Miracle-dz/UniFAR-FTUs huggingface dataset:
Model Informed Dosing Regimen and Phase I Results of the Anti‐PD‐1 Antibody Budigalimab (ABBV‐181)

Budigalimab is a humanized, recombinant, Fc mutated IgG1 monoclonal antibody targeting programmed cell death 1 (PD‐1) receptor, currently in phase I clinical trials. The safety, efficacy, pharmacokinetics (PKs), pharmacodynamics (PDs), and budigalimab dose selection from monotherapy dose escalation and multihistology expansion cohorts were evaluated in patients with previously treated advanced solid tumors who received budigalimab at 1, 3, or 10 mg/kg intravenously every 2 weeks (Q2W) in dose escalation, including Japanese patients that received 3 and 10 mg/kg Q2W. PK modeling and PK/PD assessments informed the dosing regimen in expansion phase using data from body‐weight‐based dosing in the escalation phase, based on which patients in the multihistology expansion cohort received flat doses of 250 mg Q2W or 500 mg every four weeks (Q4W). Immune‐related adverse events (AEs) were reported in 11 of 59 patients (18.6%), of which 1 of 59 (1.7%) was considered grade ≥ 3 and the safety profile of budigalimab was consistent with other PD‐1 targeting agents. No treatment‐related grade 5 AEs were reported. Four responses per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were reported in the dose escalation cohort and none in the multihistology expansion cohort. PK of budigalimab was approximately dose proportional and sustained > 99% peripheral PD‐1 receptor saturation was observed by 2 hours postdosing, across doses. PK/PD and safety profiles were comparable between Japanese and Western patients, and exposure‐safety analyses did not indicate any trends. Observed PK and PD‐1 receptor saturation were consistent with model predictions for flat doses and less frequent regimens, validating the early application of PK modeling and PK/PD assessments to inform the recommended dose and regimen, following dose escalation.
Spatio-temporal variability of gross primary productivity in moist and dry deciduous plant functional types of Northwest Himalayan foothills of India using temperature-greenness model

Abstract The present study aims to estimate the spatio-temporal variability of gross primary productivity (GPP) in moist and dry deciduous plant functional types (PFTs) of northwest Himalayan foothills of India using remote sensing-based Temperature-Greenness (TG) model and to study the response of GPP to environmental variables. TG model was implemented in Google Earth Engine platform using Moderate Resolution Imaging Spectroradiometer enhanced vegetation index (MOD13A2) and land surface temperature (MOD11A2) from 2001 to 2018. The mean monthly GPP ranged from 1.80 to 18.57 gCm−2day−1 in moist deciduous and from 0.20 to 12.06 gCm−2day−1 in dry deciduous PFTs. On site-scale validation with eddy covariance flux tower GPP, the modelled GPP showed R2=0.79 for moist deciduous and R2=0.77 for dry deciduous PFT. Leaf area index showed the highest correlation with the predicted GPP (r = 0.74 for moist and 0.83 for dry deciduous PFTs). The study revealed that TG model could predict the long-term forest GPP with minimum in-situ inputs.
The experience of infection prevention for coronavirus disease 2019 (COVID-19) during general anesthesia in an epidemic of COVID-19: including unexpected exposure case - Two cases report -

Background Coronavirus disease 2019 (COVID-19) has been an epidemic in the Republic of Korea since the first patient who came in China was confirmed as having the disease on January 19, 2020. Therefore, surgery for COVID-19-related patients is expected to increase. Case We experienced two cases of COVID-19-related patients who underwent surgery for femur fracture under general anesthesia. In one case, infection control to prevent transmission was achieved, while in the second case, healthcare workers were exposed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Conclusions In areas where there is COVID-19 epidemic, SARS-CoV-2 real-time polymerase chain reaction should be performed before surgery in patients with symptoms of respiratory infection such as fever, cough, and sputum, or for those in whom the possibility of COVID-19 cannot be completely excluded. Efforts should be made to prevent healthcare worker’s exposure and the contamination of the operating room.
The effects of external carbon loading on nitrogen removal in sequencing batch reactors

A bench-scale study was undertaken to examine the effects of easily biodegradable organic carbon substrate on denitrification reaction and overall nitrogen removal from domestic wastewater under a modified sequencing batch reactor (SBR) system. The operation strategy of the SBR consisted of 0.75 h FILL, 8 h REACT separated into 4 h aerobic, 3 h anoxic and 1 h aerobic stages, 1.5 h SETTLE, 1 h DRAW and 0.75 h IDLE. Methanol, sodium acetate and sodium propionate, at the concentrations equivalent to theoretical COD values of 50, 100 and 150 mg O2 1−1 were used as the external carbon sources and added to the reactors prior to the anoxic stage. The study reveals that 4 h aerobic stage was sufficient to nitrify more than 98% NH4+-N and carbon addition caused slightly more nitrification than the control. Addition of sodium propionate at a low concentration (50 mg O2 1−1) significantly enhanced the denitrification process, the nitrate content in this reactor dropped to 3 mg 1−1 (89% reduction) at the end of the anoxic stage. Among the three substrate added at low dose, sodium propionate was the most effective carbon source, followed by acetate and the least effective one was methanol. When the carbon substrate were added at the doses of 100 and 150 mg O2 1−1, the denitrification rates of the acetate reactors recorded at the first hour of the anoxic stage were similar to those of the propionate's and significantly higher than the methanol reactors. When high dose (150 mg O2 1−1) of acetate or propionate was used, 95% reduction in wastewater NOx-N was found after 1 h anoxic stage while 3 h anoxic stage was required when the carbon dose was at 100 mg O2 1−1, indicating that addition of external carbon substrate at large quantity could shorten the denitrification time. However, the final effluent discharged from reactors treated with high dose of acetate and propionate contained more than 20 mg 1−1 BOD5 which might cause a contamination problem. Therefore, addition of sodium acetate or propionate at the concentration equivalent to theoretical COD values of 100 mg O2 1−1 appeared to be the most economical and reliable option.
Stakeholder approach to selecting enterprise-bank interaction strategies

Stakeholder theory dominates in revealing the features of the stakeholders’ influence on various entities; however, only few studies rely on it in the field of enterprises that select banks as financial partners. Considering the enterprise-bank relationship from the stakeholder theory perspective, this paper represents an approach to selecting strategies for interaction with this stakeholder type.The proposed approach includes the following steps: determining the interaction objectives for enterprises and banks; specifying and comparing potential partners; ranking banks to justify the chosen partner/partners for interaction; and selecting interaction strategies and forming the content of the behavior patterns inherent in enterprises (offensive or negotiation strategies). The criteria for choosing a strategy include the objectives of the interaction between enterprises (providing comprehensive services or satisfying individual financial needs) and their financial status that determines the interest of banks in partnership.The application of the proposed methodology for calculating rating indicators and the respective bank ranking showed that 18% of the banks included in the studied list of reliable Ukrainian banks have a high level of innovation activity and an acceptable level of banking service costs for business customers (that is, they implement a customer-oriented policy). Therefore, to receive comprehensive banking services combined with high or medium levels of banks’ interest in interaction, the paper recommends enterprises to choose a large-scale offensive strategy or a large-scale negotiation strategy, respectively.The stakeholder theory, as well as consideration of the criteria defined in the paper, will allow enterprises to choose interaction strategies that meet their needs for financial services and harmonize the interests of partners.
Bank deposits and Google searches in a crisis economy: Bayesian non‐linear evidence for Greece (2009–2015)

Due to a variety of reasons, the Greek economy faced a severe crisis being a member of EMU. Nonetheless, the country’s banking system experienced a dramatic outflow of deposits, in the period 2009-2015. The present paper attempts to shed light on the possibility of forecasting bank deposits, based on the keyword “Grexit” of Google searches. In this context, apart from standard forecasting models like AR (p) and ARDL (p, q) we estimate a novel Neural Network ARDL (p, q, G) model and its respective Bayesian modification. We show that extending standard autoregressive models with the information provided by Internet Searches leads to significant improvement in the forecasting accuracy of the Bank Deposits, compared with other standard models. Furthermore, the forecasting performance of the models, which are extended with Google searches, is shown to be better than models containing only the well-known indicators. Our findings are robust and econometrically sound.
Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases.

The role of Discoidin Domain Receptors (DDRs) is poorly understood in neurodegeneration. DDRs are upregulated in Alzheimer's and Parkinson's disease, and DDRs knockdown reduces neurotoxic protein levels. Here we show that potent and preferential DDR1 inhibitors reduce neurotoxic protein levels in vitro and in vivo. Partial or complete deletion or inhibition of DDR1 in a mouse model challenged with alpha-synuclein increases autophagy and reduces inflammation and neurotoxic proteins. Significant changes of cerebrospinal fluid miRNAs that control inflammation, neuronal injury, autophagy and vesicular transport genes are observed in Parkinson's disease with and without dementia and Lewy body dementia, but these changes are attenuated or reversed after treatment with the DDR1 inhibitor, nilotinib. Collectively, these data demonstrate that DDR1 regulates autophagy and reduces neurotoxic proteins and inflammation and is a therapeutic target in neurodegeneration.
Regulation of Microclimatic Conditions inside Native Beehives and Its Relationship with Climate in Southern Spain

In this study, the Wbee Sensor System was used to record data from 10 Iberian beehives for two years in southern Spain. These data were used to identify potential conditioning climatic factors of the internal regulatory behavior of the hive and its weight. Categorical principal components analysis (CATPCA) was used to determine the minimum number of those factors able to capture the maximum percentage of variability in the data recorded. Then, categorical regression (CATREG) was used to select the factors that were linearly related to hive internal humidity, temperature and weight to issue predictive regression equations in Iberian bees. Average relative humidity values of 51.7% ± 10.4 and 54.2% ± 11.7 were reported for humidity in the brood nest and in the food area, while average temperatures were 34.3 °C ± 1.5 in the brood nest and 29.9 °C ± 5.8 in the food area. Average beehive weight was 38.2 kg ± 13.6. Some of our data, especially those related to humidity, contrast with previously published results for other studies about bees from Central and northern Europe. Conclusively, certain combinations of climatic factors may condition within hive humidity, temperature and hive weight. Southern Iberian honeybees’ brood nest humidity regulatory capacity could be lower than brood nest thermoregulatory capacity, maintaining values close to 34 °C, even in dry conditions.
Innovation Beyond the Buzzwords: The Rocky Road Towardsa Digital First-based Newsroom

ABSTRACT In this paper, we report on an 18-month ethnographic field study inside the newsroom of a popular newspaper in Belgium, chronicling the endeavours of editors and journalists as they shift from a classic division between print and online beats to an integrated digital first-based newsroom. Throughout the paper, we stress the messiness and contingencies of changing the fixed structures of working journalists who are forced to undergo radical changes in their daily work, and how top-down communication affects their disposition towards, acceptance of and commitment or resistance towards the shift. We establish three types of newsroom tension (vertical, horizontal and diagonal), as well as five recurring steps faced by all hierarchical levels of the newsroom in its innovation attempts (contemplation, preparation, frustration, negotiation and adaptation). We conclude that flawed communication impacts dispositions towards innovation at various stages of the integration process and fuels tensions between various hierarchical levels. With journalistic practice in a constant state of flux, in-depth ethnography-based studies remain vital to analyse newsroom innovation and change.
Asymptotic energy distribution of one-dimensional nonlinear wave equation.

In this work we consider the defocusing nonlinear wave equation in one-dimensional space. We show that almost all energy is located near the light cone $|x|=|t|$ as time tends to infinity. We also prove that any light cone will eventually contain some energy. As an application we obtain a result about the asymptotic behaviour of solutions to focusing one-dimensional wave equation with compact-supported initial data.
Airborne in situ measurements of aerosol size distributions and black carbon across the Indo-Gangetic Plain during SWAAMI–RAWEX

Abstract. During the combined South-West Asian Aerosol–Monsoon Interactions and Regional Aerosol Warming Experiment (SWAAMI–RAWEX), collocated airborne measurements of aerosol number–size distributions in the size (diameter) regime 0.5 to 20 µm and black carbon (BC) mass concentrations were made across the Indo-Gangetic Plain (IGP), for the first time, from three distinct locations, just prior to the onset of the Indian summer monsoon. These measurements provided an east–west transect of region-specific properties of aerosols as the environment transformed from mostly arid conditions of the western IGP (represented by Jodhpur, JDR) having dominance of natural aerosols to the central IGP (represented by Varanasi, VNS) having very high anthropogenic emissions, to the eastern IGP (represented by the coastal station Bhubaneswar, BBR) characterized by a mixture of the IGP outflow and marine aerosols. Despite these, the aerosol size distribution revealed an increase in coarse mode concentration and coarse mode mass fraction (fractional contribution to the total aerosol mass) with the increase in altitude across the entire IGP, especially above the well-mixed region. Consequently, both the mode radii and geometric mean radii of the size distributions showed an increase with altitude. However, near the surface and within the atmospheric boundary layer (ABL), the features were specific to the different subregions, with the highest coarse mode mass fraction (FMC∼72 %) in the western IGP and highest accumulation fraction in the central IGP with the eastern IGP in between. The elevated coarse mode fraction is attributed to mineral dust load arising from local production as well as due to advection from the west. This was further corroborated by data from the Cloud-Aerosol Transport System (CATS) on board the International Space Station (ISS), which also revealed that the vertical extent of dust aerosols reached as high as 5 km during this period. Mass concentrations of BC were moderate (∼1 µg m−3) with very little altitude variation up to 3.5 km, except over VNS where very high concentrations were seen near the surface and within the ABL. The BC-induced atmospheric heating rate was highest near the surface at VNS (∼0.81 K d−1), while showing an increasing pattern with altitude at BBR (∼0.35 K d−1 at the ceiling altitude).
Interactive language learning activities for learners’ communicative ability

Learners’ communicative in English language has been unsatisfactory due to the factors that affect their self-confidence and motivation to speak. However, the problem persisted even though ways were used to overcome the lack of communicative ability among learners in Malaysia. Therefore, this study was conducted to address learners’ perceptions of interactive language learning activities in improving English-speaking ability. The study aimed to analyse the effectiveness of the interactive language learning activities in motivating learners to speak in language classroom. A set of questionnaires containing two sections with 30 questions was administered. There were 50 primary school learners selected randomly to participate in this study. The results were collected and presented in the form of tables. The finding showed that self-confidence, motivation and learning environment affect the learners’ English language speaking ability and the results indicated that interactive language learning activities are able to overcome problems pertaining to communicative in language classroom. In conclusion, interactive language learning activities improved the learners’ English language speaking ability.
Applying BIM to support dispute avoidance in managing multi-owned buildings

With the growth of high-density living, disputes experienced by residents in multi-owned buildings (MOBs) have become an ongoing challenge in urban areas. A significant number of the disputations have found their root cause in the issues concerning improper use and management of MOBs by residents. It stems from their inaccurate understanding of ownership rights that are inherently 3D but using 2D cadastral survey plans, authoritative documents of ownership. This research explores the ability of building information modeling (BIM) to address required information for improving the perception of ownership rights that affect resident behaviors in managing MOBs. An open data model of BIM is extended to accommodate the necessary information for preventing resident misbehaviors that led to dispute cases in Victoria state, Australia. In this study, we implement BIM data of an MOB where a real dispute happened to demonstrate the validity of the enriched data model on the information delivery and an enhanced understanding of ownership rights. It is confirmed that the use of BIM facilitates the alleviation of the misbehaviors by informing residents with accurate communication of ownership rights and could support the avoidance of disputes in MOBs.
Teachers’ reflections on mathematics teaching practices in a vulnerable context

The objective of this research is to show the difficulties and the challenges identified by teachers in their mathematics teaching practices. The research is based on the concept of reflection-action, thus a workshop-course centered on collaborative work and on reflections about teaching practices was designed in order to achieve the objective. Ten mathematics teachers the Telebachillerato (Higher Secondary Education Subsystem, Mexico) participated in this research. The results show that teachers have a variety of challenges, but also difficulties, particularly involving getting students to construct knowledge autonomously, as well as teachers selecting and using resources in accordance to the subject matter to be taught. In addition, there is also lack of mathematical and pedagogical knowledge in the participants. Collaborative work is required, leading teachers towards building the necessary knowledge for Higher Secondary Education in order to avoid student obstacles.
Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.
ResFinder 4.0 for predictions of phenotypes from genotypes

Abstract Objectives WGS-based antimicrobial susceptibility testing (AST) is as reliable as phenotypic AST for several antimicrobial/bacterial species combinations. However, routine use of WGS-based AST is hindered by the need for bioinformatics skills and knowledge of antimicrobial resistance (AMR) determinants to operate the vast majority of tools developed to date. By leveraging on ResFinder and PointFinder, two freely accessible tools that can also assist users without bioinformatics skills, we aimed at increasing their speed and providing an easily interpretable antibiogram as output. Methods The ResFinder code was re-written to process raw reads and use Kmer-based alignment. The existing ResFinder and PointFinder databases were revised and expanded. Additional databases were developed including a genotype-to-phenotype key associating each AMR determinant with a phenotype at the antimicrobial compound level, and species-specific panels for in silico antibiograms. ResFinder 4.0 was validated using Escherichia coli (n = 584), Salmonella spp. (n = 1081), Campylobacter jejuni (n = 239), Enterococcus faecium (n = 106), Enterococcus faecalis (n = 50) and Staphylococcus aureus (n = 163) exhibiting different AST profiles, and from different human and animal sources and geographical origins. Results Genotype–phenotype concordance was ≥95% for 46/51 and 25/32 of the antimicrobial/species combinations evaluated for Gram-negative and Gram-positive bacteria, respectively. When genotype–phenotype concordance was <95%, discrepancies were mainly linked to criteria for interpretation of phenotypic tests and suboptimal sequence quality, and not to ResFinder 4.0 performance. Conclusions WGS-based AST using ResFinder 4.0 provides in silico antibiograms as reliable as those obtained by phenotypic AST at least for the bacterial species/antimicrobial agents of major public health relevance considered.