bluuebunny/crossref_metadata_2025 huggingface dataset:
The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer
Authors: Di Giorgio Cristina , Bellini Rachele , Lupia Antonio , Massa Carmen , Urbani Ginevra , Bordoni Martina , Marchianò Silvia , Rosselli Rosalinda , De Gregorio Rosa , Rapacciuolo Pasquale , Sepe Valentina , Morretta Elva , Monti Maria Chiara , Moraca Federica , Cari Luigi , Ullah Khan Rana Sami , Natalizi Nicola , Graziosi Luigina , Distrutti Eleonora , Biagioli Michele , Catalanotti Bruno , Donini Annibale , Zampella Angela , Fiorucci Stefano
Published: November 2023

Purpose

The gastric adenocarcinoma (GC) represents the third cause of cancer-related mortality worldwide, and available therapeutic options remain sub-optimal. The Fibroblast growth factor receptors (FGFRs) are oncogenic transmembrane tyrosine kinase receptors. FGFR inhibitors have been approved for the treatment of various cancers and a STAT3-dependent regulation of FGFR4 has been documented in the H.pylori infected intestinal GC. Therefore, the modulation of FGFR4 might be useful for the treatment of GC.

Methods

To investigate wich factors could modulate FGFR4 signalling in GC, we employed RNA-seq analysis on GC patients biopsies, human patients derived organoids (PDOs) and cancer cell lines.

Results

We report that FGFR4 expression/function is regulated by the leukemia inhibitory factor (LIF) an IL-6 related oncogenic cytokine, in JAK1/STAT3 dependent manner. The transcriptomic analysis revealed a direct correlation between the expression of LIFR and FGFR4 in the tissue of an exploratory cohort of 31 GC and confirmed these findings by two external validation cohorts of GC. A LIFR inhibitor (LIR-201) abrogates STAT3 phosphorylation induced by LIF as well as recruitment of pSTAT3 to the promoter of FGFR4. Furthermore, inhibition of FGFR4 by roblitinib or siRNA abrogates STAT3 phosphorylation and oncogentic effects of LIF in GC cells, indicating that FGFR4 is a downstream target of LIF/LIFR complex. Treating cells with LIR-201 abrogates oncogenic potential of FGF19, the physiological ligand of FGFR4.

Conclusions

Together these data unreveal a previously unregnized regulatory mechanism of FGFR4 by LIF/LIFR and demonstrate that LIF and FGF19 converge on the regulation of oncogenic STAT3 in GC cells.

Graphical abstract
Orchestration of inflammation in contact allergy by innate immune and cellular stress responses
Authors: Martin Stefan F. , Rühl-Muth Anne-Catherine , Esser Philipp R.
Published: November 2023

Background

Inflammation is central to the initiation of immune responses and to the pathogenesis of many diseases such as allergic contact dermatitis (ACD). ACD is an inflammatory skin disease caused by low molecular weight organic chemicals and metal ions. The immune system plays a decisive role. After protein binding, the triggering chemicals act as contact allergens that are recognized by specific T cells. Before this can happen, however, the chemicals must trigger inflammation in the skin, without which the adaptive immune system in particular is not activated.

Methods

In recent years, the inflammatory mechanisms of contact allergy have been studied at the cellular and molecular level in vivo and in vitro.

Results

Contact allergens activate the innate immune system and additionally cellular stress responses, which in interaction are responsible for skin inflammation. In this context, inflammation is required for both initial sensitization and elicitation of ACD.

Conclusion

Skin inflammation in ACD is orchestrated by the interplay of the innate immune system and cellular stress responses.
Healing and Meaning Making Through Storytelling and Poetry
Authors: Joranger Line
Published: November 2023

The article highlights the way storytelling and poetry can heal a worried mind and make sense of life events. Three main focuses will be presented and discussed. First is the nature and quality of storytelling and how it relates to meaning making and life events. Second is the healing power and freedom of the words used in poetry. Third is storytelling and poetry as imagination and everyday experiences. The relationship between meaning making and storytelling is something neither determined by innate biological drives nor solely created in the individual mind. To speak of meaning making in first-person narratives, one must include the concepts of culture, politics, history, and living in the world with others. By weaving concepts from the field of art, philosophy, history, psychology, sociology, and anthropology, the manuscript shows how storytelling and poetry deal with experiences and emotions that affect our understanding of life events. First-person narratives guide us back to people’s everyday experiences and let us understand human experiences and meaning making in the way that they are seamlessly lived. Meaning making and storytelling are universal cultural activities that we need to understand to communicate and understand oneself and others.
Fabrication and investigation of agricultural monitoring system with IoT & AI
Authors: Indira P. , Arafat I. Sheik , Karthikeyan R. , Selvarajan Shitharth , Balachandran Praveen Kumar
Published: November 2023

Artificial intelligence (AI) can be used in a variety of fields and has the potential to alter how we currently view farming. Due to its emphasis on effectiveness and usability artificial intelligence has the largest impact on agriculture of all industries. We highlight the automation-supporting technologies such as Artificial Intelligence (AI), Machine Learning, and Long-Range (LoRa) technology which provides data integrity and protection. We also offer a structure for smart farming that depends on the location of data processing after a comprehensive investigation of numerous designs. As part of our future study we have divided the unresolved difficulties in smart agriculture into two categories such as networking issues and technology issues. Artificial Intelligence and Machine Learning are examples of technologies whereas the Moderate Resolution Imaging Spectroradiometer satellite and LoRa are used for all network-related jobs. The goal of the research is to deploy a network of sensors throughout agricultural fields to gather real-time information on a variety of environmental factors including temperature, humidity, soil moisture and nutrient levels. The seamless data transmission and communication made possible by these sensors’ integration with Internet of Things technologies. With the use of AI techniques and algorithms the gathered data is examined. The technology may offer practical insights and suggestions for improving agricultural practices because the AI models are trained to spot patterns, correlations, and anomalies in the data. We are also focusing on indoor farming by supplying Ultra Violet radiation and artificial lighting in accordance with plant growth. When a pest assault is detected using AI and LoRa even in poor or no network coverage area and notifies the farmer’s mobile in any part of the world. The irrigation system is put to the test with various plants at various humidity and temperature levels in both dry and typical situations. To keep the water content in those specific regions soil moisture sensors are used.
Institutional Challenges at the Early Stages of Development
Authors: Bourguignon François , Platteau Jean-Philippe
Published: November 2023

Despite strong interest in the role of institutions; methods of operation, underlying political forces and their precise nature are still misunderstood. Partial analysis of specific aspects of public interventions simplified historical examples, or rough cross-country relationships tend to be the main guides to policy recommendations. Along with four in-depth country studies, published in companion volumes, Institutional Challenges at the Early Stages of Development gives a thorough review of the experiences of South Korea and Taiwan, offering a new perspective for identifying critical institutional issues. Including those related to state-business relations and the economic structure, and its transformation, analytical tools and concept are provided to help diagnose important hurdles at the early stage of a country's development. This title is also available as Open Access.
Lexical Reconstruction in Central Chadic
Authors: Wolff H. Ekkehard
Published: November 2023

Due to a long history of contact, the Chadic languages are the internally most diverse of the Afroasiatic language families, especially in terms of their sound systems. In this ground-breaking study, the author draws on his extensive research experience to unpack the morpho-phonological principles that underpin the languages' diverse prosody effects, arguing that massive variation results from diachronic processes called 'prosodification' of segmental units. The study compares data from 66 of the 79 known languages from the Central branch of the Chadic language family, most of them unwritten and under-researched. It traces language changes for 228 lexical items that can be reconstructed from the proto-language's basic vocabulary, unearthing typological features that link Central Chadic to its deep Afroasiatic heritage. It is accompanied by a set of online appendixes, providing the full analytical apparatus of all lexical reconstructions, with explicit identification of each of the diachronic sound changes and processes involved.
Strategic Foresight and Policy Evaluation: Insights for an Integrated Approach
Authors: De Vito Laura , Taffoni Gaia
Published: November 2023

Grand challenges are shaping twenty-first-century politics. Threats connected to health, climate, demographics and welfare are increasingly intruding on the lives of citizens. Still, governments are often found off-guard, and policymakers need strategies grounded in longer-term perspectives. Strategic foresight (SF) helps us to design and shape policies to prepare to withstand shocks, anticipating and adapting to changes. However, as governments work towards embedding SF into their policymaking processes, the empirical evidence suggests that applications are still piecemeal and predominantly limited to the agenda-settings and policy formulation stages. In this article, we argue that to drive anticipatory governance, foresight needs to be applied at all stages of the policy cycle, including in evaluating policies to draw lessons for future interventions. We maintain that considering SF systemically throughout the policymaking cycle, from agenda setting to evaluation, strengthens anticipatory governance.
Subglottic stenosis—instrumentation and documentation
Authors: Bull P. D.
Published: November 2023

Historically, tracheostomy has been performed from about the first
century, and instruments were devised to carry out such a procedure. Relief
of airway obstruction was later facilitated by instruments to perforate the
cricothyroid membrane and at the turn of the century, O'Dwyer introduced an
instrument to allow blind intubation of the larynx with a metal cannula.
Direct visualization of the larynx for the purposes of diagnosis and
treatment was effectively delayed until general anaesthesia became
available, and early laryngoscopes and bronchoscopes were hampered by poor
illumination and difficulty in maintaining oxygenation. The invention of
fibreoptic lighting overcame the former problem to a large degree, but easy
maintenance of oxygenation and anesthesia during bronchoscopy has been
revolutionized by the invention of rigid ventilating bronchoscopes.
Speech and language development in children with acquired subglottic
stenosis
Authors: Sell Debbie , MacCurtain Frances
Published: November 2023

Most children with acquired subglottic stenosis require a tracheostomy.
This paper describes the communication skills of children with
tracheostomies before and after decannulation.

There are also a small number of children with acquired subglottic
stenosis who do not require a tracheostomy. They are rarely referred for
speech therapy. Quiney et al. (1986) in a
retrospective review described this group as all having normal speech
development. It should be noted, however, that the lack of comment of a
speech delay in the medical notes is inconclusive. Unless there is an
ongoing study with a speech therapist routinely assessing the speech and
language development of this group, one cannot conclude categorically that
this group is always free of problems in their speech development.
Staging Theatre Historiography: The Afterlives of Ottoman Armenian Drama in Contemporary Turkish Public Theatre
Authors: YILDIRIM ŞEYDA NUR
Published: November 2023

In the last twenty years, memory has gained broader attention in Turkey's social, cultural and political arena. In line with this movement, independent and subsidized theatres produced plays engaging with Armenian history through diverse political and aesthetic agendas. Among these works, public and state theatre productions remained mostly invisible in theatre scholarship due to their ambiguous position that does not directly align with the framework of political theatre. This article examines the adaptation of the Ottoman Armenian playwright Hagop Baronian's Adamnapuyj aravelyan (1868) as Şark Dişçisi (The Oriental Dentist) (2011) by the Istanbul Metropolitan Municipality City Theatres (İBBŞT). While promoting confrontation with the past, Şark Dişçisi eliminates the crucial political insights of its source text and their ramifications for contemporary demands for historical justice regarding the 1915 Armenian Genocide. The intersection of revisionist theatre historiography and broader political dynamics in the adaptation process reveals the ambivalences of post-Genocide memory work in Turkey.
Conservation, uncertainty and intellectual humility
Authors: Michaels Sarah , Auld Graeme , Cooke Steven J , Young Nathan , Bennett Joseph R , Vermaire Jesse C
Published: November 2023

Interventions in environmental conservation are intended to make things better, not worse. Yet unintended and unanticipated consequences plague environmental conservation; key is how uncertainty plays out. Insights from the intellectual humility literature offer constructive strategies for coming to terms with uncertainty. Strategies such as self-distancing and self-assessment of causal complexity can be incorporated into conservation decision-making processes. Including reflection on what we know and do not know in the decision-making process potentially reduces unintended and unanticipated consequences of environmental conservation and management decisions. An important caution is not to have intellectual humility legitimate failing to act in the face of uncertainty.
Automated VR therapy for improving positive self-beliefs and psychological well-being in young patients with psychosis: a proof of concept evaluation of Phoenix VR self-confidence therapy
Authors: Freeman Daniel , Freeman Jason , Ahmed Memoona , Haynes Phoebe , Beckwith Helen , Rovira Aitor , Lages Miguel Andre , Ward Rupert , Bousfield Matthew , Riffiod Ludovic , Kabir Thomas , Waite Felicity , Rosebrock Laina
Published: November 2023

Background:

Low self-confidence in patients with psychosis is common. This can lead to higher symptom severity, withdrawal from activities, and low psychological well-being. There are effective psychological techniques to improve positive self-beliefs but these are seldom provided in psychosis services. With young people with lived experience of psychosis we developed a scalable automated VR therapy to enhance positive-self beliefs.

Aims:

The aim was to conduct a proof of concept clinical test of whether the new VR self-confidence therapy (Phoenix) may increase positive self-beliefs and psychological well-being.

Method:

Twelve young patients with non-affective psychosis and with low levels of positive self-beliefs participated. Over 6 weeks, patients were provided with a stand-alone VR headset so that they could use Phoenix at home and were offered weekly psychologist meetings. The outcome measures were the Oxford Positive Self Scale (OxPos), Brief Core Schema Scale, and Warwick-Edinburgh Well-being Scale (WEMWBS). Satisfaction, adverse events and side-effects were assessed.

Results:

Eleven patients provided outcome data. There were very large end-of-treatment improvements in positive self-beliefs (OxPos mean difference = 32.3; 95% CI: 17.3, 47.3; Cohen’s d=3.0) and psychological well-being (WEMWBS mean difference = 11.2; 95% CI: 8.0, 14.3; Cohen’s d=1.5). Patients rated the quality of the VR therapy as: excellent (n=9), good (n=2), fair (n=0), poor (n=0). An average of 5.3 (SD=1.4) appointments were attended.

Conclusions:

Uptake of the VR intervention was high, satisfaction was high, and side-effects extremely few. There were promising indications of large improvements in positive self-beliefs and psychological well-being. A randomized controlled clinical evaluation is warranted.
Three visions of the global: global international relations, global history, global historical sociology
Authors: Barnett Michael , Lawson George
Published: November 2023

Global international relations (IR) generates space for theoretical expressions drawn from outside the experiences of the modern West. Alongside these demands for theoretical pluralism can be found a concern for widening IR's historical frames of reference. Yet, to date, the relationship between global IR and history is the least developed part of the project's agenda. This article suggests two ways in which this relationship can be strengthened. One draws from global history, shows how transboundary connections and relational dynamics forge the units used by advocates of global IR in their analysis: West and non-West, core and periphery, metropole and colony. The other draws from global historical sociology as it advances the role of power asymmetries for understanding the patterns and entanglements in transboundary connections. Connecting global IR to global history and global historical sociology can help produce a fuller understanding of the interactive connections and asymmetrical entanglements between peoples, places, ideas, and institutions that drive historical development. We illustrate this potential through a brief analysis of the rise of the West. This, in turn, demonstrates the ways in which three visions of the global – global IR, global history, and global historical sociology – can be mutually beneficial.
Characterizing Performance of Freshwater Wetland Methane Models Across Time Scales at FLUXNET‐CH4 Sites Using Wavelet Analyses
Authors: Zhang Zhen , Bansal Sheel , Chang Kuang‐Yu , Fluet‐Chouinard Etienne , Delwiche Kyle , Goeckede Mathias , Gustafson Adrian , Knox Sara , Leppänen Antti , Liu Licheng , Liu Jinxun , Malhotra Avni , Markkanen Tiina , McNicol Gavin , Melton Joe R. , Miller Paul A. , Peng Changhui , Raivonen Maarit , Riley William J. , Sonnentag Oliver , Aalto Tuula , Vargas Rodrigo , Zhang Wenxin , Zhu Qing , Zhu Qiuan , Zhuang Qianlai , Windham‐Myers Lisamarie , Jackson Robert B. , Poulter Benjamin
Published: November 2023

Process‐based land surface models are important tools for estimating global wetland methane (CH4) emissions and projecting their behavior across space and time. So far there are no performance assessments of model responses to drivers at multiple time scales. In this study, we apply wavelet analysis to identify the dominant time scales contributing to model uncertainty in the frequency domain. We evaluate seven wetland models at 23 eddy covariance tower sites. Our study first characterizes site‐level patterns of freshwater wetland CH4 fluxes (FCH4) at different time scales. A Monte Carlo approach was developed to incorporate flux observation error to avoid misidentification of the time scales that dominate model error. Our results suggest that (a) significant model‐observation disagreements are mainly at multi‐day time scales (<15 days); (b) most of the models can capture the CH4 variability at monthly and seasonal time scales (>32 days) for the boreal and Arctic tundra wetland sites but have significant bias in variability at seasonal time scales for temperate and tropical/subtropical sites; (c) model errors exhibit increasing power spectrum as time scale increases, indicating that biases at time scales <5 days could contribute to persistent systematic biases on longer time scales; and (d) differences in error pattern are related to model structure (e.g., proxy of CH4 production). Our evaluation suggests the need to accurately replicate FCH4 variability, especially at short time scales, in future wetland CH4 model developments.
An Ensemble Machine Learning Approach for Tropical Cyclone Localization and Tracking From ERA5 Reanalysis Data
Authors: Accarino Gabriele , Donno Davide , Immorlano Francesco , Elia Donatello , Aloisio Giovanni
Published: November 2023

Tropical Cyclones (TCs) are counted among the most destructive phenomena that can be found in nature. Every year, globally an average of 90 TCs occur over tropical waters, and global warming is making them stronger and more destructive. The accurate localization and tracking of such phenomena have become a relevant and interesting area of research in weather and climate science. Traditionally, TCs have been identified in large climate data sets through the use of deterministic tracking schemes that rely on subjective thresholds. This study presents a Machine Learning (ML) ensemble approach for locating TCs center coordinates. The ensemble combines TCs center estimates of different ML models that agree about the presence of a TC in input data. ERA5 reanalysis data was used for model training and testing jointly with the International Best Track Archive for Climate Stewardship (IBTrACS) records. Compared to single models estimates, the ML ensemble approach was able to improve TCs localization in terms of Euclidean Distance with respect to the observed TCs locations from IBTrACS. Moreover, a hybrid tracking scheme was defined: starting from the individual TC center locations detected by the ML ensemble approach, a deterministic tracking algorithm was used for reconstructing TC trajectories. The hybrid tracking scheme was then compared with four deterministic trackers reported in literature, achieving a Probability of Detection and a False Alarm Rate of 71.49% and 23%, respectively, over 40 years of reanalysis data.
Future Supercontinent Will Be Inhospitable for Mammals
Authors: Owen Rebecca
Published: November 2023

Pangea returns in 250 million years, and it’s not looking good for us.
Silica‐Bearing Mounds and Strata in the Southwest Melas Basin, Valles Marineris, Mars: Evidence for a Hydrothermal Origin
Authors: Rogers Emma R. , Qualizza Briar R. , Heidenreich Joseph R. , Dawson Henry G. , Horgan Briony H. N.
Published: November 2023

A small basin on the Southwest (SW) margin of Melas Chasma in Valles Marineris, Mars, hosts a variety of previously identified sedimentary fans and layered strata hypothesized to have been formed by one or more paleolakes. This basin also contains light‐toned layered mounds that have distinct spectral absorption bands consistent with amorphous hydrated silica (e.g., opal). While the general morphology and mineralogy of these features and the basin itself have been previously characterized, the formation mechanism of the hydrated silica features and their temporal relationships with the proposed paleolake remain to be determined. We use Compact Reconnaissance Imaging Spectrometer for Mars visible through short‐wave infrared reflectance spectra (0.35–2.65 μm) and High Resolution Imaging Science Experiment digital terrain models and images to analyze the stratigraphic location and morphology of the opaline silica‐bearing features in the SW Melas basin. We find that the basin hosts fourteen high‐relief “mounds,” eight low‐relief “patches,” and two extended layers within the sedimentary strata that are light‐toned, fractured, and often exhibit hydrated silica‐like spectral signatures. We hypothesize that the mounds are spring deposits formed by sub‐aerial hydrothermal activity, while the patches and layers correspond to sub‐lacustrine hydrothermal activity. The varied elevations of the mounds and patches indicate at least one fluctuation of lake level in the basin during its history. The combination of contemporaneous hydrothermal and lacustrine activity to form silica‐cemented sedimentary deposits in a nutrient‐rich subaqueous environment would have been conducive to forming and preserving biosignatures in the SW Melas basin.
Late Pleistocene Evolution of Tides and Tidal Dissipation
Authors: Wilmes S.‐B. , Pedersen V. K. , Schindelegger M. , Green J. A. M.
Published: November 2023

Studies of the Last Glacial Maximum (LGM; 26.5–19 ka) tides showed strong enhancements in open ocean tidal amplitudes and dissipation rates; however, changes prior to the LGM remain largely unexplored. Using two different ice sheet and sea level reconstructions, we explicitly simulate the evolution of the leading semi‐diurnal and diurnal tidal constituents (M2, S2, K1, and O1) over the last glacial cycle with a global tide model. Both sets of simulations show that global changes, dominated by the Atlantic, take place for the semi‐diurnal constituents, while changes for the diurnal constituents are mainly regional. Irrespective of the reconstruction, open ocean dissipation peaks during the sea level lowstands of MIS 2 (∼20 ka) and MIS 4 (∼60 ka), although dissipation values prior to MIS 2 are sensitive to differences in reconstructed ice sheet extent. Using the statistically significant relationship between global mean sea level and dissipation, we apply regression analysis to infer open ocean and shelf dissipation, respectively, over the last four glacial cycles back to 430 ka. Our analysis shows that open ocean tidal energy was probably increased for most of this period, peaking during glacial maxima, and returning to near‐present‐day values during interglacials. Due to tidal resonance during glacial phases, small changes in bathymetry could have caused large changes in tidal amplitudes and dissipation, emphasizing the need for accurate ice margin reconstructions. During glacial phases, once global mean sea level decreased by more than ∼100 m, the amount of open ocean tidal energy available for ocean mixing approximately doubled.
Low-noise fluorescent detection of cardiac troponin I in human serum based on surface acoustic wave separation
Authors: Chen Xuan , Zhang Chuanyu , Liu Xianglian , Dong Yangchao , Meng Hao , Qin Xianming , Jiang Zhuangde , Wei Xueyong
Published: November 2023

Acute myocardial infarction (AMI) is a life-threatening disease when sudden blockage of coronary artery occurs. As the most specific biomarker, cardiac troponin I (cTnI) is usually checked separately to diagnose or eliminate AMI, and achieving the accurate detection of cTnI is of great significance to patients’ life and health. Compared with other methods, fluorescent detection has the advantages of simple operation, high sensitivity and wide applicability. However, due to the strong fluorescence interference of biological molecules in body fluids, it is often difficult to obtain high sensitivity. In order to solve this problem, in this study, surface acoustic wave separation is designed to purify the target to achieve more sensitive detection performance of fluorescent detection. Specifically, the interference of background noise is almost completely removed on a microfluidic chip by isolating microbeads through acoustic radiation force, on which the biomarkers are captured by the immobilized detection probe. And then, the concentration of cTnI in human serum is detected by the fluorescence intensity change of the isolated functionalized beads. By this way, the detection limit of our biosensor calculated by 3σ/K method is 44 pg/mL and 0.34 ng/mL in PBS buffer and human serum respectively. Finally, the reliability of this method has been validated by comparison with clinical tests from the nephelometric analyzer in hospital.
Fabrication of 3D-printed molds for polydimethylsiloxane-based microfluidic devices using a liquid crystal display-based vat photopolymerization process: printing quality, drug response and 3D invasion cell culture assays
Authors: Poskus Matthew D. , Wang Tuo , Deng Yuxuan , Borcherding Sydney , Atkinson Jake , Zervantonakis Ioannis K.
Published: November 2023

Microfluidic platforms enable more precise control of biological stimuli and environment dimensionality than conventional macroscale cell-based assays; however, long fabrication times and high-cost specialized equipment limit the widespread adoption of microfluidic technologies. Recent improvements in vat photopolymerization three-dimensional (3D) printing technologies such as liquid crystal display (LCD) printing offer rapid prototyping and a cost-effective solution to microfluidic fabrication. Limited information is available about how 3D printing parameters and resin cytocompatibility impact the performance of 3D-printed molds for the fabrication of polydimethylsiloxane (PDMS)-based microfluidic platforms for cellular studies. Using a low-cost, commercially available LCD-based 3D printer, we assessed the cytocompatibility of several resins, optimized fabrication parameters, and characterized the minimum feature size. We evaluated the response to both cytotoxic chemotherapy and targeted kinase therapies in microfluidic devices fabricated using our 3D-printed molds and demonstrated the establishment of flow-based concentration gradients. Furthermore, we monitored real-time cancer cell and fibroblast migration in a 3D matrix environment that was dependent on environmental signals. These results demonstrate how vat photopolymerization LCD-based fabrication can accelerate the prototyping of microfluidic platforms with increased accessibility and resolution for PDMS-based cell culture assays.
Shallow whole genome sequencing approach to detect Homologous Recombination Deficiency in the PAOLA-1/ENGOT-OV25 phase-III trial
Authors: Callens Celine , Rodrigues Manuel , Briaux Adrien , Frouin Eleonore , Eeckhoutte Alexandre , Pujade-Lauraine Eric , Renault Victor , Stoppa-Lyonnet Dominique , Bieche Ivan , Bataillon Guillaume , Karayan-Tapon Lucie , Rochelle Tristan , Heitz Florian , Cecere Sabrina Chiara , Pérez Maria Jesús Rubio , Grimm Christoph , Nøttrup Trine Jakobi , Colombo Nicoletta , Vergote Ignace , Yonemori Kan , Ray-Coquard Isabelle , Stern Marc-Henri , Popova Tatiana
Published: November 2023

The bevacizumab (bev)/olaparib (ola) maintenance regimen was approved for BRCA1/2-mutated (BRCAmut) and Homologous Recombination Deficient (HRD) high-grade Advanced Ovarian Cancer (AOC) first line setting, based on a significantly improved progression-free survival (PFS) compared to bev alone in the PAOLA-1/ENGOT-ov25 trial (NCT02477644), where HRD was detected by MyChoice CDx PLUS test. The academic shallowHRDv2 test was developed based on shallow whole-genome sequencing as an alternative to MyChoice. Analytical and clinical validities of shallowHRDv2 as compared to MyChoice on 449 PAOLA-1 tumor samples are presented. The overall agreement between shallowHRDv2 and MyChoice was 94% (369/394). Less non-contributive tests were observed with shallowHRDv2 (15/449; 3%) than with MyChoice (51/449; 11%). Patients with HRD tumors according to shallowHRDv2 (including BRCAmut) showed a significantly prolonged PFS with bev+ola versus bev (median PFS: 65.7 versus 20.3 months, hazard ratio (HR): 0.36 [95% CI: 0.24–0.53]). This benefit was significant also for BRCA1/2 wild-type tumors (40.8 versus 19.5 months, HR: 0.45 [95% CI: 0.26–0.76]). ShallowHRDv2 is a performant, clinically validated, and cost-effective test for HRD detection.
Coupling to octahedral tilts in halide perovskite nanocrystals induces phonon-mediated attractive interactions between excitons
Authors: Yazdani Nuri , Bodnarchuk Maryna I. , Bertolotti Federica , Masciocchi Norberto , Fureraj Ina , Guzelturk Burak , Cotts Benjamin L. , Zajac Marc , Rainò Gabriele , Jansen Maximilian , Boehme Simon C. , Yarema Maksym , Lin Ming-Fu , Kozina Michael , Reid Alexander , Shen Xiaozhe , Weathersby Stephen , Wang Xijie , Vauthey Eric , Guagliardi Antonietta , Kovalenko Maksym V. , Wood Vanessa , Lindenberg Aaron M.
Published: November 2023

Understanding the origin of electron–phonon coupling in lead halide perovskites is key to interpreting and leveraging their optical and electronic properties. Here we show that photoexcitation drives a reduction of the lead–halide–lead bond angles, a result of deformation potential coupling to low-energy optical phonons. We accomplish this by performing femtosecond-resolved, optical-pump–electron-diffraction-probe measurements to quantify the lattice reorganization occurring as a result of photoexcitation in nanocrystals of FAPbBr3. Our results indicate a stronger coupling in FAPbBr3 than CsPbBr3. We attribute the enhanced coupling in FAPbBr3 to its disordered crystal structure, which persists down to cryogenic temperatures. We find the reorganizations induced by each exciton in a multi-excitonic state constructively interfere, giving rise to a coupling strength that scales quadratically with the exciton number. This superlinear scaling induces phonon-mediated attractive interactions between excitations in lead halide perovskites.
The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions
Authors: Braxton Julian R. , Altobelli Chad R. , Tucker Maxwell R. , Tse Eric , Thwin Aye C. , Arkin Michelle R. , Southworth Daniel R.
Published: November 2023

p97, also known as valosin-containing protein, is an essential cytosolic AAA+ (ATPases associated with diverse cellular activities) hexamer that unfolds substrate polypeptides to support protein homeostasis and macromolecular disassembly. Distinct sets of p97 adaptors guide cellular functions but their roles in direct control of the hexamer are unclear. The UBXD1 adaptor localizes with p97 in critical mitochondria and lysosome clearance pathways and contains multiple p97-interacting domains. Here we identify UBXD1 as a potent p97 ATPase inhibitor and report structures of intact human p97–UBXD1 complexes that reveal extensive UBXD1 contacts across p97 and an asymmetric remodeling of the hexamer. Conserved VIM, UBX and PUB domains tether adjacent protomers while a connecting strand forms an N-terminal domain lariat with a helix wedged at the interprotomer interface. An additional VIM-connecting helix binds along the second (D2) AAA+ domain. Together, these contacts split the hexamer into a ring-open conformation. Structures, mutagenesis and comparisons to other adaptors further reveal how adaptors containing conserved p97-remodeling motifs regulate p97 ATPase activity and structure.
Visualizing software refactoring using radar charts
Authors: Al-Ghuwairi Abdel-Rahman , Al-Fraihat Dimah , Sharrab Yousef , Alrashidi Huda , Almujally Nouf , Kittaneh Ahmed , Ali Ahmed
Published: November 2023

Refactoring tools have advanced greatly and are being used in many large projects. As a result, a great deal of information is now available about past refactoring and its effects on the source code. However, when multiple refactoring is performed at once, it becomes more difficult to analyze their impact. Refactoring visualization can help developers create more maintainable code that is easier to understand and modify over time. Although there is an increasing interest in visualizing code changes in software engineering research, there has been relatively little research on visualizing the process of refactoring. In this paper, we propose a Radar Chart Refactoring Visualization (RcRV) approach to visualize software refactoring of source code across multiple software releases. Radar charts are a form of 2D visualization that can show multiple variables on a single chart. The RcRv receives input from developers or through refactoring identification tools, such as Ref-Finder, to generate charts. The generated charts can show the changes made during the refactoring process, highlighting areas of the trend of refactoring over evolution for multiple refactoring, multiple methods, and multiple classes. The evaluation study conducted to assess the usefulness of the RcRV tool has shown that the proposed tool is useful to developers, appealing, and easy to use. The proposed method of visualization can be beneficial for developers and maintainers to detect design violations and potential bugs in the code, thus saving time and effort during the development and maintenance process. Therefore, this research presents a significant contribution to the software engineering field by providing developers with an efficient tool to enhance code quality and maintainability.
Artificial axons as a biomimetic 3D myelination platform for the discovery and validation of promyelinating compounds
Authors: Jagielska Anna , Radzwill Kristin , Espinosa-Hoyos Daniela , Yang Mingyu , Kowsari Kavin , Farley Jonathan E. , Giera Stefanie , Byrne Ann , Sheng Guoqing , Fang Nicholas X. , Dodge James C. , Pedraza Carlos E. , Van Vliet Krystyn J.
Published: November 2023

Multiple sclerosis (MS), a chronic neurodegenerative disease driven by damage to the protective myelin sheath, is currently incurable. Today, all clinically available treatments modulate the immune-mediated symptoms of the disease but they fail to stop neurodegeneration in many patients. Remyelination, the regenerative process of myelin repair by oligodendrocytes, which is considered a necessary step to protect demyelinated axons and stop neuronal death, is impaired in MS patients. One of the major obstacles to finding effective remyelinating drugs is the lack of biomimetic drug screening platforms that enable quantification of compounds’ potential to stimulate 3D myelination in the physiologically relevant axon-like environment. To address this need, we built a unique myelination drug discovery platform, by expanding our previously developed technology, artificial axons (AAs), which enables 3D-printing of synthetic axon mimics with the geometry and mechanical properties closely resembling those of biological axons. This platform allows for high-throughput phenotypic myelination assay based on quantification of 3D wrapping of myelin membrane around axons in response to compounds. Here, we demonstrate quantification of 3D myelin wrapping by rat oligodendrocytes around the axon mimics in response to a small library of known pro-myelinating compounds. This assay shows pro-myelinating activity for all tested compounds consistent with the published in vitro and in vivo data, demonstrating predictive power of AA platform. We find that stimulation of myelin wrapping by these compounds is dose-dependent, providing a facile means to quantify the compounds’ potency and efficacy in promoting myelin wrapping. Further, the ranking of relative efficacy among these compounds differs in this 3D axon-like environment as compared to a traditional oligodendrocyte 2D differentiation assay quantifying area of deposited myelin membrane. Together, we demonstrate that the artificial axons platform and associated phenotypic myelin wrapping assay afford direct evaluation of myelin wrapping by oligodendrocytes in response to soluble compounds in an axon-like environment, providing a predictive tool for the discovery of remyelinating therapies.
Association of daily health behavior and activity of daily living in older adults in China
Authors: Wang Ling-Ying , Feng Mei , Hu Xiu-Ying , Tang Meng-Lin
Published: November 2023

This study aims to describe the activity of daily living (ADL) situation and determine the relationship between health behavior and ADL among older adults in China. A cross-sectional, observational study was conducted in one urban community and one rural community in Chengdu (a city located in Southwest China), China, from October 2022 to March 2023. A total of 706 older adults were included in this study. The associations between health behaviour and ADL were assessed by logistic regression model. Of the 706 older adults, 169 (23.9%) were disabled in ADL. According to the logistic regression analysis, age (60–69 years old: OR = 0.015, 95% CI 0.007 to 0.035, P < 0.001; 70–79 years old: OR = 0.116, 95% CI 0.060 to 0.227, P < 0.001), resident(OR = 0.568, 95% CI 0.330 to 0.976, P = 0.041), chronic disease (0 type: OR = 0.023, 95% CI 0.001 to 0.379, P = 0.008; 1–4 types: OR = 0.357, 95% CI 0.219 to 0.582, P < 0.001), no exercise (OR = 4.562, 95% CI 2.263 to 8.026, P < 0.001), and physical examination (OR = 2.217, 95% CI 1.294 to 3.496, P = 0.003) were significantly associated with ADL among older adults in Southwest China. This study showed that older adults had a higher ADL disability ratio. Age, resident, chronic disease, exercise and physical examination were associated with ADL among older adults. The study indicates that medium/high exercise maybe a protective factor for older adults, and nursing staff can encourage older adults to exercise when carrying out primary prevention measures. The government and public health institutions should give special attention to older adults and help them to acquire the habit of having an annual physical examination.
The effect of cuproptosis-relevant genes on the immune infiltration and metabolism of gynecological oncology by multiply analysis and experiments validation
Authors: Ran Xiao-min , Xiao Hui , Tang Yan-xiang , Jin Xia , Tang Xing , Zhang Juan , Li Hui , Li Yu-kun , Tang Zhen-zi
Published: November 2023

Gynecological cancers are a leading cause of mortality for women, including ovarian cancer (OC), cervical squamous cell carcinoma (CESC), and uterine corpus endometrial carcinoma (UCEC). Nevertheless, these gynecological cancer types have not elucidated the role of cuproptosis and the correlated tumor microenvironment (TME) infiltration features. CRGs had important potential molecular functions and prognostic significance in gynecological cancers, especially in UCEC. Hub CRG, FDX1, was correlated with the CD8+ T cell immune infiltration in UCEC and CESC. FDX1 OE could significantly repress the proliferation ability in UCEC cells by MTT, EdU, and clone formation. High levels of FDX1 could repress ATP and lactic acid but enhance ROS and glucose levels by metabolism assay. The xenograft tumor model indicated that FDX1 OE significantly inhibited the growth of UCEC and attenuated the PCNA, HK2, PKM2, and Ki-67 expression. These CRGs are significant roles that could be potential markers and treatment targets to optimize the TME immune cell infiltration features for gynecological cancer types. FDX1 is a hub CRGs in UCEC to promote immune infiltration and attenuate proliferation and metabolism.
Polarization-insensitive Archimedes’-spiral-shaped ultrathin metamaterial absorbers for microwave sensing application
Authors: Lateef Omar S. , Al-Badri Mohammed , Al-badri Khalid Saeed Lateef , Mohammed Sarah Adnan
Published: November 2023

This work has developed and simulated a planar complementary Archimedes-based metamaterial absorber with the goal of its application in refractive index sensing. Unlike designs that employ multiple layers or numerous resonators within a single unit cell, our proposed absorber adopts a more streamlined approach. It consists of three layers, with an FR4 dielectric substrate sandwiched between two copper layers. It's important to note that the absorption characteristics of this design are polarization-dependent. This polarization dependence arises from the asymmetrical resonance behavior observed in both the x and y directions. The absorber exhibits impressive absorption rates at various resonance frequencies, namely 98.5% at f1 = 8.49 GHz, 77.1% at f2 = 8.88 GHz, 88.7% at f3 = 9.3 GHz, 98.2% at f4 = 9.87 GHz, 99.7% at f5 = 10.65 GHz, 83.4% at f6 = 11.58 GHz, and 99.9% at f7 = 12.24 GHz. Furthermore, the article explored the refractive index sensing capabilities of this structure by introducing a 1 mm analyte layer on top of the patch structure. Through refractive index sensing analysis, we've determined that this absorber-based sensor yields an impressive high-quality factor value of 84.5, highlighting its remarkable sensitivity and precision. A more profound comprehension of the physical mechanisms in action has been attained by examining the distribution of surface currents. Furthermore, the behavior of the absorber has been investigated under varying polarization and incident angle conditions, ranging from zero degrees to sixty degrees. The thorough characterization establishes this absorber as a promising choice for microwave sensing applications.
Association between cigarette smoking and serum alpha klotho levels among US adults over 40-years-old: a cross-sectional study
Authors: Du Rui , Tang Xiaoyan , Jiang Meihua , Qian Shengli , Yang Li , Tong Xiaoling , Huang Wei
Published: November 2023

Alpha klotho (α-Klotho) is an anti-aging molecule associated with aging and several diseases. Previous studies have reported inconsistent levels of α-Klotho in smokers. This study aimed to demonstrate serum α-Klotho levels in smokers among the US population. This cross-sectional study recruited 11,559 participants (aged 40–79 years; 48.2% males). All data were collected from the 2007–2016 National Health and Nutrition Examination Survey. The study comprised adults with reliable Klotho and smoking questionnaire results. The relationship between smoking and serum α-klotho levels was assessed using multivariate linear regression models after adjusting for potential confounders. We also performed a stratified analysis of clinically important variables. The mean serum α-klotho level among the 11,559 participants was 843.85 pg/mL. After full adjustment, habitual smoking was significantly associated with decreased serum levels of α-klotho level (β = − 34.89; 95% CI − 54.97, − 14.81; P = 0.0013) in the total study population. Furthermore, the stratified analysis indicated that the association was insignificant in the 60–79 age group. Quitting smoking was not significantly associated with serum levels of α-klotho as expected (P = 0.1148) in the total study population. However, stratified analyses showed a significant inversed association in the male, those with chronic kidney disease, or those with cancer who quit smoking (all P < 0.05). Cigarette smoking was inversely associated with serum α-Klotho levels among US adults.
Detection of factors related to treatment reduction in docetaxel and ramucirumab for non-small cell lung cancer treatment
Authors: Saito Yoshitaka , Tamaki Shinya , Hirate Daisuke , Takada Shinya , Takahashi Kenta , Takekuma Yoh , Sakakibara-Konishi Jun , Shimizu Yasushi , Kinoshita Ichiro , Sugawara Mitsuru
Published: November 2023

Treatment using docetaxel (DOC) and ramucirumab (RAM) is an effective regimen in second or later line advanced non-small cell lung carcinoma (NSCLC) treatment. However, it induces severe adverse effects, resulting in treatment reduction such as dose reduction and/or discontinuation. This study aimed to reveal the factor(s) associated with treatment reduction in DOC + RAM. We retrospectively evaluated patients with advanced NSCLC (n = 155). Treatment reduction of the second course due to severe adverse effects was conducted in 25.8% of the participants, and relative dose intensity at the second course was 95.7 ± 8.4% for DOC and 91.9 ± 24.8% for RAM. Multivariate logistic regression analyses identified that baseline anemia and prophylactic granulocyte colony-stimulating factor (G-CSF) administration are preventive factors for the reduction (adjusted odds ratio, 0.29; 95% confidence interval, 0.12–0.66; P = 0.004 for baseline anemia, 0.18; 0.08–0.42; P < 0.0001 for prophylactic G-CSF administration). The primary cause of the reduction was febrile neutropenia, and the same factors were identified. Our study revealed that patients with baseline anemia and prophylactic G-CSF administration have less risk for treatment reduction in DOC + RAM for NSCLC treatment.