bluuebunny/crossref_metadata_2025 huggingface dataset:
Waste Prediction Approach Using Hybrid Long Short-Term Memory with Support Vector Machine
Authors: Fatovatikhah Farnaz , Ahmedy Ismail , Noor Rafidah Md
Published: April 2024

As climate change increases the risk of extreme rainfall events, concerns over flood management have also increased. To recover quickly from flood damage and prevent further consequential damage, flood waste prediction is of utmost importance. Therefore, developing a rapid and accurate prediction of flood waste generation is important in order to reduce disaster. Several approaches of flood waste classification have been proposed by various researchers, however only a few focus on prediction of flood waste. In this study, a Long Short-Term Memory (LSTM) and Support Vector Machine (SVM) approach is adapted to address these challenges. Two different raw datasets were obtained from the “Advancing Sustainable Materials Management: Facts and Figures 2015” source. The datasets were for 9 years (1960, 1970, 1980, 1990, 2000, 2005, 2010, 2014, 2015), and are labelled as the materials generated in the Municipal Waste Stream from 1960 to 2015 and the materials Recycled and Composted in Municipal Solid Waste from 1960 to 2015. The waste types were grouped as paper and paperboard (PP), glass (GI), metals (Mt), plastics (PI), rubber and leather (RL), textiles (Tt), wood (Wd), food (Fd), yard trimmings (YT) and miscellaneous inorganic wastes (IW).
Experimental investigation of a Y-shaped engine inlet at subsonic flow conditions
Authors: Küçük U.C.
Published: April 2024

In this paper, the results of an experimental investigation for a Y-shaped engine inlet are presented. The experiment is performed at subsonic flow conditions. The main focus is given to time-dependent total pressures measured at the aerodynamic interface plane. Distinctive frequencies carrying high energy contents of the fluctuating total pressures are given and the relation between time-dependent and time-average performance parameters is presented. The cross-correlation coefficients of the high frequency probe readings distributed through the aerodynamic interface plane are also investigated.
Gas turbine prognostics via Temporal Fusion Transformer
Authors: Fentaye A.D. , Kyprianidis K.G.
Published: April 2024

Gas turbines play a vital role in various industries. Timely and accurately predicting their degradation is essential for efficient operation and optimal maintenance planning. Diagnostic and prognostic outcomes aid in determining the optimal compressor washing intervals. Diagnostics detects compressor fouling and estimates the trend up to the current time. If the forecast indicates fast progress in the fouling trend, scheduling offline washing during the next inspection event or earlier may be crucial to address the fouling deposit comprehensively. This approach ensures that compressor cleaning is performed based on its actual health status, leading to improved operation and maintenance costs. This paper presents a novel prognostic method for gas turbine degradation forecasting through a time-series analysis. The proposed approach uses the Temporal Fusion Transformer model capable of capturing time-series relationships at different scales. It combines encoder and decoder layers to capture temporal dependencies and temporal-attention layers to capture long-range dependencies across the encoded degradation trends. Temporal attention is a self-attention mechanism that enables the model to consider the importance of each time step degradation in the context of the entire degradation profile of the given health parameter. Performance data from multiple two-spool turbofan engines is employed to train and test the method. The test results show promising forecasting ability of the proposed method multiple flight cycles into the future. By leveraging the insights provided by the method, maintenance events and activities can be scheduled in a proactive manner. Future work is to extend the method to estimate remaining useful life.
Utilization of at-home tests for coronavirus disease 2019 (COVID-19) among healthcare workers in Chicago
Authors: Valdivia Nathaly , Hirschhorn Lisa R. , Vu Thanh-Huyen , Dubois Cerina , Moskowitz Judith T. , Wilkins John T. , Evans Charlesnika T.
Published: April 2024

Objective:

To describe utilization of at-home coronavirus disease 2019 (COVID-19) testing among healthcare workers (HCW).

Design:

Serial cross-sectional study.

Setting and participants:

HCWs in the Chicago area.

Methods:

Serial surveys were conducted from the Northwestern Medicine (NM HCW SARS-CoV-2) Serology Cohort Study. In April 2022, participants reflected on the past 30 days to complete an online survey regarding COVID-19 home testing. Surveys were repeated in June and November 2022. The percentage of completed home tests and ever-positive tests were reported. Multivariable Poisson regression was used to calculate prevalence rate ratios (PRR) and univariate analysis was used for association between participant characteristics with home testing and positivity.

Results:

Overall, 2,226 (62.4%) of 3,569 responded to the survey in April. Home testing was reported by 26.6% of respondents and 5.9% reported having at least one positive home test. Testing was highest among those 30–39 years old (35.9%) and nurses (28.3%). A positive test was associated (P < .001) with exposure to people, other than patients with known or suspected COVID-19. Home testing increased in June to 36.4% (positivity 19.9%) and decreased to 25% (positivity 13.5%) by November.

Conclusion:

Our cohort findings show the overall increase in both home testing and ever positivity from April to November – a period where changes in variants of concern of SARS-CoV-2 were reported nationwide. Having an exposure to people, other than patients with known or suspected COVID-19 was significantly associated with both, higher home testing frequency and ever-test positivity.
Impact of time to treatment in first occurrence, non-severe Clostridioides difficile infection for elderly patients: are we waiting too long to treat?
Authors: Vandervelde Rhett , Mlynarek Mark E. , Ramesh Mayur , Patel Nimish , Veve Michael P. , August Benjamin A.
Published: April 2024

Objective:

Data evaluating timeliness of antibiotic therapy in Clostridioides difficile infections (CDI) are not well established. The study’s purpose was to evaluate the impact of time-to-CDI treatment on disease progression.

Methods:

A case–control study was performed among hospitalized patients with CDI from 1/2018 to 2/2022. Inclusion criteria were age ≥65 years, first occurrence, non-severe CDI at symptom onset, and CDI treatment for ≥72 hours. Cases included patients who progressed to severe or fulminant CDI; controls were patients without CDI progression. Time to CDI treatment was evaluated in three ways: a classification and regression tree (CART)-defined threshold, time as a continuous variable, and time as a categorical variable.

Results:

272 patients were included; 136 with CDI progression, 136 patients without. The median (IQR) age was 74 (69–81) years, 167 (61%) were women, and 108 (40%) were immunosuppressed. CDI progression patients more commonly were toxin positive (66 [49%] vs 52 [38%], P = .087) with hospital-acquired disease (57 [42%] vs 29 [21%], P < 0.001). A CART-derived breakpoint for optimal time-to-CDI treatment of 64 hours established early (184, 68%) and delayed treatment (88, 32%). When accounting for confounding variables, delayed CDI treatment was associated with disease progression (adjOR, 4.6; 95%CI, 2.6–8.2); this was observed regardless of how time-to-CDI-active therapy was evaluated (continuous adjOR, 1.02; categorical adjOR, 2.11).

Conclusion:

Delayed CDI treatment was associated with disease progression and could represent an important antimicrobial stewardship measure with future evaluation.
Jordanian Nurses’ Perceptions of Disaster Preparedness and Core Competencies
Authors: Alfuqaha Alia N. , Alosta Mohammad R. , Khalifeh Anas H. , Oweidat Islam Ali
Published: April 2024

Objective:

This study aims to identify the Jordanian nurses’ perception of their disaster preparedness and core competencies.

Methods:

A descriptive, cross-sectional research design was used. The data was collected via an online self-reported questionnaire using the disaster preparedness evaluation tool and the core disaster competencies tool.

Results:

A total of 126 nurses participated in the study. Jordanian nurses had moderate to high levels of core disaster competencies and moderate levels of disaster preparedness. Core disaster competencies and disaster preparedness levels differed based on previous training on disaster preparedness, and the availability of an established emergency plan in their hospitals. Lastly, a previous training on disaster preparedness and core disaster competencies were statistically significant predictors of disaster preparedness among Jordanian nurses.

Conclusions:

Organizational factors and environmental contexts play a role in the development of such capabilities. Future research should focus on understanding the barriers and facilitators of developing core disaster competencies and disaster preparedness among nurses.
Philosophical Intuitions about Socially Significant Language
Authors: Hesni Samia
Published: April 2024

As we theorize about philosophy of language that bears on social and political issues, it is worth revisiting the methodological question of how we as theorists rely on our philosophical and linguistic intuitions, and what assumptions underlie our justification of such a reliance. Two threads in the philosophical literature are relevant to this question: the discussion of situatedness in feminist epistemology and the debate about philosophical expertise and philosophical intuitions. I argue that philosophers examining social and political philosophy of language should be careful—perhaps more careful than we have been—when we rely on our intuitions to draw conclusions about socially significant language, such as racist, sexist, homophobic, and other derogatory speech. I don’t claim we should give up relying on our intuitions. Instead, I argue that we should be more explicit that our intuitions are limited, and open to the possibility that they might not align with the intuitions of those who have more experience with the kinds of speech we are analyzing. As a result, we might find that the conclusions we draw from our intuitions have to be revised or qualified.
Practices to prevent central line-associated bloodstream infection: A 2021 survey of infection preventionists in US hospitals
Authors: Pisney Larissa , Camplese Lisa , Greene M. Todd , Saint Sanjay , Fowler Karen E. , Chopra Vineet
Published: April 2024

Objective:

To determine prevalence of technical and behavioral interventions aimed at preventing central line-associated bloodstream infection (CLABSI) following the COVID19 pandemic.

Design:

Cross-sectional survey.

Setting:

US acute care hospitals.

Participants:

Infection preventionists at participating hospitals.

Methods:

Surveys were sent to infection preventionists from a national random sample of 881 US acute care hospitals. Questions covered use of technical interventions to prevent CLABSI (eg, alcohol-containing chlorhexidine gluconate [CHG] for skin antisepsis, use of coated catheters), socio-adaptive interventions (eg, feedback of CLABSI rates, use of appropriateness criteria), and leadership support for CLABSI prevention.

Results:

Survey response rate was 47% (415/881). Technical interventions such as maximal sterile barriers (99%) or CHG-impregnated dressings (92%) were highly prevalent, but routine use of CHG bathing was less common (68% indicated regular use in intensive care unit [ICU] vs 18% in non-ICU settings). Although 97% of respondents indicated use of systems to monitor CLABSI, feedback to providers on CLABSI events was reported by 89%. Only 53% of respondents indicated regular use of tools to determine appropriateness of central venous catheters (CVC). Three-quarters of respondents indicated their hospital assessed CVC necessity daily, but only 23% reported strategies to reduce routine blood cultures. CLABSI prevention was extremely important to hospital leadership at 82% of responding hospitals.

Conclusions:

Most US hospitals continue to use evidence-based methods to prevent CLABSI as recommended by leading organizations. Opportunities to focus on socio-adaptive interventions such as feedback of infection rates, use of appropriateness criteria for CVC placement, and improving the “culture of pan-culturing” remain.
Short-term calving front dynamics and mass loss at Sálajiegna glacier, northern Sweden, assessed by uncrewed surface and aerial vehicles
Authors: Vacek Florian , Deutsch Clemens , Kuttenkeuler Jakob , Kirchner Nina
Published: April 2024

Uncrewed aerial vehicles (UAVs) are frequently used in glaciological applications, among other things, for photogrammetric assessments of calving dynamics at glacier termini. However, UAVs are often limited by battery endurance and weight constraints on the scientific payload that can be added. At Sálajiegna, the largest freshwater calving glacier in Sweden, we explored the combined use of a versatile maritime robot (uncrewed surface vehicle, USV) and a UAV to characterise Sálajiegna's short-term and seasonal calving front dynamics and mass loss. For this, a photogrammetric payload suite was integrated into the USV. Consecutive USV surveys of Sálajiegna's front, followed by point cloud based calving detection and surface-reconstruction based volume quantification, allowed for a detailed description of calving-induced terminus changes and is hence suggested as a viable alternative to the differencing of digital elevation models. By combining USV and UAV measurements, we identify sectors of high and low calving activity, a calving front retreat of up to 56 m and a thinning rate in the terminus region of 5.4 cm d−1 during the summer of 2022.
La experimentación como herramienta para el estudio de la alfarería de la transición pampeano-patagónica oriental (Provincia de Buenos Aires, Argentina)
Authors: Borges Vaz Erika , Martínez Gustavo , Domingorena Lucas Pereyra
Published: April 2024

En este trabajo se presentan los resultados de estudios experimentales realizados en pastas cerámicas con el objetivo de comprender las elecciones técnicas realizadas por los grupos cazadores-recolectores que habitaron el curso inferior del Río Colorado (transición pampeano-patagónica oriental) en los últimos 2000 años aP aproximadamente. A tal efecto, con la guía de ceramistas locales, se realizaron ensayos tanto en el campo como en el laboratorio, empleando materias primas (arcillas y arenas) obtenidas del área de estudio. Durante las tareas de campo se realizó el testeo inicial y la cocción de las materias primas, actividades que se repitieron en el laboratorio. A esto se agregó una batería de estudios arqueométricos (e.g., petrografías, DRX, FTIR, SEM-EDAX) cuyos resultados fueron comparados con la información arqueológica del área. En este sentido, la composición de las materias primas, las temperaturas y condiciones de quema, así como los patrones tecnológicos de las pastas experimentales, son concordantes con las registradas en las cerámicas arqueológicas. La integración de estos datos indicaría la producción preponderantemente local de las vasijas como también la transmisión de una práctica alfarera a lo largo del Holoceno tardío.
Governadoras: Women Administrators, Gender, and Colonization in Sixteenth-Century Portuguese America
Authors: O'Leary Jessica
Published: April 2024

In sixteenth-century Brazil, several European women governed the captaincies of their late or absent husbands during the first century of Portuguese colonization. A contextual and lexical analysis of the male-authored sources reveals that these women acted decisively to protect and expand familial patrimonies and, in doing so, were part of the colonizing movement. Although extensive written evidence survives that attests to their authority and agency over colonial affairs, their importance has been overlooked in the scholarship. Therefore, this essay argues that a small group of elite European women became imperial agents who wielded power against colonial subjects in select circumstances.
ETHEL ANN BURTON-BROWN WITH BONI IN THE FORUM, 1898–1904
Authors: Dixon Susan M.
Published: April 2024

This essay has two objectives. First, it acknowledges and situates the contribution of Ethel Ann Burton-Brown (1868–1927) to the history of the archaeology of the Roman Forum as it was excavated between 1898 and 1905 under the direction of Giacomo Boni (1859–1925). Her English-language handbook on the discoveries, now overlooked in literature on Boni, showcased her education at Girton College, her experience with traditional cultures such as those of northern India, and her understanding of established and newly emerging methods of classical archaeology. Unlike Esther van Deman and Eugénie Sellers Strong, who embraced careers in archaeology just years after Burton-Brown's publication, she did not pursue working in the discipline because of her personal situation. Secondly, it investigates the manner in which Burton-Brown received Boni's presentation of the excavations. Trained as an architect and experienced in architectural restoration, Boni brought innovative scientific methods to the task of uncovering Rome's archaic past. He did so while deliberately distancing himself from those scholars before him who applied traditional academic approaches, i.e., those reliant on classical literature, to archaeological practice. In large part, Burton-Brown's handbook echoes the descriptions and analyses of Boni's finds in the Roman Forum. However, a closer reading of her text reveals that her personal experiences shaped some of her explanations of the archaeological past in ways that differed from Boni's. In addition, their respective nationalities, British versus Italian, shade how they each value Rome's early history.
Practitioners respond to Carol Griffiths ‘What about the teacher?’ (Language Teaching, 56(2), 210–222)
Authors: Trotman Wayne
Published: April 2024

I read Carol Griffiths' article with great interest. This is due in part to being in what I feel is a privileged position as book reviewer for a UK journal, the EL Gazette,1 for whom I have read several titles by authors she references on teacher wellbeing, such as Mercer and Gregersen (2020). I wondered, however, why Brierton and Gkonou (2022) was not listed there as it also deals with issues raised by Griffiths such as how academic managers can help create an environment that reduces stress and mental health problems. It was also interesting to note that Griffiths, like myself, has spent most of her working life involved in English language teaching, almost all of which has taken place in Turkey. Her article also resonated with my own experience as a teacher-educator as it draws upon research carried out in a Turkish context (Griffiths & Sönmez, 2020).
Case report: Prinzmetal angina in adolescent
Authors: Rahmadhany Anisa , Karim Birry , Amal Mohamad Yanuar
Published: April 2024

Prinzmetal angina is a rare condition more likely to be reported in adults. Vasospasm is by far notable for causing this condition. We present a case of Prinzmetal angina in a 17-year-old male who experienced unexplained resting chest pain for 2 days.
Oncology social workers’ involvement in palliative care: Secondary data analysis from nationwide oncology social workers survey
Authors: Guan Ting , BrintzenhofeSzoc Karlynn , Middleton Alyssa , Otis-Green Shirley , Schapmire Tara , Rayton Makeeta , Nelson Krista , Grignon Michael L. , Zebrack Brad
Published: April 2024

Objectives

Social workers are vital in delivering psychosocial services in palliative care, yet their specific roles in palliative oncology remain undefined. This study aimed to delineate the current practice role of oncology social workers involvement in palliative care in the United States.

Methods

This study utilized a cross-sectional design and involved secondary analysis of data from a nationwide survey focused on workforce conditions for oncology social workers. The participants were social workers who were directly involved in providing care to cancer patients and delivering palliative care services. They completed an online survey in which they indicated the relevance of 91 tasks related to their practice. The survey also collected individual demographic and work-related characteristics. Exploratory factor analysis was used to achieve the study objective.

Results

Responses from a secondary data set of 243 oncology social workers involved in palliative care results in a 6-factor solution comprising 34 tasks. These factors were identified as: Therapeutic Interventions for Individuals, Couples, and Families; Facilitate Patient Care Decision-making; Care Coordination; Assessment and Emotional Support; Organization and Community Service; and Equity and Justice. All 6 factors demonstrated good internal reliability, as indicated by Cronbach’s alpha scores above 0.70.

Significance of results

The findings can be used to develop job descriptions and education for social workers employed in palliative cancer care. The clear role descriptions also make social work visible to other professionals in palliative oncology. By clarifying the roles of oncology social workers, this study contributes to the improvement of palliative care delivery and enhances interprofessional collaboration within cancer care teams.
Drying Over Eastern China Driven by the Depletion of Arctic Stratospheric Ozone During Boreal Spring
Authors: Hu Dingzhu , Zhang Zhuohua , Guan Zhaoyong
Published: April 2024

Given the significant importance of spring precipitation for agricultural production in China and the presence of the spring predictability barrier, scientists have dedicated extensive efforts to understand the factors influencing spring precipitation variability and explore new predictors. However, the effects of Arctic stratospheric ozone (ASO) on precipitation in China during boreal spring, if any, and the underlying mechanisms remain unclear. We found the robust influences of March ASO on the differences in the precipitation and evaporation in April over Eastern China during 1980–2020. When ASO decreases in March, it tends to result in a higher and colder tropopause in the polar, a stronger subtropical jet stream, an intensified local Hadley circulation accompanied by anomalous downward motion over Eastern China, and consequently, drying in this region, and vice versa. These findings suggest that the likelihood of April moistening over East Asia may be potentially predicted by employing the ASO index.
Estimation of Nighttime Aerosol Optical Depths Using Atmospheric Infrared Sounder Longwave Radiances
Authors: Liu Guanyu , Li Jing , Li Jun , Yue Sheng , Zhou Ronglian
Published: April 2024

Aerosol remote sensing typically relies on reflected shortwave radiation and thus lacks nighttime retrievals. Here we made an original attempt to retrieve nighttime aerosol optical depth (AOD) by utilizing longwave measurements in the atmospheric window region from the Atmospheric InfraRed Sounder (AIRS) instrument. A machine‐learning based algorithm is developed using AIRS longwave radiance and auxiliary data as the input and AOD from Moderate Resolution Imaging Spectroradiometer (MODIS) as well as reanalysis surface temperature as the output. Independent validation indicates good agreement with lunar AOD derived from surface photometers. An overall increase in nighttime AOD compared to daytime is also uncovered, which is further corroborated by surface and space lidar measurements. The theoretical basis of the algorithm is further verified using radiative transfer simulations. Our approach substantially extends the potential of hyperspectral longwave measurements and offers valuable insights into nighttime aerosol properties.
Paleoenvironmental Controls on the Abundances of Magnetofossils in the Southwestern Iberian Margin
Authors: He Kuang , Zhao Xiangyu , Jiang Zhaoxia , Li Sanzhong
Published: April 2024

Magnetofossils are nanosized magnetic fossil remnants of magnetotactic bacteria (MTB) that are widely distributed in marine and freshwater sediments. Past studies have revealed that changes in the morphology and abundance of magnetofossils are linked with diverse paleoenvironmental changes, such as glacial‐interglacial variation, redox conditions associated with primary productivity and organic matter supply, chemical weathering and diagenesis. Besides, it has long been speculated that changes in geomagnetic field intensity could also affect the abundance of magnetofossils. However, it is not yet clear, how these environmental factors controlled past MTB populations in combination. To answer this question, we studied magnetofossils‐rich sediments from cores MD01‐2443 and 2444 off the Southwest Iberian Margin. The paleomagnetic records of our samples reveal geomagnetic excursions corresponding to the Laschamp, Blake, Iceland Basin, and Pringle Falls events. We estimated the relative abundance of magnetofossils in the samples based on isothermal remanent magnetization unmixing and found it to increase during warmer periods and decrease during colder periods, while not covary with changes in the geomagnetic field intensity. To further distinguish the role of different paleoenvironmental factors, we compared magnetofossil abundance with planktonic δ18O, δ13C of organic matter, K/Al and Si/Al, which indicate continental ice volume (paleotemperature), organic matter origin, run‐off intensity and productivity, respectively. The results indicate that less continental ice volume (higher paleotemperature), enhanced productivity and run‐off intensity are closely related and jointly promoted magnetofossil production and preservation. Our study offers a comprehensive approach to understanding how magnetofossil assemblages relate to paleoenvironmental changes off the SW Iberian Margin.
What’s Next for the Anthropocene?
Authors: Rodrigues Meghie
Published: April 2024

Researchers weigh in on the meaning and aftermath of the decision to reject designating “Anthropocene” as an official geological epoch.
Mantle Heat May Have Boosted Earth’s Crust 3 Billion Years Ago
Authors: Owen Rebecca
Published: April 2024

Information from igneous zircon molecules gives researchers new insight into the workings of inner Earth.
Alternative splicing in prostate cancer progression and therapeutic resistance
Authors: Rawat Chitra , Heemers Hannelore V.
Published: April 2024

Prostate cancer (CaP) remains the second leading cause of cancer deaths in western men. CaP mortality results from diverse molecular mechanisms that mediate resistance to the standard of care treatments for metastatic disease. Recently, alternative splicing has been recognized as a hallmark of CaP aggressiveness. Alternative splicing events cause treatment resistance and aggressive CaP behavior and are determinants of the emergence of the two major types of late-stage treatment-resistant CaP, namely castration-resistant CaP (CRPC) and neuroendocrine CaP (NEPC). Here, we review recent multi-omics data that are uncovering the complicated landscape of alternative splicing events during CaP progression and the impact that different gene transcript isoforms can have on CaP cell biology and behavior. We discuss renewed insights in the molecular machinery by which alternative splicing occurs and contributes to the failure of systemic CaP therapies. The potential for alternative splicing events to serve as diagnostic markers and/or therapeutic targets is explored. We conclude by considering current challenges and promises associated with splicing-modulating therapies, and their potential for clinical translation into CaP patient care.
ATF3 characterizes aggressive drug-tolerant persister cells in HGSOC
Authors: Böpple Kathrin , Oren Yaara , Henry Whitney S. , Dong Meng , Weller Sandra , Thiel Julia , Kleih Markus , Gaißler Andrea , Zipperer Damaris , Kopp Hans-Georg , Aylon Yael , Oren Moshe , Essmann Frank , Liang Chunguang , Aulitzky Walter E.
Published: April 2024

High-grade serous ovarian cancer (HGSOC) represents the most common and lethal subtype of ovarian cancer. Despite initial response to platinum-based standard therapy, patients commonly suffer from relapse that likely originates from drug-tolerant persister (DTP) cells. We generated isogenic clones of treatment-naïve and cisplatin-tolerant persister HGSOC cells. In addition, single-cell RNA sequencing of barcoded cells was performed in a xenograft model with HGSOC cell lines after platinum-based therapy. Published single-cell RNA-sequencing data from neo-adjuvant and non-treated HGSOC patients and patient data from TCGA were analyzed. DTP-derived cells exhibited morphological alterations and upregulation of epithelial-mesenchymal transition (EMT) markers. An aggressive subpopulation of DTP-derived cells showed high expression of the stress marker ATF3. Knockdown of ATF3 enhanced the sensitivity of aggressive DTP-derived cells to cisplatin-induced cell death, implying a role for ATF3 stress response in promoting a drug tolerant persister cell state. Furthermore, single cell lineage tracing to detect transcriptional changes in a HGSOC cell line-derived xenograft relapse model showed that cells derived from relapsed solid tumors express increased levels of EMT and multiple endoplasmic reticulum (ER) stress markers, including ATF3. Single cell RNA sequencing of epithelial cells from four HGSOC patients also identified a small cell population resembling DTP cells in all samples. Moreover, analysis of TCGA data from 259 HGSOC patients revealed a significant progression-free survival advantage for patients with low expression of the ATF3-associated partial EMT genes. These findings suggest that increased ATF3 expression together with partial EMT promote the development of aggressive DTP, and thereby relapse in HGSOC patients.
Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development
Authors: Xing Lei , Gkini Vasiliki , Nieminen Anni I. , Zhou Hui-Chao , Aquilino Matilde , Naumann Ronald , Reppe Katrin , Tanaka Kohichi , Carmeliet Peter , Heikinheimo Oskari , Pääbo Svante , Huttner Wieland B. , Namba Takashi
Published: April 2024

Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B’s ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.
Flow interactions lead to self-organized flight formations disrupted by self-amplifying waves
Authors: Newbolt Joel W. , Lewis Nickolas , Bleu Mathilde , Wu Jiajie , Mavroyiakoumou Christiana , Ramananarivo Sophie , Ristroph Leif
Published: April 2024

Collectively locomoting animals are often viewed as analogous to states of matter in that group-level phenomena emerge from individual-level interactions. Applying this framework to fish schools and bird flocks must account for visco-inertial flows as mediators of the physical interactions. Motivated by linear flight formations, here we show that pairwise flow interactions tend to promote crystalline or lattice-like arrangements, but such order is disrupted by unstably growing positional waves. Using robotic experiments on “mock flocks” of flapping wings in forward flight, we find that followers tend to lock into position behind a leader, but larger groups display flow-induced oscillatory modes – “flonons” – that grow in amplitude down the group and cause collisions. Force measurements and applied perturbations inform a wake interaction model that explains the self-ordering as mediated by spring-like forces and the self-amplification of disturbances as a resonance cascade. We further show that larger groups may be stabilized by introducing variability among individuals, which induces positional disorder while suppressing flonon amplification. These results derive from generic features including locomotor-flow phasing and nonreciprocal interactions with memory, and hence these phenomena may arise more generally in macroscale, flow-mediated collectives.
High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue
Authors: Zhang Ning , Harbers Luuk , Simonetti Michele , Diekmann Constantin , Verron Quentin , Berrino Enrico , Bellomo Sara E. , Longo Gabriel M. C. , Ratz Michael , Schultz Niklas , Tarish Firas , Su Peng , Han Bo , Wang Wanzhong , Onorato Sofia , Grassini Dora , Ballarino Roberto , Giordano Silvia , Yang Qifeng , Sapino Anna , Frisén Jonas , Alkass Kanar , Druid Henrik , Roukos Vassilis , Helleday Thomas , Marchiò Caterina , Bienko Magda , Crosetto Nicola
Published: April 2024

Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: ‘pseudo-diploid’ cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.
Scalable computation of anisotropic vibrations for large macromolecular assemblies
Authors: Lam Jordy Homing , Nakano Aiichiro , Katritch Vsevolod
Published: April 2024

The Normal Mode Analysis (NMA) is a standard approach to elucidate the anisotropic vibrations of macromolecules at their folded states, where low-frequency collective motions can reveal rearrangements of domains and changes in the exposed surface of macromolecules. Recent advances in structural biology have enabled the resolution of megascale macromolecules with millions of atoms. However, the calculation of their vibrational modes remains elusive due to the prohibitive cost associated with constructing and diagonalizing the underlying eigenproblem and the current approaches to NMA are not readily adaptable for efficient parallel computing on graphic processing unit (GPU). Here, we present eigenproblem construction and diagonalization approach that implements level-structure bandwidth-reducing algorithms to transform the sparse computation in NMA to a globally-sparse-yet-locally-dense computation, allowing batched tensor products to be most efficiently executed on GPU. We map, optimize, and compare several low-complexity Krylov-subspace eigensolvers, supplemented by techniques such as Chebyshev filtering, sum decomposition, external explicit deflation and shift-and-inverse, to allow fast GPU-resident calculations. The method allows accurate calculation of the first 1000 vibrational modes of some largest structures in PDB ( > 2.4 million atoms) at least 250 times faster than existing methods.
EZH2 mutations in follicular lymphoma distort H3K27me3 profiles and alter transcriptional responses to PRC2 inhibition
Authors: Romero Pierre , Richart Laia , Aflaki Setareh , Petitalot Ambre , Burton Megan , Michaud Audrey , Masliah-Planchon Julien , Kuhnowski Frédérique , Le Cam Samuel , Baliñas-Gavira Carlos , Méaudre Céline , Luscan Armelle , Hamza Abderaouf , Legoix Patricia , Vincent-Salomon Anne , Wassef Michel , Holoch Daniel , Margueron Raphaël
Published: April 2024

Mutations in chromatin regulators are widespread in cancer. Among them, the histone H3 lysine 27 methyltransferase Polycomb Repressive Complex 2 (PRC2) shows distinct alterations according to tumor type. This specificity is poorly understood. Here, we model several PRC2 alterations in one isogenic system to reveal their comparative effects. Focusing then on lymphoma-associated EZH2 mutations, we show that Ezh2Y641F induces aberrant H3K27 methylation patterns even without wild-type Ezh2, which are alleviated by partial PRC2 inhibition. Remarkably, Ezh2Y641F rewires the response to PRC2 inhibition, leading to induction of antigen presentation genes. Using a unique longitudinal follicular lymphoma cohort, we further link EZH2 status to abnormal H3K27 methylation. We also uncover unexpected variability in the mutational landscape of successive biopsies, pointing to frequent co-existence of different clones and cautioning against stratifying patients based on single sampling. Our results clarify how oncogenic PRC2 mutations disrupt chromatin and transcription, and the therapeutic vulnerabilities this creates.
DenRAM: neuromorphic dendritic architecture with RRAM for efficient temporal processing with delays
Authors: D’Agostino Simone , Moro Filippo , Torchet Tristan , Demirağ Yiğit , Grenouillet Laurent , Castellani Niccolò , Indiveri Giacomo , Vianello Elisa , Payvand Melika
Published: April 2024

Neuroscience findings emphasize the role of dendritic branching in neocortical pyramidal neurons for non-linear computations and signal processing. Dendritic branches facilitate temporal feature detection via synaptic delays that enable coincidence detection (CD) mechanisms. Spiking neural networks highlight the significance of delays for spatio-temporal pattern recognition in feed-forward networks, eliminating the need for recurrent structures. Here, we introduce DenRAM, a novel analog electronic feed-forward spiking neural network with dendritic compartments. Utilizing 130 nm technology integrated with resistive RAM (RRAM), DenRAM incorporates both delays and synaptic weights. By configuring RRAMs to emulate bio-realistic delays and exploiting their heterogeneity, DenRAM mimics synaptic delays and efficiently performs CD for pattern recognition. Hardware-aware simulations on temporal benchmarks show DenRAM’s robustness against hardware noise, and its higher accuracy over recurrent networks. DenRAM advances temporal processing in neuromorphic computing, optimizes memory usage, and marks progress in low-power, real-time signal processing
Large-scale cross-ancestry genome-wide meta-analysis of serum urate
Authors: Cho Chamlee , Kim Beomsu , Kim Dan Say , Hwang Mi Yeong , Shim Injeong , Song Minku , Lee Yeong Chan , Jung Sang-Hyuk , Cho Sung Kweon , Park Woong-Yang , Myung Woojae , Kim Bong-Jo , Do Ron , Choi Hyon K. , Merriman Tony R. , Kim Young Jin , Won Hong-Hee
Published: April 2024

Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.
Whole-cortex in situ sequencing reveals input-dependent area identity
Authors: Chen Xiaoyin , Fischer Stephan , Rue Mara C. P. , Zhang Aixin , Mukherjee Didhiti , Kanold Patrick O. , Gillis Jesse , Zador Anthony M.
Published: April 2024

The cerebral cortex is composed of neuronal types with diverse gene expression that are organized into specialized cortical areas. These areas, each with characteristic cytoarchitecture1,2, connectivity3,4 and neuronal activity5,6, are wired into modular networks3,4,7. However, it remains unclear whether these spatial organizations are reflected in neuronal transcriptomic signatures and how such signatures are established in development. Here we used BARseq, a high-throughput in situ sequencing technique, to interrogate the expression of 104 cell-type marker genes in 10.3 million cells, including 4,194,658 cortical neurons over nine mouse forebrain hemispheres, at cellular resolution. De novo clustering of gene expression in single neurons revealed transcriptomic types consistent with previous single-cell RNA sequencing studies8,9. The composition of transcriptomic types is highly predictive of cortical area identity. Moreover, areas with similar compositions of transcriptomic types, which we defined as cortical modules, overlap with areas that are highly connected, suggesting that the same modular organization is reflected in both transcriptomic signatures and connectivity. To explore how the transcriptomic profiles of cortical neurons depend on development, we assessed cell-type distributions after neonatal binocular enucleation. Notably, binocular enucleation caused the shifting of the cell-type compositional profiles of visual areas towards neighbouring cortical areas within the same module, suggesting that peripheral inputs sharpen the distinct transcriptomic identities of areas within cortical modules. Enabled by the high throughput, low cost and reproducibility of BARseq, our study provides a proof of principle for the use of large-scale in situ sequencing to both reveal brain-wide molecular architecture and understand its development.
Optical clocks at sea
Authors: Roslund Jonathan D. , Cingöz Arman , Lunden William D. , Partridge Guthrie B. , Kowligy Abijith S. , Roller Frank , Sheredy Daniel B. , Skulason Gunnar E. , Song Joe P. , Abo-Shaeer Jamil R. , Boyd Martin M.
Published: April 2024

Deployed optical clocks will improve positioning for navigational autonomy1, provide remote time standards for geophysical monitoring2 and distributed coherent sensing3, allow time synchronization of remote quantum networks4,5 and provide operational redundancy for national time standards. Although laboratory optical clocks now reach fractional inaccuracies below 10−18 (refs. 6,7), transportable versions of these high-performing clocks8,9 have limited utility because of their size, environmental sensitivity and cost10. Here we report the development of optical clocks with the requisite combination of size, performance and environmental insensitivity for operation on mobile platforms. The 35 l clock combines a molecular iodine spectrometer, fibre frequency comb and control electronics. Three of these clocks operated continuously aboard a naval ship in the Pacific Ocean for 20 days while accruing timing errors below 300 ps per day. The clocks have comparable performance to active hydrogen masers in one-tenth the volume. Operating high-performance clocks at sea has been historically challenging and continues to be critical for navigation. This demonstration marks a significant technological advancement that heralds the arrival of future optical timekeeping networks.
PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells
Authors: Lacher Sebastian B. , Dörr Janina , de Almeida Gustavo P. , Hönninger Julian , Bayerl Felix , Hirschberger Anna , Pedde Anna-Marie , Meiser Philippa , Ramsauer Lukas , Rudolph Thomas J. , Spranger Nadine , Morotti Matteo , Grimm Alizee J. , Jarosch Sebastian , Oner Arman , Gregor Lisa , Lesch Stefanie , Michaelides Stefanos , Fertig Luisa , Briukhovetska Daria , Majed Lina , Stock Sophia , Busch Dirk H. , Buchholz Veit R. , Knolle Percy A. , Zehn Dietmar , Dangaj Laniti Denarda , Kobold Sebastian , Böttcher Jan P.
Published: April 2024

Cancer-specific TCF1+ stem-like CD8+ T cells can drive protective anticancer immunity through expansion and effector cell differentiation1–4; however, this response is dysfunctional in tumours. Current cancer immunotherapies2,5–9 can promote anticancer responses through TCF1+ stem-like CD8+ T cells in some but not all patients. This variation points towards currently ill-defined mechanisms that limit TCF1+CD8+ T cell-mediated anticancer immunity. Here we demonstrate that tumour-derived prostaglandin E2 (PGE2) restricts the proliferative expansion and effector differentiation of TCF1+CD8+ T cells within tumours, which promotes cancer immune escape. PGE2 does not affect the priming of TCF1+CD8+ T cells in draining lymph nodes. PGE2 acts through EP2 and EP4 (EP2/EP4) receptor signalling in CD8+ T cells to limit the intratumoural generation of early and late effector T cell populations that originate from TCF1+ tumour-infiltrating CD8+ T lymphocytes (TILs). Ablation of EP2/EP4 signalling in cancer-specific CD8+ T cells rescues their expansion and effector differentiation within tumours and leads to tumour elimination in multiple mouse cancer models. Mechanistically, suppression of the interleukin-2 (IL-2) signalling pathway underlies the PGE2-mediated inhibition of TCF1+ TIL responses. Altogether, we uncover a key mechanism that restricts the IL-2 responsiveness of TCF1+ TILs and prevents anticancer T cell responses that originate from these cells. This study identifies the PGE2–EP2/EP4 axis as a molecular target to restore IL-2 responsiveness in anticancer TILs to achieve cancer immune control.
Antisense oligonucleotide therapeutic approach for Timothy syndrome
Authors: Chen Xiaoyu , Birey Fikri , Li Min-Yin , Revah Omer , Levy Rebecca , Thete Mayuri Vijay , Reis Noah , Kaganovsky Konstantin , Onesto Massimo , Sakai Noriaki , Hudacova Zuzana , Hao Jin , Meng Xiangling , Nishino Seiji , Huguenard John , Pașca Sergiu P.
Published: April 2024

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2–6. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed7, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology.