bluuebunny/crossref_metadata_2025 huggingface dataset:
A Two-Step E-Nose System for Vehicle Drunk Driving Rapid Detection
Authors: Wang Fangrong , Bai Dongsheng , Liu Zhaoyang , Yao Zongwei , Weng Xiaohui , Xu Conghao , Fan Kaidi , Zhao Zihan , Chang Zhiyong
Published: March 2023

With the rapid development of shared cars, to reduce the phenomenon of drunk driving in shared cars, we have studied the onboard drunk driving rapid detection electronic nose system suitable for shared cars. To accurately judge whether the driver is drunk while driving in the presence of interfering gases such as passenger exhalation and the volatile smell containing alcohol, this paper proposes a two-step drunk driving detection frame for shared cars that first judges whether someone in the car is drunk and then judges whether the driver is drunk. To reduce the cost and volume of the electronic nose, the sensor array was optimized based on the random forest algorithm. To find the optimal sampling time, we processed the original data by time slicing. Finally, using the two-step framework proposed by us, the accuracy of the first step and the second step of driver drunk driving detection reached 99.44% and 100%, respectively, with a sampling time of 5 s. After algorithm optimization, only 9 of the 21 sensors were left. This paper presents a practical electronic nose system for the detection of drunk driving in shared cars.
Automated Arabic Long-Tweet Classification Using Transfer Learning with BERT
Authors: Alruily Meshrif , Manaf Fazal Abdul , Mostafa Ayman Mohamed , Ezz Mohamed
Published: March 2023

Social media platforms like Twitter are commonly used by people interested in various activities, interests, and subjects that may cover their everyday activities and plans, as well as their thoughts on religion, technology, or the products they use. In this paper, we present bidirectional encoder representations from transformers (BERT)-based text classification model, ARABERT4TWC, for classifying the Arabic tweets of users into different categories. This work aims to provide an enhanced deep-learning model that can automatically classify the robust Arabic tweets of different users. In our proposed work, a transformer-based model for text classification is constructed from a pre-trained BERT model provided by the hugging face transformer library with custom dense layers. The multi-class classification layer is built on top of the BERT encoder to categorize the tweets. First, data sanitation and preprocessing were performed on the raw Arabic corpus to improve the model’s accuracy. Second, an Arabic-specific BERT model was built and input embedding vectors were fed into it. Using five publicly accessible datasets, substantial experiments were executed, and the fine-tuning technique was assessed in terms of tokenized vector and learning rate. In addition, we assessed the accuracy of various deep-learning models for classifying Arabic text.
The Differences in Transient Characteristics of Postural Control between Young and Older Adults across Four Different Postural Tasks
Authors: Kozinc Žiga , Marjanov Nika , Šarabon Nejc
Published: March 2023

Recently, the transient characteristics of postural sway have been suggested as an alternative or an improvement to traditional whole-trial analyses, possibly reflecting the sensory reweighing process. The purpose of this study was to assess if the transient characteristics of postural sway are sensitive to age and postural tasks. Twenty young adults (18–27 years old) and fifteen older adults (67–80 years old) performed parallel (eyes open and eyes closed), tandem and single-leg postural tasks for 30 s. Centre of pressure (CoP) velocity, amplitude and frequency were derived from force plate data. In addition to whole-trial estimates, we calculated the relative differences between the 1st and the 2nd (DIF_21) and the 1st and the 3rd (DIF_31) 10 s time intervals. Postural sway increased with the difficulty of the task, and the increase was more pronounced in the older adult group (p < 0.001; η2 = 0.31–0.38 for group × task interactions). Large and statistically significant age × task interactions were shown for both DIF_21 and DIF_31 for CoP anterior–posterior frequency (p < 0.001; η2 = 0.17–0.18). Possible age differences were also indicated for the transient response in CoP medial–lateral velocity in the parallel stance task. Specifically, we found an exaggerated transient response (i.e., relatively higher COP velocity in the first 10 s) in older adults compared to young adults when visual information was restored during the parallel quiet stance. This study shows the potential for an application of measures of the transient behavior of postural sway after the removal or restoration of visual information.
Performing Everydayness and Feminist Aesthetics
Authors: Gontovnik Hobrecht Monica Margarita
Published: March 2023

As a Colombian scholar and artist, the author of this essay interrogates feminist aesthetics and artistic practice in a choreographic mode; improvising to see where movement takes her. This first impulse creates the space for performing writing and opening the space of creation. The movement starts at home, immersed in everydayness, aided by poetry and the analysis of the work of three other contemporary Colombian artists who also start at home in their artistic practice. Here, home is also a reference to all the artists’ (including the author’s) place of birth: Barranquilla, Colombia. The aesthetic philosophical tradition comes into play against the backdrop of the ideas presented by Simone de Beauvoir in her seminal The Second Sex (1949), who urges women in the middle of the twentieth century, to transcend, to fight against immanence. The works of Clara Gaviria, Raisa Galofre and Jessica Sofía Mitrani accompany the author’s journey while she arrives at the realization that it all starts with the need to transcend the quotidian while using, precisely, the apparent banality of such everyday things and tasks. Through the created art objects, the author creates an essay about, around and beyond artistic feminist practice and aesthetics.
Multi-Model Ensemble Forecasts of Surface Air Temperatures in Henan Province Based on Machine Learning
Authors: Wang Tian , Zhang Yutong , Zhi Xiefei , Ji Yan
Published: March 2023

Based on the China Meteorological Administration Land Data Assimilation System (CLDAS) reanalysis data and 12–72 h forecasts of the surface (2-m) air temperature (SAT) from the European Centre for Medium-Range Weather Forecasts (ECMWF) and three numerical weather prediction (NWP) models of the China Meteorological Administration (CMA-GFS, CMA-SH, and CMA-MESO), multi-model ensemble forecasts are conducted with a convolutional neural network (CNN) and a feed-forward neural network (FNN) to improve the SAT forecast in Henan Province, China. The results show that there are large errors in the 12–72 h forecasts of SAT from the CMA, while the ECMWF outperforms the other raw NWP models, especially in eastern and southern Henan. The CNN has the best short-term forecasting skills. The difference in the geographical distribution of the CNN forecast errors is small, without any apparent large-value areas. The CNN shows its advantages in its bias correction in the mountainous region (western Henan), indicating that the CNN can capture the spatial features of the atmospheric fields and is therefore more robust in regions with varied topography. In addition, the CNN can extract data features through the convolution kernel and focus on local features; it can assimilate the local features at a higher level and obtain global features. Therefore, the CNN takes advantage of the four models in the SAT forecast and further improves the forecast skill.
Reduction in the Arctic Surface Warm Bias in the NCAR CAM6 by Reducing Excessive Low-Level Clouds in the Arctic
Authors: Bae Jungeun , Sung Hyun-Joon , Baek Eun-Hyuk , Choi Ji-Hun , Lee Hyo-Jung , Kim Baek-Min
Published: March 2023

High-latitude low clouds in the Northern winter have been known to be closely related to the Arctic surface air temperature by controlling downward longwave radiation, but Earth system models often fail to accurately simulate this relationship. In this study, we conducted a series of model experiments to examine the role of winter high-latitude low-level clouds in determining the Arctic surface temperature. Our findings show that low-level clouds play a significant role in regulating the Arctic surface temperature. We used the NCAR CAM6 model and compared the results of an unforced simulation run with those of an experiment using an empirical low-level cloud scheme to alleviate the typical overestimation of the low cloud fraction of state-of-the-art general circulation models at high latitudes. The unforced simulation exhibited excessive downward longwave radiation in the Arctic, resulting in a significant warm bias compared to reanalysis data. On the other hand, the experiment using a modified scheme more closely resembled the reanalysis data in terms of low-level cloud simulation. Overall, our study underscores the importance of accurately representing low-level clouds in high-latitude regions to reduce surface temperature bias in the model.
Design and Experiments of a Naturally-Ventilated Radiation Shield for Ground Temperature Measurement
Authors: Liu Qingquan , Jin Wei , Yang Jie , Zhu Huanan , Dai Wei
Published: March 2023

Temperature sensors may produce a measurement error of up to 1 °C because of the influence of solar radiation. In order to obtain a relatively minimal temperature error, a new temperature observation system was proposed in this paper for measuring surface air temperatures. Firstly, a radiation shield was designed with two aluminum plates, eight vents, and a multi-layer structure which is able to resist direct solar radiation, reflected radiation, and upwelling long-ware radiation, as well as ensuring the temperature sensor probe could work effectively. Then, the effect of different solar radiation intensities, wind speeds, scattered radiation intensities, long-wave radiation intensities, and underlying surface reflectivity levels on radiation error was calculated through a computational fluid dynamics (CFD) method. The mapping relationship was established between the various influencing factors and the solar radiation error. A back-propagation (BP) network algorithm was used to fit the discrete data obtained from the simulation to obtain the solar radiation error correction equation. Finally, the solar radiation error correction equation was verified. Outdoor experiments were conducted to confirm this system’s measurement accuracy. According to the experimental findings, the root-mean-square error was only 0.095 °C, which is a relatively high degree by which to reduce the temperature error. In addition, the average difference between the corrected value of the temperature observation system and the reference value was barely 0.084 °C.
An Accelerated Double-Integral ZNN with Resisting Linear Noise for Dynamic Sylvester Equation Solving and Its Application to the Control of the SFM Chaotic System
Authors: Han Luyang , He Yongjun , Liao Bolin , Hua Cheng
Published: March 2023

The dynamic Sylvester equation (DSE) is frequently encountered in engineering and mathematics fields. The original zeroing neural network (OZNN) can work well to handle DSE under a noise-free environment, but may not work in noise. Though an integral-enhanced zeroing neural network (IEZNN) can be employed to solve the DSE under multiple-noise, it may fall flat under linear noise, and its convergence speed is unsatisfactory. Therefore, an accelerated double-integral zeroing neural network (ADIZNN) is proposed based on an innovative design formula to resist linear noise and accelerate convergence. Besides, theoretical proofs verify the convergence and robustness of the ADIZNN model. Moreover, simulation experiments indicate that the convergence rate and anti-noise ability of the ADIZNN are far superior to the OZNN and IEZNN under linear noise. Finally, chaos control of the sine function memristor (SFM) chaotic system is provided to suggest that the controller based on the ADIZNN has a smaller amount of error and higher accuracy than other ZNNs.
Visual Blood, Visualisation of Blood Gas Analysis in Virtual Reality, Leads to More Correct Diagnoses: A Computer-Based, Multicentre, Simulation Study
Authors: Bergauer Lisa , Akbas Samira , Braun Julia , Ganter Michael T. , Meybohm Patrick , Hottenrott Sebastian , Zacharowski Kai , Raimann Florian J. , Rivas Eva , López-Baamonde Manuel , Spahn Donat R. , Noethiger Christoph B. , Tscholl David W. , Roche Tadzio R.
Published: March 2023

Interpreting blood gas analysis results can be challenging for the clinician, especially in stressful situations under time pressure. To foster fast and correct interpretation of blood gas results, we developed Visual Blood. This computer-based, multicentre, noninferiority study compared Visual Blood and conventional arterial blood gas (ABG) printouts. We presented six scenarios to anaesthesiologists, once with Visual Blood and once with the conventional ABG printout. The primary outcome was ABG parameter perception. The secondary outcomes included correct clinical diagnoses, perceived diagnostic confidence, and perceived workload. To analyse the results, we used mixed models and matched odds ratios. Analysing 300 within-subject cases, we showed noninferiority of Visual Blood compared to ABG printouts concerning the rate of correctly perceived ABG parameters (rate ratio, 0.96; 95% CI, 0.92–1.00; p = 0.06). Additionally, the study revealed two times higher odds of making the correct clinical diagnosis using Visual Blood (OR, 2.16; 95% CI, 1.42–3.29; p < 0.001) than using ABG printouts. There was no or, respectively, weak evidence for a difference in diagnostic confidence (OR, 0.84; 95% CI, 0.58–1.21; p = 0.34) and perceived workload (Coefficient, 2.44; 95% CI, −0.09–4.98; p = 0.06). This study showed that participants did not perceive the ABG parameters better, but using Visual Blood resulted in more correct clinical diagnoses than using conventional ABG printouts. This suggests that Visual Blood allows for a higher level of situation awareness beyond individual parameters’ perception. However, the study also highlighted the limitations of today’s virtual reality headsets and Visual Blood.
Interdisciplinary Approaches for Integrating Materials Science and Dentistry
Authors: Lin Galvin Sim Siang , Jurado Carlos A. , Afrashtehfar Kelvin I.
Published: March 2023

Dental materials science is a core course in most undergraduate dental curricula [...]
FBA-PRCC. Partial Rank Correlation Coefficient (PRCC) Global Sensitivity Analysis (GSA) in Application to Constraint-Based Models
Authors: Sorokin Anatoly , Goryanin Igor
Published: March 2023

Background: Whole-genome models (GEMs) have become a versatile tool for systems biology, biotechnology, and medicine. GEMs created by automatic and semi-automatic approaches contain a lot of redundant reactions. At the same time, the nonlinearity of the model makes it difficult to evaluate the significance of the reaction for cell growth or metabolite production. Methods: We propose a new way to apply the global sensitivity analysis (GSA) to GEMs in a straightforward parallelizable fashion. Results: We have shown that Partial Rank Correlation Coefficient (PRCC) captures key steps in the metabolic network despite the network distance from the product synthesis reaction. Conclusions: FBA-PRCC is a fast, interpretable, and reliable metric to identify the sign and magnitude of the reaction contribution to various cellular functions.
Spontaneous Mutation Rates and Spectra of Respiratory-Deficient Yeast
Authors: Tu Xinyu , Wang Fan , Liti Gianni , Breitenbach Michael , Yue Jia-Xing , Li Jing
Published: March 2023

The yeast petite mutant was first discovered in the yeast Saccharomyces cerevisiae, which shows growth stress due to defects in genes encoding the respiratory chain. In a previous study, we described that deletion of the nuclear-encoded gene MRPL25 leads to mitochondrial genome (mtDNA) loss and the petite phenotype, which can be rescued by acquiring ATP3 mutations. The mrpl25Δ strain showed an elevated SNV (single nucleotide variant) rate, suggesting genome instability occurred during the crisis of mtDNA loss. However, the genome-wide mutation landscape and mutational signatures of mitochondrial dysfunction are unknown. In this study we profiled the mutation spectra in yeast strains with the genotype combination of MRPL25 and ATP3 in their wildtype and mutated status, along with the wildtype and cytoplasmic petite rho0 strains as controls. In addition to the previously described elevated SNV rate, we found the INDEL (insertion/deletion) rate also increased in the mrpl25Δ strain, reinforcing the occurrence of genome instability. Notably, although both are petites, the mrpl25Δ and rho0 strains exhibited different INDEL rates and transition/transversion ratios, suggesting differences in the mutational signatures underlying these two types of petites. Interestingly, the petite-related mutagenesis effect disappeared when ATP3 suppressor mutations were acquired, suggesting a cost-effective mechanism for restoring both fitness and genome stability. Taken together, we present an unbiased genome-wide characterization of the mutation rates and spectra of yeast strains with respiratory deficiency, which provides valuable insights into the impact of respiratory deficiency on genome instability.
Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology
Authors: Martín-Márquez Beatriz Teresita , Sandoval-García Flavio , Corona-Meraz Fernanda Isadora , Martínez-García Erika Aurora , Sánchez-Hernández Pedro Ernesto , Salazar-Páramo Mario , Fletes-Rayas Ana Lilia , González-Inostroz Daniel , Vazquez-Del Mercado Monica
Published: March 2023

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN’s multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.
StemRegenin 1 Mitigates Radiation-Mediated Hematopoietic Injury by Modulating Radioresponse of Hematopoietic Stem/Progenitor Cells
Authors: Hwang You Jung , Shin Dong-Yeop , Kim Min-Jung , Jang Hyosun , Kim Soyeon , Yang Hyunwon , Jang Won Il , Park Sunhoo , Shim Sehwan , Lee Seung Bum
Published: March 2023

Hematopoietic injury resulting from the damage of hematopoietic stem/progenitor cells (HSPCs) can be induced by either nuclear accident or radiotherapy. Radiomitigation of HSPCs is critical for the development of medical countermeasure agents. StemRegenin 1 (SR1) modulates the maintenance and function of HSPCs under non-stress conditions. However, the impact of SR1 in radiation-induced hematopoietic injury both in vivo and in vitro remains unknown. In this study, we found that treatment with SR1 after irradiation of C57BL/6 mice significantly mitigates TBI-induced death (80% of SR1-treated mice survival vs. 30% of saline-treated mice survival) with enhanced recovery of peripheral blood cell counts, with the density and cell proliferation of bone marrow components as observed by Hematoxylin and Eosin (H&E) and Ki-67 staining. Interestingly, in vitro analysis of human HSPCs showed that SR1 enhanced the population of human HSPCs (CD34+) under both non-irradiating and irradiating conditions, and reduced radiation-induced DNA damage and apoptosis. Furthermore, SR1 attenuated the radiation-induced expression of a member of the pro-apoptotic BCL-2 family and activity of caspase-3. Overall, these results suggested that SR1 modulates the radioresponse of HSPCs and might provide a potential radiomitigator of hematopoietic injury, which contributes to increase the survival of patients upon irradiation.
The Role of ERα and ERβ in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches
Authors: Jefferi Nur Erysha Sabrina , Shamhari Asma’ ‘Afifah , Noor Azhar Nur Khayrin Zulaikha , Shin Joyce Goh Yi , Kharir Nur Annisa Mohd , Azhar Muhammad Afiq , Hamid Zariyantey Abd , Budin Siti Balkis , Taib Izatus Shima
Published: March 2023

Castration-resistant prostate cancer, or CRPC, is an aggressive stage of prostate cancer (PCa) in which PCa cells invade nearby or other parts of the body. When a patient with PCa goes through androgen deprivation therapy (ADT) and the cancer comes back or worsens, this is called CRPC. Instead of androgen-dependent signalling, recent studies show the involvement of the estrogen pathway through the regulation of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in CRPC development. Reduced levels of testosterone due to ADT lead to low ERβ functionality in inhibiting the proliferation of PCa cells. Additionally, ERα, which possesses androgen independence, continues to promote the proliferation of PCa cells. The functions of ERα and ERβ in controlling PCa progression have been studied, but further research is needed to elucidate their roles in promoting CRPC. Finding new ways to treat the disease and stop it from becoming worse will require a clear understanding of the molecular processes that can lead to CRPC. The current review summarizes the underlying processes involving ERα and ERβ in developing CRPC, including castration-resistant mechanisms after ADT and available medication modification in mitigating CRPC progression, with the goal of directing future research and treatment.
Recent Development of Advanced Fluorescent Molecular Probes for Organelle-Targeted Cell Imaging
Authors: Lu Sha , Dai Zhiqi , Cui Yunxi , Kong De-Ming
Published: March 2023

Fluorescent molecular probes are very powerful tools that have been generally applied in cell imaging in the research fields of biology, pathology, pharmacology, biochemistry, and medical science. In the last couple of decades, numerous molecular probes endowed with high specificity to particular organelles have been designed to illustrate intracellular images in more detail at the subcellular level. Nowadays, the development of cell biology has enabled the investigation process to go deeply into cells, even at the molecular level. Therefore, probes that can sketch a particular organelle’s location while responding to certain parameters to evaluate intracellular bioprocesses are under urgent demand. It is significant to understand the basic ideas of organelle properties, as well as the vital substances related to each unique organelle, for the design of probes with high specificity and efficiency. In this review, we summarize representative multifunctional fluorescent molecular probes developed in the last decade. We focus on probes that can specially target nuclei, mitochondria, endoplasmic reticulums, and lysosomes. In each section, we first briefly introduce the significance and properties of different organelles. We then discuss how probes are designed to make them highly organelle-specific. Finally, we also consider how probes are constructed to endow them with additional functions to recognize particular physical/chemical signals of targeted organelles. Moreover, a perspective on the challenges in future applications of highly specific molecular probes in cell imaging is also proposed. We hope that this review can provide researchers with additional conceptual information about developing probes for cell imaging, assisting scientists interested in molecular biology, cell biology, and biochemistry to accelerate their scientific studies.
Caloric Restriction Can Ameliorate Postoperative Cognitive Dysfunction by Upregulating the Expression of Sirt1, MeCP2 and BDNF in the Hippocampal CA1 Region of Aged C57BL/6 Mice
Authors: Wei Lan , Tao Qiang , Yao Minmin , Zhao Zhimeng , Ge Shengjin
Published: March 2023

This study aimed to investigate the impact of caloric restriction (CR) on cognitive function in aged C57BL/6 mice after surgery, as well as the underlying mechanisms. Forty 14-month-old male C57BL/6 mice were randomly assigned to the ad libitum (AL, n = 20) group and the CR (n = 20) group. After feeding for 12 weeks, they were subdivided into four groups: AL control (ALC, n = 10), AL with surgery (ALS, n = 10), CR control (CRC, n = 10), and CR with surgery (CRS, n = 10). The Morris Water Maze (MWM) test was used to assess learning and memory capacity. By using western blot and immunofluorescence, the expression of Sirt1, MeCP2, and BDNF in the hippocampus and hippocampal CA1 region was quantified. According to the behavioral test, the CRC and CRS groups had significantly better learning and memory abilities than the ALC and ALS groups, respectively. Sirt1, MeCP2, and BDNF expression in the hippocampus and CA1 region in the hippocampus of the ALC and CRC groups of mice were correlated with cognitive improvement. In conclusion, CR could enhance the postoperative cognitive function in aged mice, most likely by increasing the expression of Sirt1, MeCP2, and BDNF in the CA1 region of the hippocampus.
Numerical Study of Smoke Distribution in Inclined Tunnel Fire Ventilation Modes Considering Traffic Conditions
Authors: Tung Po-Wei , Chung Hung-Chieh , Kawabata Nobuyoshi , Seike Miho , Hasegawa Masato , Chien Shen-Wen , Shen Tzu-Sheng
Published: March 2023

Japan and Europe have adopted significantly different ventilation modes with regard to traffic conditions (with or without congestion). This study focuses on the smoke behavior of different ventilation modes by conducting a 3D CFD analysis of smoke distribution and CO concentration variation and then comparing these modes based on two groups (relatively low target velocity: 0 and 1 m/s; relatively high target velocity: 2 and 3 m/s). The considered fire size is 30 MW for four longitudinal gradients (0, 2, 4, and 6%). In the simulation results, velocities of both 0 and 1 m/s reveal good performance in maintaining the stratification of smoke and ensuring the safety of the environment in 10 min in the occurrence of traffic jams. However, in 15 min, the smoke conditions change. Thus, it is difficult to distinguish which ventilation mode (0 and 1 m/s) shows relatively better performance during traffic congestion. When traffic is uncongested, the comparison of Um = 2 and 3 m/s reveals that a target velocity of Um = 2 m/s (lower than critical velocity) can also prevent the risk of smoke on the upstream side because no descending phenomenon is observed. Moreover, Um = 2 m/s causes the relatively slow propagation of descending smoke, increasing the possibility of evacuation once a second traffic incident occurs on the downstream side of the fire source.
A Grammar-Based Approach for Generating Spatial Layout Solutions for the Adaptive Reuse of Sobrado Buildings
Authors: Paulino Daniele M. S. , Ligler Heather , Napolitano Rebecca
Published: March 2023

This research develops a shape grammar to generate solutions for the adaptive reuse of historic buildings. More precisely, it proposes a transformation grammar for sobrado buildings, a typology present in the historic center of São Luís, Brazil. The methodology defines a workflow for adapting sobrado buildings, once characterized for single-families, into multi-family apartments considering spatial and structural requirements. The grammar specifies a framework for repurposing historic buildings into social housing and considers the allocation of three types of apartments in the floor plan: studios, one-bedroom apartments, and two-bedroom apartments. The adopted strategy for spatial planning prioritizes access to natural daylight. The grammar supports different layout solutions for the same building and aims to accelerate the reuse of historic structures for contemporary housing needs. This paper describes the grammar rules and their application to three case study buildings.
Introducing Matrix for the Reprogramming of Mass Housing Neighbourhoods (MHN) Based on EU Design Taxonomy: The Observatory Case of Serbia
Authors: Milovanović Aleksandra , Nikezić Ana , Ristić Trajković Jelena
Published: March 2023

This article addresses the contemporary framework of housing at the EU level in the era of the ‘Housing at the Centre’ approach. More specifically, the research focuses on mass housing neighbourhoods (MHN) as the leading pattern of urban transformation in European cities in the second half of the 20th century, with the intention being to decode the possibilities for its rehabilitation in line with integrated approaches. The article combines (1) a review-based and systematically-oriented approach, in order to provide a state of the art of EU design taxonomy related to the housing issue, and, more specifically, related to MHN, with (2) a comparative study between EU and national design taxonomies, in order to address their conditionality and possible mismatches. The research considers design taxonomy to gain a more comprehensive insight into the content and coherence between programme values and the relevant EU documents (declarations, statements, policy positions, resolutions, reports, communications, charters, action plans, opinions) related to the housing issue, or broader urban issues that include housing as the scope of observation. The taxonomy enables a conceptual methodological framework for a systematic, consistent, and complete description of key research relations. Accordingly, the specific objective of this article is to establish an evaluation framework for reprogramming of MHN based on the EU design taxonomy through (1) the development of the programming matrix for evaluation, which corresponds to the value-based architectural programming model; and (2) introducing Serbian national design taxonomy, in order to demonstrate the anticipation of design values based on the EU taxonomy within the local context. The results indicate the need to examine and test regulatory experimental settings through middle-out approaches, whose central research perspective will be built parallel and coherently through bottom-up inputs, created as the result of collaborative approaches at the community level, and top-down inputs which are the result of the strategic framework established in relation to priorities at the European level.
Skin Toxicity as a Predictor of Survival in Metastatic Colorectal Cancer Patients Treated with Anti-EGFR: Fact or Fallacy?
Authors: Chiang Ting-Yu , Hsu Hung-Chih , Chern Yih-Jong , Liao Chun-Kai , Hsu Yu-Jen , Tsai Wen-Sy , Hsieh Pao-Shiu , Lin Yu-Fen , Lee Hsiu-Lan , You Jeng-Fu
Published: March 2023

The primary treatment for metastatic colorectal cancer (mCRC) consists of targeted therapy and chemotherapy to improve survival. A molecular target drug with an anti-epidermal growth factor receptor (EGFR) antagonist is recommended when the RAS and BRAF genes are normal. About 50–70% of patients using anti-EGFR antagonists will experience skin reactions. Some studies have shown that severe skin reactions caused by anti-EGFR antagonists may be linked to overall survival (OS) and progression-free survival (PFS), but the results are still uncertain. These data of mCRC patients who underwent anti-EGFR therapy between October 2017 and October 2018 were analyzed retrospectively. A total of 111 patients were included in this study. The survival results showed that gender, age, body mass index, primary tumor site, and recurrence did not significantly affect OS and PFS. However, the first-line anti-EGFR inhibitor treatment was significantly associated with OS (p < 0.001) and PFS (p < 0.001). There was no significant difference in the incidence of acne between males and females in grades 1 and 2, while males have a greater risk in grades 3 and 4 than females (20.3 vs. 4.8%; p-value = 0.041). Skin toxicity was not a predictor of anti-EGFR treatment response in this investigation.
Demographic and Clinical Features of Patients with Metastatic Breast Cancer: A Retrospective Multicenter Registry Study of the Turkish Oncology Group
Authors: Dogan Izzet , Aksoy Sercan , Cakar Burcu , Basaran Gul , Ercelep Ozlem , Molinas Mandel Nil , Korkmaz Taner , Gokmen Erhan , Sener Cem , Aydiner Adnan , Saip Pinar , Eralp Yesim
Published: March 2023

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0–55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.
The Role of Type 2 Diabetes in Patient Symptom Attribution, Help-Seeking, and Attitudes to Investigations for Colorectal Cancer Symptoms: An Online Vignette Study
Authors: Smith Lauren , Von Wagner Christian , Kaushal Aradhna , Rafiq Meena , Lyratzopoulos Georgios , Renzi Cristina
Published: March 2023

Objectives: Type 2 diabetes is associated with a higher risk of colorectal cancer (CRC) and advanced-stage cancer diagnosis. To help diagnose cancer earlier, this study aimed at examining whether diabetes might influence patient symptom attribution, help-seeking, and willingness to undergo investigations for possible CRC symptoms. Methods: A total of 1307 adults (340 with and 967 without diabetes) completed an online vignette survey. Participants were presented with vignettes describing new-onset red-flag CRC symptoms (rectal bleeding or a change in bowel habits), with or without additional symptoms of diabetic neuropathy. Following the vignettes, participants were asked questions on symptom attribution, intended help-seeking, and attitudes to investigations. Results: Diabetes was associated with greater than two-fold higher odds of attributing changes in bowel habits to medications (OR = 2.48; 95% Cl 1.32–4.66) and of prioritising diabetes-related symptoms over the change in bowel habits during medical encounters. Cancer was rarely mentioned as a possible explanation for the change in bowel habits, especially among diabetic participants (10% among diabetics versus 16% in nondiabetics; OR = 0.55; 95% CI 0.36–0.85). Among patients with diabetes, those not attending annual check-ups were less likely to seek help for red-flag cancer symptoms (OR = 0.23; 95% Cl 0.10–0.50). Conclusions: Awareness of possible cancer symptoms was low overall. Patients with diabetes could benefit from targeted awareness campaigns emphasising the importance of discussing new symptoms such as changes in bowel habits with their doctor. Specific attention is warranted for individuals not regularly attending healthcare despite their chronic morbidity.
Release of Interferon-β (IFN-β) from Probiotic Limosilactobacillus reuteri-IFN-β (LR-IFN-β) Mitigates Gastrointestinal Acute Radiation Syndrome (GI-ARS) following Whole Abdominal Irradiation
Authors: Hamade Diala F. , Epperly Michael W. , Fisher Renee , Hou Wen , Shields Donna , van Pijkeren Jan-Peter , Mukherjee Amitava , Yu Jian , Leibowitz Brian J. , Vlad Anda M. , Coffman Lan , Wang Hong , Huq M. Saiful , Huang Ziyu , Rogers Claude J. , Greenberger Joel S.
Published: March 2023

Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Thus, strategies to mitigate toxicity are important and can revitalize the current standard of care. We previously established that LR-IL-22 protects the intestine from WAI. We now hypothesize that LR-IFN-β is an effective radiation protector and mitigator and is rapidly cleared from the digestive tract, making it an option for intestinal radioprotection. We report that the gavage of LR-IFN-β during WAI provides improved intestinal barrier integrity and significantly preserves the numbers of Lgr5+GFP+ intestinal stem cells, improving survival. The rapid clearance of the genetically engineered probiotic from the digestive tract renders it a safe and feasible radiation mitigator. Therefore, the above genetically engineered probiotic is both a feasible and effective radiation mitigator that could potentially revolutionize the management of OC patients. Furthermore, the subsequent addition of platinum/taxane-based chemotherapy to the combination of WAI and LR-IFN-β should reduce tumor volume while protecting the intestine and should improve the overall survival in OC patients.
Sinonasal Cancer: Improving Classification, Stratification and Therapeutic Options
Authors: Hermsen Mario A. , Bossi Paolo , Franchi Alessandro , Lechner Matt
Published: March 2023

The nasal cavities and paranasal sinuses are the site of origin of a wide spectrum of histologically and clinically distinct disease entities [...]
Therapy Resistance of Glioblastoma in Relation to the Subventricular Zone: What Is the Role of Radiotherapy?
Authors: Ermiş Ekin , Althaus Alexander , Blatti Marcela , Uysal Emre , Leiser Dominic , Norouzi Shokoufe , Riggenbach Elena , Hemmatazad Hossein , Ahmadli Uzeyir , Wagner Franca
Published: March 2023

Glioblastoma is a highly heterogeneous primary malignant brain tumor with marked inter-/intratumoral diversity and a poor prognosis. It may contain a population of neural stem cells (NSC) and glioblastoma stem cells that have the capacity for migration, self-renewal and differentiation. While both may contribute to resistance to therapy, NSCs may also play a role in brain tissue repair. The subventricular zone (SVZ) is the main reservoir of NSCs. This study investigated the impact of bilateral SVZ radiation doses on patient outcomes. We included 147 patients. SVZs were delineated and the dose administered was extracted from dose–volume histograms. Tumors were classified based on their spatial relationship to the SVZ. The dose and outcome correlations were analyzed using the Kaplan–Meier and Cox proportional hazards regression methods. Median progression-free survival (PFS) was 7 months (range: 4–11 months) and median overall survival (OS) was 14 months (range: 9–23 months). Patients with an ipsilateral SVZ who received ≥50 Gy showed significantly better PFS (8 versus 6 months; p < 0.001) and OS (16 versus 11 months; p < 0.001). Furthermore, lower doses (<32 Gy) to the contralateral SVZ were associated with improved PFS (8 versus 6 months; p = 0.030) and OS (15 versus 11 months; p = 0.001). Targeting the potential tumorigenic cells in the ipsilateral SVZ while sparing contralateral NSCs correlated with an improved outcome. Further studies should address the optimization of dose distribution with modern radiotherapy techniques for the areas surrounding infiltrated and healthy SVZs.
LL-37 Might Promote Local Invasion of Melanoma by Activating Melanoma Cells and Tumor-Associated Macrophages
Authors: Ohuchi Kentaro , Ikawa Tetsuya , Amagai Ryo , Takahashi Toshiya , Roh Yuna , Endo Junko , Kambayashi Yumi , Asano Yoshihide , Fujimura Taku
Published: March 2023

LL-37 can stimulate various skin-resident cells to contribute to tumor development. Since tumor (T) stage is determined by the vertical invasion of tumor cells in melanoma, we hypothesized that the LL-37 expression level is correlated with the T stage in melanoma patients. Immunohistochemical staining of LL-37 was performed in each stage of melanoma (Tis-T4), suggesting the ratio of LL-37-expressing cells correlate positively to T stage severity. Next, to examine pro-angiogenetic factors induced by LL-37 stimulation, the B16F10 melanoma model was used. Intra-tumorally administered CRAMP, the mouse ortologe of LL-37, significantly increased the mRNA expression of CXCL5, IL23A, MMP1a, and MMP9 in B16F10 melanoma. To confirm the induction of pro-angiogenic factors, A375 human melanoma cells were stimulated by LL-37 in vitro. The mRNA expression of CXCL5, IL23A, and MMP9, but not MMP1, were significantly increased by LL-37 stimulation. Moreover, LL-37-stimulated A375 culture supernatant promoted tube networks, suggesting that these tumor-derived factors promote the pro-angiogenic effect on tumor development. In contrast to melanoma cell lines, M2 macrophages stimulated by LL-37 in vitro significantly increased their expression and secretion of MMP-1, but not MMP-9 expression. Collectively, these results suggest that LL-37 stimulates both tumor cells and macrophages to promote melanoma invasion by the induction of pro-angiogenic factors.
A De Novo Sequence Variant in Barrier-to-Autointegration Factor Is Associated with Dominant Motor Neuronopathy
Authors: Marcelot Agathe , Rodriguez-Tirado Felipe , Cuniasse Philippe , Joiner Mei-ling , Miron Simona , Soshnev Alexey A. , Fang Mimi , Pufall Miles A. , Mathews Katherine D. , Moore Steven A. , Zinn-Justin Sophie , Geyer Pamela K.
Published: March 2023

Barrier-to-autointegration factor (BAF) is an essential component of the nuclear lamina. Encoded by BANF1, this DNA binding protein contributes to the regulation of gene expression, cell cycle progression, and nuclear integrity. A rare recessive BAF variant, Ala12Thr, causes the premature aging syndrome, Néstor–Guillermo progeria syndrome (NGPS). Here, we report the first dominant pathogenic BAF variant, Gly16Arg, identified in a patient presenting with progressive neuromuscular weakness. Although disease variants carry nearby amino acid substitutions, cellular and biochemical properties are distinct. In contrast to NGPS, Gly16Arg patient fibroblasts show modest changes in nuclear lamina structure and increases in repressive marks associated with heterochromatin. Structural studies reveal that the Gly16Arg substitution introduces a salt bridge between BAF monomers, reducing the conformation ensemble available to BAF. We show that this structural change increases the double-stranded DNA binding affinity of BAF Gly16Arg. Together, our findings suggest that BAF Gly16Arg has an increased chromatin occupancy that leads to epigenetic changes and impacts nuclear functions. These observations provide a new example of how a missense mutation can change a protein conformational equilibrium to cause a dominant disease and extend our understanding of mechanisms by which BAF function impacts human health.
High-Throughput Quantitative Screening of Glucose-Stimulated Insulin Secretion and Insulin Content Using Automated MALDI-TOF Mass Spectrometry
Authors: Delannoy Clément Philippe , Heuson Egon , Herledan Adrien , Oger Frederik , Thiroux Bryan , Chevalier Mickaël , Gromada Xavier , Rolland Laure , Froguel Philippe , Deprez Benoit , Paul Sébastien , Annicotte Jean-Sébastien
Published: March 2023

Type 2 diabetes (T2D) is a metabolic disorder characterized by loss of pancreatic β-cell function, decreased insulin secretion and increased insulin resistance, that affects more than 537 million people worldwide. Although several treatments are proposed to patients suffering from T2D, long-term control of glycemia remains a challenge. Therefore, identifying new potential drugs and targets that positively affect β-cell function and insulin secretion remains crucial. Here, we developed an automated approach to allow the identification of new compounds or genes potentially involved in β-cell function in a 384-well plate format, using the murine β-cell model Min6. By using MALDI-TOF mass spectrometry, we implemented a high-throughput screening (HTS) strategy based on the automation of a cellular assay allowing the detection of insulin secretion in response to glucose, i.e., the quantitative detection of insulin, in a miniaturized system. As a proof of concept, we screened siRNA targeting well-know β-cell genes and 1600 chemical compounds and identified several molecules as potential regulators of insulin secretion and/or synthesis, demonstrating that our approach allows HTS of insulin secretion in vitro.
Developing Trusted Voices for Planetary Health: Findings from a Clinicians for Planetary Health (C4PH) Workshop
Authors: Xie Michael , Góes Vanessa , Lem Melissa , Raab Kristin , Souza de Camargo Tatiana , Falceto de Barros Enrique , Maharaj Sandeep , Potter Teddie
Published: March 2023

Climate change, biodiversity loss, and other environmental changes are rapidly impacting the health of people worldwide, but many clinicians and other health professionals feel unprepared to deal with this burgeoning issue. During the Planetary Health Annual Meeting held in Boston in late 2022, the Clinicians for Planetary Health (C4PH) working group hosted a workshop that highlighted the latest findings of clinicians’ attitudes towards climate change, connections with the related fields of lifestyle medicine and integrative health, lessons learned from implementing “one minute for the planet” in a rural Brazilian clinic, and the benefits of clinicians prescribing time in nature for their patients. This article ends with a few suggestions for healthcare providers to begin implementing planetary health into their professional practice.