bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investor Protection and Post-Disclosure Disagreement: International Evidence
Authors: Chen Tao 
Published: July 2022

Synopsis The research problem Adding to the literature on investor protection, this study investigates whether nationwide institutional features may explain cross-country variation in post-disclosure disagreement. Motivation Previous research has revealed that the release of financial statements aggravates investor disagreement rather than attenuating it. However, most studies only obtain empirical evidence in the context of the United States; no work has examined this research question in an international setting. Another motivation for this paper is the attempt to understand the contradiction in the literature, which emphasizes micro-level determinants. By contrast, minimal attention has been paid to the macro-level institutional factors of a country’s information environment, which presumably prompts investors to shape heterogeneous beliefs. The test hypotheses H1: Countries with greater corporate transparency are associated with a lower level of post-disclosure investor disagreement. H2: Countries with stronger legal protection are associated with a lower level of post-disclosure investor disagreement. Target population Various stakeholders include firm managers, financial analysts, regulatory watchdogs, and users of earnings reports. Adopted methodology Ordinary Least Squares (OLS) Regressions Analyses Gao et al. ( 2012 ) to measure investor disagreement while we quantify corporate transparency (legal protection) by extracting the first principal component of nine countrywide characteristics pertinent to disclosure requirements (legal systems). Using a global sample from 38 countries, we perform a cross-sectional regression of post-disclosure disagreement on two proxies for investor protection after accounting for firm-specific control variables. Findings We find clear evidence of post-disclosure disagreement in all countries. Next, we document a negative relationship between corporate transparency (legal protection) and post-disclosure disagreement. Additional tests confirm that both better disclosures and strong regulations enhance information precision, accelerate information dissemination, and reduce informed trading, thus leading to a lower level of post-disclosure disagreement.
Suboptimal Comments in Java Projects: From Independent Comment Changes to Commenting Practices
Authors: Wang Chao , He Hao , Pal Uma , Marinov Darko , Zhou Minghui 
Published: July 2022

High-quality source code comments are valuable for software development and maintenance, however, code often contains low-quality comments or lacks them altogether. We name such source code comments as suboptimal comments. Such suboptimal comments create challenges in code comprehension and maintenance. Despite substantial research on low-quality source code comments, empirical knowledge about commenting practices that produce suboptimal comments and reasons that lead to suboptimal comments are lacking. We help bridge this knowledge gap by investigating (1) independent comment changes (ICCs)—comment changes committed independently of code changes—which likely address suboptimal comments, (2) commenting guidelines, and (3) comment-checking tools and comment-generating tools, which are often employed to help commenting practice—especially to prevent suboptimal comments.We collect 24M+ comment changes from 4,392 open-source GitHub Java repositories and find that ICCs widely exist. TheICC ratio—proportion of ICCs among all comment changes—is ~15.5%, with 98.7% of the repositories having ICC. Our thematic analysis of 3,533 randomly sampled ICCs provides a three-dimensional taxonomy forwhatis changed (four comment categories and 13 subcategories),howit changed (six commenting activity categories), andwhat factorsare associated with the change (three factors). We investigate 600 repositories to understand the prevalence, content, impact, and violations of commenting guidelines. We find that only 15.5% of the 600 sampled repositories have any commenting guidelines. We provide the first taxonomy for elements in commenting guidelines: where and what to comment are particularly important. The repositories without such guidelines have a statistically significantly higher ICC ratio, indicating the negative impact of the lack of commenting guidelines. However, commenting guidelines are not strictly followed: 85.5% of checked repositories have violations. We also systematically study how developers use two kinds of tools, comment-checking tools and comment-generating tools, in the 4,392 repositories. We find that the use ofJavadoctool is negatively correlated with the ICC ratio, while the use ofCheckstylehas no statistically significant correlation; the use of comment-generating tools leads to a higher ICC ratio.To conclude, we reveal issues and challenges in current commenting practice, which help understand how suboptimal comments are introduced. We propose potential research directions on comment location prediction, comment generation, and comment quality assessment; suggest how developers can formulate commenting guidelines and enforce rules with tools; and recommend how to enhance current comment-checking and comment-generating tools.
Data-Driven Network Path Simulation with iBox
Authors: Ashok Sachin , Tiwari Shubham , Natarajan Nagarajan , Padmanabhan Venkata N. , Sellamanickam Sundararajan 
Published: July 2022

While network simulation is widely used for evaluating network protocols and applications, ensuring realism remains a key challenge. There has been much work on simulating network mechanisms faithfully (e.g., links, buffers, etc.), but less attention on the critical task of configuring the simulator to reflect reality.
We present iBox ("Internet in a Box"), which enables data-driven network path simulation, using input/output packet traces gathered at the sender/receiver in the target network to create a model of the end-to-end behaviour of a network path. Our work builds on recent work in this direction [2, 6] and makes three contributions: (1) estimation of a lightweight non-reactive cross-traffic model, (2) estimation of a more powerful reactive cross-traffic model based on Bayesian optimization, and (3) evaluation of iBox in the context of congestion control variants in an Internet research testbed and also controlled experiments with known ground truth.
This paper represents an abridged version of [3].
Ultra-Compact Slitted Flower-Shaped Dual-Band Monopole Antenna for Modern Portable Devices
Authors: Abolade Jeremiah O , Konditi Dominic B. O. 
Published: July 2022

A meanderingly slitted bio-inspired (MSB)-shaped antenna is presented in this work. The footprint of the proposed MSB antenna is 12 × 10 mm2

0.12
×
0.10

λ
g
2

at
2.1
G
H
z

. The MSB antenna proposed in this operates at 2.1 GHz and 5.2 GHz frequencies with a bandwidth of 70 MHz and 570 MHz and a radiation efficiency of 52.5% and 96%, respectively, which is suitable for UMTS, radio navigation, Long Term Evolution (LTE), and 5 GHz Wireless Local Area Network (WLAN) applications. The proposed MSB antenna demonstrates a peak gain of 2.9 dBi at 5.2 GHz and an omnidirectional radiation pattern at both E-plane and H-plane in both operating bands. The fabrication and measurement of the proposed antenna prototype are presented. The parametric study of the proposed structure is performed and presented. Therefore, the proposed antenna is a promising candidate for modern portable devices.
Experimental Study on Nanomechanical Properties of Yunnan Red-Bed Mudstone
Authors: Ye Xian , Liu Yongcai , Xue Haibin , Li Guo , Xing Jin 
Published: July 2022

As a natural building material and building environment, red-bed mudstone has special engineering properties due to its special formation conditions. The engineering disaster caused by these special properties is becoming increasingly prominent. Therefore, it is of great theoretical significance and practical engineering value to study the macro- and micromechanical properties of red-bed mudstone. Nanoindentation mechanical tests are carried out on the red-bed mudstone from Chuxiong, Jingdong, and Nanhua in Yunnan. The microstructure, residual indentation morphology, and nanomechanical parameters of red-bed mudstone in different areas are compared and analyzed. The results show that the load-displacement curves can be divided into four stages, which are the compaction stage, linear elastic stage, holding stage, and unloading stage. Under the same loading and holding time conditions, sample 3 (Nanhua) has the deepest residual indentation, and SEM tests show that the damage to indentation is obvious. Sample 2 (Jingdong) has the shallowest residual indentation. The indentation morphology is complete and the size is small by SEM tests. The residual indentation depth of sample 1 (Chuxiong) is between sample 2 and sample 3. The average elastic modulus of sample 1 (Chuxiong) is

38.0
±
2.29

GPa. The average hardness is

1.36
±
0.42

GPa, and the fracture toughness is

0.966
±
0.048

MPa·m0.5. The average elastic modulus of sample 2 (Jingdong) is

40.1
±
2.03

GPa. The average hardness is

1.71
±
0.35

GPa, and the fracture toughness is

1.142
±
0.053

MPa·m0.5. However, the average elastic modulus of sample 3 (Nanhua) is

25.1
±
2.53

GPa. The average hardness is

0.61
±
0.21

GPa, and the fracture toughness is

0.507
±
0.043

MPa·m0.5. Overall, the elastic modulus and the hardness of sample 2 (Jingdong) are the greatest because of its high quartz crystal content. It shows that the nanomechanical properties of red-bed mudstone in Jingdong are better than those in Chuxiong and Nanhua. The results can provide a basis for revealing the regional differences in macroscopic mechanical properties of Yunnan red-bed mudstone.
Dopamine Signaling Promotes Tissue-Resident Memory Differentiation of CD8+ T Cells and Antitumor Immunity
Authors: Chen Yingshi , Yan Shu-Mei , Pu Zeyu , Feng Jinzhu , Tan Likai , Li Yuzhuang , Hu Hongrong , Huang Wenjing , Lin Yingtong , Peng Zhilin , He Xin , Huang Feng , Zhang Hui , Zhang Yiwen 
Published: July 2022

AbstractTissue-resident memory CD8+ T (TRM) cells have been associated with robust protective antitumor immune responses and improved prognosis of patients with cancer. Therefore, therapeutic strategies that modulate either the production or activity of TRM cells could be effective for treating cancer. Using a high-throughput drug screen, we showed that the neurotransmitter dopamine drives differentiation of CD8+ T cells into CD103+ TRM cells. In murine syngeneic tumor xenograft models and clinical human colon cancer samples, DRD5 served as the major functional dopamine receptor on CD8+ T cells and positively correlated with TRM cell density. DRD5 deficiency led to a failure of CD8+ T cells to accumulate in tissues, resulting in impaired TRM cell formation, reduced effector function, and uncontrolled disease progression. Moreover, dopamine treatment promoted the antitumor activity of CD8+ T cells and suppressed colorectal cancer growth in immunocompentent mouse models, and ex vivo preconditioning with dopamine enhanced the in vivo efficacy of chimeric antigen receptor (CAR)-T cells. Finally, in a patient with colorectal cancer cohort, dopamine expression was positively associated with patient survival and CD8+ T-cell infiltration. These findings suggest that dopaminergic immunoregulation plays an important role in the differentiation of CD8+ cells into CD103+ TRM cells and thereby modulates TRM-elicited antitumor immunity in colorectal cancer.Significance:Identification of an immunostimulatory function of dopamine signaling by promoting tissue-resident memory T-cell differentiation and sustaining T-cell effector functions reveals potential therapeutic strategies and prognostic biomarkers for colorectal cancer.
FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma
Authors: Baines Andrea C. , Ershler Rachel , Kanapuru Bindu , Xu Qing , Shen Guoxiang , Li Liang , Ma Lian , Okusanya Olanrewaju O. , Simpson Natalie E. , Nguyen Wanda , Theoret Marc R. , Pazdur Richard , Gormley Nicole J. 
Published: July 2022

Abstract
On August 5, 2020, the FDA granted accelerated approval to belantamab mafodotin-blmf (BLENREP; GlaxoSmithKline) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Substantial evidence of effectiveness was obtained from the phase II, multicenter DREAMM-2 trial. Patients received belantamab mafodotin 2.5 or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. The trial demonstrated an overall response rate of 31% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort. Keratopathy was the most frequent adverse event, occurring in 71% and 77% of patients, respectively. Other ocular toxicities included changes in visual acuity, blurred vision, and dry eye. The U.S. prescribing information for belantamab mafodotin includes a boxed warning for ocular toxicity, and belantamab mafodotin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy. This article summarizes the data and the FDA review process supporting accelerated approval of belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Anti-GD2 Antibodies Conjugated to IL15 and IL21 Mediate Potent Antitumor Cytotoxicity against Neuroblastoma
Authors: Nguyen Rosa , Zhang Xiyuan , Sun Ming , Abbas Shahroze , Seibert Charlie , Kelly Michael C. , Shern Jack F. , Thiele Carol J. 
Published: July 2022

AbstractPurpose:Half of the patients with high-risk neuroblastoma who receive GD2-targeted mAb do not achieve long-term remissions. Recently, the antibody hu14.18 has been linked to IL2 (hu14.18-IL2) to enhance its efficacy and shown promising preclinical and clinical activity. We developed two new immunocytokines (IC) by linking two other γc cytokines, IL15 and IL21, to hu14.18. The purpose of this study was to compare hu14.18-IL15 and -IL21 with hu14.18-IL2 in their ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC) against neuroblastoma.Experimental Design:We assessed ADCC of hu14.18-IL15 and -IL2 (human cytokines, cross-reactive to mouse) against GD2low and GD2high neuroblastoma cell lines in vitro. T-cell–deficient mice with orthotopic patient-derived xenografts (PDX) and immunocompetent mice with transplantable orthotopic neuroblastoma were used to test all three ICs, including hu14.18-IL21 (murine IL21, not cross-reactive to human). Mechanistic studies were performed using single-cell RNA-sequencing (scRNA-seq).Results:hu14.18-IL15 and hu14.18-IL2 mediated equivalent in vitro ADCC by human NK cells. When combined with chemotherapy, all three ICs similarly controlled the growth of PDXs in nude mice with murine NK effector cells. However, hu14.18-IL15 and -IL21 outperformed hu14.18-IL2 in immunocompetent mice with syngeneic neuroblastoma, inducing complete tumor regressions and extending survival. scRNA-seq data revealed an increase in CD8+ T cells and M1 tumor-associated macrophages and decreased regulatory T cells and myeloid-derived suppressor cells in the tumor microenvironment.Conclusions:Hu14.18-IL15 and Hu14.18-IL21 exhibit robust preclinical activity, warranting further consideration for clinical testing in patients with GD2-expressing neuroblastoma.
Enhancing PD-L1 Degradation by ITCH during MAPK Inhibitor Therapy Suppresses Acquired Resistance
Authors: Yang Zhentao , Wang Yan , Liu Sixue , Deng Weixian , Lomeli Shirley H. , Moriceau Gatien , Wohlschlegel James , Piva Marco , Lo Roger S. 
Published: July 2022

Abstract

MAPK inhibitor (MAPKi) therapy in melanoma leads to the accumulation of tumor-surface PD-L1/L2, which may evade antitumor immunity and accelerate acquired resistance. Here, we discover that the E3 ligase ITCH binds, ubiquitinates, and downregulates tumor-surface PD-L1/L2 in MAPKi-treated human melanoma cells, thereby promoting T-cell activation. During MAPKi therapy in vivo, melanoma cell–intrinsic ITCH knockdown induced tumor-surface PD-L1, reduced intratumoral cytolytic CD8+ T cells, and accelerated acquired resistance only in immune-competent mice. Conversely, tumor cell–intrinsic ITCH overexpression reduced MAPKi-elicited PD-L1 accumulation, augmented intratumoral cytolytic CD8+ T cells, and suppressed acquired resistance in BrafV600MUT, NrasMUT, or Nf1MUT melanoma and KrasMUT-driven cancers. CD8+ T-cell depletion and tumor cell–intrinsic PD-L1 overexpression nullified the phenotype of ITCH overexpression, thereby supporting an in vivo ITCH–PD-L1–T-cell regulatory axis. Moreover, we identify a small-molecular ITCH activator that suppresses acquired MAPKi resistance in vivo. Thus, MAPKi-induced PD-L1 accelerates resistance, and a PD-L1–degrading ITCH activator prolongs antitumor response.

Significance:
MAPKi induces tumor cell–surface PD-L1 accumulation, which promotes immune evasion and therapy resistance. ITCH degrades PD-L1, optimizing antitumor T-cell immunity. We propose degrading tumor cell–surface PD-L1 and/or activating tumor-intrinsic ITCH as strategies to overcome MAPKi resistance.
This article is highlighted in the In This Issue feature, p. 1825
Hsa_circ_0016070/micro‐340‐5p Axis Accelerates Pulmonary Arterial Hypertension Progression by Upregulating TWIST1 Transcription Via TCF4/β‐Catenin Complex
Authors: Huang Chun‐Xia , Jiang Zhi‐Xin , Du Da‐Yong , Zhang Zhi‐Min , Liu Yang , Li Yun‐Tian 
Published: July 2022

Background
Hypoxia is considered a major leading cause of pulmonary hypertension (PH). In this study, the roles and molecular mechanism of circ_0016070 in PH were studied.

Methods and Results
The expression of circ_0016070 in serum samples, human pulmonary artery smooth muscle cells and hypoxia/monocrotaline‐treated rats was determined by real‐time quantitative polymerase chain reaction. Cell viability, migration, and apoptosis were analyzed by Cell Counting Kit‐8, wound healing, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays, respectively. The molecular interactions were validated using RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase reporter assays. The levels of phenotype switch‐related proteins were evaluated by Western blot and immunohistochemistry. The pathological characteristics were assessed using hematoxylin and eosin staining. circ_0016070 was highly expressed in the serum samples, hypoxia‐induced pulmonary artery smooth muscle cells and pulmonary arterial tissues of PH rats. Downregulation of circ_0016070 ameliorated the excessive proliferation, migration, vascular remodeling, and phenotypic transformation but enhanced cell apoptosis in the PH rat model. In addition, micro (miR)‐340‐5p was verified as a direct target of circ_0016070 and negatively regulated TCF4 (transcription factor 4) expression. TCF4 formed a transcriptional complex with β‐catenin to activate TWIST1 (Twist family bHLH transcription factor 1) expression. Functional rescue experiments showed that neither miR‐340‐5p inhibition nor TWIST1 or TCF4 upregulation significantly impeded the biological roles of circ_0010670 silencing in PH.

Conclusions
These results uncovered a novel mechanism by which circ_0016070 play as a competing endogenouse RNA of miR‐340‐5p to aggravate PH progression by promoting TCF4/β‐catenin/TWIST1 complex, which may provide potential therapeutic targets for PH.
Utility of Provocative Testing in the Diagnosis and Genotyping of Congenital Long QT Syndrome: A Systematic Review and Meta‐Analysis
Authors: Yang Ying , Lv Ting‐ting , Li Si‐yuan , Liu Peng , Gao Qing‐gele , Zhang Ping 
Published: July 2022

Background
Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards.

Methods and Results

A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library through October 14, 2021. The fixed effects model was used to assess the effect of the provocative testing on QTc interval. A total of 22 studies with 1137 patients with LQTS were included. At baseline, QTc interval was 40 ms longer in patients with LQTS than in controls (mean difference [MD], 40.54 [95% CI, 37.43–43.65];
P
<0.001). Compared with the control group, patients with LQTS had 28 ms longer ΔQTc upon standing (MD, 28.82 [95% CI, 23.05–34.58];
P
<0.001), nearly 30 ms longer both at peak exercise (MD, 27.31 [95% CI, 21.51–33.11];
P
<0.001) and recovery 4 to 5 minutes (MD, 29.85 [95% CI, 24.36–35.35];
P
<0.001). With epinephrine infusion, QTc interval was prolonged both in controls and patients with QTS, most obviously in LQT1 (MD, 68.26 [95% CI, 58.91–77.60];
P
<0.001) and LQT2 (MD, 60.17 [95% CI, 50.18–70.16];
P
<0.001). Subgroup analysis showed QTc interval response to abrupt stand testing and exercise testing varied between LQT1, LQT2, and LQT3, named Type Ⅰ, Type Ⅱ, and Type Ⅲ.

Conclusions
QTc trend Type Ⅰ and Type Ⅲ during abrupt stand testing and exercise testing can be used to propose a prospective evaluation of LQT1 and LQT3, respectively. Type Ⅱ QTc trend combined epinephrine infusion testing could distinguish LQT2 from control. A preliminary diagnostic workflow was proposed but deserves further evaluation.
Single‐Center Experience of Hybrid Pulmonary Valve Replacement Using Left Anterior Thoracotomy With Pulmonary Artery Plication in Patients With Large Right Ventricular Outflow Tract
Authors: Carr Kaitlin , Mohammad Nijres Bassel , Windsor Jimmy J. , Nakamura Yuki , Karimi Mohsen , Ricci Marco , Aldoss Osamah 
Published: July 2022

Background
Until recently, a large right ventricle outflow tract interfered with the feasibility of standard transcatheter pulmonary valve replacement (PVR). We are describing our experience using a hybrid approach for PVR using a left anterior thoracotomy approach to allow for plication of the main pulmonary artery followed by a transcatheter PVR using a Sapien S3 valve.

Methods and Results
This is a single‐center, retrospective review of patients who were evaluated to be appropriate for a hybrid PVR approach. The patients' demographics, procedure details, and follow‐up data were collected. Between May 2018 and April 2021, a total of 11 patients presented for hybrid transcatheter PVR. The median age and weight were 24 years (interquartile range, 19–43 years) and 81.8 kg (interquartile range, 69–91 kg), respectively. Nine out of 11 patients received a transcatheter PVR after main pulmonary artery plication. There were no procedurally related deaths. One major complication was encountered in which the valve was malpositioned requiring successful surgical PVR. Minor complications included acute kidney injury (n=1) and a broken rib (n=1). The median length of stay was 4 days (interquartile range, 2–4 days), with median follow‐up of 7 months (interquartile range, 3–18 months). A well‐functioning pulmonary valve was observed in all patients at the last follow‐up.

Conclusions
A hybrid approach using left anterior thoracotomy with pulmonary artery plication followed by transcatheter Sapien S3 PVR provides a less‐invasive option for patients with an enlarged right ventricular outflow tract. Preliminary results demonstrated this to be a safe option with good short‐term outcomes.