bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Gene Expression of Tumors Undergoing Lepidic-Acinar Transition in Lung Adenocarcinoma
Authors: Okoshi Ethan N. , Fujita Shiro , Lami Kris , Kitamura Yuka , Matsuda Ryuta , Miyazaki Takuro , Matsumoto Keitaro , Nagayasu Takeshi , Fukuoka Junya
Published: March 2024

Lung adenocarcinoma is the most frequent subtype of thoracic malignancy, which is itself the largest contributor to cancer mortality. The lepidic subtype is a non-invasive tumor morphology, whereas the acinar subtype represents one of the invasive morphologies. This study investigates the transition from a non-invasive to an invasive subtype in the context of lung adenocarcinoma.

Patients with pathologically confirmed mixed subtype tumors consented to analysis of RNA-seq data extracted from each subtype area separately.

The study included 17 patients with tumors found to exhibit a lepidic-acinar transition. 87 genes were found to be differentially expressed between the lepidic and acinar subtypes, with 44 genes significantly upregulated in lepidic samples, and 43 genes significantly upregulated in acinar samples. Gene ontology analysis showed that many of the genes upregulated in the acinar subtype were related to immune response. Immune deconvolution analysis showed that there was a significantly higher proportion of M1 macrophages and total B cells in acinar areas. Immunohistochemistry showed that B cells were mainly localized to tertiary lymphoid structures in the tumor area.

This is the first study to investigate the molecular features of mixed subtype lepidic-acinar transitional tumors. Immunological dynamics are presumed to be involved in this transition from lepidic to acinar subtype. Further research should be conducted to elucidate the progression of disease from non-invasive to invasive morphologies.
Exploring the Psychological, Social, and Human Rights Dynamics and Consequences of COVID-19 Control Measures: A Systematic Review
Authors: Spasojevic Djurdje
Published: March 2024

This systematic review explores the social and psychological dynamics and consequences of COVID-19 control measures and their implications for human rights. Through a lens of social psychology, the review considers factors such as social influence, obedience, perceived control, social comparison, cognitive dissonance, propaganda, surveillance, fearmongering, incentives, coercion, persuasion, censorship, obfuscation, isolation, and rewards and punishment. By analyzing the influence of these factors on individuals and group responses to the pandemic and the manipulation of social and psychological dynamics by institutions to shape compliance, this review provides insights into the determinants that drive adherence to control measures and their negative consequences. The findings of the 13 selected studies contribute to understanding the multifaceted factors that influence compliance and inform the development of effective public health interventions to avoid consequences. The review emphasizes the importance of upholding human rights during the implementation of control measures, given the reported violations across the world. By providing insights to policymakers, politicians, health practitioners, and researchers, this review enables the formulation of strategies that promote public health while respecting human and individual rights and well-being. In conclusion, this study sheds light on the social and psychological dynamics, human rights, and implications of COVID-19 control measures, providing valuable insights for future interventions.
Genome-wide analyses identify 21 infertility loci and over 400 reproductive hormone loci across the allele frequency spectrum
Authors: Venkatesh Samvida S. , Wittemans Laura B. L. , Palmer Duncan S. , Baya Nikolas A. , Ferreira Teresa , Hill Barney , Lassen Frederik Heymann , Parker Melody J. , Reibe Saskia , Elhakeem Ahmed , Banasik Karina , Bruun Mie T. , Erikstrup Christian , Jensen Bitten A. , Juul Anders , Mikkelsen Christina , Nielsen Henriette S. , Ostrowski Sisse R. , Pedersen Ole B. , Rohde Palle D. , Sorensen Erik , Ullum Henrik , Westergaard David , Haraldsson Asgeir , Holm Hilma , Jonsdottir Ingileif , Olafsson Isleifur , Steingrimsdottir Thora , Steinthorsdottir Valgerdur , Thorleifsson Gudmar , Figueredo Jessica , Karjalainen Minna K. , Pasanen Anu , Jacobs Benjamin M. , Hubers Nikki ,   Genes & Health Research Team,   Estonian Biobank Research Team,   Estonian Health Informatics Research Team,   DBDS Genomic Consortium,   FinnGen, Lippincott Margaret , Fraser Abigail , Lawlor Deborah A. , Timpson Nicholas J. , Nyegaard Mette , Stefansson Kari , Magi Reedik , Laivuori Hannele , van Heel David A. , Boomsma Dorret I. , Balasubramanian Ravikumar , Seminara Stephanie B. , Chan Yee-Ming , Laisk Triin , Lindgren Cecilia M.
Published: March 2024

Genome-wide association studies (GWASs) may help inform treatments for infertility, whose causes remain unknown in many cases. Here we present GWAS meta-analyses across six cohorts for male and female infertility in up to 41,200 cases and 687,005 controls. We identified 21 genetic risk loci for infertility (P≤5E-08), of which 12 have not been reported for any reproductive condition. We found positive genetic correlations between endometriosis and all-cause female infertility (rg=0.585,P=8.98E-14), and between polycystic ovary syndrome and anovulatory infertility (rg=0.403,P=2.16E-03). The evolutionary persistence of female infertility-risk alleles inEBAG9may be explained by recent directional selection. We additionally identified up to 269 genetic loci associated with follicle-stimulating hormone (FSH), luteinising hormone, oestradiol, and testosterone through sex-specific GWAS meta-analyses (N=6,095-246,862). While hormone-associated variants nearFSHBandARL14EPcolocalised with signals for anovulatory infertility, we found norgbetween female infertility and reproductive hormones (P>0.05). Exome sequencing analyses in the UK Biobank (N=197,340) revealed that women carrying testosterone-lowering rare variants inGPC2were at higher risk of infertility (OR=2.63,P=1.25E-03). Taken together, our results suggest that while individual genes associated with hormone regulation may be relevant for fertility, there is limited genetic evidence for correlation between reproductive hormones and infertility at the population level. We provide the first comprehensive view of the genetic architecture of infertility across multiple diagnostic criteria in men and women, and characterise its relationship to other health conditions.
A user-driven framework for dose selection in pregnancy: proof-of-concept for sertraline
Authors: Koldeweij CJM , Dibbets AC , Franklin BD , Scheepers HCJ , de Wildt SN
Published: March 2024

Despite growing knowledge of pregnancy-induced changes in physiology that may alter maternal and fetal pharmacokinetics, and therefore drug efficacy and safety, evidence-based antenatal doses are lacking for most drugs. Pharmacokinetic models and expanding clinical data in pregnancy may support antenatal doses. In this article, we introduce a comprehensive and user-driven Framework for Dose Selection in Pregnancy (FDSP), developed and validated to support the clinical implementation of best-evidence and in some cases, model-informed doses for pregnant women and/or fetuses. After initial development and validation by experts, the framework prototype was piloted to formulate an antenatal dosing strategy for sertraline in depression and anxiety disorders. Next, the framework was validated and assessed for usability by a multidisciplinary working committee of end-users comprising healthcare practitioners, experts from other disciplines including pharmacometrics, reproductive toxicology and medical ethics, alongside pregnant women and a partner. The resulting framework encompasses the following: rationale for drug selection, a comprehensive analysis of pharmacokinetic and dose-related efficacy and safety data, and implementation aspects including feasibility and desirability of the recommended antenatal dose based on a structured maternal and fetal benefit-risk assessment. An antenatal dose recommendation for sertraline, as a proof-of-concept, was formulated using this approach and endorsed for clinical use by the working committee. The FDSP, as demonstrated by the example of sertraline, is fit for supporting the development of best-evidence acceptable and clinically feasible antenatal doses.
The role of fathers in feeding, care, and dental hygiene practices of children aged <6 years: A rapid scoping review
Authors: Moboshir Dina , Patil Priyanka , Chakraborty Subarna , Dwardzweska Joanna , Llewellyn Clare H. , Webb-Martin Kelley , Irish Carol , Archibong Mfon , Gilmour Jenny , Kalungi Phoebe , Batura Neha , Lakhanpaul Monica , Heys Michelle , Manikam Logan
Published: March 2024

Background

The contribution of fathers in the early stages of child development, especially in feeding care and dental hygiene practices, is increasingly recognized but not well-documented. This rapid scoping review aims to broadly map the existing literature on this subject, focusing on children aged less than six years, and to identify areas where further research is needed.

Objectives

To explore the extent and nature of research on fathers’ roles in feeding care and dental hygiene practices for children under six years old. The review aims to identify key themes, variations in fatherly involvement across different contexts, and gaps in the current literature.

Methods

A structured search of key databases, including PubMed, PsycINFO, and Scopus, was performed. Studies included in the review involved fathers of children aged less than six years and addressed aspects of feeding care or dental hygiene. The process involved screening for relevance, categorizing studies into thematic areas, and summarizing overarching themes.

Results

The search yielded 15 studies encompassing diverse geographical and socio-cultural contexts. The review underscores the variability in fathers’ roles, influenced by factors such as urbanization, education, and cultural norms. It reveals that while fathers often serve as financial providers and role models, direct involvement in feeding and dental hygiene is less common. Notably, the literature on fathers’ involvement in children’s dental hygiene is limited.

Conclusions

Fathers’ roles in feeding care and dental hygiene practices for children under six years are multifaceted and context dependent. The review highlights significant gaps, particularly in understanding the involvement of fathers in dental hygiene. Addressing these gaps through future research is essential for developing comprehensive family-centred health care strategies and policies.
Utilizing multimodal AI to improve genetic analyses of cardiovascular traits
Authors: Zhou Yuchen , Cosentino Justin , Yun Taedong , Biradar Mahantesh I. , Shreibati Jacqueline , Lai Dongbing , Schwantes-An Tae-Hwi , Luben Robert , McCaw Zachary , Engmann Jorgen , Providencia Rui , Schmidt Amand Floriaan , Munroe Patricia , Yang Howard , Carroll Andrew , Khawaja Anthony P. , McLean Cory Y. , Behsaz Babak , Hormozdiari Farhad
Published: March 2024

Electronic health records, biobanks, and wearable biosensors contain multiple high-dimensional clinical data (HDCD) modalities (e.g., ECG, Photoplethysmography (PPG), and MRI) for each individual. Access to multimodal HDCD provides a unique opportunity for genetic studies of complex traits because different modalities relevant to a single physiological system (e.g., circulatory system) encode complementary and overlapping information. We propose a novel multimodal deep learning method, M-REGLE, for discovering genetic associations from a joint representation of multiple complementary HDCD modalities. We showcase the effectiveness of this model by applying it to several cardiovascular modalities. M-REGLE jointly learns a lower representation (i.e., latent factors) of multimodal HDCD using a convolutional variational autoencoder, performs genome wide association studies (GWAS) on each latent factor, then combines the results to study the genetics of the underlying system. To validate the advantages of M-REGLE and multimodal learning, we apply it to common cardiovascular modalities (PPG and ECG), and compare its results to unimodal learning methods in which representations are learned from each data modality separately, but the downstream genetic analyses are performed on the combined unimodal representations. M-REGLE identifies 19.3% more loci on the 12-lead ECG dataset, 13.0% more loci on the ECG lead I + PPG dataset, and its genetic risk score significantly outperforms the unimodal risk score at predicting cardiac phenotypes, such as atrial fibrillation (Afib), in multiple biobanks.
Multi-decadal warming alters predator’s effect on prey community composition
Authors: Niu Jingyao , Huss Magnus , Garnier Aurélie , Vasemägi Anti , Gårdmark Anna
Published: March 2024

Predator responses to warming can occur via phenotypic plasticity and evolutionary adaptation, resulting in changes in their prey communities. However, we lack evidence of how warming-induced evolutionary changes in predators can influence the food web. Here, we ask whether fish subject to long-term warming across multiple generations differ in their impacts on prey communities compared to their nearby conspecifics experiencing a natural thermal regime. We carried out a common garden mesocosm experiment with larval perch (Perca fluviatilis), originating from one heated or one reference coastal environment, feeding on zooplankton communities under a gradient of experimental temperatures. We found that fish thermal origin influenced the zooplankton communities, and differently so depending on the experimental temperature. In presence of fish of heated origin, there were less zooplankton and also fewer individuals of large size, except for at intermediate experimental temperatures. Our findings show that differences between fish populations, potentially representing adaptation to local thermal environment, caused by multi-generational warming can cascade down via trophic interactions to also affect their zooplankton prey communities. Considering climate warming, our results suggest that rapid evolution in predators might have indirect cross-generational ecological consequences propagating through food webs.
Tree growth is better explained by absorptive fine root traits than by transport fine root traits
Authors: Sanaei Anvar , van der Plas Fons , Chen Hongmei , Davids Sophie , Eckhardt Susanne , Hennecke Justus , Kahl Anja , Möller Yasmin , Richter Ronny , Schütze Jana , Wirth Christian , Weigelt Alexandra
Published: March 2024

Quantifying plant trait variation yields insights into trade-offs inherent in the ecological strategies of plants and is the basis for a trait-based prediction of plant performance and ecosystem functioning. Although the interest in root traits has increased in recent years, we still have limited knowledge of i) whether functionally different fine roots—absorptive versus transport roots—have similar trait coordination and ii) how they help to explain plant performance, such as growth.

We measured traits of 25 European broadleaved tree species growing in a research arboretum to study i) the coordination of root traits within absorptive and transport fine roots and ii) the degree of trait-tree growth relationships. To do so, we combined a suite of morphological (root diameter, specific root length and root tissue density) and anatomical (cortex to stele ratio and arbuscular mycorrhizal colonization rate) traits for each of the absorptive and transport roots and also leaf traits (leaf mass per area, dry matter content and toughness).

Despite remarkable differences in average trait values between absorptive and transport roots, our study shows that trait coordination within absorptive and transport roots is relatively equivalent. Our results also show that, for the traits we studied, tree growth is better explained by absorptive root traits than by transport root traits and is higher in species with a thinner root diameter. This suggests that variation primarily in absorptive roots affects the uptake of soil-based resources like nutrients and water and directly influences tree growth.

The significant relationship between absorptive roots and tree growth and the lack of such a relationship for transport roots highlights that roots mostly involved with resource absorption are more important in explaining tree growth than roots involved in transport.
Comparative Analysis of Tickling and Conspecific Play in Tame Mice and Golden Hamsters
Authors: Dagher Sarah , DeAngelo Darcie , Sato Ren Y. , Norimoto Hiroaki , Koide Tsuyoshi , Ishiyama Shimpei
Published: March 2024

Social play behavior is a fundamental aspect of animal interaction, shaping social bonds and enhancing cognitive capacity. While studies on human-animal play interactions have primarily focused on a few selected species, research on rodents beyond rats remains scarce. We, therefore, addressed the dynamics of social play in tame mice, selectively bred to approach human hands, and golden hamsters, comparing their responses during interactions with humans and conspecifics. Tame mice exhibited heightened playfulness with humans, marked by increased vocalizations and chasing behavior, in addition to increased interactions with tame conspecifics compared to unselected control mice. Hamsters demonstrated a stronger inclination towards conspecific interactions. Notably, vocalization patterns varied between heterospecific and conspecific engagement in both species, suggesting context-dependent communication. These findings offer insights into the evolutionary basis influencing social play across species with differing social structures. Understanding these mechanisms enriches our comprehension of the diverse pathways through which animals form social bonds.
Predicting fine-scale distributions and emergent spatiotemporal patterns from temporally dynamic step selection simulations
Authors: Forrest Scott W , Pagendam Dan , Bode Michael , Drovandi Christopher , Potts Jonathan R , Perry Justin , Vanderduys Eric , Hoskins Andrew J
Published: March 2024

Understanding and predicting animal movement is fundamental to ecology and conservation management. Models that estimate and then predict animal movement and habitat selection parameters underpin diverse conservation applications, from mitigating invasive species spread to enhancing landscape connectivity. However, many predictive models overlook fine-scale temporal dynamics within their predictions, despite animals often displaying fine-scale behavioural variability that might significantly alter their movement, habitat selection and distribution over time. Incorporating fine-scale temporal dynamics, such as circadian rhythms, within predictive models might reduce the averaging out of such behaviours, thereby enhancing our ability to make predictions in both the short and long term. We tested whether the inclusion of fine-scale temporal dynamics improved both fine-scale (hourly) and long-term (seasonal) spatial predictions for a significant invasive species of Northern Australia, the water buffalo (Bubalus bubalis). Water buffalo require intensive management actions over vast, remote areas and display distinct circadian rhythms linked to habitat use. To inform management operations we generated hourly and dry season prediction maps by simulating trajectories from static and temporally dynamic step selection functions (SSFs) that were fitted to the GPS data of 13 water buffalo. We found that simulations generated from temporally dynamic models replicated the buffalo’s crepuscular movement patterns and dynamic habitat selection, resulting in more informative and accurate hourly predictions. Additionally, when the simulations were aggregated into long-term predictions, the dynamic models were more accurate and better able to highlight areas of concentrated habitat use that might indicate high-risk areas for environmental damage. Our findings emphasise the importance of incorporating fine-scale temporal dynamics in predictive models for species with clear dynamic behavioural patterns. By integrating temporally dynamic processes into animal movement trajectories, we demonstrate an approach that can enhance conservation management strategies and deepen our understanding of ecological and behavioural patterns across multiple timescales.
Effect of C-to-T transition at CpG sites on tumor suppressor genes in tumor development in cattle evaluated by somatic mutation analysis in enzootic bovine leukosis
Authors: Nishimori Asami , Andoh Kiyohiko , Matsuura Yuichi , Okagawa Tomohiro , Konnai Satoru
Published: March 2024

Oncogenic transformation of normal cells is caused by mutations and chromosomal abnormalities in cancer-related genes. Enzootic bovine leukosis (EBL) is a malignant B-cell lymphoma caused by bovine leukemia virus (BLV) infection in cattle. Although a small fraction of BLV-infected cattle develops EBL after a long latent period, the mechanisms for oncogenesis in EBL cattle remain largely unknown. In this study, we analyzed the types and patterns of somatic mutations in cancer cells from 36 EBL cases, targeting 21 cancer-related genes. Various somatic mutations were identified in 8 genes,TP53,NOTCH1,KMT2D,CREBBP,KRAS,PTEN,CARD11, andMYD88. In addition,TP53gene was found to be mutated in 69.4% of EBL cases, with most being biallelic mutations. In some cases, associations were observed between the ages at which cattle had developed EBL and somatic mutation patterns; young onset of EBL possibly occurs due to congenital mutations, high impact mutations affecting protein translation, and biallelic mutations. Furthermore, nucleotide substitution patterns indicated that cytosine at CpG sites tended to be converted to thymine in many EBL cases, which was considered to be the result of spontaneous deamination of 5-methylctosine. These results demonstrate how somatic mutations have occurred in cancer cells leading to EBL development, thereby explaining its pathogenic mechanism. These findings will contribute to a better understanding and future elucidation of disease progression in BLV infection.

Importance

Enzootic bovine leukosis (EBL) is a malignant and lethal disease in cattle. Currently, there are no effective vaccines or therapeutic methods against bovine leukemia virus (BLV) infection, resulting in severe economic losses in livestock industry. This study provides a renewed hypothesis to explain the general mechanisms of EBL onset by combining the previous finding that several integration sites of BLV provirus can affect the increase in survival and proliferation of infected cells. We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset.
Systematic annotation of orphan RNAs reveals blood-accessible molecular barcodes of cancer identity and cancer-emergent oncogenic drivers
Authors: Wang Jeffrey , Suh Jung Min , Woo Brian J , Navickas Albertas , Garcia Kristle , Yin Keyi , Fish Lisa , Cavazos Taylor , Hänisch Benjamin , Markett Daniel , Yu Shaorong , Hirst Gillian , Brown-Swigart Lamorna , Esserman Laura J. , van ‘t Veer Laura J. , Goodarzi Hani
Published: March 2024

From extrachromosomal DNA to neo-peptides, the broad reprogramming of the cancer genome leads to the emergence of molecules that are specific to the cancer state. We recently described orphan non-coding RNAs (oncRNAs) as a class of cancer-specific small RNAs with the potential to play functional roles in breast cancer progression1. Here, we report a systematic and comprehensive search to identify, annotate, and characterize cancer-emergent oncRNAs across 32 tumor types. We also leverage large-scalein vivogenetic screens in xenografted mice to functionally identify driver oncRNAs in multiple tumor types. We have not only discovered a large repertoire of oncRNAs, but also found that their presence and absence represent a digital molecular barcode that faithfully captures the types and subtypes of cancer. Importantly, we discovered that this molecular barcode is partially accessible from the cell-free space as some oncRNAs are secreted by cancer cells. In a large retrospective study across 192 breast cancer patients, we showed that oncRNAs can be reliably detected in the blood and that changes in the cell-free oncRNA burden captures both short-term and long-term clinical outcomes upon completion of a neoadjuvant chemotherapy regimen. Together, our findings establish oncRNAs as an emergent class of cancer-specific non-coding RNAs with potential roles in tumor progression and clinical utility in liquid biopsies and disease monitoring.
The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy
Authors: Popli Pooja , Oestreich Arin K. , Maurya Vineet K. , Rowen Marina N. , Zhang Yong , Holtzman Michael J. , Masand Ramya , Lydon John , Akira Shizuo , Moley Kelle H. , Kommagani Ramakrishna
Published: March 2024

Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by controlling inflammatory responses, thereby supporting efficient embryo transport. Specifically, the conditional depletion of the autophagy-related gene,Atg14in the oviduct causes severe structural abnormalities compromising its cellular integrity leading to the abnormal retention of embryos. Interestingly, the selective loss ofAtg14in oviduct ciliary epithelial cells did not impact female fertility, highlighting the specificity of ATG14 function in distinct cell types within the oviduct. Mechanistically, loss ofAtg14triggered unscheduled pyroptosis via altering the mitochondrial integrity leading to inappropriate embryo retention and impeded embryo transport in the oviduct. Finally, pharmacological activation of pyroptosis in pregnant mice phenocopied the genetically induced defect and caused impairment in embryo transport. Together, we found that ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport from the oviduct to uterus for the successful implantation. Of clinical significance, these findings provide possible insights into the underlying mechanism(s) of early pregnancy loss and might aid in developing novel prevention strategies using autophagy modulators.
Subjective and Objective Measures of Cognitive Function are Correlated in Persons with Post-COVID-19 Condition: A Secondary Analysis of a Randomized Controlled Trial
Authors: Kwan Angela T.H. , Lakhani Moiz , Le Gia Han , Singh Gurkaran , Teopiz Kayla M. , Ceban Felicia , Nijjar Charnjit S. , Meshkat Shakila , Badulescu Sebastian , Ho Roger , Rhee Taeho Greg , Vincenzo Joshua D. Di , Gill Hartej , McIntyre Roger S.
Published: March 2024

Background

It remains unclear whether subjective and objective measures of cognitive function in Post COVID-19 Condition (PCC) are correlated. The extent of correlation has mechanistic and clinical implications.

Methods

This post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial contains baseline data of subjective and objective measures of cognition in a rigorously characterized cohort living with PCC. Herein, we evaluated the association between subjective and objective condition function, as measured by the Perceived Deficits Questionnaire, 20-item (PDQ-20) and the Digit Symbol Substitution Test (DSST) and Trails Making Test (TMT)-A/B, respectively.

Results

A total of 152 participants comprised the baseline sample. Due to missing data, our statistical analyses included 150 for self-reported PDQ-20, 147 individuals for combined DSST-measured cognitive function (composite z-score of the Pen/Paper plus Online CogState Version,NcombinedDSST), 71 for in-person DSST-measured cognitive function (Pen/Paper Version), 70 for TMT-A-measured cognitive function, and 70 for TMT-B-measured cognitive function. After adjusting for age, sex, and education, PDQ-20 was significantly correlated with pen-and-paper DSST (β = -0.003,p= 0.002) and TMT-B (β = 0.003,p= 0.008) scores, but not with TMT-A scores (β = -0.001,p= 0.751).

Conclusions

Overall, a statistically significant correlation was observed between subjective and objective cognitive functions. Clinicians providing care for individuals with PCC who have subjective cognitive function complaints may consider taking a measurement-based approach to cognition at the point of care that focuses exclusively on patient-reported measures.
The role of telemedicine towards improved sustainability in health care and societal productivity in Turkey
Authors: Özen Figen , Kaynar Alptug H. , Korkut A. Kubilay , Teker Açıkel Melike Elif , Kaynar Z. Dilsun , Kaynar A. Murat
Published: March 2024

The COVID-19 pandemic increased utilization of telemedicine for diagnosis and treatment. While telemedicine is not the panacea for the increasing health care burden, it can alleviate the problem. Here, the hypothetical impact of delivering telehealth care to patients in a busy tertiary cardio-vascular clinic in Istanbul, Turkey, is examined. Additionally, the potential environmental and societal ramifications of telemedicine are also examined.

Demographics, health care costs, wages, productivity, and patient-specific data were exploited to develop a hypothetical telemedicine framework for the Turkish health care landscape. Specifically, the distance traveled and travel time to receive care using real-life location of the clinics and patients addresses seeking care are tabulated.

Data from August 3, 2015 to January 25, 2023 resulted in 45,602 unique encounters with 448 unique diagnoses recorded for the patient encounters. The patients in the top 5% of the most common diagnoses traveled 23.82 ± 96.3 km to reach the clinics. Based on our model and the related literature that telehealth care for chronic diseases is not inferior to face-to-face care, 656,258 km would have been saved if all patients were to take the first visit in person followed by telemedicine visits. The travel-associated carbon footprint and wage losses for in-person care in lieu of telehealth appointments is calculated and it was observed that exploiting telemedicine could have saved approximately 30% carbon footprint and prevented approximately $878,000 wage loss. As a result, it is found that application of telemedicine could ease the burden on patients, environment, increase access, and prevent the wage losses caused by unnecessary hospital visits.
Development of a Human Evaluation Framework and Correlation with Automated Metrics for Natural Language Generation of Medical Diagnoses
Authors: Croxford Emma , Gao Yanjun , Patterson Brian , To Daniel , Tesch Samuel , Dligach Dmitriy , Mayampurath Anoop , Churpek Matthew M , Afshar Majid
Published: March 2024

In the evolving landscape of clinical Natural Language Generation (NLG), assessing abstractive text quality remains challenging, as existing methods often overlook generative task complexities. This work aimed to examine the current state of automated evaluation metrics in NLG in healthcare. To have a robust and well-validated baseline with which to examine the alignment of these metrics, we created a comprehensive human evaluation framework. Employing ChatGPT-3.5-turbo generative output, we correlated human judgments with each metric. None of the metrics demonstrated high alignment; however, the SapBERT score—a Unified Medical Language System (UMLS)-showed the best results. This underscores the importance of incorporating domain-specific knowledge into evaluation efforts. Our work reveals the deficiency in quality evaluations for generated text and introduces our comprehensive human evaluation framework as a baseline. Future efforts should prioritize integrating medical knowledge databases to enhance the alignment of automated metrics, particularly focusing on refining the SapBERT score for improved assessments.
Prognostic Models Predicting Clinical Outcomes in Patients Diagnosed with Visceral Leishmaniasis: A Systematic Review
Authors: Wilson James Patrick , Chowdhury Forhad , Hassan Shermarke , Harriss Eli P , Alves Fabiana , Musa Ahmed , Dahal Prabin , Stepniewska Kasia , Guerin Philippe J
Published: March 2024

Background Visceral leishmaniasis (VL) is a neglected tropical disease prevalent in populations affected by poverty and poor nutrition. Without treatment, death is the norm. Prognostic models can steer important management decisions by identifying patients at high-risk of adverse outcomes. We therefore aim to identify, summarise, and appraise the available prognostic models predicting clinical outcomes in VL patients. Methods We reviewed all published studies that developed, validated, or updated models predicting clinical outcomes in VL patients. Five bibliographic databases were searched from database inception to March 1st 2023 with no language restriction. Screening, data extraction, and risk of bias assessment were performed in duplicate. Findings are presented with tables, figures, and a narrative review. Results Eight studies, published 2003-21, were identified describing 12 model developments and 19 external validations. All models predicted either in-hospital mortality (n=10 models) or registry-reported mortality (n=2), and were developed in either Brazilian or East African settings (n=9 and n=3 models respectively). Model discrimination (c-statistic) ranged from 0.62-0.92 when evaluated in new data (19 external validations, 10 models). Risk of bias was high for all model developments and validations: no studies presented calibration plots, 11 models were at high risk of overfitting due to small sample sizes, and six models presented risk scores that were inconsistent with reported regression coefficients. Conclusion With a high risk of bias identified for all models, caution must be exercised when interpreting model predictions and performance measures. Prior to model development or validation, we encourage investigators to review model reporting guidelines. No prognostic models were identified predicting treatment failure or relapse. Furthermore, despite South Asia representing the highest VL burden pre-2010, no models were developed in this population. In the context of the current South Asia elimination programme, these represent important evidence gaps where new model development should be prioritised.
BET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer
Authors: Mi Wen , You Jianwei , Li Liucheng , Zhu Lingzhi , Xia Xinyi , Yang Li , Li Fei , Xu Yi , Bi Junfeng , Liu Pingyu , Chen Li , Li Fuming
Published: March 2024

Bromodomain and extra-terminal domain (BET) proteins, which function partly through MYC, are critical epigenetic readers and emerging therapeutic targets in cancer. Whether and how BET inhibition simultaneously induces metabolic remodeling remains unclear. Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors blunts liver cancer cell proliferation and tumor growth. BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis. Specifically, BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1 (GDH1) independent of MYC, which produces α-ketoglutarate for mitochondrial oxidative phosphorylation (OXPHOS). Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibiton, and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growthin vitroandin vivo. Together, we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC- independent and GDH1-dependendent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.
UDP-6-glucose dehydrogenase in hormonally responsive breast cancers
Authors: Price Meghan J. , Nguyen Annee D. , Haines Corinne , Baëta César D. , Byemerwa Jovita , Murkajee Debarati , Artham Sandeep , Kumar Vardhman , Lavau Catherine , Wardell Suzanne , Varghese Shyni , Goodwin C. Rory
Published: March 2024

Survival for metastatic breast cancer is low and thus, continued efforts to treat and prevent metastatic progression are critical. Estrogen is shown to promote aggressive phenotypes in multiple cancer models irrespective of estrogen receptor (ER) status. Similarly, UDP-Glucose 6-dehydrogenase (UGDH) a ubiquitously expressed enzyme involved in extracellular matrix precursors, as well as hormone processing increases migratory and invasive properties in cancer models. While the role of UGDH in cellular migration is defined, how it intersects with and impacts hormone signaling pathways associated with tumor progression in metastatic breast cancer has not been explored. Here we demonstrate that UGDH knockdown blunts estrogen-induced tumorigenic phenotypes (migration and colony formation) in ER+ and ER- breast cancerin vitro. Knockdown of UGDH also inhibits extravasation of ER- breast cancerex vivo, primary tumor growth and animal survivalin vivoin both ER+ and ER- breast cancer. We also use single cell RNA-sequencing to demonstrate that our findings translate to a human breast cancer clinical specimen. Our findings support the role of estrogen and UGDH in breast cancer progression provide a foundation for future studies to evaluate the role of UGDH in therapeutic resistance to improve outcomes and survival for breast cancer patients.
Optimal parameter estimation of shaped phase objects
Authors: Villegas Arturo , Passos M. H. M. , Pereira Silvania F. , Torres Juan P.
Published: March 2024

We show a general method to estimate with optimum precision, i.e., the best precision determined by the light-matter interaction process, a set of parameters that characterize a phase object. The method is derived from ideas presented by Pezze []. Our goal is to illuminate the main characteristics of this method as well as its applications to the physics community probably not familiar with the quantum language usually employed in works related to quantum estimation theory. First, we derive precision bounds for the estimation of the set of parameters characterizing the phase object. We compute the Crámer-Rao lower bound for two experimentally relevant types of illumination: a multimode coherent state with mean photon number N and N copies of a multimode single-photon quantum state. We show under which conditions these two models are equivalent. Second, we show that the optimum precision can be achieved by projecting the light reflected or transmitted from the object onto a set of modes with engineered spatial shape. We describe how to construct these modes and demonstrate explicitly that the precision of the estimation using these measurements is optimum. As an example, we apply these results to the estimation of the height and sidewall angle of a cliff-like nanostructure, an object relevant in the semiconductor industry for the evaluation of nanofabrication techniques.

Published by the American Physical Society
2024
Probing scrambling and operator size distributions using random mixed states and local measurements
Authors: Blocher Philip Daniel , Chinni Karthik , Omanakuttan Sivaprasad , Poggi Pablo M.
Published: March 2024

The dynamical spreading of quantum information through a many-body system, typically called scrambling, is a complex process that has proven to be essential to describe many properties of out-of-equilibrium quantum systems. Scrambling can, in principle, be fully characterized via the use of out-of-time-ordered correlation functions, which are notoriously hard to access experimentally. In this work, we put forward an alternative toolbox of measurement protocols to experimentally probe scrambling by accessing properties of the operator size probability distribution, which tracks the size of the support of observables in a many-body system over time. Our measurement protocols require the preparation of separable mixed states together with local operations and measurements, and combine the tools of randomized operations, a modern development of near-term quantum algorithms, with the use of mixed states, a standard tool in NMR experiments. We demonstrate how to efficiently probe the probability-generating function of the operator distribution and discuss the challenges associated with obtaining the moments of the operator distribution. We further show that manipulating the initial state of the protocol allows us to directly obtain the individual elements of the distribution for small system sizes.

Published by the American Physical Society
2024
iRing: a program for two-dimensional powder diffraction image integration with automatic calibration
Authors: Sun Xiaowei , Feng Zhenjie , Lv Binfeng , Cao Jian , Chang Shihui , Dong Cheng
Published: March 2024

iRing is a processing program developed for the more convenient processing of two-dimensional diffraction images collected by image detectors. During the calibration process, iRing uses the Hough transform to achieve automatic peak finding and calibration. The speed of calibration is greatly improved and the difficulty of calibration is reduced. iRing also provides many supporting functions to help process data.
Virtual reality and perceptions of destination presence
Authors: Yu Hongxiao , Oh Haemoon , Wang Kuo-Ching
Published: March 2024

Purpose

This study aims to examine the underlying emotional process that explains how context-specific stimuli involved in virtual reality (VR) destinations translate into presence perceptions and behavioral intentions.

Design/methodology/approach

In total, 403 potential tourists participated in a self-administered online survey after they watched a randomly assigned VR tour. The Lavaan package in R software was used to conduct structural equation analysis and examine the proposed theoretical framework.

Findings

The results reveal that media content consisting of informativeness, aesthetics and novelty was positively related to users’ sense of presence in a VR tour. The effect of media content on presence was partially mediated by emotional arousal.

Practical implications

Managers and VR designers can create an emotive virtual tour that contributes to the user’s sense of presence to promote attraction to the target destination. The VR content needs to be informative, aesthetic and novel, which can excite users during the VR tour, portray virtual destinations clearly and eventually influence potential tourists’ visit intentions.

Originality/value

Research on the emotional mechanism to generate presence is still in its infancy. This study integrates presence theory into a conceptual framework to explore how media content influences presence and decision-making through the emotional mechanism.
Blockchain-based governance models in e-government: a comprehensive framework for legal, technical, ethical and security considerations
Authors: Mustafa Ghulam , Rafiq Waqas , Jhamat Naveed , Arshad Zeeshan , Rana Farhana Aziz
Published: March 2024

Purpose

This study aims to evaluate blockchain as an e-government governance model. It assesses its alignment with legal frameworks, emphasizing robustness against disruptions and adherence to existing laws.

Design/methodology/approach

The paper explores blockchain’s potential in e-government, focusing on legal, ethical and governance aspects. It conducts an in-depth analysis of blockchain’s integration into data governance, emphasizing legal compliance and resilient security protocols.

Findings

The study comprehensively evaluates blockchain’s implementation, covering privacy, interoperability, consensus mechanisms, scalability and regulatory alignment. It highlights governance’s critical role in ensuring legal compliance within blockchain paradigms.

Research limitations/implications

Ethical and legal concerns arising from blockchain adoption remain unresolved. The study underscores how blockchain challenges its core principles of anonymity and decentralization in e-government settings.

Practical implications

The framework outlined offers potential for diverse technological environments, albeit raising ethical and legal queries. It emphasizes governance’s pivotal role in achieving legal compliance in blockchain adoption.

Social implications

Blockchain’s impact on legal and ethical facets necessitates further exploration to align with its core principles while addressing governance in e-government settings.

Originality/value

This study presents a robust framework for assessing blockchain’s viability in e-government, emphasizing legal compliance, despite ethical and legal intricacies that challenge its fundamental principles.
Drivers of intention to engage in informal economy activities during maternity leave
Authors: Morkūnas Mangirdas , Rudiene Elze , Wei Jinzhao
Published: March 2024

Purpose

The present paper seeks to reveal the factors underlying the intentions of women on maternity leave to engage in informal economy activities.

Design/methodology/approach

A representative cross sectional survey of 417 women on maternity leave was selected as a main research approach. A structural equation modelling – partial equation modelling served as a research tool.

Findings

The study revealed that the most important determinants of intentions to become involved in informal economy activities during maternity leave are unsatisfactory financial situation, complicated legal regulation and fear of becoming uncompetitive in the labour market.

Originality/value

To the best of authors’ knowledge, it is the first scientific attempt to investigate the informal work/economy during maternal leave.
Dynamics of cereal product price transmission between markets in Burkina Faso
Authors: Diendere Achille Augustin , Dah Sansan Ali Bepounte
Published: March 2024

Purpose

Effective agricultural product price regulation policies depend on market integration and the degree of symmetry in the transmission of agricultural product price signals. This study analyzes the transmission and asymmetry of the price series between the Ouagadougou consumer market and assembly markets considering three primary cereal products in Burkina Faso.

Design/methodology/approach

This study applies the nonlinear autoregressive distributed lag (NARDL) econometric model, which is an asymmetric extension of the ARDL cointegration model. The price series examined covers the period extending from January 2005 to December 2020.

Findings

Our analysis provides novel insights regarding short- and long-term asymmetric effects in the transmission of price signals between assembly markets and the consumer market. We also determine that the effects of negative shocks are more persistent than those of positive shocks in several markets.

Research limitations/implications

For markets that exhibit symmetrical responses of assembly market prices to consumer market prices, the results could reflect the continuous efforts of market players, particularly the government, to eliminate market failures and ensure the long-term efficiency of cereal markets. To this end, an agricultural market information system can have a crucial role in easing information access for all market players.

Originality/value

This study provides new evidence regarding the nature of the transmission and asymmetry of price information on primary cereal products in the largest markets in Burkina Faso. Applying the NARDL model makes it possible to simultaneously estimate short- and long-term asymmetry.