bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing nullomers in cell-free RNA for early cancer detection
Authors: Montgomery Austin , Tsiatsianis Georgios Christos , Mouratidis Ioannis , Chan Candace S. Y. , Athanasiou Maria , Papanastasiou Anastasios D. , Kantere Verena , Syrigos Nikos , Vathiotis Ioannis , Syrigos Konstantinos , Yee Nelson S. , Georgakopoulos-Soares Ilias
Published: February 2024

Early detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are the shortest sequences that are absent from the human genome but can emerge due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer emergence across exonic regions of the genome. We also identify nullomer emerging mutational hotspots within tumor genes. Finally, we provide evidence for the identification of nullomers in cell-free RNA from peripheral blood samples, enabling detection of multiple tumor types. We show multiple tumor classification models with an AUC greater than 0.9, including a hepatocellular carcinoma classifier with an AUC greater than 0.99.
Ethical and social reflections on the proposed European Health Data Space
Authors: Staunton Ciara , Shabani Mahsa , Mascalzoni Deborah , Mežinska Signe , Slokenberga Santa
Published: February 2024

The COVID-19 pandemic demonstrated the benefits of international data sharing. Data sharing enabled the health care policy makers to make decisions based on real-time data, it enabled the tracking of the virus, and importantly it enabled the development of vaccines that were crucial to mitigating the impact of the virus. This data sharing is not the norm as data sharing needs to navigate complex ethical and legal rules, and in particular, the fragmented application of the General Data Protection Regulation (GDPR). The introduction of the draft regulation for a European Health Data Space (EHDS) in May 2022 seeks to address some of these legal issues. If passed, it will create an obligation to share electronic health data for certain secondary purposes. While there is a clear need to address the legal complexities involved with data sharing, it is critical that any proposed reforms are in line with ethical principles and the expectations of the data subjects. In this paper we offer a critique of the EHDS and offer some recommendations for this evolving regulatory space.
The experience of receiving a letter from a cancer genetics clinic about risk for hereditary cancer
Authors: Öfverholm Anna , Karlsson Per , Rosén Anna
Published: February 2024

Direct contact may be an option for supporting disclosure in families with hereditary cancer risk. In this qualitative interview study, we explored how healthy at-risk relatives experience receiving a letter with information about hereditary cancer directly from healthcare rather than via a relative. The study is part of an ongoing multicentre randomised clinical trial in Sweden that evaluates the effectiveness of direct letters from cancer genetics clinics to at-risk relatives. After conducting semi-structured interviews with 14 relatives who had received a letter and contacted the clinic, we analysed the data using thematic analysis. The relatives had different levels of prior knowledge about the hereditary cancer assessment. Many had been notified by family that a letter was coming but some had not. Overall, these participants believed healthcare-mediated disclosure could complement family-mediated disclosure. They expressed that the letter and the message raised concerns and a need for counselling, and they wanted healthcare to be accessible and informed when making contact. The participants found the message easier to cope with when they had been notified by a family member beforehand, with a general attitude that notifying relatives was the appropriate step to take. They thought healthcare should help patients with the disclosure process but also guard the right of at-risk relatives to be informed. The findings support a direct approach from healthcare as a possible complement to an established model of family-mediated risk disclosure, but implementation must be made within existing frameworks of good practice for genetic counselling.
Multicenter assessment and longitudinal study of the prevalence of antibodies and related adaptive immune responses to AAV in adult males with hemophilia
Authors: Pabinger Ingrid , Ayash-Rashkovsky Mila , Escobar Miguel , Konkle Barbara A. , Mingot-Castellano María Eva , Mullins Eric S. , Negrier Claude , Pan Luying , Rajavel Kavitha , Yan Brian , Chapin John
Published: February 2024

Adeno-associated virus (AAV) based gene therapy has demonstrated effective disease control in hemophilia. However, pre-existing immunity from wild-type AAV exposure impacts gene therapy eligibility. The aim of this multicenter epidemiologic study was to determine the prevalence and persistence of preexisting immunity against AAV2, AAV5, and AAV8, in adult participants with hemophilia A or B. Blood samples were collected at baseline and annually for ≤3 years at trial sites in Austria, France, Germany, Italy, Spain, and the United States. At baseline, AAV8, AAV2, and AAV5 neutralizing antibodies (NAbs) were present in 46.9%, 53.1%, and 53.4% of participants, respectively; these values remained stable at Years 1 and 2. Co-prevalence of NAbs to at least two serotypes and all three serotypes was present at baseline for ~40% and 38.2% of participants, respectively. For each serotype, ~10% of participants who tested negative for NAbs at baseline were seropositive at Year 1. At baseline, 38.3% of participants had detectable cell mediated immunity by ELISpot, although no correlations were observed with the humoral response. In conclusion, participants with hemophilia may have significant preexisting immunity to AAV capsids. Insights from this study may assist in understanding capsid-based immunity trends in participants considering AAV vector-based gene therapy.
A diagnostic model based on bioinformatics and machine learning to differentiate bipolar disorder from schizophrenia and major depressive disorder
Authors: Shen Jing , Xiao Chenxu , Qiao Xiwen , Zhu Qichen , Yan Hanfei , Pan Julong , Feng Yu
Published: February 2024

Bipolar disorder (BD) showed the highest suicide rate of all psychiatric disorders, and its underlying causative genes and effective treatments remain unclear. During diagnosis, BD is often confused with schizophrenia (SC) and major depressive disorder (MDD), due to which patients may receive inadequate or inappropriate treatment, which is detrimental to their prognosis. This study aims to establish a diagnostic model to distinguish BD from SC and MDD in multiple public datasets through bioinformatics and machine learning and to provide new ideas for diagnosing BD in the future. Three brain tissue datasets containing BD, SC, and MDD were chosen from the Gene Expression Omnibus database (GEO), and two peripheral blood datasets were selected for validation. Linear Models for Microarray Data (Limma) analysis was carried out to identify differentially expressed genes (DEGs). Functional enrichment analysis and machine learning were utilized to identify. Least absolute shrinkage and selection operator (LASSO) regression was employed for identifying candidate immune-associated central genes, constructing protein-protein interaction networks (PPI), building artificial neural networks (ANN) for validation, and plotting receiver operating characteristic curve (ROC curve) for differentiating BD from SC and MDD and creating immune cell infiltration to study immune cell dysregulation in the three diseases. RBM10 was obtained as a candidate gene to distinguish BD from SC. Five candidate genes (LYPD1, HMBS, HEBP2, SETD3, and ECM2) were obtained to distinguish BD from MDD. The validation was performed by ANN, and ROC curves were plotted for diagnostic value assessment. The outcomes exhibited the prediction model to have a promising diagnostic value. In the immune infiltration analysis, Naive B, Resting NK, and Activated Mast Cells were found to be substantially different between BD and SC. Naive B and Memory B cells were prominently variant between BD and MDD. In this study, RBM10 was found as a candidate gene to distinguish BD from SC; LYPD1, HMBS, HEBP2, SETD3, and ECM2 serve as five candidate genes to distinguish BD from MDD. The results obtained from the ANN network showed that these candidate genes could perfectly distinguish BD from SC and MDD (76.923% and 81.538%, respectively).
Risk of carditis among adolescents after extending the interdose intervals of BNT162b2
Authors: Fan Min , Peng Kuan , Zhang Yin , Lai Francisco Tsz Tsun , Chui Celine Sze Ling , Wan Eric Yuk Fai , Wong Carlos King Ho , Chan Esther Wai Yin , Li Xue , Wong Ian Chi Kei
Published: February 2024

Previous studies indicate an increased carditis risk among adolescents following the two-dose messenger RNA COVID-19 vaccine. Several jurisdictions have extended the interdose interval between the first and second doses to reduce the risk. However, the effectiveness of such an extension policy remains inconclusive. Using the territory-wide vaccine record-linked electronic health records in Hong Kong, we conducted a nested case–control study from February 23, 2021 to August 15, 2022. Adolescents aged between 12 and 17 who received two-dose BNT162b2 were included for comparing risks between standard interdose interval (21–27 days) versus extended interdose interval ( ≥ 56 days). The carditis cumulative incidence within 28 days following the second dose was calculated. The adjusted odds ratio was estimated from multivariable conditional logistic regression. We identified 49 adolescents with newly diagnosed carditis within 28 days following the second dose. The crude cumulative incidence is 37.41 [95% confidence interval (CI): 27.68–49.46] per million vaccinated adolescents. Compared to the standard interdose interval group, adolescents with an extended interval had a significantly lower risk of carditis [adjusted odds ratio (aOR) 0.34 (95% CI: 0.16–0.73)]. Sensitivity analysis of carditis occurring within 14 days following the second dose yielded a similar estimate [aOR 0.30 (95% CI: 0.13–0.73)]. Extending the interdose interval of the BNT162b2 vaccine from 21 to 27 days to 56 days or longer is associated with 66% lower risk of incident carditis among adolescents. Our findings contribute towards an evidence-based vaccination strategy for a vulnerable population and potentially informs product label updates.
Critical transitions in the Amazon forest system
Authors: Flores Bernardo M. , Montoya Encarni , Sakschewski Boris , Nascimento Nathália , Staal Arie , Betts Richard A. , Levis Carolina , Lapola David M. , Esquível-Muelbert Adriane , Jakovac Catarina , Nobre Carlos A. , Oliveira Rafael S. , Borma Laura S. , Nian Da , Boers Niklas , Hecht Susanna B. , ter Steege Hans , Arieira Julia , Lucas Isabella L. , Berenguer Erika , Marengo José A. , Gatti Luciana V. , Mattos Caio R. C. , Hirota Marina
Published: February 2024

The possibility that the Amazon forest system could soon reach a tipping point, inducing large-scale collapse, has raised global concern1–3. For 65 million years, Amazonian forests remained relatively resilient to climatic variability. Now, the region is increasingly exposed to unprecedented stress from warming temperatures, extreme droughts, deforestation and fires, even in central and remote parts of the system1. Long existing feedbacks between the forest and environmental conditions are being replaced by novel feedbacks that modify ecosystem resilience, increasing the risk of critical transition. Here we analyse existing evidence for five major drivers of water stress on Amazonian forests, as well as potential critical thresholds of those drivers that, if crossed, could trigger local, regional or even biome-wide forest collapse. By combining spatial information on various disturbances, we estimate that by 2050, 10% to 47% of Amazonian forests will be exposed to compounding disturbances that may trigger unexpected ecosystem transitions and potentially exacerbate regional climate change. Using examples of disturbed forests across the Amazon, we identify the three most plausible ecosystem trajectories, involving different feedbacks and environmental conditions. We discuss how the inherent complexity of the Amazon adds uncertainty about future dynamics, but also reveals opportunities for action. Keeping the Amazon forest resilient in the Anthropocene will depend on a combination of local efforts to end deforestation and degradation and to expand restoration, with global efforts to stop greenhouse gas emissions.
A 2D ferroelectric vortex pattern in twisted BaTiO3 freestanding layers
Authors: Sánchez-Santolino G. , Rouco V. , Puebla S. , Aramberri H. , Zamora V. , Cabero M. , Cuellar F. A. , Munuera C. , Mompean F. , Garcia-Hernandez M. , Castellanos-Gomez A. , Íñiguez J. , Leon C. , Santamaria J.
Published: February 2024

The wealth of complex polar topologies1–10 recently found in nanoscale ferroelectrics results from a delicate balance between the intrinsic tendency of the materials to develop a homogeneous polarization and the electric and mechanical boundary conditions imposed on them. Ferroelectric–dielectric interfaces are model systems in which polarization curling originates from open circuit-like electric boundary conditions, to avoid the build-up of polarization charges through the formation of flux-closure11–14 domains that evolve into vortex-like structures at the nanoscale15–17 level. Although ferroelectricity is known to couple strongly with strain (both homogeneous18 and inhomogeneous19,20), the effect of mechanical constraints21 on thin-film nanoscale ferroelectrics has been comparatively less explored because of the relative paucity of strain patterns that can be implemented experimentally. Here we show that the stacking of freestanding ferroelectric perovskite layers with controlled twist angles provides an opportunity to tailor these topological nanostructures in a way determined by the lateral strain modulation associated with the twisting. Furthermore, we find that a peculiar pattern of polarization vortices and antivortices emerges from the flexoelectric coupling of polarization to strain gradients. This finding provides opportunities to create two-dimensional high-density vortex crystals that would enable us to explore previously unknown physical effects and functionalities.
Online images amplify gender bias
Authors: Guilbeault Douglas , Delecourt Solène , Hull Tasker , Desikan Bhargav Srinivasa , Chu Mark , Nadler Ethan
Published: February 2024

Each year, people spend less time reading and more time viewing images1, which are proliferating online2–4. Images from platforms such as Google and Wikipedia are downloaded by millions every day2,5,6, and millions more are interacting through social media, such as Instagram and TikTok, that primarily consist of exchanging visual content. In parallel, news agencies and digital advertisers are increasingly capturing attention online through the use of images7,8, which people process more quickly, implicitly and memorably than text9–12. Here we show that the rise of images online significantly exacerbates gender bias, both in its statistical prevalence and its psychological impact. We examine the gender associations of 3,495 social categories (such as ‘nurse’ or ‘banker’) in more than one million images from Google, Wikipedia and Internet Movie Database (IMDb), and in billions of words from these platforms. We find that gender bias is consistently more prevalent in images than text for both female- and male-typed categories. We also show that the documented underrepresentation of women online13–18 is substantially worse in images than in text, public opinion and US census data. Finally, we conducted a nationally representative, preregistered experiment that shows that googling for images rather than textual descriptions of occupations amplifies gender bias in participants’ beliefs. Addressing the societal effect of this large-scale shift towards visual communication will be essential for developing a fair and inclusive future for the internet.
A single-cell time-lapse of mouse prenatal development from gastrula to birth
Authors: Qiu Chengxiang , Martin Beth K. , Welsh Ian C. , Daza Riza M. , Le Truc-Mai , Huang Xingfan , Nichols Eva K. , Taylor Megan L. , Fulton Olivia , O’Day Diana R. , Gomes Anne Roshella , Ilcisin Saskia , Srivatsan Sanjay , Deng Xinxian , Disteche Christine M. , Noble William Stafford , Hamazaki Nobuhiko , Moens Cecilia B. , Kimelman David , Cao Junyue , Schier Alexander F. , Spielmann Malte , Murray Stephen A. , Trapnell Cole , Shendure Jay
Published: February 2024

The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans1,2. Mouse gestation lasts only 3 weeks, during which the genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of more than 500 million cells. Here, to establish a global framework for exploring mammalian development, we applied optimized single-cell combinatorial indexing3 to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2- to 6-hour intervals spanning late gastrulation (embryonic day 8) to birth (postnatal day 0). From these data, we annotate hundreds of cell types and explore the ontogenesis of the posterior embryo during somitogenesis and of kidney, mesenchyme, retina and early neurons. We leverage the temporal resolution and sampling depth of these whole-embryo snapshots, together with published data4–8 from earlier timepoints, to construct a rooted tree of cell-type relationships that spans the entirety of prenatal development, from zygote to birth. Throughout this tree, we systematically nominate genes encoding transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most marked temporal shifts in cell states are observed within one hour of birth and presumably underlie the massive physiological adaptations that must accompany the successful transition of a mammalian fetus to life outside the womb.
IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
Authors: Wertheimer Tobias , Zwicky Pascale , Rindlisbacher Lukas , Sparano Colin , Vermeer Marijne , de Melo Bruno Marcel Silva , Haftmann Claudia , Rückert Tamina , Sethi Aakriti , Schärli Stefanie , Huber Anna , Ingelfinger Florian , Xu Caroline , Kim Daehong , Häne Philipp , Fonseca da Silva André , Muschaweckh Andreas , Nunez Nicolas , Krishnarajah Sinduya , Köhler Natalie , Zeiser Robert , Oukka Mohamed , Korn Thomas , Tugues Sonia , Becher Burkhard
Published: February 2024

Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (Treg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in Treg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector Treg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.
The social anatomy of climate change denial in the United States
Authors: Gounaridis Dimitrios , Newell Joshua P.
Published: February 2024

Using data from Twitter (now X), this study deploys artificial intelligence (AI) and network analysis to map and profile climate change denialism across the United States. We estimate that 14.8% of Americans do not believe in climate change. This denialism is highest in the central and southern U.S. However, it also persists in clusters within states (e.g., California) where belief in climate change is high. Political affiliation has the strongest correlation, followed by level of education, COVID-19 vaccination rates, carbon intensity of the regional economy, and income. The analysis reveals how a coordinated social media network uses periodic events, such as cold weather and climate conferences, to sow disbelief about climate change and science, in general. Donald Trump was the strongest influencer in this network, followed by conservative media outlets and right-wing activists. As a form of knowledge vulnerability, climate denialism renders communities unprepared to take steps to increase resilience. As with other forms of misinformation, social media companies (e.g., X, Facebook, YouTube, TikTok) should flag accounts that spread falsehoods about climate change and collaborate on targeted educational campaigns.
Global coastal wave storminess
Authors: Lobeto Hector , Semedo Alvaro , Lemos Gil , Dastgheib Ali , Menendez Melisa , Ranasinghe Roshanka , Bidlot Jean-Raymond
Published: February 2024

Coastal wave storms pose a massive threat to over 10% of the world’s population now inhabiting the low elevation coastal zone and to the trillions of $ worth of coastal zone infrastructure and developments therein. Using a ~ 40-year wave hindcast, we here present a world-first assessment of wind-wave storminess along the global coastline. Coastal regions are ranked in terms of the main storm characteristics, showing Northwestern Europe and Southwestern South America to suffer, on average, the most intense storms and the Yellow Sea coast and the South-African and Namibian coasts to be impacted by the most frequent storms. These characteristics are then combined to derive a holistic classification of the global coastlines in terms of their wave environment, showing, for example, that the open coasts of northwestern Europe are impacted by more than 10 storms per year with mean significant wave heights over 6 m. Finally, a novel metric to classify the degree of coastal wave storminess is presented, showing a general latitudinal storminess gradient. Iceland, Ireland, Scotland, Chile and Australia show the highest degree of storminess, whereas Indonesia, Papua-New Guinea, Malaysia, Cambodia and Myanmar show the lowest.
A population of faint, old, and massive quiescent galaxies at $$3<z<4$$ revealed by JWST NIRSpec Spectroscopy
Authors: Nanayakkara Themiya , Glazebrook Karl , Jacobs Colin , Kawinwanichakij Lalitwadee , Schreiber Corentin , Brammer Gabriel , Esdaile James , Kacprzak Glenn G. , Labbe Ivo , Lagos Claudia , Marchesini Danilo , Marsan Z. Cemile , Oesch Pascal A. , Papovich Casey , Remus Rhea-Silvia , Tran Kim-Vy H.
Published: February 2024

Here we present a sample of 12 massive quiescent galaxy candidates at $$z\sim 3-4$$

z
∼
3
-
4

observed with the James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec). These galaxies were pre-selected from the Hubble Space Telescope imaging and 10 of our sources were unable to be spectroscopically confirmed by ground based spectroscopy. By combining spectroscopic data from NIRSpec with multi-wavelength imaging data from the JWST Near Infrared Camera (NIRCam), we analyse their stellar populations and their formation histories. We find that all of our galaxies classify as quiescent based on the reconstruction of their star formation histories but show a variety of quenching timescales and ages. All our galaxies are massive ($$\sim 0.1-1.2\times 10^{11}$$

∼
0.1
-
1.2
×

10
11

M$$_\odot$$

⊙

), with masses comparable to massive galaxies in the local Universe. We find that the oldest galaxy in our sample formed $$\sim 1.0\times 10^{11}$$

∼
1.0
×

10
11

M$$_\odot$$

⊙

of mass within the first few hundred million years of the Universe and has been quenched for more than a billion years by the time of observation at $$z\sim 3.2$$

z
∼
3.2

($$\sim 2$$

∼
2

billion years after the Big Bang). Our results point to very early formation of massive galaxies requiring a high conversion rate of baryons to stars in the early Universe.
Distinguishing recurrence from radiation-induced lung injury at the time of RECIST progressive disease on post-SABR CT scans using radiomics
Authors: Dammak Salma , Gulstene Stephanie , Palma David A. , Mattonen Sarah A. , Senan Suresh , Ward Aaron D.
Published: February 2024

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for patients with early-stage lung cancer who are inoperable. However, SABR causes benign radiation-induced lung injury (RILI) which appears as lesion growth on follow-up CT scans. This triggers the standard definition of progressive disease, yet cancer recurrence is not usually present, and distinguishing RILI from recurrence when a lesion appears to grow in size is critical but challenging. In this study, we developed a tool to do this using scans with apparent lesion growth after SABR from 68 patients. We performed bootstrapped experiments using radiomics and explored the use of multiple regions of interest (ROIs). The best model had an area under the receiver operating characteristic curve of 0.66 and used a sphere with a diameter equal to the lesion’s longest axial measurement as the ROI. We also investigated the effect of using inter-feature and volume correlation filters and found that the former was detrimental to performance and that the latter had no effect. We also found that the radiomics features ranked as highly important by the model were significantly correlated with outcomes. These findings represent a key step in developing a tool that can help determine who would benefit from follow-up invasive interventions when a SABR-treated lesion increases in size, which could help provide better treatment for patients.
Two-dimensional high resolution electron properties of femtosecond laser-induced plasma filament in atmospheric pressure argon
Authors: Bak Junhwi , Urdaneta Gerardo , Pokharel Sagar , Miles Richard B. , Tropina Albina
Published: February 2024

This work reports the measurement of two-dimensional electron properties over a nanosecond scale integration time across a femtosecond laser-induced plasma filament in atmospheric pressure argon. Radial electron properties across the $$\sim 100$$

∼
100

 $$\upmu$$
μ
m diameter filament are obtained at discrete axial locations at 2.5 mm steps by one-dimensional high-resolution laser Thomson scattering with a spatial resolution of 10 $$\upmu$$
μ
m. These measurements reveal plasma structural information in the filament. The Thomson spectral lineshapes exhibit clear spectral sidebands with an $$\alpha$$
α
parameter $$\sim 1$$

∼
1

, enabling the measurement of both electron temperature and density profiles. These measurements yield electron densities on the order of $$10^{22}$$

10
22

/m$$^{3}$$

3

and electron temperatures of $$\sim 2$$

∼
2

 eV. Heating from the probe laser due to inverse bremsstrahlung is taken into account to correct the Thomson scattering electron temperature measurements. Under these conditions, electron-neutral collision induced bremsstrahlung becomes the dominant laser-induced plasma heating process associated with the probe laser. The measurements reveal structural features of the filament, including an asymmetrically skewed density structure in the axial direction and reversed radial distributions of electron density and temperature.
Research on time series prediction of multi-process based on deep learning
Authors: Zheng Huali , Cao Yu , Sun Dong , Wang Mingjun , Yan Binglong , Ye Chunming
Published: February 2024

Aiming at the problem of data fluctuation in multi-process production, a Soft Update Dueling Double Deep Q-learning (SU-D3QN) network combined with soft update strategy is proposed. Based on this, a time series combination forecasting model SU-D3QN-G is proposed. Firstly, based on production data, Gate Recurrent Unit (GRU) is used for prediction. Secondly, based on the model, SU-D3QN algorithm is used to learn and add bias to it, and the prediction results of GRU are corrected, so that the prediction value of each time node fits in the direction of reducing the absolute error. Thirdly, experiments were carried out on the dataset of a company. The data sets of four indicators, namely, the outlet temperature of drying silk, the loose moisture return water, the outlet temperature of feeding leaves and the inlet water of leaf silk warming and humidification, are selected, and more than 1000 real production data are divided into training set, inspection set and test set according to the ratio of 6:2:2. The experimental results show that the SU-D3QN-G combined time series prediction model has a great improvement compared with GRU, LSTM and ARIMA, and the MSE index is reduced by 0.846–23.930%, 5.132–36.920% and 10.606–70.714%, respectively. The RMSE index is reduced by 0.605–10.118%, 2.484–14.542% and 5.314–30.659%. The MAE index is reduced by 3.078–15.678%, 7.94–15.974% and 6.860–49.820%. The MAPE index is reduced by 3.098–15.700%, 7.98–16.395% and 7.143–50.000%.
Follow-up of intramyocardial bone marrow mononuclear cell transplantation beyond 10 years
Authors: Mulari Severi , Kesävuori Risto , Stewart Juhani A. , Karjalainen Pasi , Holmström Miia , Lehtinen Miia , Peltonen Juha , Laine Mika , Sinisalo Juha , Juvonen Tatu , Kupari Markku , Harjula Ari , Pätilä Tommi , Kivistö Sari , Kankuri Esko , Vento Antti ,   the Helsinki BMMC Collaboration, Hämmäinen Pekka , Schildt Jukka , Ahonen Aapo , Nikkinen Päivi , Nihtinen Anne , Alitalo Riitta , Pöyhiä Reino
Published: February 2024

Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center trial in 2006–2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (− 15.1%; 95% CI − 23 to − 6.7% vs. − 7.3%; 95% CI − 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades.
Impulsivity and aggression as risk factors for internet gaming disorder among university students
Authors: Hammad Mohammad Ahmed , AL-shahrani Hend Faye
Published: February 2024

Internet gaming addiction is a global problem, especially among young individuals. Exhibiting characteristics similar to other addictions, Internet Gaming Disorder (IGD) is linked to adverse mental health outcomes. Identified as risk factors for dependence behaviors, the association of impulsivity and aggression with IGD is relatively under-researched in the student population. The present sample of 350 university students (Mage = 21.30 years, SDage = 4.96 years) from Najran university in Saudi Arabia completed an online questionnaire that included the Internet Gaming Disorder Scale–Short-Form (IGDS9-SF), the Buss–Perry Aggression Questionnaire-Short Form, and the Barratt Impulsiveness Scale (BIS-15). Results indicated that impulsivity and aggression were positively associated with IGD severity and both personality traits explained 34.6% of the variance in IGD scores. Further bivariate analyses suggested that individuals spending 7 or more hours on internet gaming were more likely to exhibit high impulsivity and aggression, and had a relatively higher severity of IGD. These results suggest that individuals with these personality traits may be more vulnerable to developing an addiction to internet gaming. These findings need to be confirmed in future more robust studies; however, this exploratory study provides insights for potential programs to prevent IGD among young individuals.
SARS-CoV-2 infection status in corneal preservation solution and COVID-19 prevalence after corneal transplantation
Authors: Wasai Yuki , Yamada Naoyuki , Ariyoshi Nobuaki , Haraguchi Aiko , Funatsu Masahiko , Mikuni Masanori , Nakamura Riku , Sakuma Ayano , Higashijima Fumiaki , Iwamoto Nanako , Teranishi Shinichiro , Nishioka Mitsuaki , Yamasaki Takahiro , Kimura Kazuhiro
Published: February 2024

The potential risks associated with organs from COVID-19-infected donors were unclear. To determine the SARS-CoV-2 infection status of corneas transplanted during the COVID-19 pandemic, we performed a polymerase chain reaction (PCR) using the corneal preservation solution that was used for corneal transplantation. We also examined the postoperative health status of the recipients. This study included 144 transplants in 143 eyes. Ninety-nine eyes of imported corneas and 10 of the 14 corneas donated in the prefecture were PCR tested at our hospital, and all were SARS-CoV-2 negative. All corneal transplants were performed after confirming their SARS-CoV-2 negativity by a PCR using a corneal preservation solution at our hospital or a nasopharyngeal swab at a previous facility. Despite postoperative steroid administration, no patient developed COVID-19 infection until discharge. Hence, if the donor's nasopharyngeal swab test is SARS-CoV-2 negative, COVID-19 infection in the recipient due to corneal transplantation may be prevented. Since corneal transplant recipients are susceptible to infection due to prolonged steroid administration and are at high risk for severe diseases if infection occurs, SARS-CoV-2 detection testing using nasopharyngeal swabs in donors should be performed.
An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer
Authors: Jacobo Jacobo Mauricio , Donnella Hayley J. , Sobti Sushil , Kaushik Swati , Goga Andrei , Bandyopadhyay Sourav
Published: February 2024

Individual cancers are composed of heterogeneous tumor cells with distinct phenotypes and genotypes, with triple negative breast cancers (TNBC) demonstrating the most heterogeneity among breast cancer types. Variability in transcriptional phenotypes could meaningfully limit the efficacy of monotherapies and fuel drug resistance, although to an unknown extent. To determine if transcriptional differences between tumor cells lead to differential drug responses we performed single cell RNA-seq on cell line and PDX models of breast cancer revealing cell subpopulations in states associated with resistance to standard-of-care therapies. We found that TNBC models contained a subpopulation in an inflamed cellular state, often also present in human breast cancer samples. Inflamed cells display evidence of heightened cGAS/STING signaling which we demonstrate is sufficient to cause tumor cell resistance to chemotherapy. Accordingly, inflamed cells were enriched in human tumors taken after neoadjuvant chemotherapy and associated with early recurrence, highlighting the potential for diverse tumor cell states to promote drug resistance.
Life cycle assessment of nutrient recovery strategies from domestic wastewaters to quantify environmental performance and identification of trade-offs
Authors: Pausta Carla Mae , Kalbar Pradip , Saroj Devendra
Published: February 2024

Increase in anthropogenic activities proliferated the consumption of resources such as phosphorus; and increase the adverse environmental impacts especially eutrophication on water resources such as lakes. Nutrient recovery from domestic wastewaters to produce a fertiliser has been explored to address these challenges in the context of a sustainable circular nutrient economy. Life cycle assessment (LCA) was performed to holistically assess the impacts of integrating a nutrient recovery system on wastewater and water resource management using Laguna de Bay, Philippines as the geographical boundary. The inventory was developed based on the results of the emerging nutrient recovery reactor operations and the application of the recovered fertiliser on the agricultural crops. The LCA results for the proposed scenario showed environmental benefits of about 83.6% freshwater eutrophication, 102.5% terrestrial ecotoxicity, 26.9% water consumption, 100.7% mineral resource scarcity, while the global warming potential is 95.4% higher than the baseline scenario. Results imply policy review for septage management, system optimisation, and evaluation of alternative methods of wastewater management, in terms of life cycle thinking and sustainability across the globe.
Diversity of selected toll-like receptor genes in cheetahs (Acinonyx jubatus) and African leopards (Panthera pardus pardus)
Authors: Meißner René , Mokgokong Prudent , Pretorius Chantelle , Winter Sven , Labuschagne Kim , Kotze Antoinette , Prost Stefan , Horin Petr , Dalton Desire , Burger Pamela A.
Published: February 2024

The anthropogenic impact on wildlife is ever increasing. With shrinking habitats, wild populations are being pushed to co-exist in proximity to humans leading to an increased threat of infectious diseases. Therefore, understanding the immune system of a species is key to assess its resilience in a changing environment. The innate immune system (IIS) is the body’s first line of defense against pathogens. High variability in IIS genes, like toll-like receptor (TLR) genes, appears to be associated with resistance to infectious diseases. However, few studies have investigated diversity in TLR genes in vulnerable species for conservation. Large predators are threatened globally including leopards and cheetahs, both listed as 'vulnerable' by IUCN. To examine IIS diversity in these sympatric species, we used next-generation-sequencing to compare selected TLR genes in African leopards and cheetahs. Despite differences, both species show some TLR haplotype similarity. Historic cheetahs from all subspecies exhibit greater genetic diversity than modern Southern African cheetahs. The diversity in investigated TLR genes is lower in modern Southern African cheetahs than in African leopards. Compared to historic cheetah data and other subspecies, a more recent population decline might explain the observed genetic impoverishment of TLR genes in modern Southern African cheetahs. However, this may not yet impact the health of this cheetah subspecies.
RiceProteomeDB (RPDB): a user-friendly database for proteomics data storage, retrieval, and analysis
Authors: Woo Dong U , Lee Yejin , Min Cheol Woo , Kim Sun Tae , Kang Yang Jae
Published: February 2024

Rice, feeding a significant portion of the world, poses unique proteomic challenges critical to agricultural research and global food security. The complexity of the rice proteome, influenced by various genetic and environmental factors, demands specialized analytical approaches for effective study. The central challenges in rice proteomics lie in developing custom methods suited to the unique aspects of rice biology. These include data preprocessing, method selection, and result validation, all of which are essential for advancing rice research. Our aim is to decode these proteomic intricacies to facilitate breakthroughs in strain improvement, disease resistance, and yield optimization, all vital for combating global food insecurity. To achieve this, we have created the RiceProteomeDB (RPDB), a React + Django database, offering a streamlined and comprehensive platform for the analysis of rice proteomics data. RiceProteomeDB (RPDB) simplifies proteomics data management and analysis. It offers features for data organization, preprocessing, method selection, result validation, and data sharing. Researchers can access processed rice proteomics data, conduct analyses, and explore experimental conditions. The user-friendly web interface enhances navigation and interaction. RPDB fosters collaboration by enabling data sharing and proper acknowledgment of sources, contributing to proteomics research and knowledge dissemination. Availability and implementation: Web application:http://riceproteome.plantprofile.net/. The web application’s source code, user’s manual, and sample data:https://github.com/dongu7610/Riceproteome.
Water intake, baseline biopsy, and graft function after living donor kidney transplantation
Authors: Yamanaga Shigeyoshi , Hidaka Yuji , Kawabata Chiaki , Toyoda Mariko , Tanaka Kosuke , Yamamoto Yasuhiro , Inadome Akito , Takeda Asami , Yokomizo Hiroshi
Published: February 2024

Increased water intake is recommended for kidney transplant recipients; however, its efficacy remains controversial. We hypothesized that pre-existing histological findings of the allograft might modulate the impact of water intake. We retrospectively analyzed 167 adults with living-donor kidney transplants (April 2011–May 2020; median observation period, 77 months) whose baseline biopsy data were available. We compared the chronic-change group (n = 38) with the control group (n = 129) to assess the impact of self-reported daily water intake on the estimated glomerular filtration rate (eGFR). The range distribution of water intake was as follows: − 1000 ml (n = 4), 1000–1500 ml (n = 23), 1500–2000 ml (n = 64), 2000–2500 ml (n = 57), 2500–3000 ml (n = 16), and 3000 − ml (n = 3). Donor age was significantly higher in the chronic-change group. In the control group, the ΔeGFR/year increase was correlated with water intake. However, the increase in the water intake of the chronic-change group significantly decreased ΔeGFR/year (1000–1500 ml: + 1.95 ml/min/1.73 m2 and > 2000 ml: − 1.92 ml/min/1.73 m2, p = 0.014). This study suggested a potential influence of increased water intake on recipients with marginal grafts in living donor kidney transplantation.
Corticostriatal activity related to performance during continuous de novo motor learning
Authors: Park Sungbeen , Kim Junghyun , Kim Sungshin
Published: February 2024

Corticostriatal regions play a pivotal role in visuomotor learning. However, less research has been done on how fMRI activity in their subregions is related to task performance, which is provided as visual feedback during motor learning. To address this, we conducted an fMRI experiment in which participants acquired a complex de novo motor skill using continuous or binary visual feedback related to performance. We found a highly selective response related to performance in the entire striatum in both conditions and a relatively higher response in the caudate nucleus for the binary feedback condition. However, the ventromedial prefrontal cortex (vmPFC) response was significant only for the continuous feedback condition. Furthermore, we also found functional distinction of the striatal subregions in random versus goal-directed motor control. These findings underscore the substantial effects of the visual feedback indicating performance on distinct corticostriatal responses, thereby elucidating its significance in reinforcement-based motor learning.
Automated sepsis detection with vancomycin- and allantoin-polydopamine magnetic nanoparticles
Authors: Abafogi Abdurhaman Teyib , Lee Jinyeop , Kim Joochan , Lee Sei Won , Jang Seongsoo , Park Sungsu
Published: February 2024

Rapid and accurate identification of the bacteria responsible for sepsis is paramount for effective patient care. Molecular diagnostic methods, such as polymerase chain reaction (PCR), encounter challenges in sepsis due to inhibitory compounds in the blood, necessitating their removal for precise analysis. In this study we present an innovative approach that utilizes vancomycin (Van) and allantoin (Al)-conjugated polydopamine (PDA)-coated magnetic nanoparticles (MNPs) for the rapid and automated enrichment of bacteria and their DNA extraction from blood without inducing clumping and aggregation of blood. Al/Van-PDA-MNPs, facilitated by IMS, eliminate the need for preliminary sample treatments, providing a swift and efficient method for bacterial concentration and DNA extraction within an hour. Employing Al/Van-PDA-MNPs within an automated framework has markedly improved our ability to pre-concentrate various Gram-negative and Gram-positive bacteria directly from blood samples. This advancement has effectively reduced the detection threshold to 102 colony-forming unit/mL by both PCR and quantitative PCR. The method's expedited processing time, combined with its precision, positions it as a feasible diagnostic tool for diverse healthcare settings, ranging from small clinics to large hospitals. Furthermore, the innovative application of nanoparticles for DNA extraction holds promising potential for advancing sepsis diagnostics, enabling earlier interventions and improving patient outcomes.
Time and frequency analysis of daily-based nexus between global CO2 emissions and electricity generation nexus by novel WLMC approach
Authors: Kartal Mustafa Tevfik , Ulussever Talat , Pata Ugur Korkut , Depren Serpil Kılıç
Published: February 2024

The studies have focused on changes in CO2 emissions over different periods, including the COVID-19 pandemic. Even if CO2 emissions are temporarily reduced during the pandemic according to annual figures, this may be misleading. Considering annual figures is important to understand the overall trend, but using data with much higher frequency (e.g., daily) is much better suited to investigate dynamic relationships and external effects. Therefore, this study comprehensively analyzes the association between CO2 emissions and disaggregated electricity generation (EG) sources across the globe by employing the novel wavelet local multiple correlation (WLMC) approach on daily data from 1st January 2020 to 31st March 2023. The results demonstrate that (1) based on the main statistics, daily CO2 emissions range between 69 MtCO2 and 116 MtCO2, indicating that there is an oscillation, but no sharp changes over the analyzed period. (2) based on the baseline regression using the dynamic ordinary least squares (DOLS) approach, the constructed estimation models have a high predictive ability of CO2 emissions, reaching ~ 94%; (3) in the further analysis employing the WLMC approach, there are significant externalities between EG resources, which affect CO2 emissions. The results present novel insights about time- and frequency-varying effects as well as a disaggregated analysis of the effect of EG on CO2 emissions, demonstrating the significance of the energy transition towards clean sources around the world.