bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of action and resistance to Trastuzumab Deruxtecan in patients with metastatic breast cancer: the DAISY trial
Authors: Andre Fabrice , Fernanda Mosele , Deluche Elise , LUSQUE Amelie , Le-Bescond Loic , Filleron Thomas , Pradat Yoann , Ducoulombier Agnes , Pistilli Barbara , Bachelot Thomas , Viret Frederic , LEVY Christelle , Signolle Nicolas , Alfaro Alexia , Tran Diep , GARBERIS Ingrid , Talbot Hugues , Christodoulidis Stergios , Vakalopoulou Maria , Droin Nathalie , Stourm Aurelie , Kobayashi Maki , Kakegawa Tomaya , Lacroix Ludovic , Saulnier Patrick , Job Bastien , Deloger Marc , Jimenez Marta , Baris Vianney , Laplante Pierre , Kannouche Patricia , Marty Virginie , Lacroix-Triki Magali , Dieras Veronique 
Published: September 2022

Abstract
Trastuzumab deruxtecan (T-DXd) is an anti-HER2 (human epidermal growth factor receptor 2) antibody-drug conjugate which has previously shown efficacy in patients with HER2-overexpressing and HER2-low metastatic breast cancer (mBC). However, the mechanisms of action and resistance of this drug remain partially unclear. DAISY (NCT04132960) is a phase II, open-label study that included patients with mBC whose disease progressed after at least one line of chemotherapy in the metastatic setting. Patients were enrolled in three cohorts according to HER2 expression determined by immunohistochemistry (IHC); cohort 1: HER2-overexpressing (HER2 IHC 3 + or HER2 IHC 2+/ISH+, n = 72), cohort 2: HER2-low (HER2 IHC2+/ISH- or HER2 IHC 1+, n = 74), and cohort 3: HER2 IHC 0 mBC (n = 40). Patients were treated with T-DXd 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity. In the full analysis set population (n = 177), the confirmed objective response rate (ORR) was of 70.6% (95% CI: 58.3–81) in cohort 1, 37.5% (95% CI: 26.4–49.7) in cohort 2, and 29.7% (95% CI: 15.9–47) in cohort 3 (p < 0.0001). The median progression-free survival (PFS) was 11.1 months (95% CI: 8.5–14.4) in cohort 1, 6.7 months (95% CI: 4.4–8.3) in cohort 2, and 4.2 months (95% CI: 2-5.7); in cohort 3. Cohort 1 was significantly associated with longer PFS (adjusted HR: 0.53, 95% IC: 0.34–0.84, p = 0.007), and cohort 3 with shorter PFS (adjusted HR: 1.96, 95% IC: 1.21–3.15, p = 0.006) as compared to cohort 2. Exploratory analyses showed that HER2 spatial distribution predicted T-DXd response in patients with HER2-overexpressing mBC and that the transcriptomic response to T-DXd was different according to HER2 expression. No quantitative modulation of tumor microenvironment was observed after 6 to 8 weeks of treatment. Finally, recurrent mutations of the DNA repair gene SLX4 were identified in 20% of samples at resistance (4/20) as compared to 2% in baseline samples (2/88), suggesting that SLX4 mutations could mediate secondary resistance to T-DXd. These data suggest that HER2 is a key determinant of T-DXd efficacy. However, an antitumor activity is also observed in a subgroup of patients without detectable HER2 expression and resistance could be partially mediated by payload sensitivity.
Automatic classification of risk and priority in Emergency Care through the Manchester Triage System
Authors: Bastos Daniel S. , Meireles Magali R. G. 
Published: September 2022

Abstract

A large part of the population does not have access to Emergency Departments or, when they do, face a crowded environment, increasing wait time for the service without their risk situation being assessed. The Manchester Triage System was developed to identify the degree of priority of patients who come to the Emergency Department and to improve the quality of care in emergency services, redefining the flow of care by prioritizing patients who are in the most serious conditions. This work aims to make a comparison between six classifiers, based on the Manchester Triage System, with the data present during patient intake. The purpose is that the model can correctly classify their priority in emergency care. The experiments were conducted with a pediatric emergency database from hospitals in The Netherlands, Portugal and the United Kingdom. With the results obtained by the classifiers' performance, the best performing model was the Random Forest, with 78.20% for accuracy and 78.60% for F1-score. The expectation is that, by automating the classification process, health professionals will have a reliable tool to conduct risk assessment more accurately, having as a side-effect, less crowded Emergency Departments and reducing patient health deterioration due to misclassification and waiting time.
Evaluation of multivariate Gaussian transforms for geostatistical applications
Authors: Sepúlveda Exequiel , Adeli Amir , Dowd Peter A. , Ortiz Julian M. , Abulkhair Sultan , Xu Chaoshui 
Published: September 2022

Abstract
Traditional geostatistical simulation techniques rely on the assumption of multi-Gaussianity. Although the normal score transform is widely used to convert data to a Gaussian distribution, it only guarantees that the normal scores will be univariate Gaussian and the variables may still have complex multivariate relationships. For this reason, multi-Gaussian transforms became popular for simplifying multivariate geostatistical modelling. This study evaluates three multi-Gaussian transforms: flow transformation, projection pursuit multivariate transform, and rotation based iterative Gaussianisation. Three two-dimensional synthetic case studies were designed with complex multivariate relationships to make it difficult to produce good multivariate Gaussian distributions. The quality of the fitted transforms, the forward transformation of data from the same population and the back transformation from a standard multivariate Gaussian distribution were assessed based on statistical indices and visual inspection. The methods were also evaluated using a real case study with eight variables from the Prominent Hill copper deposit in South Australia. The effects of multi-Gaussian transforms on the reproduction of variograms, univariate and bivariate statistics were qualitatively and quantitatively investigated.
Metarhizium robertsii with insecticidal activity for the control of the fruit fly (Anastrepha obliqua), the main pest in mango crop in Colombia
Authors: Lozano-Tovar María Denis , Álvarez Karen Lorena Ballestas , Sandoval-Lozano Luis Andrés , Mendez Gloria Milena Palma , Barrera-Cubillos Gloria Patricia 
Published: September 2022

Abstract
The aim of this study was to evaluate and select entomopathogenic fungi that produces insecticidal compounds for the control of adults of Anastrepha obliqua Macquart (Diptera: tephritidae), that are the main pest of mango (Mangifera indica L. Bark) in Colombia. One strain of the species Metarhizium robertsii with insecticidal activity was selected. By column fractionation, an active fraction was obtained, this compound caused mortalities higher than 90% after 48 hours of exposure. By HPLC it was determined that the active fraction is composed of more than 22 metabolites. Identification of the extracts by UHPLC MS/MS reveal the presence of destruxin in the groups E, D, A and B (destruxin E-diol, destruxin D, destruxin D1, destruxin D2, destruxin A2, destruxin A, destruxin A3, dihydrodestruxin A, desmB, destruxin B2, destruxin B, and destruxin B1). The evaluation of the insecticidal capacity of the organic fractions obtained by HPLC indicated that the extract obtained from the isolate Metarhizium robertsii had a compound with high activity on adults of A. obliqua (destruxin A) causing massive mortality of up to 100%, 48 hours after treatment administration. Furthermore, two other compounds with medium activity were found (destruxin A2 and destruxin B), showing mortalities between 60.0 and 81.3% respectively. The extract of the isolate MT008 of M. robertsii showed higher insecticidal activity and is a potential source for the control of A. obliqua.
Efficacy and safety of iguratimod as an add-on therapy for refractory Lupus Nephritis: a Preliminary Investigational Study
Authors: Yan Qingran , Zhang Mei , Du Fang , Kang Yuening , Liu Bei , Ye Ping , Dai Min , Bao Chunde 
Published: September 2022

Abstract
Objectives:
Iguratimod (IGU), a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective and safe as monotherapy in a small population with refractory lupus nephritis (LN). The aim of this prospective study was to evaluate the efficacy and safety of iguratimod as an add-on therapy in patients with refractory LN in the context of clinical practice.
Methods:
We have enrolled LN patients since 2019 at Renji Hospital. All participants should have recurrent or refractory LN with at least one immunosuppressant (IS) and have a baseline urine protein/creatinine ratio (UPCR) >1.0. After enrollment, we added iguratimod (25 mg twice daily) to one of their previous IS without increasing the dose of steroids. The primary outcome was the complete renal response (CRR) in the 6th month. UPCR decrease of over 50% was defined as partial response (PR). Extended follow-up was performed after the initial 6 months.
Results:
We enrolled 26 eligible participants. 11/26 patients had chronic kidney disease (CKD) stage 2/3 at the baseline. The IS combined with IGU included mycophenolate mofetil, tacrolimus, and cyclosporin A. 80.7% of patients had baseline steroids less than 0.5mg/kg daily and there was no steroids escalation during the IGU treatment. The CRR rate was 42.3% (11/26) at month 6. With a median follow-up of 52 weeks (range: 23-116 weeks), the CRR rate at the last visit was 50% (13/26) and 73.1% (19/26) of patients had UPCR decrease of over 50%. Six patients withdrew, three for no response and three for renal flare after initial CRR. One patient had an estimated glomerular filtration rate worsening of over 20% and was classified as renal flare. Three mild to moderate adverse events were recorded.
Conclusions:
Our study merits IGU a potentially effective, safe, and versatile component of combination therapy for refractory LN.
Potash mining friction factor determination using CFD
Authors: de Felipe J. J. , Vives_Costa Jordi , Bascompte Marc , Niubó Maria , Sanmiquel Lluis 
Published: September 2022

Abstract
Friction factor is a crucial parameter for assessing and modelling the ventilation system in underground mining, becoming essential as we deepen the mining activity. This parameter is related to the loss of energy due to air friction inside the mine and consequently to the energy consumption in the fans. So, it must properly calculate in order to reduce operating costs and thus improve mineral prices. This paper presents the calculation of the friction factor through a CFD model of a potash mine case study for different mean roughness and typical velocities. Results are compared with friction factors calculated through traditional empirical relationships. The comparison of both data has given some differences, especially for relative high Reynolds numbers, for low Reynolds numbers it is verified that there is also a dependence with himself. Thus, it is proposed a correction for calculate friction factor with Colebrook-White and Von Karman expressions for the particular case of potash mines.
Prevalence of abnormal semen parameter among the male partner of infertile couple and factors associated with abnormal semen parameter
Authors: Panda Subrat , AGARWAL MANIKA , Das Ananya , Saha anusmita , Shullai Wansa , Jante Vinayak , basu Ritisha , Baruah Pratitee , Makakmayum Ruksana , Gowda Namita 
Published: September 2022

Abstract
This is a hospital-based observational study to estimate the prevalence of abnormal semen parameters in the northeast part of India and the effect of aging, lifestyle, and habits associated with it.
Methodology- This study was conducted among the male partner of the infertile couple who attended our infertility clinic from Jan 2019 to July 2021. After written consent semen samples were collected and analyzed in our andrology lab based on the 2010 WHO recommendation. For each male partner two consecutive sample collected one month apart and the study result was mean of two sample analysis. Result of seminal analysis,.age, lifestyle, habits, and occupational exposure associated with different semen parameters were collected and analyzed by using SPSS Software version 22, with unpaired T test and Logistic regression analysis.
RESULT In this study 14.8% males had oligospermia, 14.2% had Semen volume < 1.5ml,51..8% had total motility less than 50% ,(62.2%) had progressive motility less than 32%.and23.3.% had normal morphology < 4% and 25.6% had vitality < 58% .Semen volume was reduced in the age group more than 40 years (P value 0.000 ExpB 2.6) and with smoking (ExpB1.99). Sperm count was significantly less in the age group > 40years and with smokers( P VALUE-0.000,.0.012)Reduction in BMI increases sperm concentration. Smoking affects the total motility of sperms (ExpB 1.873). Progressive motility was affected by smoking and alcohol ( P value 0.000,0.000 ExpB 2.19,2.02). Vitality was affected by smoking, alcohol, and increased BMI (p-value 0.010,0.041, 0.000, ExpB 1.27.1.3,1.1). Morphology was affected by smoking, alcohol, (p-value − 0.00, 0.000, ExpB 1.57, 1.13) and with exposure to pesticide
Conclusion– Increased age above forty affect semen volume, and sperm count. Increased BMI negatively associated with sperm count, vitality ,and morphology. Alcohol intake affects progressive motility,vitality and morphology.Smoking affect all parameter of semen,and exposure to pesticide increases abnonrmal morphology
Observation of Distinct Phase Transitions in a Nonlinear Optical Ising Machine
Authors: Kumar Santosh , Li Zhaotong , Bu Ting , Qu Chunlei , Huang Yuping 
Published: September 2022

Abstract
Optical Ising machines promise to solve complex optimization problems with an optical hardware acceleration advantage. Here we study the ground state properties of a nonlinear optical Ising machine realized by spatial light modulator, Fourier optics, and second harmonic generation in a nonlinear crystal. By tuning the ratio of the light intensities at the fundamental and second-harmonic frequencies, we experimentally observe two distinct ferromagnetic-to-paramagnetic phase transitions: a second-order phase transition where the magnetization changes to zero continuously and a first-order phase transition where the magnetization drops to zero abruptly as the effective temperature increases. Our experimental results are corroborated by a numerical simulation based on the Monte Carlo Metropolis-Hastings algorithm, and the physical mechanism for the distinct phase transitions can be understood with a mean-field theory. Our results showcase the great flexibility of the nonlinear optical Ising machine, which may find important potential applications in solving combinatorial optimization problems.
A classification of meibomitis and an algorithm of its treatment
Authors: Sukhomlinov A. E. , Baranov V. I. , Kruchinina A. A. 
Published: September 2022

Purpose. To develop a classification of meibomitis accounting for the diverse course and stages of progression and offer guidelines for treatment based on the algorithm proposed.Materials and methods. We observed 56 patients aged 4 to 68 (average age 33 years), of which 42 patients (75 %) were followed up for periods from 3 to 60 days. The patients received basic complex conservative treatment, probing the meibomian gland with an eyelash during the acute inflammation and microabscess stage, in the presence of the chalazion with and without inflammation manifestations, and underwent drainage of the microabscess or the chalazion according to the classification.Results. The proposed algorithm reduced the duration of meibomitis treatment. Relapses were only noted in 2 cases; one case was complicated by corneal erosion caused by hardened oil. No complications associated with the treatment have been noted and nobody was prescribed surgical removal of the chalazion.Conclusion. A meibomitis classification with effective combined treatment has been proposed, which is convenient for practitioners, cost-effective and not requiring special instruments or materials.
Antagonistic activity of synbiotics: Response surface modeling of various factors
Authors: Evdokimova Svetlana , Karetkin Boris , Zhurikov Mikhail , Guseva Elena , Khabibulina Natalia , Shakir Irina , Panfilov Victor 
Published: September 2022

Synbiotic compositions have a great potential for curing microbial intestinal infections. Novel targeted synbiotics are a promising field of the modern functional food industry. The present research assessed the effect of various fructan fractions, initial probiotic counts, and test strains on the antagonistic properties of synbiotics.
The research involved powdered roots of Arctium lappa L. and strains of Bifidobacterium bifidum, Bacillus cereus, and Salmonella enterica. The experiment was based on the central composite rotatable design. A water extract of A. lappa roots was purified and concentrated. Fructan fractions were precipitated at various concentrations of ethanol, dried, and sub jected to carbon-13 nuclear magnetic resonance (13C-NMR) spectrometry. The bifidobacteria and the test strains were co-cultivated in the same medium that contained one of the fractions. Co-cultivation lasted during 10 h under the same conditions. The acid concentrations were determined by high-performance liquid chromatography to define the synbiotic factor.
The obtained fructans were closer to commercial oligofructose in terms of the number and location of NMR peaks. However, they were between oligofructose and inulin in terms of signal intensity. The response surface analysis for bacilli showed that the minimal synbiotic factor value corresponded to the initial probiotic count of 7.69 log(CFU/mL) and the fructan fraction precipitated by 20% ethanol. The metabolites produced by the bacilli also affected their growth. The synbiotic factor response surface for the experiments with Salmonella transformed from parabolic to saddle shape as the initial test strain count increased. The minimal synbiotic factor value corresponded to the lowest precipitant concentration and the highest probiotic count.
The research established a quantitative relationship between the fractional composition of fructans and the antagonistic activity of the synbiotic composition with bifidobacteria. It also revealed how the ratio of probiotic and pathogen counts affects the antagonism. The proposed approach can be extrapolated on other prebiotics and microbial strains in vivo.
Digital Storytelling Methods to Empower Young Black Adults in COVID-19 Vaccination Decision-Making: Feasibility Study and Demonstration
Authors: Maragh-Bass Allysha , Comello Maria Leonora , Tolley Elizabeth Ellen , Stevens Jr Darrell , Wilson Jade , Toval Christina , Budhwani Henna , Hightow-Weidman Lisa 
Published: September 2022

Background
Despite high rates of novel COVID-19, acceptance of COVID-19 vaccination is low among Black adults. In response, we developed a digital health intervention (Tough Talks-COVID) that includes digital stories created in a workshop we held with young Black adults.

Objective
Our formative research using digital storytelling workshops asked 3 research questions: (1) What issues did participants have in conceptualizing their stories, and what themes emerged from the stories they created? (2) What issues did participants have related to production techniques, and which techniques were utilized in stories? and (3) Overall, how did participants evaluate their workshop experience?

Methods
Participants were workshop-eligible if they were vaccine-accepting based on a baseline survey fielded in late 2021. Final participants (N=11) completed a consent process, all 3 workshops, and a media release form for their digital story. The first 2 workshops provided background information and hands-on digital storytelling skills from pre- to postproduction. The third workshop served as a screening and feedback session for participants’ final videos. Qualitative and quantitative feedback elements were incorporated into all 3 sessions.

Results
Digital stories addressed one or more of 4 broad themes: (1) COVID-19 vulnerability, (2) community connections, (3) addressing vaccine hesitancy, and (4) countering vaccine misinformation. Participants incorporated an array of technical approaches, including unique creative elements such as cartoon images and instant messaging tools to convey social interactions around COVID-19 decision-making. Most (9/11, 82%) strongly agreed the digital storytelling workshops were delivered as expected; 10 of 11 agreed (n=5) or strongly agreed (n=5) that they had some ideas about what story to tell by the end of the first workshop, and most (8/11, 73%) strongly agreed they had narrowed down their ideas by workshop two. Of the participants, 9 felt they would very likely (n=6) or likely (n=3) use digital storytelling techniques for personal use in the future, and even more were very likely (n=7) to use the techniques for professional use.

Conclusions
Our study is one of the first to incorporate digital storytelling as a central component to a digital health intervention and the only one to do so with exclusive focus on young Black adults. Our emphasis on digital storytelling was shown to be highly acceptable. Similar approaches, including careful consideration of the ethical challenges of community-based participatory approaches, are applicable to other populations experiencing both COVID-19 inequities and marginalization, such as other age demographics and people of color.
Online sexual harassment among young female students in Ward 10, Baneshwor, Kathmandu, Nepal
Authors: Sharma Krishna , Shrestha Prabin , Shrestha Vijaya Laxmi , Shrestha Ram Bahadur 
Published: September 2022

Background: Incidences of sexual harassment that occur over the internet
are growing with the development of new technologies and virtual
communities. This is a hidden form of sexual harassment that emerges
unpredictably and poses a public health challenge. The objective of this
study was to determine the extent of online sexual harassment
experienced by female students (aged 15–24 years) in Baneshwor (Ward
10), Kathmandu, Nepal. Methods: A total of 382 female students aged
15–24 – high school (10+2 level) to bachelor level – participated in
a quantitative cross-sectional study. A semistructured questionnaire, in
the English language, was designed for selfadministered data collection.
It comprised six sections: sociodemographic information, internet
accessibility, use of social media, experience of online sexual
harassment, student’s awareness and online behaviour.
Results: Around 66.5% of respondents reported having been exposed to
online sexual harassment at least once, and most of the respondents
(73.2%) had been exposed to online sexual harassment multiple times.
Just under twothirds (62.8%) of the respondents had been exposed to
online sexual harassment before they reached 18 years of age. The mean
age at which the young women experienced online sexual harassment was
18.94±1.79 years. Respondents studying in high school (10+2 level),
those residing in urban areas and those accepting friend requests on
social media from people they did not know offline were at higher risk
of experiencing frequent online sexual harassment (P=0.000, P=0.011, and
P=0.013 respectively). Conclusion: The rate of online sexual harassment
recorded was high. This shows an urgent need to address the problem;
universities and the government need to play a part. A new module of
comprehensive sexuality education for virtual communication is suggested
as an addition to current academic curriculums.