bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I/II Clinical Trial of Pembrolizumab and Cabozantinib in Metastatic Renal Cell Carcinoma
Authors: Kessler Elizabeth R. , Callihan Eryn , Hu Junxiao , Eule Corbin , Srivastava Geetika , Kemme Douglas J. , Iruku Praveena , Rana Vishal , Moore James , Schuster Steven R. , Amirault Mali , Flaig Thomas W. , Lam Elaine T. 
Published: May 2023

Purpose:
Immune checkpoint inhibitor and VEGFR inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC). This phase I/II clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in patients with mRCC.

Experimental Design:
Eligible patients had mRCC with clear-cell or non-clear cell histology, adequate organ function, Eastern Cooperative Oncology Group 0–1 performance status, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase II dose (RP2D). Secondary endpoints included safety, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

Results:
Forty-five patients were enrolled. A total of 40 patients were treated at the RP2D of pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally once daily, 38 of which were evaluable for response. The ORR was 65.8% [95% confidence interval (CI), 49.9–78.8] for all evaluable patients [78.6% as first-line therapy, 58.3% as second-line therapy]. The DCR was 97.4% (95% CI, 86.5–99.9). Median DoR was 8.3 months (interquartile range, 4.6–15.1). At a median follow-up of 23.54 months, the median PFS was 10.45 months (95% CI, 6.25–14.63) and median OS was 30.81 months (95% CI, 24.2–not reached). The most common grade 1 and/or 2 treatment-related adverse events (TRAE) were diarrhea, anorexia, dysgeusia, weight loss, and nausea. The most common grade 3 and/or 4 TRAEs were hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue. There was one grade 5 TRAE of reversible posterior encephalopathy syndrome related to cabozantinib.

Conclusions:
Pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable with other available checkpoint inhibitor-tyrosine kinase inhibitor combinations.

Trial Registration:
ClinicalTrials.gov Identifier: NCT03149822 https://clinicaltrials.gov/ct2/show/NCT03149822

Significance:
This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC. The safety profile was manageable. The combination showed promising activity with an objective response rate of 65.8%, median PFS of 10.45 months, and median OS of 30.81 months.
Debating Caliphs and Kings in the Twentieth Century: ʿAbd ul-Ḥalīm Sharar’s Essays on Empire and Governance
Authors: Fatima Maryam 
Published: May 2023

Abstract
The following is an English translation of three essays by the late nineteenth-century Urdu novelist, historian, and essayist ʿAbd ul-Ḥalīm Sharar (1860–1926). In the essays translated here, Sharar offers commentary on contemporaneous world-historical events such as the dissolution of the Ottoman Empire (which had garnered huge public uproar in British India, later culminating in the Khilafat movement) and the “Great Game” in Iran that resulted in its bifurcation into Russian and British spheres of influence. These polemical pieces concerning major imperial changes of the early twentieth century oscillate between impassioned pleas to the colonial government to save Islamic empires from total ruin and rousing calls to action to the Muslim community to band together and save themselves. The first essay, “The Fall of the Persians” (Zavāl-e ʿAjam), reflects on the twilight years of Qajar Iran and presents “Islamic” Persia as the civilizational fountainhead of large swathes of Asia from “the Bosphorus to China.” The second essay, “The End of Ottoman Power” (ʿUṡmānī Sat̤vat kā Ḳhātimah), responds to the dissolution of the Ottoman Empire in 1912 by analyzing the material reasons for the triumph of Europe. The third piece, “The Democratic Spirit of the Arabs” (ʿAraboñ kī Jamhūriyat-pasandī), captures the style for which Sharar was primarily known: narrating history through entertaining stories for moral edification. Here, a short vignette about the Andalusian ruler ʿAbd ul-ʿAzīz and his gradual decline towards conceit, at the behest of his Gothic wife, is framed by a historical review of the many ways in which Islamic rulers avoided inadvertent polytheism by not using grand titles like sult̤ān and bādshāh for themselves. This is held up as representing the intrinsic democratic ethos of the Arabs which was forfeited by later Islamic rulers under the influence of Persian culture. These essays will be of interest to literary scholars and historians of twentieth-century India interested in imperial transitions. They preserve trends in Urdu historiography that were central to the fashioning of national publics, providing a window into negotiations of the place of Urdu and Indian Muslims in the world.
Two new species of the genus Phlugiolopsis (Tettigoniidae: Meconematinae) and the male description of Phlugiolopsis circolobosis Bian, Shi & Chang, 2013 from Yunnan, China
Authors: ZHENG MENGJIA , SHI FUMING , CHANG YANLIN 
Published: May 2023

This paper reports two new species of the genus Phlugiolopsis from Yunnan, China, i.e. Phlugiolopsis furcicaudis sp. nov. and Phlugiolopsis breviproceris sp. nov., and describes the male of Phlugiolopsis circolobosis Bian, Shi & Chang, 2013 for the first time. Examined specimens are deposited in the Museum of Hebei University.
Electrical and electromagnetic shielding properties of thermally-stable polybenzoxazine/expanded graphite nanocomposites
Authors: Ramdani Noureddine , Mokhnache El Oualid , Razali Mohamed Seddik , Abid Nacereddine , Derradji Mehdi , Maamar Mokhtar 
Published: May 2023

The thermal, the electrical conductivity, and electromagnetic shielding properties of low cost high-performance expanded graphite (EG)-filled polybenzoxazine matrix nanocomposites produced by a solution blending and compression molding technique were investigated. At 2.26 vol.% EG, a percolation threshold was detected, at which the electrical conductivity increased by nine orders of magnitude in comparison to the unfilled matrix. The electrical conductivity values increased from 1.35 S.cm−1 to 28.3 S.cm−1 by increasing the EG ratios in the nanocomposites from 7 wt.% and 15 wt.%. In addition, the morphological analysis results revealed good nanofiller dispersion and the formation of 3D-conductive pathways of EG into the polybenzoxazine matrix, which are responsible for the electrical conductivity improvement. Moreover, the electromagnetic interference (EMI) shielding efficiencies, in the X-band, of these nanocomposites have been significantly improved, reaching 57.2 dB at a 15 wt.% EG ratio. Furthermore, the inclusion of EG nanofiller significantly improved the thermal properties of the nanocomposites in terms of first degradation temperatures, char yields, and thermal conductivities. Because of these exceptional properties, these nanocomposites are ideal for high thermal EMI shielding applications.
Effectiveness of a home-based telesurveillance program in reducing hospital readmissions in older patients with chronic disease: The eCOBAHLT randomized controlled trial
Authors: Tchalla Achille , Marchesseau Delphine , Cardinaud Noëlle , Laubarie-Mouret Cécile , Mergans Thomas , Kajeu Patrick-Joël , Luce Sandrine , Friocourt Patrick , Tsala-Effa Didier , Tovena Isabelle , Preux Pierre-Marie , Gayot Caroline 
Published: May 2023

Introduction Given that chronic, long-term conditions are increasingly common in older patients, the impact of telesurveillance program on clinical outcomes is uncertain. This study aimed to evaluate the feasibility and effectiveness of a 12-month remote monitoring program in preventing rehospitalizations in older patients with two or more chronic diseases returning home after hospitalization. Methods We conducted a multicenter randomized controlled trial in two parallel groups to evaluate the remote monitoring system. Elderly patients with chronic diseases (at least two comorbidities) aged 65 years or older and discharged home after acute hospital care for a chronic disease were randomized to receive a home telemonitoring program (intervention group, n = 267) or conventional care (control group, n = 267). The remote home monitoring program was an online biometric home life analysis technology (e-COBAHLT) with tele-homecare/automation and biometric sensors. The eCOBALTH intervention group received the automation sensors containing chronic disease clinical factor trackers to monitor their biometric parameters and detect any abnormal prodromal disease decompensation by remote monitoring and providing geriatric expertise to general practitioners. The usual care group received no eCOBALTH program. In both groups, baseline visits were conducted at baseline and the final visit at 12 months. The primary outcome was the incidence of unplanned hospitalizations for decompensation during the 12-month period. Results Among 534 randomized participants (mean [SD] age, 80.3 [8.1] years; 280 [52.4%] women), 492 (92.1%) completed the 12-month follow-up; 182 (34.1) had chronic heart failure, 115 (21.5%) had stroke, and 77 (14.4%) had diabetes. During the 12-month follow-up period, 238 patients had at least one unplanned hospitalization for decompensation of a chronic disease: 108 (40.4%) in the intervention group versus 130 (48.7%) in the control group (P = 0.04). The risk of rehospitalization was significantly reduced in the intervention group (age- and sex-adjusted relative risk: 0.72, 95% 95% confidence intervals 0.51-0.94). Conclusion A 12-month home telemonitoring program with online biometric analysis using Home life technology combining telecare and biometric sensors is feasible and effective in preventing unplanned hospitalizations for chronic disease decompensation in elderly patients with chronic diseases at high risk for hospitalizations.
Mechanical performance of steel tubes filled with demolished concrete lumps under axial compression
Authors: Yu Changxing , Pan Xiangguang , Ma Yuanhao , Zhang Aihua , Pan Yifei , Liu Chuanqi , Yu Bingyou , Zhang Yan 
Published: May 2023

Demolished concrete lumps (DCLs) have been introduced as partial coarse aggregate replacements in concrete casting process. However, limited research works have been performed on sensitive behaviors of slenderness concrete filled steel tube (CFST) filled with fresh concrete (FC) and DCLs under axial compression. Based on the previous research work, orthogonal design method was employed to investigate further mechanical performance. Experimental studied involved 12 columns of CFST with diameter 159 mm and lengths 2000, 2200 and 2400 mm. The ratios of the diameter-to-thickness (D/t) were 79, 53 and 40, while replacement ratios of FC in DCLs were 0%, 20%, 40% and 60%, respectively. The results of experimental tests of the CFST filled with DCLs and FC indicated that ratio of slenderness have a greatest effect on the bearing capacity of slender column under axial compression, followed by the D/t ratio, and the weakest effect was observed for DCLs replacement. DCLs slightly affected the mechanical performances of slender CFST columns, so the ultimate bearing capacity of CFST can ignore the influence of replacement rate of DCLs. To calculate CFST slender column ultimate bearing capacity with DCLs, design codes AIJ, AISC, CE4, CECS 28: 2012, DL/T 5085-1999 were used to predicted ultimate bearing capacity, found that the code CECS 28:2012 was employed for the calculation of slender CFST DCLs filled column bearing capacity under axial compression being comparable accuracy.
Transaxillary Branch-to-Branch-to-Branch Carotid Catheterization Technique for Triple-Branch Arch Repair
Authors: Prendes Carlota F. , Spath Paolo , Stana Jan , Hamwi Tarek , Peterss Sven , Stavroulakis Konstantinos , Pichlmaier Maximilian , Tsilimparis Nikolaos 
Published: May 2023

Purpose: To describe the transaxillary branch-to-branch-to-branch carotid catheterization technique (tranaxillary 3BRA-CCE IT) for cannulation of all supra-aortic vessels using only 1 femoral and 1 axillary access during triple-branch arch repair. Technique: After deployment of the triple-branch arch device, catheterization and bridging of the innominate artery (IA) should be performed through a right axillary access (cutdown or percutaneous). Then, the retrograde left subclavian (LSA) branch should be catheterized (if not preloaded) from a percutaneous femoral access, and a 12×90Fr sheath should be advanced to the outside of the endograft. Subsequently, catheterization of the left common carotid artery (LCCA) antegrade branch should be performed, followed by snaring of a wire in the ascending aorta which was inserted through the axillary access, creating a branch-to-branch-to-branch through-and-through guidewire. Over the axillary access, a 12×45Fr sheath should be inserted into the IA branch and looped in the ascending aorta using a push-and-pull technique so that it faces the LCCA branch, allowing for stable catheterization of the LCCA. The retrograde LSA branch should then be bridged following the standard fashion. Conclusions: This series of 5 patients demonstrates that triple-branch arch repair can be performed with the transaxillary 3BRA-CCE IT, allowing catheterization of the supra-aortic vessels without manipulation of the carotid arteries. Clinical Impact The transaxillary 3BRA-CCE IT allows catheterization and bridging of all supra-aortic vessels in triple-branch arch repair through only 2 vascular access points, the femoral artery and the right axillary artery. This technique avoids carotid surgical cutdown and manipulation during these procedures, reducing the risk of access site complications, including bleeding and reintervention, reintubation, cranial nerve lesions, increased operating time, and so on, and has the potential to change the current vascular access standard used during triple-branch arch repair.
Totally Endoscopic Surgery for Repairing Sinus Venosus Atrial Septal Defect Using Double-Patch Technique on Beating Heart
Authors: Dang Huy Q. , Le Huong T. , Nguyen Hien S. 
Published: May 2023

Objective: Minimally invasive cardiac surgery has not been widely applied in repairing sinus venosus atrial septal defect (SV-ASD). Most were minithoracotomy using the single-patch technique for patients with anomalous pulmonary veins (APVs) connecting to the superior vena cava–right atrium (SVC-RA) junction. It is unclear whether patients with APVs draining high to the SVC can be repaired safely and effectively through port access. Methods: From May 2019 to October 2022, 11 consecutive SV-ASD patients with APVs connecting high to the SVC were enrolled in this prospective study. One 12 mm port and 2 trocars (5.5 mm and 10 mm) were established. The pleural and pericardial spaces were filled with CO2. The SVC was snared just below the azygos vein. The RA incision was longitudinally extended along the SVC-RA junction to the SVC. The bovine pericardial patches were used to redirect the APV flow to the left atrium through the ASD and to enlarge the SVC and the SVC-RA junction. Results: There were no early or late deaths and no reoperations. The concomitant procedures included 5 patients (45.5%) with patent foramen ovale closure, 2 with ASD extension, and 3 with tricuspid valve repair. No endoscopic failure was recorded. The average cardiopulmonary bypass and operative times were 96 (23) min and 190 (30) min, respectively. No cases of venous stenosis or sinus node dysfunction were noted during follow-up of 16.4 ± 12.2 months. Conclusions: SV-ASD with the APVs draining high to the SVC could be repaired safely and effectively through port access with a double-patch technique.
Partial Humeral Head Arthroplasty, Glenoid Allograft Augmentation, and Open Bankart Reconstruction for Critical Glenoid Bone Loss and Engaging Hill-Sachs Lesion
Authors: Young Bradley L. , Karas Spero G. 
Published: May 2023

Background: Shoulder instability with critical bipolar bone loss can be difficult to treat. Anterior glenoid bone block augmentation and partial humeral head resurfacing is a viable option. Indications: This procedure is indicated in patients with both critical anterior glenoid bone loss (≥20%) and an engaging Hill-Sachs lesion. Technique Description: A deltopectoral approach is performed, followed by a subscapularis tenotomy. The Hill-Sachs lesion is resurfaced with a partial humeral head arthroplasty. The anterior glenoid bone loss is replaced with a prefabricated allograft. An open Bankart repair is then performed. Results: Three case reports give evidence that this technique is a viable surgical option for patients with critical glenoid bone loss and an engaging Hill-Sachs lesion. Discussion/Conclusion: Partial humeral head resurfacing, glenoid allograft augmentation, and open Bankart is a viable surgical option for patients with critical anterior glenoid bone loss and an engaging Hill-Sachs lesion. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Real-world experience with low-dose IL-2 for children and young adults with refractory chronic graft-versus-host disease
Authors: Wobma Holly , Kapadia Malika , Kim Haesook T. , Alvarez-Calderon Francesca , Baumeister Susanne H. C. , Duncan Christine , Forrest Suzanne , Gorfinkel Lev , Huang Jennifer , Lehmann Leslie E. , Li Hojun , Schwartz Marc , Koreth John , Ritz Jerome , Kean Leslie S. , Whangbo Jennifer S. 
Published: May 2023

Abstract
The majority of patients with chronic graft-versus-host disease (cGVHD) are steroid refractory (SR), creating a need for safe and effective therapies. Subcutaneous low-dose interleukin-2 (LD IL-2), which preferentially expands CD4+ regulatory T cells (Tregs), has been evaluated in 5 clinical trials at our center with partial responses (PR) in ∼50% of adults and 82% of children by week 8. We now report additional real-world experience with LD IL-2 in 15 children and young adults. We conducted a retrospective chart review of patients with SR-cGVHD at our center who received LD IL-2 from August 2016 to July 2022 not on a research trial. The median age at start of LD IL-2 was 10.4 years (range, 1.2-23.2 years) at a median of 234 days from cGVHD diagnosis (range, 11-542 days). Patients had a median of 2.5 (range, 1-3) active organs at LD IL-2 start and received a median of 3 (range, 1-5) prior therapies. The median duration of LD IL-2 therapy was 462 days (range, 8-1489 days). Most patients received 1 × 106 IU/m2 per day. There were no serious adverse effects. The overall response rate in 13 patients who received &gt;4 weeks of therapy was 85% (complete response, n = 5; PR, n = 6) with responses in diverse organs. Most patients significantly weaned corticosteroids. Tregs preferentially expanded with a median peak fold increase of 2.8 in the ratio of Tregs to CD4+ conventional T cells (range, 2.0-19.8) by 8 weeks on therapy. LD IL-2 is a well-tolerated, steroid-sparing agent with a high response rate in children and young adults with SR-cGVHD.
MAF functions as a pioneer transcription factor that initiates and sustains myelomagenesis
Authors: Katsarou Alexia , Trasanidis Nikolaos , Ponnusamy Kanagaraju , Kostopoulos Ioannis V. , Alvarez-Benayas Jaime , Papaleonidopoulou Foteini , Keren Keren , Sabbattini Pierangela M. R. , Feldhahn Niklas , Papaioannou Maria , Hatjiharissi Evdoxia , Sudbery Ian M. , Chaidos Aristeidis , Caputo Valentina S. , Karadimitris Anastasios 
Published: May 2023

Abstract
Deregulated expression of lineage-affiliated transcription factors (TFs) is a major mechanism of oncogenesis. However, how the deregulation of nonlineage affiliated TF affects chromatin to initiate oncogenic transcriptional programs is not well-known. To address this, we studied the chromatin effects imposed by oncogenic MAF as the cancer-initiating driver in the plasma cell cancer multiple myeloma. We found that the ectopically expressed MAF endows myeloma plasma cells with migratory and proliferative transcriptional potential. This potential is regulated by the activation of enhancers and superenhancers, previously inactive in healthy B cells and plasma cells, and the cooperation of MAF with the plasma cell-defining TF IRF4. Forced ectopic MAF expression confirms the de novo ability of oncogenic MAF to convert transcriptionally inert chromatin to active chromatin with the features of superenhancers, leading to the activation of the MAF-specific oncogenic transcriptome and the acquisition of cancer-related cellular phenotypes such as CCR1-dependent cell migration. These findings establish oncogenic MAF as a pioneer transcription factor that can initiate as well as sustain oncogenic transcriptomes and cancer phenotypes. However, despite its pioneer function, myeloma cells remain MAF-dependent, thus validating oncogenic MAF as a therapeutic target that would be able to circumvent the challenges of subsequent genetic diversification driving disease relapse and drug resistance.
Physiological and molecular response and tolerance of Macleaya cordata to lead toxicity
Authors: Zhang Hongxiao , Hu Linfeng , Du Xinlong , Sun Xijing , Wang Ting , Mu Zhiying 
Published: May 2023

Abstract
Background
Macleaya cordata is a traditional medicinal herb, and it has high tolerance and accumulation ability to heavy metals, which make it a good candidate species for studying phytoremediation. The objectives of this study were to investigate response and tolerance of M. cordata to lead (Pb) toxicity based on comparative analysis of transcriptome and proteome.

Results
In this study, the seedlings of M. cordata cultured in Hoagland solution were treated with 100 µmol·L− 1 Pb for 1 day (Pb 1d) or 7 days (Pb 7d), subsequently leaves of M. cordata were taken for the determination of Pb accumulation and hydrogen peroxide production (H2O2), meanwhile a total number of 223 significantly differentially expressed genes (DEGs) and 296 differentially expressed proteins (DEPs) were screened between control and Pb treatments. The results showed leaves of M. cordata had a special mechanism to maintain Pb at an appropriate level. Firstly, some DEGs were iron (Fe) deficiency-induced transporters, for example, genes of vacuolar iron transporter and three ABC transporter I family numbers were upregulated by Pb, which can maintain Fe homeostasis in cytoplasm or chloroplast. In addition, five genes of calcium (Ca2+) binding proteins were downregulated in Pb 1d, which may regulate cytoplasmic Ca2+ concentration and H2O2 signaling pathway. On the other hand, the cysteine synthase upregulated, glutathione S-transferase downregulated and glutathione reductase downregulated in Pb 7d can cause reduced glutathione accumulation and decrease Pb detoxification in leaves. Furthermore, DEPs of eight chlorophyll a/b binding proteins, five ATPases and eight ribosomal proteins can play a pivotal role on chloroplast turnover and ATP metabolism.

Conclusions
Our results suggest that the proteins involved in Fe homeostasis and chloroplast turnover in mesophyll cells may play key roles in tolerance of M. cordata to Pb. This study offers some novel insights into Pb tolerance mechanism of plants, and the potential valuable for environmental remediation of this important medicinal plant.