bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONTACT-01: A phase III, randomized study of atezolizumab plus cabozantinib versus docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC) previously treated with PD-L1/PD-1 inhibitors and platinum-containing chemotherapy.
Authors: Neal Joel W. , Kundu Palak , Tanaka Tomohiro , Enquist Ida , Patel Sid , Balestrini Alessia , Wang Jin , Newsom-Davis Thomas , Goto Yasushi , Pavlakis Nick , Kim Sang-We 
Published: June 2021

TPS9134 Background: Patients with mNSCLC who progress on anti–PD-L1/PD-1 therapy administered in combination with or after platinum-based chemotherapy (PBC) are mainly treated with docetaxel or pemetrexed monotherapy. These therapies only have modest clinical activity, leaving a high unmet medical need. Cabozantinib, a tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment and may enhance the efficacy of PD-L1/PD-1 inhibitors, offering a promising second/third-line therapeutic opportunity for patients with mNSCLC. In a Phase Ib multi-cohort study (COSMIC-021; NCT03170960), cabozantinib plus atezolizumab (anti–PD-L1) showed an acceptable safety profile and promising efficacy (ORR: 27%; mDOR: 5.7 mo [range: 2.6-6.9]; disease control rate [CR + PR + SD]: 83%) in 30 patients with mNSCLC who had progressed after prior anti–PD-L1/PD-1 therapy plus chemotherapy (Neal et al. J Clin Oncol 2020). The Phase III CONTACT-01 study will further evaluate the efficacy and safety of atezolizumab plus cabozantinib versus docetaxel monotherapy in patients with mNSCLC who have progressed during or after prior treatment with anti–PD-L1/PD-1 therapy and PBC. Methods: CONTACT-01 (NCT04471428) is a Phase III, multi-center, randomized, open-label study that will enroll ≈350 patients from 150 to 200 sites internationally. Key eligibility criteria include histologically or cytologically confirmed mNSCLC, disease progression with concurrent or sequential anti–PD-L1/PD-1 treatment and PBC, measurable disease (RECIST 1.1), ECOG PS of 0-1 and the availability of tissue specimens for centralized PD-L1 testing or known PD-L1 status using a health authority–approved PD-L1 assay. Patients with NSCLC previously treated with cabozantinib, docetaxel or anti–PD-L1/PD-1 + VEGFR TKIs are excluded. Patients with known sensitizing EGFR/ALK mutations and active or untreated CNS metastases are also excluded. Patients will be randomized 1:1 to receive either atezolizumab (1200 mg IV every 3 weeks) + cabozantinib (40 mg orally once daily) or docetaxel (75 mg/m2 IV every 3 weeks). The primary endpoint is OS. Secondary endpoints include investigator-assessed PFS, ORR and DOR per RECIST 1.1; TTD in patient-reported physical function and global health status (EORTC QLQ-C30); investigator-assessed PFS rates at 6 months and 1 year; OS rates at 1 and 2 years; safety and PK. Clinical trial information: NCT04471428.
Characteristics of Patients with Type 1 Diabetes and Additional Autoimmune Disease in the DPV Registry
Authors: Prinz Nicole , Tittel Sascha R , Bachran Rainer , Birnbacher Robert , Brückel Joachim , Dunstheimer Désirée , Haberland Holger , Hess Melanie , Karges Wolfram , Oeverink Rudolf , Veigel Andreas , Holl Reinhard W 
Published: June 2021

Abstract

Context
Autoimmune diseases affect ~8% of the population. Type 1 diabetes mellitus (T1DM) is linked to other autoimmune diseases (AIDs), such as autoimmune thyroid disease or Addison’s disease (AD), that may impact diabetes therapy and outcome.

Objective
To analyze demographic and clinical characteristics of other AIDs in T1DM from a large standardized registry, the Prospective Diabetes Follow-up Registry (DPV).

Methods
We searched the registry for T1DM with the additional diagnosis of Hashimoto’s thyroiditis (HT), Graves’ disease (GD), and/or AD. T1DM with other AIDs (n = 6166, 5.4%) were compared with isolated T1DM (n = 107 457). For group comparisons, we used multivariable regression models with age, sex, diabetes duration, migration background, and type of insulin regimen as basic adjustments (microvascular endpoints: additionally adjusted for glycated hemoglobin).

Results
Patients with additional AIDs were more often female (54.7 vs 32.0%, P &lt; .001) and had a longer diabetes duration (7.9 [4.2-12.5] vs 6.7 [2.7-12.9] years, P &lt; .001). After adjustment, daily insulin dosage was higher in AD and HT than in isolated T1DM (0.858 ± 0.032 and 0.813 ± 0.005 vs 0.793 ± 0.001 IU/kg per day). Retinopathy was less common in HT (1.5%), whereas it was more frequent in GD (3.1%) than in isolated T1DM (1.8%). In both GD and HT, microalbuminuria occurred less often (10.6% and 14.3% vs 15.5%) and neuropathy (2.1% and 1.8% vs 0.8%) was more common than in isolated T1DM. All P &lt; .05.

Conclusion
T1DM with additional AIDs show heterogeneous differences compared with isolated T1DM. T1DM plus AD or HT requires more insulin. Further, the rate of neuropathy is higher in HT or GD, whereas the rate of microalbuminuria is lower.
Adding Branched-Chain Amino Acids to an Enhanced Standard-of-Care Treatment Improves Muscle Mass of Cirrhotic Patients With Sarcopenia: A Placebo-Controlled Trial
Authors: Hernández-Conde Marta , Llop Elba , Gómez-Pimpollo Lucía , Fernández Carrillo Carlos , Rodríguez Luís , Van Den Brule Enrique , Perelló Christie , López-Gómez Marta , Abad Javier , Martínez-Porras José Luís , Fernández-Puga Natalia , Ferre Carlos , Trapero María , Fraga Enrique , Calleja José Luis 
Published: June 2021

INTRODUCTION:
The effect of branched-chain amino acid (BCAA) supplementation on muscle mass in patients with cirrhosis and sarcopenia is unknown.

METHODS:
This is a pilot, prospective, randomized, and double-blind study of a cohort of 32 patients with cirrhosis and sarcopenia diagnosed by computed tomography scan who underwent a nutritional and physical activity intervention for 12 weeks. They were divided into 2 groups (placebo: 17 patients; BCAA: 15 patients). The study protocol was registered at ClinicalTrials.gov (NCT04073693).

RESULTS:
Baseline characteristics were similar in both groups. After treatment, only the BCAA group presented a significant improvement in muscle mass (43.7 vs 46 cm2/m2; P = 0.023). Seventeen patients (63%) presented improvement in muscle mass overall, which was more frequent in the BCAA group (83.3 vs 46.7%; P = 0.056). Regarding frailty, there was a significant improvement in the Liver Frailty Index in the global cohort (n = 32) after the 12 weeks (4.2 vs 3.9; P < 0.001). This difference was significant in both groups: in the placebo group (4.2 vs 3.8; P < 0.001) and in the BCAA group (4.2 vs 3.9; P < 0.001). After treatment, the BCAA group had a higher increase in zinc levels than the placebo group (Δzinc: 12.3 vs 5.5; P = 0.026). In addition, there was a trend for greater improvement of albumin levels in the BCAA group (Δalbumin: 0.19 vs 0.04; P = 0.091).

DISCUSSION:
BCAA supplementation improves muscle mass in cirrhotic patients with sarcopenia.
Coordinated control among PSS, WTG and BESS for improving Small-Signal Stability
Authors: Alias Feba , Singh Manohar 
Published: June 2021

Abstract
The goal towards attaining a sustainable future has led to the rapid increase in the integration of converter control based generators (CCBGs). The low inertia response characteristics of CCBGs and the weak tie lines in interconnected systems pose a huge threat to Small-Signal Stability (SSS). Adequate damping of low-frequency oscillations (LFO) is pivotal in ensuring the maximum power transfer through the critical transmission corridors. These operational issues become more serious with the significant reduction in system inertia as a result of the high penetration of CCBGs. Therefore, appropriate control techniques are an absolute requirement for preventing LFOs from limiting the penetration of CCBGs in interconnected networks. This may also eventually lead to revisions in grid codes mandating CCBGs to provide auxiliary damping control. But, the progressive addition of multiple damping controllers for specific target modes can lead to the drifting of eigenvalues (EVs) associated with other electromechanical modes (EMs) in the system. This is due to the adverse interactions between multiple damping controllers in the uncoordinated control approach and may result in deteriorating SSS. Therefore, this paper proposes a simultaneous coordinated control among Battery Energy Storage System (BESS), Wind Turbine Generators (WTG) and Power System Stabilizer (PSS) for enhancing SSS in networks with high wind penetration by considering both inter-area (IA) and local modes. The performance of the proposed coordinated control is corroborated using IEEE 68 bus system for multiple operating scenarios for which the critical modes in the system have the lowest damping index (DI). The effectiveness of modulating the active power, reactive power and simultaneous modulation of both active and reactive power injected by BESS along with a dual-channel Optimized WTG Damping Controller (DOWDC) and PSS is evaluated. The impact of the different coordinated control strategies on voltage dynamics is also investigated. The simulation results validate the better performance of the proposed coordinated control over uncoordinated control approaches.
How to have fun with sticks, bowls, and colored water: insights into multimodal signifier operations through Lacan’s four discourses
Authors: Ranker Jason 
Published: June 2021

Abstract
In this manuscript, I present a signifier-based, multimodal discourse analysis of a focal event involving four children (ages 4–5) as they interacted with materials and with one another in their preschool classroom. I draw upon Jacques Lacan’s theory of the four discourses, applying the mathemes, or formulas that he developed, in order to map the multimodal signifier operations as they occurred in the moment-to-moment interactions during the event. My purpose was to use the signifier as a conceptual tool for multimodal discourse analysis, which revealed the highly particular discursive agencies that are characteristic aspects of signifier operations. Further, I examined the movement and operations of the signifiers as they were drawn from across modes and combined to create opportunities for the subjects to participate in the discourse. These signifier operations occurred according to discursive agencies of an educational discourse that both reduced and delimited subjectivities, as well as agencies that the focal subjects introduced to challenge and re-signify toward new ways to participate in the discourse.
Indeterminate thyroid cytology: detecting malignancy using analysis of nuclear images
Authors: Hayashi Caroline Y , Jaune Danilo T A , Oliveira Cristiano C , Coelho Bárbara P , Miot Hélio A , Marques Mariângela E A , Tagliarini José Vicente , Castilho Emanuel C , Soares Carlos S P , Oliveira Flávia R K , Soares Paula , Mazeto Gláucia M F S 
Published: June 2021

Background
Thyroid nodules diagnosed as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS) or 'follicular neoplasm/suspected follicular neoplasm' (FN/SFN), according to Bethesda’s classification, represent a challenge in clinical practice. Computerized analysis of nuclear images (CANI) could be a useful tool for these cases. Our aim was to evaluate the ability of CANI to correctly classify AUS/FLUS and FN/SFN thyroid nodules for malignancy.

Methods
We studied 101 nodules cytologically classified as AUS/FLUS (n = 68) or FN/SFN (n = 33) from 97 thyroidectomy patients. Slides with cytological material were submitted for manual selection and analysis of the follicular cell nuclei for morphometric and texture parameters using ImageJ software. The histologically benign and malignant lesions were compared for such parameters which were then evaluated for the capacity to predict malignancy using the classification and regression trees gini model. The intraclass coefficient of correlation was used to evaluate method reproducibility.

Results
In AUS/FLUS nodule analysis, the benign and malignant nodules differed for entropy (P < 0.05), while the FN/SFN nodules differed for fractal analysis, coefficient of variation (CV) of roughness, and CV-entropy (P < 0.05). Considering the AUS/FLUS and FN/SFN nodules separately, it correctly classified 90.0 and 100.0% malignant nodules, with a correct global classification of 94.1 and 97%, respectively. We observed that reproducibility was substantially or nearly complete (0.61–0.93) in 10 of the 12 nuclear parameters evaluated.

Conclusion
CANI demonstrated a high capacity for correctly classifying AUS/FLUS and FN/SFN thyroid nodules for malignancy. This could be a useful method to help increase diagnostic accuracy in the indeterminate thyroid cytology.
The relationship between insulin sensitivity and serum antithrombin 3 activity in patients with type 2 diabetes
Authors: Wang Hong , Cao Jie , Su Jian-bin , Wang Xue-qin , Zhang Dong-mei , Wang Xiao-hua 
Published: June 2021

Background
Antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and serum AT3 activity was found to decrease at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity indices and serum AT3 activity in patients with T2D.

Methods
We conducted a cross-sectional study in patients with T2D who consented to participate in the study at the Endocrinology Department of Affiliated 2 Hospital of Nantong University from January 2015 to June 2018. All patients received serum AT3 activity test and 75 g oral glucose tolerance test (OGTT). Basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISIMatsuda), respectively, from the OGTT. And other relevant clinical data were also collected.

Results
Total of 1612 patients with T2D were enrolled in the study, with a mean age of 58.67 ± 13.09 years and a median diabetes duration of 6 years (interquartile range, 1–10 years). Across ascending quartiles of serum AT3 activity, HOMA-IR progressively decreased, while ISIMatsuda progressively increased (all P for trend < 0.001). Moreover, serum AT3 activity was negatively correlated with HOMA-IR (r = −0.189, P < 0.001) and positively correlated with ISIMatsuda (r = 0.221, P < 0.001). After adjusting for other metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate linear regression analysis, HOMA-IR (β = −0.185, t = −5.960, P < 0.001) and ISIMatsuda (β = 0.197, t = 6.632, P < 0.001) remained independently associated with the serum AT3 activity in patients with T2D, respectively.

Conclusions
Reduced basal and systemic insulin sensitivity are associated with decreased serum AT3 activity in patients with T2D.
Potentiality of a residential area: Practical design at Brigittaplatz
Authors: He Qingchang , Reith Andras 
Published: June 2021

Abstract
Brigittaplatz located in the 20th district of Vienna, which is a mixed culture residential community with various issues. This paper attempts to uncover the existing problems, weaknesses, potential opportunities of the site and explore a set of local interventions to accomplish site regeneration through architectural and landscape measures. Study utilizes two axes to improve and reconnect the public service, green corridor as well as the interactive relationship. All the proposed interventions are not merely public facility renewal but a new functional and social design, which is trying to reactivate the various relationships in the site that can enhance the quality of life and carry over the impact to larger scales. Authors seek a holistic approach to regenerate Brigittaplatz.
Parameterization of the rainfall-runoff model in changing climate
Authors: Aleksić Milica , Sleziak Patrik , Hlavčová Kamila 
Published: June 2021

Abstract
A conceptual rainfall-runoff model was used for estimating the impact of climate change on the runoff regime in the Myjava River basin. Changes in climatic characteristics for future decades were expressed by a regional climate model using the A1B emission scenario. The model was calibrated for 1981–1990, 1991–2000, 2001–2010, 2011–2019. The best set of model parameters selected from the recent calibration period was used to simulate runoff for three periods, which should reflect the level of future climate change. The results show that the runoff should increase in the winter months (December and January) and decrease in the summer months (June to August). An evaluation of the long-term mean monthly runoff for the future climate scenario indicates that the highest runoff will occur in March.
Hydropriming Improves Germination and Plant Recovery During Embryo Rescue of Wild Banana Musa acuminata var. tomentosa
Authors: Prawestri Apriliana Dyah , Riastiwi Indira , Rahayu Resa Sri , Handayani Tri , Leksonowati Aryani , Poerba Yuyu Suryasari 
Published: June 2021

Wild bananas are believed to have genes for resistance to biotic and abiotic stress in nature, making them potential genetic resources for creating superior varieties. Wild banana seeds, such as Musa acuminata var. tomentosa are generally difficult to germinate in vivo, so that in vitro embryo culture technique is needed. This study aimed to increase embryo germination and regeneration of wild banana M. acuminata var. tomentosa by soaking the seeds as hydropriming. The treatment comprised of soaking the seeds in sterile distilled water for four periods of time: 0 (control), 1, 4, and 7 days. A total of 45 embryos for each treatment were planted on petri dishes containing MS + 0.5 mg/L BA + 1 mg/L biotin + 1 mg/L proline. The results showed that hydropriming increased the rate of embryo germination and regeneration. Seeds soaked for 1, 4, and 7 days successfully resulted in embryo germination percentages of 87%, 62%, and 62%, respectively, while the control unsoaked seeds germinated with a lower percentage of 42%. One-day soaking treatment was the most optimal treatment to increase the rate of germination and regeneration as well as obtained the best vigor as demonstrated by the highest average height of plantlets, number of leaves, and roots than other treatments. Thus, 1-day seed hydropriming is the best treatment for embryo rescue and regeneration of wild banana M. acuminata var. tomentosa
Manajemen Pelayanan Haji dan Umroh di Kementerian Agama Kabupaten Mojokerto
Authors: Herlyanda Dea Fajar , Ali Mukti , M Nurul Wahidatul , Ayu Wilis , Sholihah Ni’matus 
Published: June 2021

Penelitian ini bertujuan untuk mengetahui dan mendeskripsian tentang manajemen pelayanan haji dan umroh di kementerian agama kabupaten Mojokerto. Metode penelitian yang digunakan adalah penelitian kualitatif. Teknik pengumpulan data menggunakan wawancara, observasi dan dokumentasi dengan informan yaitu pengelola bagian penyelenggaraan haji dan umroh dan petugas PHU. Hasil penelitian menunjukkan bahwa bagian penyelenggaraan Haji dan Umrah Kantor Kementerian Agama Kabupaten Mojokerto memiliki sebuah pelayanan yang dapat memudahkan jama'ah untuk melakukan pendaftaran yakni pelayanan satu atap yang berdiri pada tahun 2016 Pada awalnya, fungsi secara umum dari pelayanan haji dan umrah adalah untuk meningkatkan pelayanan dan penyelenggaraan ibadah haji dan umrah. Setelah dilakukan penelitian ini, dapat disimpulkan bahwa dengan adanya manajemen pelayanan haji dan umroh, kegiatan atau aktivitas dalam layanan bisa terkoordinir atau terstruktur dengan baik, sehingga calon jamaah haji dan umroh merasa nyaman.
Manajemen Pelayanan Kantor Kementerian Agama Kabupaten Lamongan di Era Industrialisasi 4.0
Authors: Roihannah Nur Hidayati , Fitria Hidayatul , Ningrum Irma Erviyana 
Published: June 2021

Penelitian ini mengkaji tentang pelayanan manajemen kantor di Kantor Kementerian Agama Kabupaten Lamongan. Fokus dalam penelitian ini adalah gambaran layanan manajemen kantor di Era Industrialisasi 4.0 di Kantor Kementerian Agama Kabupaten Lamongan. Berdasarkan fokus penelitian tersebut, selanjutnya penelitian ini bertujuan untuk mengetahui gambaran pelayanan manajemen kantor pada Kantor Kementerian Agama Kabupaten Lamongan. Pendekatan yang digunakan dalam penelitian ini adalah pendekatan deskriptif kualitatif, sedangkan yang menjadi unit analisis dalam penelitian ini adalah Kepala Sub Bagian TU, Kepala Seksi masing-masing bidang dan Tamu Kantor Kementerian Agama Kabupaten Lamongan. Teknik pengumpulan data yang digunakan adalah observasi, wawancara dan dokumentasi. Berdasarkan hasil reduksi data maka hasil penelitian ini menunjukkan bahwa, layanan manajemen kantor yang berkualitas di Kantor Kementerian Agama Kabupaten Lamongan masih belum terlaksana secara efektif dan efesien.
Manajemen Kesiswaan dalam Meningkatan Kualitas Peserta Didik melalui Program Karya Tulis Ilmiah
Authors: Ichsani Ilyas , Pamungkas Bayu Candra , Subty Taufiq , Wahyudin Anton 
Published: June 2021

Manajemen kesiswaan merupakan seluruh kegiatan pembinaan dan pengembangan peserta didik yang dilaksanakan secara kontinu untuk menumbuhkan bakat, minat, dan kemampuan peserta didik melalui kegiatan kurikuler dan ekstrakulikuler. Program karya tulis ilmiah merupakan salah satu program dalam ranah kesiswaan yang dibuat dan dijalankan untuk melatih dan mengembangkan para peserta didik dalam melaksanakan penelitian dan penulisan suatu karangan ilmiah. Tujuan penelitian ini adalah untuk menjelaskan: (1) Manajemen kesiswaan dalam implementasi program karya tulis ilmiah; (2) kendala yang dihadapi dalam pelaksanaan program karya tulis ilmiah; dan (3) peningkatan kualitas peserta didik dengan adanya program karya tulis ilmiah. Jenis penelitian yang digunakan adalah jenis penelitian lapangan (field research) atau penelitian kualitatif. Sasaran penelitian (subjek penelitian) ini adalah Kepala Madrasah, Wakil Kepala Madrasah Bidang Kesiswaan, dan guru yang menjadi pembimbing dan penguji Karya Tulis Ilmiah di MA Muhammadiyah 9 Lamongan. Teknik pengumpulan data yang digunakan adalah observasi, wawancara, dan dokumentasi. Teknik analisis data yang digunakan adalah teknik analisis data Miles dan Huberman, yakni reduksi data, penyajian data, dan simpulan. Hasil penelitian menunjukkan bahwa: (1) Manajemen kesiswaan dalam implementasi program karya tulis ilmiah terdiri dari empat tahap, yakni perencaaan, pengorganisasian, pelaksanaan, dan pengendalian program karya tulis ilmiah; (2) kendala yang dihadapi dalam pelaksanaan program karya tulis ilmiah diantaranya adalah faktor siswa, faktor pembimbing, dan faktor fasilitas madrasah; (3) peningkatan kualitas siswa dengan adanya program karya tulis ilmiah dapat dilihat dari pengembangan penalaran peserta didik, terbentuknya mental peserta didik, dan penguasaan teknologi oleh peserta didik.