Miracle-dz/UniFAR-FTUs huggingface dataset:
HER2-Targeted Antibody–Drug Conjugates Display Potent Antitumor Activities in Preclinical Extramammary Paget’s Disease Models: In Vivo and Immunohistochemical Analyses

Simple Summary The prognosis for advanced Extramammary Paget’s disease (EMPD) is almost always poor. HER2-targeted antibody–drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven to be effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. Our results suggest that HER2-targeted ADCs could be novel and promising treatment options for patients with EMPD, especially in cases with the ERBB2-mutation or ERBB2-overexpression. Abstract Extramammary Paget’s disease (EMPD) is an adenocarcinoma that develops mainly in the genital region of older adults. The prognosis for advanced EMPD is almost always poor; thus, novel therapeutic strategies need to be developed. HER2-targeted antibody–drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations and investigate the expression levels of HER2 using EMPD clinical samples. Trastuzumab emtansine or trastuzumab deruxtecan was administered intravenously to tumor-bearing NOD/Scid mice. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. EMPD tumors extracted 48 h after drug administration revealed the TUNEL-positive ratio to be significantly higher for the HER2-targeted ADC-treated tumors than for the control tumors. EMPD patients’ clinical samples revealed a significant correlation between HER2 positivity and invasion, suggesting that HER2 status is associated with tumor progression. Our results suggest that HER2-targeted ADCs could be novel and promising treatment options for patients with EMPD, especially in ERBB2-mutant or ERBB2-overexpressed cases.
Simulation Aided Hardening of Power Diodes to Prevent Single Event Burnout

This article presents the coupled electrothermal simulation results of single event burnout (SEB) in power diode with field limiting rings termination structure. Two different hardening techniques of low carrier lifetime control and introducing the buffer layer are investigated comparatively in both the radiation tolerance improvement and the electrical performance degradation. Our simulations reveal that a significant reduction in the carrier lifetime is needed for the hardening of the power diode using only the carrier lifetime control method. However, the sharp increases in the forward voltage drop and the leakage current at the lower carrier lifetime make this hardening technique unacceptable. On the contrary, the addition of the buffer layer is able to improve the safe operating area under the heavy ion irradiation even up to the breakdown voltage, while the breakdown characteristics and the leakage current are kept unchanged and the increases in the forward voltage drop and the reverse recovery charge can be well controlled. In conclusion, adding a buffer layer is considered a superior and promising hardening technique.
Mechanical properties of concrete containing recycled coarse aggregate at and after exposure to elevated temperatures

This paper presents the effect of recycled coarse aggregate (RCA) of 50% and 100% by wt. on compressive strength and elastic modulus of concrete at elevated temperatures of 600 and 800 °C. The residual compressive strengths of above recycled aggregate concretes after exposure to elevated temperatures are also evaluated and compared to those measured during heating. The effect of polypropylene (PP) fibers on residual compressive strength and cracking behavior of above recycled aggregate concretes after exposure to elevated temperatures is also evaluated in this study. Results show that the loss of compressive strength of recycled aggregate concretes at 600 and 800 °C is slightly higher (about 10%) than its counterpart control concrete containing natural coarse aggregates. Concrete containing 100% RCA exhibited about 50% loss of its ambient temperature compressive strength at 800 °C, which is about 25% less in concrete containing 50% RCA. The residual compressive strength, which is measured after cooling of heated specimens, of both recycled aggregate concretes and control concrete is higher at both elevated temperatures. The measured elastic modulus of both recycled aggregate concretes show no significant reduction compared to their counterpart control concrete at both elevated temperatures. A strong correlation between elastic modulus and square root of compressive strength of recycled aggregate concretes is observed at elevated temperatures. The model proposed in Eurocode to predict the elevated temperature compressive strength and elastic modulus agrees well with the measured values for recycled aggregate concretes. The addition of PP fibers reduced the residual compressive strength of concrete containing 100% RCA at both temperatures with significant reduction at 800 °C. However, mixed results are obtained in the case of concrete containing 50% RCA. The cracking patterns of concrete containing RCA and those containing PP fibers also correlated well with the observed residual compressive strength results.
Differentially-Driven Robots Moving in Formation—Leader–Follower Approach

The paper is devoted to the leader–follower approach for multiple mobile robots control and its experimental verification. The formation control of mobile robots is motivated by the concept of virtual leader tracking, which is enhanced by the collision avoidance between the robots proposed in our previous work. The effectiveness of this approach was verified through realisation of experiments with use of MTracker mobile robots. The OptiTrack vision system was used for robots localization. Software part with control algorithms and communication was prepared with use of the Robot Operating System.
β-Glucan-Functionalized Nanoparticles Down-Modulate the Proinflammatory Response of Mononuclear Phagocytes Challenged with Candida albicans

Systemic fungal infections are associated with significant morbidity and mortality, and Candida albicans is the most common causative agent. Recognition of yeast cells by immune cell surface receptors can trigger phagocytosis of fungal pathogens and a pro-inflammatory response that may contribute to fungal elimination. Nevertheless, the elicited inflammatory response may be deleterious to the host by causing excessive tissue damage. We developed a nanoparticle-based approach to modulate the host deleterious inflammatory consequences of fungal infection by using β1,3-glucan-functionalized polystyrene (β-Glc-PS) nanoparticles. β-Glc-PS nanoparticles decreased the levels of the proinflammatory cytokines TNF-α, IL-6, IL-1β and IL-12p40 detected in in vitro culture supernatants of bone marrow-derived dendritic cells and macrophage challenged with C. albicans cells. Moreover, β-Glc-PS nanoparticles impaired the production of reactive oxygen species by bone marrow-derived dendritic cells incubated with C. albicans. This immunomodulatory effect was dependent on the nanoparticle size. Overall, β-Glc-PS nanoparticles reduced the proinflammatory response elicited by fungal cells in mononuclear phagocytes, setting the basis for a targeted therapy aimed at protecting the host by lowering the inflammatory cost of infection.
Innovation in Pediatric Clinical Education: The Development of a Clinical Instructor Toolkit

Supplemental Digital Content is Available in the Text. Introduction/Literature Review: Clinical education (CE) experiences are essential components of physical therapist assistant (PTA) and professional physical therapist education requiring qualified clinical instructors (CIs). The 2014 CE Summit recognized the need for CI development. The Academy of Pediatric Physical Therapy Academic and Clinical Educators special interest group assembled a task force to address the need for pediatric CI resources. The purposes of this study are to describe the process used to create a pediatric CI Toolkit and describe the results of the task force's work as a mechanism to meet the needs of CIs to facilitate clinical teaching. Participants: Pediatric PTAs and physical therapists (PTs) engaged in physical therapy CE were included in the needs assessment survey. The target population of the survey also represented the intended users of the created CI Toolkit. Method: A task force composed of individuals with diverse pediatric subspecialties, geographic regions, and roles in CE convened to create the CI Toolkit. The task force completed a literature search and online CE resources search to assist with survey development and with guidance in the development of the CI Toolkit. A needs assessment survey was created and deployed to gather information from pediatric PTAs and PTs. The task force developed the structure of the CI Toolkit and collected resources to populate the online tool. Results: An online CI Toolkit was created and contained 160 resources organized into topics, settings, and descriptors. Tools include resources for clinical reasoning, student assignments, general resources, weekly objectives, and CI development. A four-person committee was created to review proposed additions to the CI Toolkit. Discussion and Conclusion: The CI Toolkit is a model for accessible CI professional development for clinical teaching and learning. Health professions educators interested in creating resources for clinical educators will benefit from the lessons learned in the creation of the CI Toolkit.
Drivers Influencing the Adoption Intention towards Mobile Fintech Services: A Study on the Emerging Bangladesh Market

People’s acceptance of technological changes has escalated with time. However, the acceptance and adoption of fintech services hiked after the outbreak of the virulent coronavirus. With this breakout, the adoption of mobile fintech services (MFS) increased among general citizens and business sectors around the world, including in developed, emerging, and developing economies. This study aimed to identify the factors that impact the adoption intention of consumers to embrace and enhance the use of mobile fintech services in an emerging market, Bangladesh. A research model was developed to strengthen the objective of this paper. A total of 218 respondents responded to the questionnaire. The study utilized structural equation modeling to analyze the results in SmartPLS software. The results showed significant positive effects of social influence, trust, perceived benefit, and facilitating conditions on the adoption intention towards MFS. Mobile fintech service providers must keep their users’ needs and literacy rates in mind when designing the user interface (UI). Moreover, they should also cater more efficient services to the users and work based on the feedback received. The customers’ satisfaction will ultimately lead to customers conducting more digital transactions and will contribute to the escalation of fintech transactions, resulting in more financial inclusion.
Reversible and irreversible effects of mild thermal treatment on the properties of wood used for making musical instruments: comparing mulberry to spruce

Thermal treatments can be considered as an accelerated ageing, bringing partly similar changes in properties as naturally aged wood. Thermal treatment was applied on white mulberry ( Morus alba L.), a dominant species for making musical instruments from middle-East to Far-East, to investigate the effects on the vibro-mechanical and physical properties of this wood, and the results compared to previously published data on spruce ( Picea abies Karst.) as a reference for the soundboard of Western string instruments. Thermal treatment (TT) at 150 °C and 0% of relative humidity was applied to five anal-ogous groups of specimens with five different durations (2.5, 8, 24, 72, 261 hours). Humidity re-conditioning of specimens was done to explore the reversibility of TT effects. Physical and vibrational properties such as specific gravity ( γ ), equilibrium moisture content (EMC), CIELab colorimetric values, specific modulus of elasticity ( E ’/ γ ) and damping coefficient (tan δ ) in longitudinal (L) and radial (R) directions, have been measured after stabilisation of samples in standard conditions (20 °C, 65% RH), before and after TT and then after re-conditioning. Untreated mulberry had a low EMC, very low L/R anisotropy and low E ’ L / γ , and relatively low tan δ . Weight loss (WL) and CIELab values evolved similarly during TT for mulberry and for previous results on spruce, however, their EMC and vibrational properties were affected differently. This could be explained in part by the low anisotropy of mulberry, and in part by its particular extractives. The parts of irreversible effects, linked to chemical modification or degradation, and of reversible effects, linked to physical con-figuration, were different between mulberry and spruce. The applied treatments did not bring permanent “improvements” in vibrational properties of mulberry, yet its colour appearance was enhanced.
An Application of Multiple-Criteria Decision Analysis for Risk Prioritization and Management: A Case Study of the Fisheries Sector in Pakistan

In Pakistan, the fisheries sector is capable of making a significant contribution to the national economy. However, the proper and sustainable development of this sector is essential to its success, and we need to be aware of all the risks that it faces. At present, there is a dearth of comprehensive research that details, compares, and proposes applied measures to mitigate the risks facing the fisheries sector. Thus, this study is the first novel attempt to fill this gap. The data were collected through a survey and analyzed by multi-criteria decision analysis (MCDA). The study postulates that Sindh fisheries are affected by five main risk factors, namely technical, market, ecological, natural, and management. These risk factors are arranged from least to most significant. With regard to the performances of the main risk factors, management risk was ranked as the greatest risk, followed by ecological risk, natural risk, and technical risk. The findings of this study provide a road map for managerial decisions. Furthermore, this study also presents some potential limitations related to the scale of the data and analysis methods. Future studies may therefore use data collected on a large scale and alternative quantitative approaches.
THE EFFECTIVENESS OF USING AUDIOVISUAL MEDIA IN LEARNING TO WRITE INDONESIAN DRAMA SCRIPT

This research aims to prove the effectiveness of using audiovisual media in learning to write drama scripts for students. The population in this research were students of class XII Social Science which collected 90 people from three classes. The sample was determined by purposive sampling technique in order to obtain 2 classes as the experimental and control classes. The research design was a quasi-experimental. The instrument used is a drama writing test. The collected data were analyzed using descriptive analysis and inferential analysis in the form of independent t-test. The results showed that the group using audiovisual media obtained better results than audio media. The results of the study were evidenced by a t-test which showed that audiovisual media was effectively used in learning to write drama scripts. The implication of this research is that teachers can improve students' ability to write Indonesian drama scripts using audiovisual media. Abstrak: Penelitian ini bertujuan untuk membuktikan keefektifan penggunaan media audiovisual dalam pembelajaran menulis naskah drama siswa. Populasi dalam penelitian ini adalah siswa kelas XII IPS yang berjumlah 90 orang dari tiga kelas. Sampel ditentukan dengan teknik purposive sampling sehingga diperoleh 2 kelas sebagai kelas eksperimen dan kelas kontrol. Desain penelitian adalah eksperimen semu. Instrumen yang digunakan adalah tes menulis drama. Data yang terkumpul dianalisis menggunakan analisis deskriptif dan analisis inferensial berupa independent t-test. Hasil penelitian menunjukkan bahwa kelompok yang menggunakan media audiovisual memperoleh hasil yang lebih baik dibandingkan media audio. Hasil penelitian tersebut dibutikan dengan uji-t yang menunjukkan bahwa media audiovisual efektif digunakan dalam pembelajaran menulis naskah drama. Implikasi penelitian ini adalah guru dapat meningkatkan kemampuan siswa menulis naskah drama bahasa Indonesia dengan menggunakan media audiovisual.
Mast Cell Population and Histamine Content in Hypothyroid Rat Tissues

Simple Summary In this study, we investigated the putative regulatory role of the pituitary–thyroid axis on mast cells (MCs). We found that hypothyroidism resulted in a significant increase in number of MCs and the histamine content in the skin and exorbital lacrimal gland of Wistar rats, Rattus norvegicus. Furthermore, an increase in the percentage of degranulating MCs suggests that the thyroid status also influences the activation state of these cells. Abstract The morphological features and relative number of mast cells (MCs) were studied in the skin and exorbital lacrimal glands of hypothyroid Wistar rats, Rattus norvegicus. Hypothyroidism significantly increased the number of MCs (up to 4.5-fold) and histamine content (up to 50%) in the examined tissues. The magnitude of the increase in the number of MCs was greater in the cheek skin and exorbital lacrimal glands than in the back skin. In the skin, the MCs were mainly located within the hypodermis and closely associated with the blood vessels, nerve fascicles, and adipocytes. In the exorbital lacrimal gland, which is a seromucous gland located lateral to the cheek below the ear, the MCs were distributed in the connective tissue surrounding the acini. The secretory granules of MCs showed histochemical characteristics of connective tissue MCs. They were metachromatic with Toluidine blue and safranin positive with the Alcian blue/safranin reactions. Finally, a significant increase in degranulating MCs was observed in hypothyroid tissues, relative to euthyroid tissues. At the ultrastructural level, the MCs of euthyroid rats were predominantly non-degranulating (Stage I). In hypothyroid animals, numerous MCs showed partial degranulation (Stage II–III) or were in a stage of complete degranulation. Our results concerning the skin and exorbital lacrimal gland suggested that the thyroid status might be involved in regulating the frequency and activation state of MCs.
Behavioral Patterns beyond Posting Negative Reviews Online: An Empirical View

Negative reviews on e-commerce platforms are posted to express complaints about unsatisfactory experiences. However, the exact knowledge of how online consumers post negative reviews still remains unknown. To obtain an in-depth understanding of how users post negative reviews on e-commerce platforms, a big-data-driven approach with text mining and sentiment analysis is employed to detect various behavioral patterns. Specifically, using 1,450,000 negative reviews from JD.com, the largest B2C platform in China, the posting patterns from temporal, perceptional and emotional perspectives are comprehensively explored. A massive amount of consumers across four sectors in recent 10 years is split into five levels to reveal group discrepancies at a fine resolution. The circadian rhythms of negative reviewing after making purchases are found, suggesting stable habits in online consumption. Consumers from lower levels express more intensive negative feelings, especially on product pricing and customer service attitudes, while those from upper levels demonstrate a stronger momentum of negative emotion. The value of negative reviews from higher-level consumers is thus unexpectedly highlighted because of less emotionalization and less biased narration, while the longer-lasting characteristic of these consumers’ negative responses also stresses the need for more attention from sellers. Our results shed light on implementing distinguished proactive strategies in different buyer groups to help mitigate the negative impact due to negative reviews.
Association Between Serum Uric Acid Levels and Suicide Attempts in Adolescents and Young Adults with Major Depressive Disorder: A Retrospective Study

Purpose Uric acid (UA) is thought to exert neuroprotective roles. The purpose of this study was to examine the association of serum UA with suicide attempts (SA) in adolescents and young adults with major depressive disorder (MDD). Patients and Methods We retrospectively recruited 533 participants with MDD aged 13 to 25 years, of which 168 had a history of SA in the past three months and 365 did not have a history of SA. Serum UA levels were measured using the uricase-peroxidase coupling method. In addition to overall serum UA level comparison in MDD individuals with and without SA, a stratified analysis by biological sex was carried out. Results Compared to MDD individuals without a history of SA, serum UA levels were significantly lower in MDD individuals with SA (P < 0.001). Female MDD, but not male MDD individuals, with SA exhibited lower levels of UA than those without SA (P < 0.01). Importantly, serum UA remained significantly associated with SA in MDD individuals (OR = 0.996, 95% CI: 0.993~0.999, P < 0.01) when controlling for possible confounding variables. Conclusion This research identifies a relationship between serum UA levels and SA in adolescents and young adults with MDD. UA may represent a biological risk marker for SA, in particular for female MDD individuals.
The Impact of Vertical Theories of Harm on Investor Returns: An Event Study of US Vertical Mergers

The welfare implications of vertical mergers have been a subject of disagreement for decades. Similar to horizontal mergers, economists need to weigh the efficiency gains relative to the market power concerns when considering the competitive effects of vertical mergers. However, in vertical mergers, regulators are also concerned with other potential harmful effects, such as input and customer foreclosure. Using an event style technique, this paper explores these vertical theories of harm by comparing the abnormal returns of acquirers, targets, and the two combined in vertical and horizontal mergers that were challenged by regulators as potentially anticompetitive. Our results indicate that abnormal returns to targets were similar between vertical and horizontal mergers, but the gains to targets relative to acquirers were far higher in vertical versus horizontal mergers (53.6% versus 39.5%). In addition, we found that exclusionary effects have a positive impact (0.24% of the dollar abnormal return) on the bargaining position of targets. In contrast, acquirers gain 0.45% and 0.39% of the dollar abnormal return relative to targets when the antitrust concern entails collusive effects or elimination of potential competition, respectively.