES. The nuanced understanding gained with this study offers practical guidance for enhanced efficiency of feasibility studies. It proves that the DGSA methodology can significantly speed up the development of ATES in more complex hydrogeological settings.
Hypertrophic cardiomyopathy: insights into pathophysiology and novel therapeutic strategies from clinical studies
Authors: Olalekan Samuel Oluwadare , Bakare Olalekan Olanrewaju , Okwute Patrick Godwin , Osonuga Ifabunmi Oduyemi , Adeyanju Muinat Moronke , Edema Victoria Biola
Published: January 2025

Background

Hypertrophic cardiomyopathy (HCM) is a frequently encountered cardiac condition worldwide, often inherited, and characterized by intricate phenotypic and genetic manifestations. The natural progression of HCM is diverse, largely due to mutations in the contractile and relaxation proteins of the heart. These mutations disrupt the normal structure and functioning of the heart muscle, particularly affecting genes that encode proteins involved in the contraction and relaxation of cardiac muscle.

Main body

This review focused on understanding the role of contractile and relaxation proteins in the pathogenesis of hypertrophic cardiomyopathy. Mutations in contractile proteins such as myosin, actin, tropomyosin, and troponin are associated with hypercontractility and increased sensitivity of the heart muscle, leading to HCM. Additionally, impaired relaxation of the heart muscle, linked to abnormalities in proteins like phospholamban, sarcolipin, titin, myosin binding protein-C, and calsequestrin, contributes significantly to the disease. The review also explored the impact of targeted therapeutic approaches aimed at modulating these proteins to improve patient outcomes. Recent advances in therapeutic strategies, including novel pharmacological agents like mavacamten and aficamten, were examined for their potential to help patients manage the disease and lead more accommodating lifestyles.

Conclusions

The review underscored the significance of early diagnosis and personalized treatment approaches in managing HCM. Future research should prioritize the development of robust biomarkers for early detection and risk stratification, particularly in diverse populations, to enhance clinical outcomes. Furthermore, it is imperative to delve deeper into the genetic mutations and molecular mechanisms associated with HCM, with a focus on exploring the roles of less-studied myocardial relaxation proteins and their interactions with sarcomere constituents.
EBUS-TBNA in diagnosis of pulmonary hamartoma: is it possible?
Authors: Emam Wael , Hafez Fatma , Osman Nehad
Published: January 2025

Background

Pulmonary hamartoma is an extremely rare benign neoplasm of the lungs. Patients usually present in the 4th and 5th decades of life and usually present as a hilar mass that needs to be biopsied to confirm the nature of the lesion. We report a case of pulmonary hamartoma that was diagnosed with EBUS-TBNA.

Case presentation

A 45-year-old female patient, non-smoker presented with dyspnea at moderate exertion. A CT scan showed a well-circumscribed left hilar mass. EBUS was planned and 3 passes EBUS-TBNA were taken and the final histopathological diagnosis was surprisingly pulmonary hamaroma.

Conclusions

EBUS-TBNA allows to locating of undiagnosed mediastinal lesions and performing a targeted needle aspiration, in a less invasive way, that can provide enough material for a certainty diagnosis in mediastinal hamartoma disease.
Concomitant Statin Use and Survival in Patients With Cancer on Immune Checkpoint Inhibitors: A Meta-Analysis
Authors: Liao Yonghe , Lin Yuxuan , Ye Xinqi , Shen Jinhai
Published: January 2025

PURPOSE

The prognostic significance of concomitant statin use in cancer treatment with immune checkpoint inhibitors (ICIs) remains a subject of ongoing investigation. This study aims to clarify the prognostic value of statin use in this patient population and to provide a robust, evidence-based foundation to guide therapeutic decisions.

METHODS

A systematic search strategy was used across a multitude of digital archives to exhaustively identify all relevant academic literature published up until June 20, 2024. Studies published in English that reported hazard ratios (HRs) for overall survival (OS) and/or progression-free survival (PFS), along with corresponding 95% CIs, were considered eligible for inclusion. Meta-analyses were conducted to calculate combined HRs with 95% CIs.

RESULTS

A total of 25 studies, involving 46,154 patients with cancer, were included in the meta-analysis. The pooled results indicated that concomitant statin use was linked to better OS (HR, 0.80 [95% CI, 0.71 to 0.92]) and PFS (HR, 0.80 [95% CI, 0.69 to 0.92]) in patients with cancer under ICI therapy. Sensitivity analyses further validated the consistency and robustness of the combined results.

CONCLUSION

On the basis of the available clinical evidence, the concomitant use of statin is linked to an improved prognosis in oncology patients on ICI-based therapy. These observations underscore the potential of statin as an important adjunctive therapy in the treatment paradigm for ICI-treated patients with cancer, thereby establishing their significance as a key consideration in clinical management strategies. Further randomized controlled trials are imperative to validate the effect of statin use within the realm of ICI therapy.
Novel Treatment Options for Multiple Myeloma
Authors: Portuguese Andrew J. , Banerjee Rahul , Chen GuiZhen , Reddi Swetha , Cowan Andrew J.
Published: January 2025

Multiple myeloma (MM), the second most common hematologic malignancy in the United States, is characterized by repeated cycles of remission and relapse, with increasing resistance to treatment after each line of therapy. Despite the virtually incurable nature of MM, recent therapeutic breakthroughs have fundamentally reshaped its treatment landscape. This review explores evolving care paradigms, spanning from newly diagnosed MM to relapsed or refractory disease. In the frontline setting, treatment strategies have shifted beyond their traditional emphasis on autologous stem-cell transplant eligibility to a broader categorization of patients on the basis of their suitability for quadruplet therapy. In the relapsed/refractory setting, novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, have revolutionized treatment, offering new hope for patients with previously limited options. Precision medicine is playing a growing role in MM treatment, with venetoclax showing significant efficacy in patients with t(11;14) translocation, advancing targeted therapy for this subgroup. On the horizon, investigational CAR-T products and cereblon E3 ligase modulators, such as mezigdomide and iberdomide, may provide faster, more durable responses compared with current therapies. In addition, belantamab mafodotin, an antibody-drug conjugate withdrawn from the US market in 2022, is on the verge of reapproval after positive results from recent randomized trials. While these therapies offer significant potential, challenges remain in managing toxicity, ensuring treatment accessibility, and optimizing sequencing strategies. As the therapeutic arsenal expands, the need for personalized MM treatment plans that balance efficacy with quality of life becomes even more essential.
Optimizing Radiotherapy Timing for Nasopharyngeal Carcinoma: The Impact of Radiation Scheduling on Survival
Authors: Li Ying , Weng Youliang , Huang Zongwei , Wu Lishui , Xu Siqi , Xie Yingjie , Li Haolan , Lai Jinghua , Hu Dan , Qiu Sufang
Published: January 2025

PURPOSE

Chronoradiobiology has emerged as a potential field of study with therapeutic implications for cancer treatment. We aimed to investigate the association between radiation chronotherapy and the efficacy and toxicity of patients with nasopharyngeal carcinoma (NPC).

PATIENTS AND METHODS

Patients with nonmetastatic NPC treated with intensity-modulated radiotherapy in Fujian Cancer Hospital between January 2017 and December 2019 were included. Propensity score matching (PSM) with 1:1:1 was used to account for selection bias. Cox regression analysis was performed to explore the impact of radiotherapy timing on patient survival. Sensitivity analysis was implemented to determine the size and directional stability.

RESULTS

One thousand forty patients met study inclusion criteria and 332 patients were included in a PSM cohort. In the unmatched cohort analysis, morning radiotherapy exhibited a significantly superior overall survival (OS) outcome (hazard ratio [HR], 0.60 [95% CI, 0.40 to 0.91], adjusted log-rank
P
= .028) than the afternoon one. After PSM analysis, it was observed that individuals undergoing radiotherapy in the afternoon group (HR, 5.88 [95% CI, 2.55 to 13.58], adjusted log-rank
P
= .004) and the night group (HR, 4.81 [95% CI, 1.91 to 12.11], adjusted log-rank
P
= .018) displayed a tendency toward shorter OS compared with the morning group. No significant differences in acute treatment-related adverse effects were observed among the three groups. Morning radiotherapy demonstrated consistent robustness in the multivariable analysis, thereby establishing an association with higher OS. The directionality of the effect size was consistent across sensitivity analysis.

CONCLUSION

These results underscore the potential benefits of scheduling radiotherapy in the morning for NPC management, although prospective studies are needed to confirm these findings.
Digenic Inheritance Mode in Congenital Hypothyroidism Due to Thyroid Dysgenesis: HYPOTYGEN Translational Cohort Study
Authors: Stoupa Athanasia , Kariyawasam Dulanjalee , Jabot-Hanin Fabienne , Nguyen-Quoc Adrien , Hanein Sylvain , Rabeony Tioka , Elie Caroline , Colas Sandra , Thalassinos Caroline , Oliver-Petit Isabelle , Houang Muriel , Coutant Régis , Barat Pascal , Nicolino Marc , Reynaud Rachel , de Kerdanet Marc , Bensignor Candace , Baron Sabine , Raynaud-Ravni Catherine , Souchon Pierre-François , Léger Juliane , Castanet Mireille , Bole-Feysot Christine , Nitschke Patrick , Lyonnet Stanislas , Polak Michel , Carré Aurore
Published: January 2025

Context

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and is chiefly caused by thyroid dysgenesis (CHTD). The inheritance mode of the disease remains complex.

Objective

Gain insight into the inheritance mode of CHTD.

Methods

Prospective multicenter nationwide translational study in France including 514 patients with CH diagnosed through systematic newborn screening (HYPOTYGEN cohort). We focused on CHTD cases and studied their clinical and molecular phenotypes. Targeted next-generation sequencing using a 78-gene panel, including genes involved in thyroid development, function, transport, metabolism and action of thyroid hormones. Statistical analysis, familial segregation, and in vitro functional studies focusing on cell migration have been performed.

Results

We analyzed the clinical phenotypes of 458 patients with CH. Cardiac and renal malformations were present in 7.7% (14/182) and 3.9% (7/178) of patients, respectively. Genetic analysis was performed on 292 patients of the cohort, based on criteria for ethnicity and availability of DNA samples for index cases and their parents. A disease-causing mutation in 1 of the 10 known genes for CHTD was identified in 20/292 (6.8%) patients. We found a digenic mode of inheritance in 16 (5.5%) patients, each carrying a variant in a thyroid development gene and a variant in the H2O2 generation complex gene DUOX2/DUOXA2. Familial segregation analysis and in vitro functional studies supported this model.

Conclusion

This work expands our understanding of the molecular causes of CHTD by demonstrating that digenic inheritance can be implicated, with deleterious variants in thyroid development and DUOX2/DUOXA2 genes. The complexity of this model implies a revision of the genetic landscape of CHTD and specific clinical care of patients during long-term follow-up.
Optimized husbandry and targeted gene-editing for the cnidarian Nematostella vectensis
Authors: Carvalho João E. , Burtin Maxence , Detournay Olivier , Amiel Aldine R. , Röttinger Eric
Published: January 2025

Optimized laboratory conditions for research models are crucial for the success of scientific projects. This includes controlling the entire life cycle, having access to all developmental stages and maintaining stable physiological conditions. Reducing the life cycle of a research model can also enhance the access to biological material and speed up genetic tool development. Thus, we optimized the rearing conditions for the sea anemone Nematostella vectensis, a cnidarian research model, to study embryonic and post-metamorphic processes, such as regeneration. We adopted a semi-automated aquaculture system for N. vectensis and developed a dietary protocol optimized for the different life stages. Thereby, we increased spawning efficiencies, juvenile growth and survival rates, and considerably reduced the overall life cycle down to 2 months. To further improve the obtention of CRISPR-Cas9 mutants, we optimized the design of sgRNAs leading to full knockout animals in F0 polyps using a single sgRNA. Finally, we show that NHEJ-mediated transgene insertion is possible in N. vectensis. In summary, our study provides additional resources for the scientific community that uses or plans to use N. vectensis as a research model.
Transcriptional dynamics during karyogamy in rice zygotes
Authors: Toda Erika , Koshimizu Shizuka , Kinoshita Atsuko , Higashiyama Tetsuya , Izawa Takeshi , Yano Kentaro , Okamoto Takashi
Published: January 2025

Upon fertilization, male and female nuclei fuse to form the zygotic nucleus in angiosperms. Karyogamy is considered to be essential for proper embryogenesis; however, the transcriptional dynamics during karyogamy in plant zygotes remain unclear. In this study, we performed a single-cell transcriptome analysis of rice zygotes at six early developmental stages (15 min, 30 min, 1 h, 2 h, 4 h, and 6 h after gamete fusion) to reveal gene expression profiles during karyogamy in plant zygotes. The time-series RNA-sequencing analysis detected possible de novo and altered gene expression in zygotes from 15 min post-fertilization. Fertilization-induced transcription during karyogamy was characterized by protein interaction database and gene ontology (GO) analyses. Furthermore, paternal allele transcription was initiated approximately 30 min to 1 h after gamete fusion, when nuclear fusion begins in the zygote. Some transcripts preferentially expressed in egg cells were downregulated after gamete fusion. Moreover, a dynamic shift from maternal-biased transcripts to bi-parental expression occurred during early zygotic development. These results suggest that transcriptional dynamics during karyogamy plays an initial role in proper and sequential zygotic development and embryogenesis.
Έλληνες μουσικοί «ανάμεσα»:
Authors: Σβάρνα Σοφία
Published: January 2025

Το θέμα της διατριβής κινείται στον χώρο της εθνομουσικολογίας και εστιάζει στις σύγχρονες διαστάσεις μουσικών και πολιτισμικών συσχετισμών στην Μεσόγειο, έτσι όπως αυτοί εκφράστηκαν μέσα από την καλλιτεχνική δράση τεσσάρων σχημάτων παλαιάς μουσικής, δυο ελληνικών και δυο ευρωπαϊκών. Τα σχήματα αυτά ήταν ειδικευμένα στο φάσμα της παλαιάς μουσικής και της λεγόμενης «ιστορικής ερμηνείας» και εξερευνούσαν νέες μουσικές κατευθύνσεις προς τις τροπικές παραδόσεις της Μεσογείου, μέσα από συναυλίες που συχνά αποκαλούσαν «μουσικές συναντήσεις». Στις συναυλίες πρωταγωνιστούσαν μουσικοί από πολλές τροπικές παραδόσεις της Μεσογείου. Οι μουσικοί της ευρωπαϊκής παλαιάς μουσικής, Έλληνες ή μη, κοιτούσαν προς την ανατολή και οι μουσικοί των τροπικών παραδόσεων της Μεσογείου αντίστροφα, κοιτούσαν προς τη «δύση», μουσικά, επιτελεστικά και αισθητικά. Τα ερευνητικά ερωτήματα είναι: Γιατί η παλαιά μουσική ακούγεται «νέα»; Πώς κάνουν οι μουσικοί τις «μουσικές συναντήσεις» και πώς μιλούν για αυτό που κάνουν; Πώς συμβάλλουν οι μουσικοί της παλαιάς μουσικής και πώς εκείνοι των τροπικών παραδόσεων της Μεσογείου στην συνάντηση; Ποιες σχέσεις (συμμετρικές και ασύμμετρες) γεννά η μεταξύ τους συνάντηση; Ποια η συμβολή της εθνομουσικολογίας στην επιστημονική μελέτη της παλαιάς μουσικής και ποια η συμβολή της στην επιστημονική μελέτης της συνάντησης παλαιάς μουσικής και τροπικών παραδόσεων της Μεσογείου; Το θεωρητικό υπόβαθρο της διατριβής εδράζεται στην συνάντηση εθνομουσικολογίας και ιστορικής μουσικολογίας, με άξονα τη δυτική έντεχνη μουσική και εν προκειμένω, τη λεγόμενη «παλαιά μουσική» (μουσική του μεσαίωνα, της αναγέννησης και του μπαρόκ). Από την σκοπιά της εθνομουσικολογίας, εξετάζεται το υπόβαθρο της ιστορικής εθνομουσικολογικής μελέτης λόγιων παραδόσεων της Μεσογείου. Επίσης καταγράφεται η ένταση της συνάντησης ιστορικής μουσικολογίας και εθνομουσικολογίας που θεωρείται από κάποιους μουσικούς επιστήμονες αδύνατη, ενώ από κάποιους άλλους ως μια δημιουργική πιθανότητα ώσμωσης ή συγχώνευσης, που έχει ήδη συντελεστεί ως έναν βαθμό. Στην εθνογραφική μελέτη αναδύονται: οι μουσικές συναντήσεις λογίων παραδόσεων στο πλαίσιο της εθνομουσικολογικής συζήτησης για την μουσική ως αναβίωση, η ολίσθηση από την «ιστορικά ενημερωμένη ερμηνεία» στην «πολιτισμικά ενημερωμένη ερμηνεία», συμμετρικές ή ασύμμετρες σχέσεις στο πεδίο ανάμεσα στους μουσικούς που πραγματοποιούν τις μουσικές συναντήσεις, το ζήτημα της αναζήτησης κοινής αισθητικής στη βάση υιοθέτησης «νέων παλαιών πρακτικών», τα όρια μεταξύ συμμετοχικής και παραστασιακής επιτέλεσης καθώς και η συμβολή των Ελλήνων μουσικών στην κουλτούρα της προφορικότητας ως προς την επιτέλεση της παλαιάς μουσικής. Κλείνοντας, η ιδέα του «ανάμεσα» αναδύεται ως μια λύση στον δυισμό δύση/ανατολή σκέψης και δράσης, ιδωμένη με πολιτισμικούς και μουσικούς όρους, και ερμηνεύεται ως μια ισορροπία «ανάμεσα» και πέρα από ανάμεσα σε ανατολή και δύση.
Ανάπτυξη, αλγοριθμική επίλυση και υλοποίηση μοντέλων βελτιστοποίησης της εφοδιαστικής αλυσίδας στα τεχνικά έργα
Authors: Κουτσοκώστα Ασπασία
Published: January 2025

Το παρόν έργο εξετάζει το πρόβλημα βέλτιστου σχεδιασμού και ενοποίησης της εφοδιαστικής αλυσίδας στην κατασκευαστική βιομηχανία σε αιτιοκρατικά και στοχαστικά περιβάλλοντα, αναπτύσσοντας μια σειρά από μοντέλα για τη βελτιστοποίηση μιας δυναμικής τριεπίπεδης εφοδιαστικής αλυσίδας που εξυπηρετεί πολλαπλά τεχνικά έργα με πολλαπλά προϊόντα υπό την ηγεσία του κύριου εργολάβου. Με στόχο την ελαχιστοποίηση του συνολικού κόστους της εφοδιαστικής αλυσίδας, λαμβάνονται βέλτιστες αποφάσεις σχετικά με τον σχεδιασμό του δικτύου, την παραγωγή, την αποθήκευση και τη μεταφορά προϊόντων, επιτρέποντας την εφαρμογή εκπτώσεων για μαζικές αγορές, τη χρήση κέντρων εφοδιαστικής, τις ελλείψεις υλικών στα εργοτάξια και την προετοιμασία αποθεμάτων πριν την έναρξη των έργων. Τα μοντέλα ενοποιούν τις λειτουργίες προσωρινών και εργοκεντρικών εφοδιαστικών αλυσίδων σε ένα βιώσιμο δίκτυο με επαναλαμβανόμενες ροές, συμβάσεις ευρύτερου αντικειμένου, στρατηγικές συμμαχίες και οικονομίες κλίμακας. Αρχικά, παρουσιάζονται δύο αιτιοκρατικά μοντέλα μεικτού–ακέραιου γραμμικού προγραμματισμού και, στη συνέχεια, η μετάβαση σε ένα μοντέλο στοχαστικού προγραμματισμού υπό τυχαίους περιορισμούς και η μετάβαση σε ένα μοντέλο στοχαστικού προγραμματισμού δύο σταδίων, θεωρώντας αβέβαιες παραμέτρους υπό τη μορφή διαφορετικών τύπων κατανομών πιθανοτήτων ή σεναρίων, ακόμα και αλληλεξαρτώμενες αβεβαιότητες —προσεγγίσεις που δεν έχουν εξεταστεί εκτενώς στο πλαίσιο της εφοδιαστικής αλυσίδας του κατασκευαστικού κλάδου. Τα μοντέλα αυτά επιτρέπουν τη λήψη αποφάσεων τύπου «εδώ και τώρα» ή/και «βλέποντας και κάνοντας» ανάλογα με τη φύση του προβλήματος και τη στάση του λήπτη αποφάσεων ως προς τη διαχείριση κινδύνων. Η καινοτομία αυτής της διατριβής έγκειται στην ανάπτυξη ενός ευέλικτου, ολοκληρωμένου εργαλείου βελτιστοποίησης της εφοδιαστικής αλυσίδας στα τεχνικά έργα, το οποίο λαμβάνει υπόψη πολλαπλά ενδιαφερόμενα μέρη (προμηθευτές/κατασκευαστές και παρόχους υπηρεσιών εφοδιαστικής), εργοτάξια, προϊόντα, χρονικές περιόδους και λειτουργίες υπό διαφορετικές παραδοχές και διαφορετικά περιβάλλοντα λήψης αποφάσεων. Η έρευνα που πραγματοποιήθηκε συνεισφέρει σημαντικά στο ταχέως αναπτυσσόμενο ερευνητικό πεδίο της βελτιστοποίησης της εφοδιαστικής αλυσίδας στα τεχνικά έργα με ποσοτικά μοντέλα και μια πλούσια συζήτηση σχετικά με προσεγγίσεις μοντελοποίησης και αλγοριθμικής επίλυσης ενόψει των διαφορετικών λύσεων που προέκυψαν με τη βοήθεια λογισμικού υπολογιστικών φύλλων.
Terroni and polentoni
Authors: Παρδάλης Στέργιος
Published: January 2025

Στην παρούσα διατριβή, υποστηρίζω ότι ενώ το Παλέρμο και η Σικελία πρέπει να κατανοηθούν στο πλαίσιο τόσο της Μεσογειακής όσο και της Ιταλικής εθνογραφίας, οι μοναδικοί παράγοντες που οδήγησαν στην υποδεέστερη οικονομική θέση της Σικελίας οδήγησαν επίσης σε ξεχωριστές πολιτικές εθνότητας και ταυτότητας. Τελικά, ωστόσο, προτείνω ότι η μειούμενη σημασία του ιταλικού έθνους-κράτους, σε σχέση με την αναδυόμενη Ευρωπαϊκή Ένωση, καθιστά μεγάλο μέρος της Παλερμιτάνικης ιδιαιτερότητας λιγότερο σημαντική τόσο οικονομικά όσο και πολιτισμικά. Παρόλο που ο διαχωρισμός της Ιταλίας μεταξύ Βορρά και Νότου βασίζεται κυρίως σε οικονομικά κριτήρια, η μετατροπή των δυσμενών οικονομικών συνθηκών του Ιταλικού Νότου σε πολιτιστικό ζήτημα συμβάλλει στη διαιώνιση των στερεοτύπων που τροφοδοτούν τις εντάσεις μεταξύ Βορρά και Νότου. Οι πρόσφατες εθνοτικές συγκρούσεις στην Ευρώπη, καθώς και οι συγκρούσεις για την επέκταση της Ευρωπαϊκής Ένωσης, έχουν θέσει υπό αμφισβήτηση τη σταθερότητα των εθνικών συνόρων και έχουν καταστήσει την έρευνα για την εθνική ταυτότητα τόσο επίκαιρη όσο και αναγκαία. Αυτή η ανθρωπολογική μελέτη, που πραγματοποιήθηκε στο Παλέρμο, την πρωτεύουσα της αυτόνομης περιοχής της Σικελίας, μελετά συγκεκριμένα τις διαδικασίες εθνικής ολοκλήρωσης αξιολογώντας κριτικά έννοιες και θέματα που έχουν σημαδέψει την Ανθρωπολογία της Μεσογείου. Εκτός από την εθνογραφική συμβολή των ιδιαιτεροτήτων της κατασκευής της εθνότητας και της ταυτότητας των Παλερμιτών, η παρούσα διατριβή αποσκοπεί στην αποδόμηση των στερεοτύπων που παραποιούν τη Σικελική κοινωνία. Το Παλέρμο και οι κάτοικοί του διαμορφώνονται μέσα από σχέσεις άνισης δύναμης μεταξύ κέντρου και περιφέρειας. Η ένταξη της Σικελίας στην Ευρωπαϊκή Ένωση, παραδόξως, φαίνεται να επιλύει διάφορα τρέχοντα ζητήματα εθνικής ολοκλήρωσης. Ένα από τα κύρια εννοιολογικά ζητήματα της Ανθρωπολογίας της Μεσογείου ήταν η εξέταση της τιμής/ντροπής που υπήρξε δημοφιλής από τη δεκαετία του 1960. Υποστηρίζω ότι ενώ οι διαβουλεύσεις αυτές έχουν εξυπηρετήσει ποικίλους γόνιμους σκοπούς, παραμελούν τις πολυπλοκότητες της σύγχρονης Σικελίας. Αντίθετα, επικεντρώνομαι στο εννοιολογικό σύμπλεγμα της τιμής, της οικογένειας, των κοινωνικών δικτύων και της εξουσίας, ως τα μέσα με τα οποία αλληλεπιδρούν τα διάφορα επίπεδα της κοινωνίας, προκειμένου να εξηγήσω καλύτερα τη δυναμική σχέση μεταξύ της τοπικής και της εθνοτικής ταυτότητας. Εξετάζω τους τρόπους με τους οποίους το τοπικό και το εθνικό έρχονται σε αντιπαράθεση μεταξύ τους και πώς μέσα από αυτές τις αντιθέσεις αναδύεται μια αναγνωρίσιμη Σικελική, αν όχι Παλερμιτάνικη, ταυτότητα. Η διατριβή βασίζεται σε δεδομένα που παρήχθησαν κατά τη διάρκεια εκτεταμένης επιτόπιας έρευνας στο Παλέρμο από τον Απρίλιο του 2005 έως τον Αύγουστο του 2006, καθώς και σε σύντομες επακόλουθες επισκέψεις το 2008.