bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Tropical Cyclone Tracks and Rainfall by the North Atlantic Oscillation
Authors: Mazza Edoardo , Chen Shuyi S.
Published: June 2023

Understanding and quantifying the large‐scale environmental control of spatio‐temporal tropical cyclone (TC) variability beyond a few weeks remains a challenge with significant implications for societal impacts. This study focuses on the relationship between the North Atlantic Oscillation (NAO) and year‐to‐year changes in TC activity and rainfall using observational data and reanalysis products. We use Poisson regression models to show that low‐frequency NAO (LF‐NAO) variability is associated with a distinct pattern of TC activity, which extends across the western North Atlantic, the Caribbean Basin, and the Gulf of Mexico. The negative LF‐NAO phase is characterized by enhanced TC activity: an interquartile range decrease in the NAO corresponds to a 30%–40% increase in TC track density. While the NAO is known to affect the weather regimes of the mid‐latitudes, we show that its low‐frequency component has a strong correlation to the large‐scale environment across the Main Development Region of TCs. The negative LF‐NAO phase is associated with two favorable environmental conditions for TCs: significantly higher sea‐surface temperature and weaker deep‐tropospheric wind shear. The LF‐NAO relationship to TC activity is strongest during El Niño Southern Oscillation positive or neutral conditions and during the negative Atlantic Multidecadal Oscillation phase, and it can also be detected in the basin‐scale variations of TC rainfall. By developing annual TC rainfall composites from satellite data and reanalysis products, we show that TC rainfall is strongly enhanced in the Caribbean and in the Gulf of Mexico during the negative LF‐NAO phase.
Spike- and nucleocapsid-based gold colloid assay toward the development of an adhesive bandage for rapid SARS-CoV-2 immune response detection and screening
Authors: Boumar Imen , Deliorman Muhammedin , Sukumar Pavithra , Qasaimeh Mohammad A.
Published: June 2023

Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are important biomarkers used for the diagnosis and screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in both symptomatic and asymptomatic individuals. These antibodies are highly specific to the spike (S) and nucleocapsid (N) proteins of the SARS-CoV-2 virus. This paper outlines the development steps of a novel hybrid (vertical-lateral-vertical) flow assay in the form of a finger-stick point-of-care device, similar to an adhesive bandage, designed for the timely detection and screening of IgM and IgG immune responses to SARS-CoV-2 infections. The assay, comprising a vertically stacked plasma/serum separation membrane, conjugate pad, and detection (readout) zone, utilizes gold nanoparticles (AuNPs) conjugated with SARS-CoV-2 S and N proteins to effectively capture IgM and IgG antibodies from a pinprick (~15 µL) of blood in just one step and provides results of no immune IgM−/IgG−, early immune IgM+/IgG−, active immune IgM+/IgG+ or immune IgM−/IgG+ in a short amount of time (minutes). The adhesive bandage-like construction is an example of the design of rapid, low-cost, disposable, and easy-to-use tests for large-scale detection and screening in households. Furthermore, the bandage can be easily adjusted and optimized to detect different viral infections as they arise by simply selecting appropriate antigens related to pandemics and outbreaks.
A Comprehensive dataset for Australian mine production 1799 to 2021
Authors: Mudd Gavin M.
Published: June 2023

Given that metals, minerals and energy resources extracted through mining are fundamental to human society, it follows that accurate data describing mine production are equally important. Although there are often national statistical sources, this typically includes data for metals (e.g., gold), minerals (e.g., iron ore) or energy resources (e.g., coal). No such study has ever compiled a national mine production data set which includes basic mining data such as ore processed, grades, extracted products (e.g., metals, concentrates, saleable ore) and waste rock. These data are crucial for geological assessments of mineable resources, environmental impacts, material flows (including losses during mining, smelting-refining, use and disposal or recycling) as well as facilitating more quantitative assessments of critical mineral potential (including possible extraction from tailings and/or waste rock left by mining). This data set achieves these needs for Australia, providing a world-first and comprehensive review of a national mining industry and an exemplar of what can be achieved for other countries with mining industry sectors.
County augmented transformer for COVID-19 state hospitalizations prediction
Authors: Er Siawpeng , Yang Shihao , Zhao Tuo
Published: June 2023

The prolonged COVID-19 pandemic has tied up significant medical resources, and its management poses a challenge for the public health care decision making. Accurate predictions of the hospitalizations are crucial for the decision makers to make informed decision for the medical resource allocation. This paper proposes a method named County Augmented Transformer (CAT). To generate accurate predictions of four-week-ahead COVID-19 related hospitalizations for every states in the United States. Inspired by the modern deep learning techniques, our method is based on a self-attention model (known as the transformer model) that is actively used in Natural Language Processing. Our transformer based model can capture both short-term and long-term dependencies within the time series while enjoying computational efficiency. Our model is a data based approach that utilizes the publicly available information including the COVID-19 related number of confirmed cases, deaths, hospitalizations data, and the household median income data. Our numerical experiments demonstrate the strength and the usability of our model as a potential tool for assisting the medical resources allocation.
Enhancement in mechanical and antimicrobial properties of epoxidized natural rubber via reactive blending with chlorhexidine gluconate
Authors: Kanthiya Thidarat , Thajai Nanthicha , Chaiyaso Thanongsak , Rachtanapun Pornchai , Thanakkasaranee Sarinthip , Kumar Anbarasu , Boonrasri Siwarote , Kittikorn Thorsak , Phimolsiripol Yuthana , Leksawasdi Noppol , Tanadchangsaeng Nuttapol , Jantanasakulwong Kittisak
Published: June 2023

An epoxidized natural rubber (ENR) blend with chlorhexidine gluconate (CHG) was prepared using a two-roll mill at 130 °C. CHG was added at concentrations of 0.2, 0.5, 1, 2, 5, and 10% (w/w) as an antimicrobial additive. The ENR blend with 10% (w/w) CHG showed the best tensile strength, elastic recovery, and Shore A hardness. The ENR/CHG blend exhibited a smooth fracture surface. The appearance of a new peak in the Fourier transform infrared spectrum confirmed that the amino groups of CHG reacted with the epoxy groups of ENR. The ENR with 10% CHG exhibited an inhibition zone against Staphylococcus aureus. The proposed blending improved the mechanical properties, elasticity, morphology, and antimicrobial properties of the ENR.
Booster effect of the third dose of SARS-CoV-2 mRNA vaccine in Japanese kidney transplant recipients
Authors: Kawabe Mayuko , Kuroda Takafumi , Yamamoto Izumi , Kobayashi Akimitsu , Ohki Yutaro , Hayashi Ayaka , Urabe Fumihiko , Miki Jun , Yamada Hiroki , Kimura Takahiro , Matsuo Nanae , Tanno Yudo , Horino Tetsuya , Ohkido Ichiro , Yamamoto Hiroyasu , Yokoo Takashi
Published: June 2023

The humoral response of kidney transplant recipients (KTR) to the mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is generally poor. We evaluated the booster effect of the third dose (D3) of two SARS-CoV-2 mRNA vaccines 6 months after the second dose (D2) in Japanese KTR. The anti-spike (anti-S) antibody titer 1 and 3 months after the D3 was evaluated in 82 Japanese KTR. The primary endpoint was the seropositivity rate, and factors associated with the lack of a response were evaluated in a logistic regression model. Overall, the anti-S antibody seropositivity rate 1 and 3 months after the D3 was 74.7% and 76.0%. The anti-S antibody titers after the first and second doses were higher in patients vaccinated with the mRNA-1273 than with the BNT162b2 vaccine. Among the 38 KTR who were seronegative 5 months after the D2, 18 (47.4%) became seropositive following the D3. Factors associated with a non-response were mycophenolic acid dose, post-transplant duration, hemoglobin, and lymphocyte count. A humoral response 1 and 3 months after the D3 was obtained in ~ 75% of KTR, but 20% were non-responders. Additional studies are needed to clarify the factors hindering a vaccine response.
Circulating extracellular vesicle-derived MARCKSL1 is a potential diagnostic non-invasive biomarker in metastatic colorectal cancer patients
Authors: Rong Wenqing , Shao Shiyun , Pu Yunzhou , Ji Qing , Zhu Huirong
Published: June 2023

Extracellular vesicle-derived proteins are closely related to colorectal cancer metastasis, and early detection and diagnosis of colorectal cancer metastasis is very important to improve the prognosis. In this study, we evaluated the clinical significance of plasma EV-derived MARCKSL1 in differentiating patients with metastatic and nonmetastatic CRC. This study included 78 patients, including 40 patients with nonmetastatic colorectal cancer, 38 patients with metastatic colorectal cancer, and 15 healthy volunteers. The extracellular vesicles extracted from the participants' plasma were characterized through transmission electron microscopy, nanoparticle tracking analysis and western blotting. MARCKSL1 protein expression in the EVs was detected by ELISA, and the diagnostic efficacy of MARCKSL1 alone or in combination with CA125 and lymphocyte levels was evaluated by receiver operating characteristic curve (ROC) analysis. Pearson's correlation test was performed to detect the correlation between MARCKSL1, CA125, lymphocyte level and clinicopathological characteristics of tumors. The present study demonstrated that the level of circulating EV-derived MARCKSL1 in patients with metastatic colorectal cancer was significantly higher than that in patients with nonmetastatic colorectal cancer and healthy people. Combined with CA125 and lymphocyte levels, the best diagnostic effect was achieved, and the area under the ROC curve was 0.7480. Together, our findings indicated that circulating EV-derived MARCKSL1 could be used as a new potential diagnostic biomarker for metastatic CRC.
Clinical feasibility of CS-VIBE accelerates MRI techniques in diagnosing intracranial metastasis
Authors: Park Sang Ik , Yim Younghee , Chung Mi Sun
Published: June 2023

Our objective was to evaluate and compare the diagnostic performance of post-contrast 3D compressed-sensing volume-interpolated breath-hold examination (CS-VIBE) and 3D T1 magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) in detecting intracranial metastasis. Additionally, we analyzed and compared the image quality between the two. We enrolled 164 cancer patients who underwent contrast-enhanced brain MRI. Two neuroradiologists independently reviewed all the images. The signal-to-noise ratio (SNR), contrast-to noise ratio (CNR) were compared between two sequences. For patients with intracranial metastasis, we measured enhancement degree and CNRlesion/parenchyma of the lesion. The overall image quality, motion artifact, gray-white matter discrimination and enhancing lesion conspicuity were analyzed. Both MPRAGE and CS-VIBE showed similar performance in diagnosing intracranial metastasis. Overall image quality of CS-VIBE was better with less motion artifact; however conventional MPRAGE was superior in enhancing lesion conspicuity. Overall, the SNR and CNR of conventional MPRAGE were higher than those of CS-VIBE. For 30 enhancing intracranial metastatic lesions, MPRAGE showed a lower CNR (p = 0.02) and contrast ratio (p = 0.03). MPRAGE and CS-VIBE were preferred in 11.6 and 13.4% of cases, respectively. In comparison with conventional MPRAGE, CS-VIBE achieved comparable image quality and visualization, with the scan time being half of that of MPRAGE.
Controllable hybrid plasmonic integrated circuit
Authors: Khodadadi Maryam , Moshiri Seyyed Mohammad Mehdi , Nozhat Najmeh , Khalily Mohsen
Published: June 2023

In this paper, a controllable hybrid plasmonic integrated circuit (CHPIC) composed of hybrid plasmonic waveguide (HPW)-based rhombic nano-antenna, polarization beam splitter, coupler, filter, and sensor has been designed and investigated for the first time. In order to control the power into a corresponding input port, a graphene-based 1 × 3 power splitter with switchable output has been exploited. The functionality of each device has been studied comprehensively based on the finite element method and the advantages over state-of-the-art have been compared. Moreover, the effect of connection of CHPIC to the photonic and plasmonic waveguides has been studied to exhibit the capability of variety excitation methods of the CHPIC. Furthermore, the performance of the proposed CHPIC connected to inter/intra wireless transmission links has been investigated. The wireless transmission link consists of two HPW-based nano-antennas as transmitter and receiver with the maximum gain and directivity of 10 dB and 10.2 dBi, respectively, at 193.5 THz. The suggested CHPIC can be used for applications such as optical wireless communication and inter/intra-chip optical interconnects.
Removal of strontium by ion exchange and lime softening at eight drinking water treatment plants
Authors: Lytle Darren A. , Keithley Asher E. , Williams Daniel , Chait Hannah
Published: June 2023

The United States (US) Environmental Protection Agency (EPA) included strontium (Sr) in the Contaminant Candidate List 3 as a chemical for potential future regulatory consideration.
Resistance profiles of microbial communities in maize rhizospheres to the introduction of exogenous antibiotics to agricultural systems with a high arsenic geological background
Authors: Xu Moxin , Jiang Jinping , Feng Ying , Li Xiaofeng , Ye Lili , Chen Yongshan
Published: June 2023

The soil environment in regions with a high arsenic geological background may have enabled microbial adaptation, through co-selection mechanisms, to withstand the introduction of exogenous antibiotics.
Comparable antibacterial effects and action mechanisms of ethyl cyanoacrylate nanoparticles on Bacillus subtilis and Escherichia coli evaluated by transcriptome and morphological changes
Authors: Sarian Fean Davisunjaya , Ohama Takeshi
Published: June 2023

We previously demonstrated that ethyl cyanoacrylate nanoparticles (ECA-NPs) inhibit the growth specific rate of B. subtilis and E. coli under culture conditions, indicating their antibacterial effect.
A unique [Sb6O2S13]12−finite chain in oxychalcogenide Ba6Sb6O2S13leading to ultra-low thermal conductivity and giant birefringence
Authors: Shi Yong-Fang , Zhou Sheng-Hua , Liu Peng-Fei , Wu Xin-Tao , Lin Hua , Zhu Qi-Long
Published: June 2023

A novel 0D Sb-based oxysulfide, Ba6Sb6O2S13, possesses an unprecedented [Sb6O2S13]12−finite chain and exhibits an ultra-low thermal conductivity and giant birefringence.
Enantioselective Ni-catalyzedsyn-hydrometalative cyclization of alkyne-tethered ketoamides to α-hydroxy-γ-lactams
Authors: Zeng Hai-Xiang , Zhang Xiao-Wen , Li Qi-Yang , Liu Wen-Bo
Published: June 2023

A ligand-enabled enantioselective and regioselective Ni-catalyzedsyn-hydrocyclization of alkyne-tethered ketoamides for the synthesis of α-hydroxy γ-lactams is reported.
Consecutive regulation of catalytic activities of B(C6F5)3·H2O: direct nucleophilic substitution of benzyl fluorides with alcohol via dual activation
Authors: Wang Shi-Jun , Zhai Jun-Jia , Wang Long , Tang Xiang-Ying
Published: June 2023

A simple strategy for the consecutive regulation of the catalytic activity of B(C6F5)3·H2O was established, enabling the challenging base-free C–F bond nucleophilic substitution by alcohol.
Synthesis, properties, and application of phenanthrenone: an undeveloped building block and a photocatalyst
Authors: Gan Ziyang , Zhou Jie , Zhu Lingyun , Chen Xinyu , Ma Qiang , Yan Jianfeng , Jiang Wei , Liao Saihu , Li Yuanming
Published: June 2023

The phenanthrenone derivatives could serve as an attractive class of building blocks for constructing novel curved PAHs with five-membered rings. In addition, the substituted phenanthrenones also showed promising potential as effective and tunable organic photocatalysts.
Recent trends in macromolecule-conjugated hybrid quantum dots for cancer theranostic applications
Authors: Boopathy Lokesh Kumar , Gopal Thiyagarajan , Roy Anitha , Kalari Kandy Rakhee Rathnam , Arumugam Madan Kumar
Published: June 2023

Hybrid quantum dots can be used as a biosensor and as a cancer therapeutic material for effective cancer theranostic applications.
Recyclization of morpholinochromonylidene–thiazolidinone using nucleophiles: facile synthesis, cytotoxic evaluation, apoptosis, cell cycle and molecular docking studies of a novel series of azole, azine, azepine and pyran derivatives
Authors: Ali Tarik E. , Assiri Mohammed A. , Alqahtani Maha N. , Shati Ali. A. , Alfaifi Mohammad. Y. , Elbehairi Serag. E. I.
Published: June 2023

Construction of a novel series of substituted azoles, azines, azepines and pyrans clubbed with a morpholinothiazolidinone hybrid with anticancer properties, was achieved.
“d-electron interactions” induced CoV2O6–Fe–NF for efficient oxygen evolution reaction
Authors: Guo Yuchao , Yan Gaojie , Sun Xi , Wang Shuo , Chen Li , Feng Yi
Published: June 2023

Through a redox reaction, Fe2+ was introduced into CoV2O6-NF and was transformed into high oxidation state Fe(2+δ)+, acting as a partial active center to accelerate the OER process. CoV2O6-Fe-NF exhibited an overpotential of 298 mV at 100 mA cm−2.
Veranstaltung des BDDH im Rahmen der 67. Jahrestagung der Gesellschaft für Thrombose- und Hämostaseforschung in Frankfurt
Authors: Sucker Christoph , Koscielny Jürgen
Published: June 2023

Im Rahmen der 67. Jahrestagung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH) in Frankfurt veranstaltete der BDDH am 23.2.2022 nach der Mitgliederversammlung eine öffentliche Sitzung zu berufspolitischen Themen. Die Sitzung war sehr gut besucht, wobei neben BDDH- Mitgliedern auch andere interessierte Ärzte und Vertreter der Industrie teilnahmen. In dieser Ausgabe der „BDDH News“ berichten wir über 2 Themenkomplexe aus dieser Sitzung und fassen die gehaltenen Vorträge zusammen.
Province-specific policies offer best option as China deploys renewable energy storage systems
Authors: Johnson-Groh Mara
Published: June 2023

How energy storage systems are implemented alongside renewable energy can have a large impact on energy prices.
Parents’ indirect utterances in an Indonesian family
Authors: Setiawan Budi
Published: June 2023

This present study examines Indonesian parents’ utterance to instruct each other. The results show that Indonesian parents’ speeches in the family were situated in context and situation. Parents did not mention themselves nor their spouse as the addressee, instead using indirect utterance to instruct the addressee. They produced indirect utterances with implied meanings, instructing their spouse via speaking to their children or about other objects. Each parent understood their spouse’s intention from the context and physical condition of family members.
Livestock for Livelihoods: Role of Goats in Improving the Livelihood and Well-being of Women Pastoralists in Ethiopia and Uganda
Authors: Adhiambo Onyango Dr Diana
Published: June 2023

Farm Africa worked with semi-nomadic pastoralist women living in the South Omo region of Ethiopia and Karamoja subregion in Uganda, thereby supporting them to set up sustainable, small-scale goat-rearing enterprises that contributed to increased household income, improved dietary diversity and nutritional status of their families. The project also supported community-based animal health service delivery as part of the integrated approach.

Livestock is the main source of livelihood for the pastoralist communities in East Africa, though disease, drought and degraded grasslands make it unproductive. Rural women in pastoralist communities in Ethiopia and Uganda lack nutritional knowledge, financial skills, credit access and a voice in household decision making, which result in them having a low economic status and which contribute to malnutrition. Declining animal health services, due in part to reduced government capacity, exacerbate the challenge of increasing goat productivity. Farm Africa through the Livestock for Livelihoods project (March 2019–July 2021) supported 10,000 women to improve their socio-economic status and improve household nutrition. It supported women beneficiaries to be more economically empowered through access to finance provided by Village Savings and Loans Associations (VSLAs) and facilitated them to be involved in profitable enterprises in the goat value chain (goat breeding, leather tanning and milk value addition). These activities stimulated livelihood diversification and trade, contributing to reduced levels of poverty and malnutrition. Some of the remarkable results include increased revenue that women acquired from the sale of live goats, meat, hides, skins and milk; improved dietary diversity in children under 5 years and women; and increased Women’s Economic Empowerment (WEE) scores. This project created and strengthened a network of Community-Based Animal Health Workers (CAHWs) linked to agro-input dealers to enhance pastoralists’ access to quality animal health services. A total of 155 CAHWs (127 men and 28 women) in the two countries were empowered to provide animal health services to the pastoralists across the project area.

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The physical determinants of maximal jumping time of flight in elite trampolining
Authors: Dyas Natalie , Green David , Thomas Kevin , Matthew Esme , Howatson Glyn
Published: June 2023

Time of flight (ToF) is an objective scoring component of elite trampolining, assessed in training by maximal jump tests. The aim of this study was to assess the relationship between physical floor based performance meaures and 20‐maximum ToF. Thirty‐two elite level gymnasts (13 senior; 19 junior) performed a battery of floor based tests and a 20‐maximum jump test. Floor based tests included cycling peak power output, reactive strength index (RSI), unloaded countermovement jumps (CMJ), and loaded CMJ's to construct a load‐velocity profile for prediction of theoretical maximum force (CMJ F0). Very large and large, positive bivariate relationships were observed between CMJ F0 and ToF for the seniors (r = 0.85) and juniors (r = 0.56), respectively. Very large, positive bivariate relationships were observed between CMJ height and total ToF for both seniors (r = 0.74) and juniors (r = 0.77). Step‐wise multiple regression analyses revealed CMJ F0 predicted 72% of ToF variability between seniors, and CMJ height (59%), 10 to 5 RSI (13%), and CMJ F0 (10%) predicting 82% of ToF variability between juniors. This suggests CMJ F0, lower limb maximal isometric capabilities, and CMJ height are important floor based predictors of maximal ToF in elite gymnasts.
Detection of EEG signals in normal and epileptic seizures with multiscale multifractal analysis approach via weighted horizontal visibility graph
Authors: Ma 马 Lu 璐 , Ren 任 Yan-Lin 彦霖 , He 何 Ai-Jun 爱军 , Cheng 程 De-Qiang 德强 , Yang 杨 Xiao-Dong 小冬
Published: June 2023

Electroencephalogram (EEG) signals contain important information about the regulation of brain system. Thus, automatic detection of epilepsy by analyzing the characteristics obtained from EEG signals has important research implications in the field of clinical medicine. In this paper, the horizontal visibility graph (HVG) algorithm is used to map multifractal EEG signals into complex networks. Then, we study the structure of the networks and explore the nonlinear dynamics properties of the EEG signals inherited from these networks. In order to better describe complex brain behaviors, we use the angle between two connected nodes as the edge weight of the network and construct the weighted horizontal visibility graph (WHVG). In our studies, fractality and multifractality of WHVG are innovatively used to analyze the structure of related networks. However, these methods only analyze the reconstructed dynamical system in general characterizations, they are not sufficient to describe the complex behavior and cannot provide a comprehensive picture of the system. To this effect, we propose an improved multiscale multifractal analysis (MMA) for network, which extends the description of the network dynamics features by focusing on the relationship between the multifractality and the measured scale-free intervals. Furthermore, neural networks are applied to train the above-mentioned parameters for the classification and identification of three kinds of EEG signals, i.e., health, interictal phase, and ictal phase. By evaluating our experimental results, the classification accuracy is 99.0%, reflecting the effectiveness of the WHVG algorithm in extracting the potential dynamic characteristics of EEG signals.
Kinesin-microtubule interaction reveals the mechanism of kinesin-1 for discriminating the binding site on microtubule
Authors: Geng 耿 Yi-Zhao 轶钊 , Lu 鲁 Li-Ai 丽爱 , Jia 贾 Ning 宁 , Zhang 张 Bing-Bing 冰冰 , Ji 纪 Qing 青
Published: June 2023

Microtubule catalyzes the mechanochemical cycle of kinesin, a kind of molecular motor, through its crucial roles in kinesin’s gating, ATPase and force-generation process. These functions of microtubule are realized through the kinesin-microtubule interaction. The binding site of kinesin on the microtubule surface is fixed. For most of the kinesin-family members, the binding site on microtubule is in the groove between α-tubulin and β-tubulin in a protofilament. The mechanism of kinesin searching for the appropriate binding site on microtubule is still unclear. Using the molecular dynamics simulation method, we investigate the interactions between kinesin-1 and the different binding positions on microtubule. The key non-bonded interactions between the motor domain and tubulins in kinesin’s different nucleotide-binding states are listed. The differences of the amino-acid sequences between α- and β-tubulins make kinesin-1 binding to the α–β groove much more favorable than to the β–α groove. From these results, a two-step mechanism of kinesin-1 to discriminate the correct binding site on microtubule is proposed. Most of the kinesin-family members have the conserved motor domain and bind to the same site on microtubule, the mechanism may also be shared by other family members of kinesin.
Correlation of H- beam properties to Cs-coverage
Authors: Lettry J. , Vnuchenko A. , Bertolo S. , Mastrostefano C. , O'Neil M. , di Lorenzo F. , Coutron Y. , Steyeart D. , Riffaud B. , Thiboud J. , Guida R. , Kapusniak K. , Charvet C. , Teissandier B. , Moyret P. , Roncarolo F. , Bart Pedersen S. , Duraffourg M. , Vuitton C. , Joffe S. , Machado C. , Fantz U. , Mochalskyy S. , Wunderlich D. , Lindqvist M. , den Harder N. , Briefi S. , Hurlbatt A. , Kalvas T. , Minea T. , Revel A.
Published: June 2023

A caesiated RF driven source delivers H- ions that, after stripping at the end of the 160 MeV H- linear injector, provides protons to CERN's accelerator complex including LHC, where the protons reached a record energy of 6.8 TeV. In Caesiated RF sources, H- ions are produced via dissociative attachment of electrons onto roto-vibrationally excited H2-molecules (volume) and re-emission as negative ions of protons or hydrogen atoms colliding on a low work function caesiated molybdenum plasma electrode (surface). During initial caesiation, the production mechanism evolves from the initial Cs-free volume production to a predominant surface production mode; the observed stunning reduction of co-extracted electrons is concomitant to an increase of the H- ion current to RF-power yield. This paper describes the evolution of the beam-profile at today's operational beam intensities of 35 mA for various ratios of volume and surface ion-origin. The presence of surface produced ions occurring on a conical plane is characterized by the electron to ion ratio and by measurement of the Cs-coverage of the molybdenum plasma electrode down to a fraction of a monolayer. Angular distributions are extracted from beam profile and Beam Emission Spectroscopy (BES) measurements. These experimental results provide an initial comparison to beam formation simulation that, at a later stage, could be coupled to beam transport software packages.

The paper focuses on the caaesiation transient to present experimental evidence for 3D beam formation studies, it provides insight into the mixing of volume and surface production modes, reduction of co-extracted electrons and Cs-coverage. The paper also establishes magnetic field induced asymmetries in the beam's current density.
Chicken utricle stromal cell-derived decellularized extracellular matrix coated nanofibrous scaffolds promote auditory cell production
Authors: Zhang Junming , Li Yuexia , Liu Li , Shen Rong , Lou Xiangxin
Published: June 2023

Stem cell therapy has a broad future in treating sensorineural hearing loss in mammals. But how to produce sufficient functional auditory cells including hair cells, supporting cells as well as spiral ganglion neurons from potential stem cells is the bottleneck. In this study, we aimed to simulate inner ear development microenvironment to induce inner ear stem cells to differentiate into auditory cells. The different mass ratios of poly-l-lactic acid/gelatin (PLLA/Gel) scaffolds were fabricated by electrospinning technology to mimic the structure of the native cochlear sensory epithelium. The chicken utricle stromal cells were isolated and cultured, and then seeded on the PLLA/Gel scaffolds. The chicken utricle stromal cell-derived decellularized extracellular matrix (U-dECM)-coated PLLA/Gel bioactive nanofiber scaffolds (U-dECM/PLLA/Gel) were prepared by decellularization. The U-dECM/PLLA/Gel scaffolds were used for culture of inner ear stem cells, and the effects of the modified scaffolds on the differentiation of inner ear stem cells were analyzed by RT-PCR and immunofluorescent staining. The results showed that U-dECM/PLLA/Gel scaffolds possessed good biomechanical properties can significantly promote the differentiation of inner ear stem cells and make them differentiate into auditory cells. Collectively, these findings indicated that U-dECM-coated biomimetic nanomaterials may be a promising strategy for auditory cell production.
Reconstructing groundwater and lake level histories in Northern Wisconsin: isolation of groundwater’s influence on tree rings from climatic and environmental drivers
Authors: Ciruzzi Dominick M , Loheide II Steven P
Published: June 2023

Tree rings can reveal long-term environmental dynamics and drivers of tree growth. However, individual ecological drivers of tree growth need to be disentangled from the effects of other co-occurring environmental and climatic conditions in tree rings to examine the histories of stand- to landscape-level ecological processes. Here, we integrate ecohydrological theory of groundwater–tree interactions with dendrochronological approaches and develop a new framework to isolate water-level effects on tree rings from climate induced variability in tree ring growth. Our results indicate that changing depth to groundwater within 1–2.3 m of the land surface exerts a substantial influence on red pine growth and this influence can be quantified and used to reconstruct long-term groundwater and lake level histories from tree ring patterns in Northern Wisconsin. This research suggests a substantial influence of groundwater on tree growth with implications for improving the mechanistic understanding of climate-induced tree mortality and reduce uncertainty in forest productivity models. Further, this is a transferable approach to isolate and reconstruct strong environmental drivers of tree growth that co-occur with other environmental signals.
Chloroform exposure in air and water in Swedish indoor swimming pools—urine as a biomarker of occupational exposure
Authors: Ragnebro Oskar , Helmersmo Kristin , Fornander Louise , Olsen Raymond , Bryngelsson Ing-Liss , Graff Pål , Westerlund Jessica
Published: June 2023

Introduction

Disinfection by-products are produced in water disinfected with chlorine-based products. One such group is trihalomethanes, and chloroform is the most abundant trihalomethane in swimming pool areas. Chloroform can be absorbed by inhalation, ingestion, and dermal absorption, and is classified as possibly carcinogenic.

Aim

To investigate if chloroform concentrations in air and water affect the chloroform concentration in urine samples of exposed swimming pool workers.

Methods

Workers from 5 adventure indoor swimming pools carried personal chloroform air samplers and provided up to 4 urine samples during one workday. Chloroform concentrations were analyzed with a linear mixed model analysis to investigate a possible correlation between air and urine concentrations.

Results

The geometric mean chloroform concentration was 11 μg/m3 in air and 0.009 µg/g creatinine in urine among individuals with ≤2 h at work, 0.023 µg/g creatinine among those with >2–5 working hours, and 0.026 µg/g creatinine in the group with >5–10 working hours. A risk of higher levels of chloroform in urine was associated with longer hours at work (≤2 h versus >5–10 h, odds ratio [OR] 2.04, 95% confidence interval [CI] 1.25–3.34), personal chloroform concentrations in air (≤17.00 µg/m3 versus >28.00 µg/m3, OR 9.23, 95% CI 3.68–23.13) and working at least half the working day near the swimming pools (OR 3.16, 95% CI 1.33–7.55). Executing work tasks in the swimming pool water was not associated with higher chloroform concentrations in urine compared to only working on land (OR 0.82, 95% CI 0.27–2.45).

Conclusion

There is an accumulation of chloroform concentrations in urine during a workday and a correlation between personal air and urine concentrations of chloroform among workers in Swedish indoor swimming pools.
A novel statistical method for decontaminating T-cell receptor sequencing data
Authors: Li Ruoxing , Altan Mehmet , Reuben Alexandre , Lin Ruitao , Heymach John V , Tran Hai , Chen Runzhe , Little Latasha , Hubert Shawna , Zhang Jianjun , Li Ziyi
Published: June 2023

The T-cell receptor (TCR) repertoire is highly diverse among the population and plays an essential role in initiating multiple immune processes. TCR sequencing (TCR-seq) has been developed to profile the T cell repertoire. Similar to other high-throughput experiments, contamination can happen during several steps of TCR-seq, including sample collection, preparation and sequencing. Such contamination creates artifacts in the data, leading to inaccurate or even biased results. Most existing methods assume ‘clean’ TCR-seq data as the starting point with no ability to handle data contamination. Here, we develop a novel statistical model to systematically detect and remove contamination in TCR-seq data. We summarize the observed contamination into two sources, pairwise and cross-cohort. For both sources, we provide visualizations and summary statistics to help users assess the severity of the contamination. Incorporating prior information from 14 existing TCR-seq datasets with minimum contamination, we develop a straightforward Bayesian model to statistically identify contaminated samples. We further provide strategies for removing the impacted sequences to allow for downstream analysis, thus avoiding any need to repeat experiments. Our proposed model shows robustness in contamination detection compared with a few off-the-shelf detection methods in simulation studies. We illustrate the use of our proposed method on two TCR-seq datasets generated locally.
The spread of infectious diseases from a physics perspective
Authors: Brabers J H V J
Published: June 2023

This article deals with the spread of infectious diseases from a physics perspective. It considers a population as a network of nodes representing the population members, linked by network edges representing the (social) contacts of the individual population members. Infections spread along these edges from one node (member) to another. This article presents a novel, modified version of the SIR compartmental model, able to account for typical network effects and percolation phenomena. The model is successfully tested against the results of simulations based on Monte-Carlo methods. Expressions for the (basic) reproduction numbers in terms of the model parameters are presented, and justify some mild criticisms on the widely spread interpretation of reproduction numbers as being the number of secondary infections due to a single active infection. Throughout the article, special emphasis is laid on understanding, and on the interpretation of phenomena in terms of concepts borrowed from condensed-matter and statistical physics, which reveals some interesting analogies. Percolation effects are of particular interest in this respect and they are the subject of a detailed investigation. The concept of herd immunity (its definition and nature) is intensively dealt with as well, also in the context of large-scale vaccination campaigns and waning immunity. This article elucidates how the onset of herd-immunity can be considered as a second-order phase transition in which percolation effects play a crucial role, thus corroborating, in a more pictorial/intuitive way, earlier viewpoints on this matter. An exact criterium for the most relevant form of herd-immunity to occur can be derived in terms of the model parameters. The analyses presented in this article provide insight in how various measures to prevent an epidemic spread of an infection work, how they can be optimized and what potentially deceptive issues have to be considered when such measures are either implemented or scaled down.
377 Real-world use of OPZELURA™: safety analysis at 1 year
Authors: Hu Wilson , Thornton Michele , Livingston Robert A  
Published: June 2023

OPZELURA™ (ruxolitinib cream) became the first approved topical Janus kinase inhibitor (JAKi) in the USA on September 21, 2021, for treatment of mild to moderate atopic dermatitis and on July 18, 2022 for nonsegmental vitiligo. This study aims to review postmarketing safety encompassing nearly 14,000 patient-years of treatment during the first year of market approval through September 20, 2022. The Incyte global safety database and the US Food and Drug Administration (FDA) Adverse Event Reporting System were queried for adverse event (AE) reports received for OPZELURA between September 21, 2021 and September 20, 2022. Search of these databases found 294 postmarketing individual case safety reports (ICSRs) containing 585 nonserious AEs, four serious AEs and no fatal AEs. Of the 294 ICSRs, 220 (75%) were received from spontaneous sources and 74 (25%) were received from noninterventional/solicited sources. Consumers reported 221 ICSRs (75%) and 73 (25%) were medically confirmed by a healthcare professional (i.e. nurse, pharmacist and physician). Gender was reported in 257 ICSRs; of these, 81 (32%) involved male patients and 176 (68%) involved female patients. Age was reported in 64 ICSRs (22%), with a median age of 39 years. The AEs (any unfavorable sign, symptom or disease) with frequency >2% out of all events included application site pain (16 events), dermatitis atopic, skin irritation (15 events each), scratch (14 events) and condition aggravated (13 events). Application site pain, skin irritation and scratch were mostly related to an initial issue with cream texture that was rapidly addressed. ‘Dermatitis atopic’ and ‘condition aggravated’ reflected worsening of the underlying condition or lack of improvement. The four serious AEs were skin cancer (two events), pericarditis and thrombocytopenia (one event each), all of which had insufficient information for assessment of relatedness to OPZELURA. Because indications for OPZELURA are inflammatory conditions, OPZELURA has been subject to the same class warnings as oral JAKi that include the risk of serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis, imposed by FDA subsequent to the ORAL Surveillance trial of tofacitinib in rheumatoid arthritis (Kragstrup et al., RMD Open, 2022; 8:e002236). Topical application of OPZELURA results in low systemic bioavailability of ruxolitinib, and serious AEs associated with oral JAKi were not reported with OPZELURA. Safety data from the first year of marketing confirm that OPZELURA is well tolerated, without significant systemic AEs, and with a low incidence of application site reactions.
388 Efficacy and safety of roflumilast foam 0.3% in patients with seborrheic dermatitis in a phase 3 trial: assessment of pruritus
Authors: Blauvelt Andrew , Draelos Zoe D , Gooderham Melinda  , Lain Edward , Moore Angela Y , Papp Kim A , Zirwas Matthew , Krupa David , Burnett Patrick , Berk David R , Chu David H
Published: June 2023

Itch is a major complaint among patients with seborrheic dermatitis (SD). Roflumilast is a selective, nonsteroidal, highly potent phosphodiesterase-4 inhibitor under investigation as a once-daily foam for treatment of SD. This phase 3 randomized, parallel-group, double-blind, vehicle-controlled trial (NCT04973228) was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or nonscalp areas. Patients were randomized 2 : 1 to apply once-daily roflumilast foam 0.3% (n = 304) or vehicle (n = 153) for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. Secondary efficacy endpoints included Worst Itch Numeric Rating Scale (WI-NRS), which was completed daily by patients. Safety and local tolerability were also evaluated. Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved IGA success (79.5% vs. 58.0%; P < 0.0001) and IGA status of Clear (50.6% vs. 27.7%; P < 0.0001) at Week 8. Significantly greater percentages of roflumilast- than vehicle-treated patients had ≥4-point improvement on WI-NRS at Weeks 2 (32.7% vs. 15.5%; P = 0.0016), 4 (47.6% vs. 29.1%; P = 0.0007) and 8 (62.8% vs. 40.6%; P = 0.0001). Greater improvement in itch was observed among roflumilast-treated patients as early as 48 h after the first application (mean percent change from baseline: −27.87% vs. −13.11%; nominal P = 0.0024). Local tolerability and safety were favorable. Once-daily roflumilast foam provided improvement across multiple efficacy endpoints including rapid itch improvement, while demonstrating favorable safety and tolerability.
392 Safety of amlitelimab in a Phase 2a clinical trial of patients with moderate-to-severe atopic dermatitis
Authors: Weidinger Stephan , Cork Michael , Reich Adam , Bieber Thomas , Gilbert Sally , Quaratino Sonia , Wilson Rosamund , Porter-Brown Ben
Published: June 2023

Amlitelimab (SAR445229), a fully human, nondepleting, noncytotoxic, monoclonal antibody, binds to OX40Ligand (OX40L) on antigen-presenting cells to block OX40-OX40L interactions. Outcomes from a 36-week, double-blind, Phase 2a trial (NCT03754309) in patients with moderate-to-severe atopic dermatitis are described. This study aims to assess the safety of OX40-OX40L signaling blockade with amlitelimab in patients with moderate-to-severe atopic dermatitis. Eighty-nine patients were randomized to amlitelimab low-dose (LD; 200-mg loading/100-mg maintenance Q4W), high-dose (HD; 500 mg/250 mg Q4W) or placebo. The coprimary safety endpoint was treatment-emergent adverse event (TEAE) incidence to W16. Safety was assessed to W36. Amlitelimab was well tolerated. Related TEAE incidence was similar between amlitelimab [LD 35% (10/29); HD 20% (6/30)] and placebo [31% (9/29)] to W16 and W36 [LD 10% (2/20); HD 0 (0/22); placebo 0 (0/17)]. The TEAEs more common with amlitelimab vs. placebo (≥5% difference) to W16 included headache [LD 0; HD 3 (10%); placebo 1 (3.4%)], upper respiratory tract infection [3 (10.3%); 0; 1 (3.4%)], hyperhidrosis [0; 2 (6.7%); 0], pyrexia [2 (6.9%); 0; 0], aspartate aminotransferase increased [0; 2 (6.7%); 0] and iron-deficiency anemia [2 (6.9%); 0; 0]; and to W36, Herpes simplex [0; 2 (9.1%); 0]. Before W16, one severe adverse event (SAE) of infected dermal cyst was reported as possibly related; it resolved, and the patient completed the study. Post-W16, one unrelated SAE of sudden death occurred 87 days following the final amlitelimab dose. No hypersensitivity or tolerability events, or clinically meaningful changes in laboratory values, vital signs or electrocardiogram recordings were reported. Amlitelimab was well tolerated in a Phase 2a trial of patients with moderate-to-severe atopic dermatitis, confirming the unremarkable safety profile observed in Phase 1.
411 Long term laboratory safety of dupilumab in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis
Authors: Siegfried Elaine , Cork Michael J , Lockshin Benjamin  , Boguniewicz Mark , Uppal Sumeet  , Khokhar Faisal A , Bansal Ashish , Sierka Debra , Cyr Sonya
Published: June 2023

Systemic treatments often require laboratory monitoring. Here we report 52-week laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe AD. LIBERTY AD PED-OLE (NCT02612454) is an open-label extension study of children aged 6 months to <18 years with moderate-to-severe AD. This analysis includes hematologic and chemistry laboratory parameters in children aged 6 months to 5 years treated with dupilumab every 4 weeks (q4w; 200 mg: ≥5 to <15 kg; 300 mg: ≥15 to <30 kg). Of the 180 patients enrolled, 122 (67.8%) completed up to 16 weeks and 30 (16.7%) completed up to 52 weeks. Mean (SD) eosinophil counts increased slightly from baseline [1.15 × 109/L (1.18) ] to Week 16 [1.5 × 109/L (1.91)], but then decreased below baseline by Week 52 [0.80 × 109/L (0.64)]. Mean (SD) platelet counts were relatively stable with a modest decrease from baseline [388.7 × 109/L (102.51)] to Week 52 [356.1 × 109/L (107.48)]. Chemistry parameters remained within the normal reference ranges. One patient (0.6%) reported a mild case of anemia, and one patient (0.6%) reported a mild case of thrombocytopenia, which were resolving and resolved at the time of this interim analysis, respectively. Overall safety was consistent with the known dupilumab safety profile. No clinically meaningful changes in hematologic and chemistry parameters were observed during 52 weeks of dupilumab treatment. As with adults, adolescents and older children, routine laboratory monitoring is unnecessary in children aged 6 months to 5 years with moderate-to-severe AD.