bluuebunny/crossref_metadata_2025 huggingface dataset:
Fragility of randomised controlled trials for systemic lupus erythematosus and lupus nephritis therapies
Authors: Figueroa-Parra Gabriel , Putman Michael S , Crowson Cynthia S , Duarte-García Alí
Published: January 2024

Objective

We aimed to evaluate the robustness of phase III randomised controlled trials (RCTs) for SLE and lupus nephritis (LN) using the fragility index (FI), the reverse FI (RFI) and the fragility quotient (FQ).

Methods

We searched for phase III RCTs that included patients with active SLE or LN. Data on primary endpoints, total participants and the number of events for each arm were obtained. We calculated the FI score for RCTs with statistically significant results (number of patients required to change from event to non-event to make the study lose statistical significance), the RFI for RCTs without statistically significant results (number of patients required to change from non-event to event to make study gain statistical significance) and the FQ score for both (FI or RFI score divided by the sample size).

Results

We evaluated 20 RCTs (16 SLE, four LN). The mean FI/RFI score was 13.6 (SD 6.6). There were nine RCTs with statistically significant results (seven SLE, two LN), and the mean FI score was 10.2 (SD 6.2). The lowest FI was for the ILLUMINATE-2 trial (FI=2), and the highest FI was for the BLISS-52 trial (FI=17).

Twelve studies had non-statistically significant results (10 SLE, two LN) with a mean RFI score of 15.6 (SD 6.1). The lowest RFI was for the ILLUMINATE-1 trial (RFI=4), and the highest RFI was for the TULIP-1 trial (RFI=27). The lowest FQ scores were found in the ILLUMINATE trials and the highest in the Rituximab trials (EXPLORER and LUNAR), meaning that the last ones were the most robust results after accounting for sample size.

Conclusions

The evidence of therapies for patients with SLE and LN is derived mostly from fragile RCTs. Clinicians and trialists must be aware of the fragility of these RCTs for clinical decision-making and designing trials for novel therapeutics.
Severe gastrointestinal involvements in patients with adult dermatomyositis with anti-NXP2 antibody
Authors: Fu Yakai , Gu Liyang , Chen Jie , Dai Yuting , Feng Qi , Chen Zhiwei , Fan Jie , Gao Mingshi , Wang Xiaodong , Fu Qiong , Ye Shuang
Published: January 2024

Objective

Gastrointestinal (GI) involvements were scarcely reported in adult anti-nuclear matrix protein 2 (NXP2) dermatomyositis (NXP2+DM). In this study, we investigated the clinical, pathological and molecular features as well as treatment options of this rare yet life-threatening disease.

Methods

We retrospectively collected the data of the cohort of NXP2+DM from 2012 to 2022 in our hospital. RNA sequencing was performed in intestinal samples of perforated patients compared with healthy controls data set.

Results

A total of 56 patients with adult NXP2+DM were collected including 10 cases with GI involvements. Abdominal pain and melena were the initial manifestations for GI involvements with a median 10-month time lag after the diagnosis of NXP2+DM when myositis largely subsided. Within weeks, GI perforation occurred in 8 of 10 patients, while five patients underwent eight surgical interventions subsequently. The short-term mortality was observed in four patients. NXP2+DM with GI involvements presented with more extramuscular systemic manifestations such as interstitial lung disease and subcutaneous calcinosis. The GI pathological features encompassed vasculitis/vasculopathy with high MxA expression, intestinal smooth muscle necrosis and serosal calcinosis. Gene expression profile validated the type-I interferon activation and revealed that epithelial mesenchymal transition and focal adhesion pathway may also contribute. Finally, vedolizumab, an anti-α4β7-integrin monoclonal antibody, exhibited promising therapeutic signals which should be further investigated.

Conclusions

GI involvement is a unique complication in patients with adult NXP2+DM. Timely recognition and targeted therapy may turn out to be lifesaving.
Cretaceous palaeoceanographic events of the northern South Atlantic: an overview
Authors: Koutsoukos Eduardo A. M. , Bengtson Peter
Published: January 2024

The break-up of Gondwana in the latest Jurassic and earliest Cretaceous and the subsequent opening and evolution of the South Atlantic Ocean as a new widening seaway linking northern and southern high latitudes, was the single most significant palaeoceanographic event during the Cretaceous with global consequences for the climate and the biotic evolution, both on land and at sea. Its main evolutionary stages are now becoming well known but, despite that, their global impact has been widely underestimated. Aiming to shed light on some of these unanswered questions, this work presents an overview of research carried out during the past decades in the Sergipe Basin in northeastern Brazil, integrating foraminiferal and ammonite biostratigraphic data, coupled with an assessment of their biogeographic patterns. Three main topics are discussed, and the key findings presented and set against their possible global impact: the opening of the Equatorial Atlantic Gateway in the late early to mid Aptian (
c.
118–119 Ma); the mid-Cretaceous dysoxic–anoxic events recorded in the northern South Atlantic (maxima in the late Aptian–earliest Albian, early Cenomanian and at the Cenomanian–Turonian boundary); and the timing of the North Atlantic–South Atlantic oceanic connection in the late Coniacian to early Santonian (
c.
85–87 Ma).
Compiler Autotuning through Multiple-phase Learning
Authors: Zhu Mingxuan , Hao Dan , Chen Junjie
Published: January 2024

Widely used compilers like GCC and LLVM usually have hundreds of optimizations controlled by optimization flags, which are enabled or disabled during compilation to improve the runtime performance (e.g., small execution time) of the compiler program. Due to the large number of optimization flags and their combination, it is difficult for compiler users to manually tune compiler optimization flags. In the literature, a number of autotuning techniques have been proposed, which tune optimization flags for a compiled program by comparing its actual runtime performance with different optimization flag combinations. Due to the huge search space and heavy actual runtime cost, these techniques suffer from the widely recognized efficiency problem. To reduce the heavy runtime cost, in this article we propose a lightweight learning approach that uses a small number of actual runtime performance data to predict the runtime performance of a compiled program with various optimization flag combinations. Furthermore, to reduce the search space, we design a novel particle swarm algorithm that tunes compiler optimization flags with the prediction model. To evaluate the performance of the proposed approach, CompTuner, we conduct an extensive experimental study on two popular C compilers, GCC and LLVM, with two widely used benchmarks, cBench and PolyBench. The experimental results show that CompTuner significantly outperforms the six compared techniques, including the state-of-the-art technique BOCA.
Industry Practices for Challenging Autonomous Driving Systems with Critical Scenarios
Authors: Song Qunying , Engström Emelie , Runeson Per
Published: January 2024

Testing autonomous driving systems for safety and reliability is essential, yet complex. A primary challenge is identifying relevant test scenarios, especially the critical ones that may expose hazards or harm to autonomous vehicles and other road users. Although numerous approaches and tools for critical scenario identification are proposed, the industry practices for selection, implementation, and evaluation of approaches, are not well understood. Therefore, we aim at exploring practical aspects of how autonomous driving systems are tested, particularly the identification and use of critical scenarios. We interviewed 13 practitioners from 7 companies in autonomous driving in Sweden. We used thematic modeling to analyse and synthesize the interview data. As a result, we present 9 themes of practices and 4 themes of challenges related to critical scenarios. Our analysis indicates there is little joint effort in the industry, despite every approach has its own limitations, and tools and platforms are lacking. To that end, we recommend the industry and academia combine different approaches, collaborate among different stakeholders, and continuously learn the field. The contributions of our study are exploration and synthesis of industry practices and related challenges for critical scenario identification and testing, and potential increase of industry relevance for future studies.
ARCTURUS
: Full Coverage Binary Similarity Analysis with Reachability-guided Emulation
Authors: Zhou Anshunkang , Hu Yikun , Xu Xiangzhe , Zhang Charles
Published: January 2024

Binary code similarity analysis is extremely useful, since it provides rich information about an unknown binary, such as revealing its functionality and identifying reused libraries. Robust binary similarity analysis is challenging, as heavy compiler optimizations can make semantically similar binaries have gigantic syntactic differences. Unfortunately, existing semantic-based methods still suffer from either incomplete coverage or low accuracy.

In this article, we propose
ARCTURUS
, a new technique that can achieve high code coverage and high accuracy simultaneously by manipulating program execution under the guidance of code reachability. Our key insight is that the compiler must preserve program semantics (e.g., dependences between code fragments) during compilation; therefore, the code reachability, which implies the interdependence between code, is invariant across code transformations. Based on the above insight, our key idea is to leverage the stability of code reachability to manipulate the program execution such that deep code logic can also be covered in a consistent way. Experimental results show that
ARCTURUS
achieves an average precision of 87.8% with 100% block coverage, outperforming compared methods by 38.4%, on average.
ARCTURUS
takes only 0.15 second to process one function, on average, indicating that it is efficient for practical use.
Understanding Developers Well-being and Productivity: A 2-year Longitudinal Analysis during the COVID-19 Pandemic—RCR Report
Authors: Russo Daniel , Hanel Paul H. P. , van Berkel Niels
Published: January 2024

The artifact accompanying the paper “Understanding Developers Well-Being and Productivity: A 2-year Longitudinal Analysis during the COVID-19 Pandemic” provides a comprehensive set of tools, data, and scripts that were utilized in the longitudinal study. Spanning 24 months, from April 2020 to April 2022, the study delves into the shifts in well-being, productivity, social contacts, needs, and several other variables of software engineers during the COVID-19 pandemic. The artifact facilitates the reproduction of the study’s findings, offering a deeper insight into the systematic changes observed in various variables, such as well-being, quality of social contacts, and emotional loneliness. By providing access to the evidence-generating mechanisms and the generated data, the artifact ensures transparency and reproducibility and allows researchers to use our rich dataset to test their own research question. This Replicated Computational Results report aims to detail the contents of the artifact, its relevance to the main paper, and guidelines for its effective utilization.
An Underwater Organism Image Dataset and a Lightweight Module Designed for Object Detection Networks
Authors: Huang Jiafeng , Zhang Tianjun , Zhao Shengjie , Zhang Lin , Zhou Yicong
Published: January 2024

Long-term monitoring and recognition of underwater organism objects are of great significance in marine ecology, fisheries science and many other disciplines. Traditional techniques in this field, including manual fishing-based ones and sonar-based ones, are usually flawed. Specifically, the method based on manual fishing is time-consuming and unsuitable for scientific researches, while the sonar-based one, has the defects of low acoustic image accuracy and large echo errors. In recent years, the rapid development of deep learning and its excellent performance in computer vision tasks make vision-based solutions feasible. However, the researches in this area are still relatively insufficient in mainly two aspects. First, to our knowledge, there is still a lack of large-scale datasets of underwater organism images with accurate annotations. Second, in consideration of the limitation on hardware resources of underwater devices, an underwater organism detection algorithm that is both accurate and lightweight enough to be able to infer in real time is still lacking. As an attempt to fill in the aforementioned research gaps to some extent, we established the Multiple Kinds of Underwater Organisms (MKUO) dataset with accurate bounding box annotations of taxonomic information, which consists of 10,043 annotated images, covering eighty-four underwater organism categories. Based on our benchmark dataset, we evaluated a series of existing object detection algorithms to obtain their accuracy and complexity indicators as the baseline for future reference. In addition, we also propose a novel lightweight module, namely Sparse Ghost Module, designed especially for object detection networks. By substituting the standard convolution with our proposed one, the network complexity can be significantly reduced and the inference speed can be greatly improved without obvious detection accuracy loss. To make our results reproducible, the dataset and the source code are available online at
https://cslinzhang.github.io/MKUO-and-Sparse-Ghost-Module/
.
A Poly(L-Arginine)-Based Electrochemical Sensor for Simultaneous Determination of Uric Acid, Tryptophan, and Hypoxanthine
Authors: Kodakat Keerthi , Sam Sonia , Kumar K. Girish
Published: January 2024

This study presents the development of an efficient and cost-effective voltammetric sensor for the individual and simultaneous determination of uric acid (UA), tryptophan (Try) and hypoxanthine (HX), the three important biomarkers in the human body. The sensor consists of glassy carbon electrode (GCE) modified with the conducting layer of poly(L-Arginine) (p-Arg) prepared by the electropolymerisation of L-Arginine using cyclic voltammetry. p-Arg modified GCE (p-Arg/GCE) provided well-resolved and improved electrooxidation responses for UA, Try, and HX due to the greater electrocatalytic activity and fast electron transfer ability of the polymer layer. The fabricated sensor was characterised using Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), Atomic Force Microscopy (AFM), Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Electrochemical Impedance Spectroscopy (EIS) and electroactive surface area calculations. Under optimal analytical conditions, determination of the three analytes was possible over wide linear ranges with the limit of detection of 1.97 × 10−8 M, 4.43 × 10−8 M, and 8.44 × 10−9 M, respectively for UA, Try, and HX. Practical utility of the sensor was successfully verified in synthetic urine and blood serum samples and determination of Try and HX was carried out in dietary supplements and commercially available samples of tea and coffee, respectively.
Long-Term Cycling and Mechanisms of Cell Degradation of Single Crystal LiNi0.95Mn0.04Co0.01O2/Graphite Cells
Authors: Zhang Ning , Yu Svena , Hamam Ines , Tang Ben , Johnson Michel , Dahn J. R.
Published: January 2024

Extremely high nickel content positive electrode materials have high specific capacity leading to high energy density Li-ion cells. The long-term cycling stability of pouch cells with a single crystal LiNi0.95Mn0.04Co0.01O2 positive electrode material was studied here. Cells with such high nickel content demonstrated excellent cycling when only charged to 4.04 V (about 75% state of charge (SOC)), while they showed more capacity loss when charged to 4.18 V or 100% SOC. Lowering the upper cut-off voltage is in favor of the cycling stability however decreases the cell energy density. The main reason for the capacity loss at 40 °C is due to positive electrode impedance growth, which originated from parasitic reactions between the positive electrode material and the electrolyte, especially when the cells are operated to 4.18 V. There was no noticeable positive electrode particle cracking by scanning electron microscopy and no significant active mass loss even for cells operated to 4.18 V. XRD of cycled positive electrodes indicated no appreciable amount of nickel migrating into the lithium layer, so the impedance growth mainly comes from the positive electrode particle surfaces. Using 1.2 M LiPF6 fluoroethylene carbonate: ethyl methyl carbonate 20:80 electrolyte with 1 wt% lithium difluorophosphate allows cycle life to be extended by reducing impedance growth of the cells.
The Role of Current Collector Corrosion on the Performance of Thermal Batteries
Authors: Zeng Zikang , Zhang Chengcheng , Zhu Jiajun , Yang Wulin , Zhou Lingping , Fu Licai
Published: January 2024

As a bridge connecting external circuits and electrodes, current collectors are critical for battery performance. While numerous studies have investigated lithium-ion battery current collectors at room temperature, fewer address high-temperature batteries (>500 °C). The interfacial properties of thermal battery collector and cathode at high temperatures remain unclear, and collector selection is more empirical. In this paper, the effects of 304 stainless steel on the discharge performance of NiS2 cathode were investigated. At 500 °C, 100 mA cm−2 and 1.5 V cutoff voltage, NiS2 first-voltage plateau specific capacity with 304 stainless steel current collector exhibits a high specific capacity of 320 mAh g−1 and total specific capacity of 700 mAh g−1, 146% and 17% higher than Ni, respectively. The Ni current collector of the thermal battery underwent severe chemical reactions at high operating temperatures, consuming active mass and increasing interfacial impedance. In contrast, stainless steel formed an iron-chromium sulfide passivation layer inhibiting further chemical reactions and accelerating charge transfer rate at the interface, resulting in effective increase in the discharge capacity of the thermal battery. This study provides theoretical guidance for selecting current collectors for thermal batteries based on high-temperature chemical reactions.
Effect of Water on Zn Electrodeposition from a Deep Eutectic Solvent
Authors: Lahiri Abhishek , Hirani Pranay , Haghani Sophia , Endres Frank
Published: January 2024

The electrodeposition of Zn films from a deep eutectic solvent (DES) of ZnCl2 and formamide and its mixture with water was studied. From spectroscopic analyses it was observed that water up to 30 v/v% does not change the Zn coordination in the electrolyte after which significant change in the coordination was observed. Electrochemical studies showed that with increase in water concentration in the DES, higher deposition/stripping current was achieved which was related to lowering of viscosity. The Zn deposit morphology changed significantly with water concentration. At low concentrations of water (up to 20 v/v%), porous Zn nanoplates formed whereas the morphology changed to a dense hexagonal structure on increasing the water concentration. X-ray diffraction results confirmed that at low water concentrations (up to 20 v/v%) Zn-Cu alloy formed. Above 20 v/v% water concentration in the DES, Zn peaks evolved with Zn-Cu alloy forming a shoulder. Based on the electrochemical and spectroscopic studies, it appears that 20–30 v/v% water is the critical region wherein significant changes occur from a DES rich region to a water-rich region.
The pulmonary physiology of exercise
Authors: Dominelli Paolo B. , Sheel A. William
Published: January 2024

Our narrative review is written with the student of the pulmonary physiology of exercise in mind, be it a senior undergraduate or graduate student or those simply refreshing their knowledge. We also aim to provide examples where the reader can incorporate real scenarios.
Design, Optimization, and Application of Nonlinear Energy Sink in Energy Harvesting Device
Authors: Kang Xiaofang , Tang Jianjun , Xia Guanghui , Wei Jiachen , Zhang Fuyi , Sheng Ziyi
Published: January 2024

Vibration control has been of great interest to scientists and engineers for many years. Although linear vibration absorbers have been shown to be effective in mitigating vibrations at specific frequencies, their vibration reduction effect is usually limited to a narrow frequency bandwidth. Nonlinear energy sinks have attracted attention due to their better vibration reduction effect over a wider frequency bandwidth. In practical applications, the nonlinear energy sink devices can effectively absorb, dissipate, and convert energy from broadband excitation, so as to achieve vibration reduction and energy harvesting. However, research on energy harvesting based on the nonlinear energy sink is less mature than in linear systems. Multiple parameters of device design (e.g., damping size) affect the actual performance of the nonlinear energy sinks, but there is no exact method to simplify the design of the multiparameter nonlinear energy sinks. Since it is more difficult to implement electromagnetic and electrostatic energy harvesters, more research has focused on piezoelectric energy harvesters. This paper summarizes the research on the nonlinear energy sink and energy harvesting technology, including the introduction of the nonlinear energy sink, energy harvesting based on the nonlinear energy sink, and its application in various fields of energy harvesting. The paper also summarizes some important methods for solving the dynamical equations, as well as their advantages and disadvantages. The conclusions provide an outlook on the subsequent research of the nonlinear energy sink technology, such as the introduction of piezoelectric materials with high energy density, the benefits of balanced vibration suppression and harvesting of vibration energy, and the self‐tuning of parameters in complex environments. It provides a powerful reference for the popularization and application of energy harvesting technology based on nonlinear energy sinks.
Automatic History Matching for Adjusting Permeability Field of Fractured Basement Reservoir Simulation Model Using Seismic, Well Log, and Production Data
Authors: Son Le Ngoc , Duc Nguyen The , Murata Sumihiko , Trung Phan Ngoc
Published: January 2024

Developing automatic history matching (AHM) methods to replace the traditional manual history matching (MHM) approach in adjusting the permeability distribution of the reservoir simulation model has been studied by many authors. Because permeability values need to be evaluated at hundreds of thousands of grid cells in a typical reservoir simulation model, it is necessary to apply a reparameterization technique to allow the optimization algorithms to be implemented with fewer variables. In basic reparameterization techniques including zonation and pilot point methods, the calibrations are usually based solely on the production data with no systematic link to the geological and geophysical data, and therefore, the obtained permeability distribution may be not geologically consistent. Several other reparameterization techniques have attempted to preserve geological consistency by incorporating 4D seismic data; however, these techniques cannot be applied to our fractured basement reservoirs (FBRs) as they do not have 4D seismic data. Taking into account these challenges, in this study, an AHM methodology and workflow have been developed using a new reparameterization technique. This approach attempts to minimize the potential for geological nonconsistency of the calibrated results by linking the permeability to geophysical data. The proposed methodology can be applied to fields with only traditional geophysical data (3D seismic and conventional well logs). In the proposed workflow, the spatial distributions of seismic attributes and geomechanical properties were calculated and estimated from 3D seismic data and well logs, respectively. After that, a feed-forward artificial neural network (ANN) model trained by the back-propagation algorithm of the relationship between initial permeability with seismic attributes and geomechanical properties of their grid cell values is developed. Then, the calibration of the permeability distribution is performed by adjustment of the ANN model. Modification of the ANN model is performed using the simultaneous perturbation stochastic approximation (SPSA) algorithm to calibrate transmission coefficients in the ANN model to minimize the discrepancy between the simulated results and observed data. The developed methodology is applied to calibrate the permeability distribution of a simulation model of Bach Ho FBR in Vietnam. The effectiveness of the methodology is evident by comparing the historical matches with an available manually history-matched simulation model. The application shows that the proposed methodology could be considered as a suitable practical approach for adjusting the permeability distribution for FBR reservoir simulation models.
Experiences regarding Home Care for Older Adults from the Viewpoint of Family, Paid Caregivers, Nurses, and Experts: A Qualitative Study
Authors: Mobasseri Khorshid , Allahverdipour Hamid , Matlabi Hossein , Kousha Ahmad
Published: January 2024

Home care (HC) is recommended for older adults who want to live at home as long as possible despite life‐limiting conditions. It is more convenient and cost‐effective than institutionalization and hospitalization. However, HC for older adults in Iran faces many challenges. The purpose of this study was to explore the perspectives of different stakeholders involved in HC for older adults about their experiences and suggestions for HC improvement. This qualitative study was conducted based on the explorative content analysis approach between 2021 and 2022 in Tabriz, Iran. The participants were selected using the purposeful sampling method, and the data were collected through in‐depth semistructured personal interviews. A total of 27 individuals who participated in individual interviews were family members, HC workers (including nurses and unqualified paid caregivers), heads of counseling and nursing care at home centers, and experts who had clinical or research experience in the field of geriatric care. Collected data were categorized into three main themes: defects in home care governance, concern about the efficiency of home care, and caregivers’ job security concerns. These themes reflected the problems of HC, such as conflicts between multiple trustees, lack of evaluation and monitoring, inadequate competence and financial barriers of families and caregivers, and poor integration and coordination of services. Therefore, it is recommended to develop a national model for HC for Iranian older adults and allocation of different financial resources for HC, implementing quality improvement and evaluation tools, enhancing the training of caregivers, providing them with adequate compensation and benefits, and ensuring the safety and quality of services. These findings can inform the policymakers and planners of care services about the needs and challenges of this population and facilitate the collaboration among different stakeholders to provide better HC for older adults.
Robust Decentralized Formation Tracking Control of Complex Multiagent Systems
Authors: Mazhar Naveed , Khan Rameez , Raza Abid , Malik Fahad Mumtaz , Azim Raja Amer , Ullah Hameed
Published: January 2024

This article investigates the decentralized formation tracking problem for complex multiagent systems in finite settling time, subjected to output constraints and external disturbances. The barrier Lyapunov function is used to constrain the output of each agent. Therefore, starting inside a closed boundary, the agents are guaranteed to remain inside it for all future time. Under directed communication topology, decentralized time-varying formation tracking is achieved in finite time. Furthermore, in the proposed work, the linear sliding manifold is employed to mitigate the singularity problem that occurs in the conventional robust finite-time methods, i.e., terminal sliding mode-based control schemes. The stability properties of the proposed framework are established through the Lyapunov method which not only ensures the finite-time formation tracking of nonlinear multiagent systems under directed communication but also guarantees that for all time the agents remain inside a closed boundary if they are initially inside it. Consequently, the uniqueness of this article is that it presents a novel formation tracking control framework for multiagent systems that simultaneously considers three performance metrics of robustness, finite-time convergence, and output constraints while mitigating the singularity problem. The proposed topology is validated by implementing the numerical examples in MATLAB/SIMULINK.
Idiosyncratic Drug-Induced Liver Injury in a Healthy Patient following PCSK9-Inhibitor Injection
Authors: Stüben B.-O. , Hoyer D. P. , Radunz S. , Saner F. , Schmidt H. , Baba H. A. , Treckmann J. W. , Mazilescu L. I.
Published: January 2024

Background. Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion. This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge.
Visualizing the Future of Knowledge Sharing in SMEs in the Construction Industry: A VOSviewer Analysis of Emerging Trends and Best Practices
Authors: López Salvador , Yepes Víctor
Published: January 2024

This review paper systematically synthesizes existing literature on knowledge sharing (KS) and knowledge transfer (KT) in the context of small and medium‐sized enterprises (SMEs) in the construction industry, updating previous research and making predictions about emerging issues. The comprehensive literature review employs three different bibliometric techniques: (1) textual analysis of keywords and abstracts to identify relevant research areas, (2) cocitation analysis of references to analyze the evolution of KS and KT in SMEs, and (3) bibliographic linkage analysis of documents to summarize the background and results. The resulting conceptual map outlines the historical development of KS and KT at individual, group, and organizational levels in the construction industry. The study emphasizes the critical significance of KS and KT for SMEs in this industry. It highlights the role of innovation and open innovation in facilitating the successful implementation of KS and KT. The analysis also reveals the need for enhanced knowledge management in SMEs through better data management, implementation of digital systems for internal management, identification of inefficiencies in KT in collaborative networks, and adjustment of knowledge management approaches to suit different cultural and geographic contexts. Finally, the paper suggests future trends in KS and KT, emphasizing the importance of collaboration, continuous learning, technological capabilities, and developing a suitable organizational culture and structure for open innovation in the construction industry. This article offers an innovative approach to KS and KT in SMEs and practical recommendations for improving knowledge management and innovation capacity in construction‐related businesses. Its systematic approach and focus on SMEs in the construction industry make it highly relevant for research and business practice.
Analysis of Factors Influencing Spatial Distribution of Soil Erosion under Diverse Subwatershed Based on Geospatial Perspective: A Case Study at Citarum Watershed, West Java, Indonesia
Authors: Nahib Irmadi , Wahyudin Yudi , Amhar Fahmi , Ambarwulan Wiwin , Nugroho Nunung Puji , Pranoto Bono , Cahyana Destika , Ramadhani Fadhlullah , Suwedi Nawa , Darmawan Mulyanto , Turmudi Turmudi , Suryanta Jaka , Karolinoerita Vicca
Published: January 2024

The application of remote sensing data has been significant in modeling soil erosion. However, previous studies have fallen short in elucidating and lacked an understanding of the multifactor influencing erosion. This study addresses these limitations by employing the InVEST and the Geodetector models. Specifically, it aims (1) to delineate both spatial and temporal variations in soil erosion within the Citarum watershed from 2010 to 2020, (2) to identify the key drivers of soil erosion and unravel the underlying mechanisms, and (3) to identify the high-risk zones for soil erosion. Both models consider a range of natural predictors, including topography (slope factor), climate (precipitation factor), and vegetation cover (vegetation factor). In addition, they incorporate social parameters such as income per capita and population density, which interact with the watershed’s position in the downstream, middle, and upper streams. The results reveal that, over a decade, the average soil erosion increased by 15.50 × 106 tons, marking a 16.65% surge. The impact of factors varies significantly across different subwatershed areas. For example, fraction vegetation cover interactions influence upper- and middle-stream regions, while the downstream area is notably affected by precipitation interactions. The high-risk erosion areas in the watershed are primarily influenced by slope, precipitation, and fractional vegetation cover. In these areas, factors causing high erosion risks include slope, precipitation, and other environmental variables categorized into strata. The study highlights the varying influential factors in different watershed areas.
Tofacitinib for the Treatment of Refractory Progressive Vitiligo: A Retrospective Case Series
Authors: Sun Xiu-kun , Sheng An-qi , Xu Ai-e
Published: January 2024

Treatment of progressive vitiligo aims to halt the spread of the disease and facilitate repigmentation of lesions. JAK inhibitor has been shown some therapeutic effects on vitiligo, but the data for the progressive vitiligo are limited. This retrospective study was performed to evaluate the efficacy and safety of oral tofacitinib in 25 refractory progressive vitiligo patients who experienced failure to previous steroid treatments. 16 (64%) of the 25 patients noted stopping disease progression, and nearly half of the 16 cases halted progression within one month. 10 (40%) patients had repigmentation in varying degrees. Combination with phototherapy was a key factor affecting the rate of repigmentation. Oral tofacitinib might be a potentially effective treatment for intractable progressive vitiligo. The limitations of the study include the retrospective, single‐centre study with small sample size and lack of comparison with other systemic therapies.
Raludotatug Deruxtecan, a CDH6-Targeting Antibody–Drug Conjugate with a DNA Topoisomerase I Inhibitor DXd, Is Efficacious in Human Ovarian and Kidney Cancer Models
Authors: Suzuki Hirokazu , Nagase Shotaro , Saito Chiemi , Takatsuka Atsuko , Nagata Motoko , Honda Kokichi , Kaneda Yuki , Nishiya Yumi , Honda Tomoyo , Ishizaka Tomomichi , Nakamura Kensuke , Nakada Takashi , Abe Yuki , Agatsuma Toshinori
Published: January 2024

Cadherin-6 (CDH6) is expressed in several cancer types, but no CDH6-targeted therapy is currently clinically available. Here, we generated raludotatug deruxtecan (R-DXd; DS-6000), a novel CDH6-targeting antibody–drug conjugate with a potent DNA topoisomerase I inhibitor, and evaluated its properties, pharmacologic activities, and safety profile. In vitro pharmacologic activities and the mechanisms of action of R-DXd were assessed in serous-type ovarian cancer and renal cell carcinoma cell lines. In vivo pharmacologic activities were evaluated with several human cancer cell lines and patient-derived xenograft mouse models. The safety profile in cynomolgus monkeys was also assessed. R-DXd exhibited CDH6 expression-dependent cell growth-inhibitory activity and induced tumor regression in xenograft models. In this process, R-DXd specifically bound to CDH6, was internalized into cancer cells, and then translocated to the lysosome. The DXd released from R-DXd induced the phosphorylation of Chk1, a DNA damage marker, and cleaved caspase-3, an apoptosis marker, in cancer cells. It was also confirmed that the DXd payload had a bystander effect, passing through the cell membrane and impacting surrounding cells. The safety profile of R-DXd was favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys. R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting.
PROTACs: Current and Future Potential as a Precision Medicine Strategy to Combat Cancer
Authors: Rutherford Kailee A. , McManus Kirk J.
Published: January 2024

Proteolysis targeting chimeras (PROTAC) are an emerging precision medicine strategy, which targets key proteins for proteolytic degradation to ultimately induce cancer cell killing. These hetero-bifunctional molecules hijack the ubiquitin proteasome system to selectively add polyubiquitin chains onto a specific protein target to induce proteolytic degradation. Importantly, PROTACs have the capacity to target virtually any intracellular and transmembrane protein for degradation, including oncoproteins previously considered undruggable, which strategically positions PROTACs at the crossroads of multiple cancer research areas. In this review, we present normal functions of the ubiquitin regulation proteins and describe the application of PROTACs to improve the efficacy of current broad-spectrum therapeutics. We subsequently present the potential for PROTACs to exploit specific cancer vulnerabilities through synthetic genetic approaches, which may expedite the development, translation, and utility of novel synthetic genetic therapies in cancer. Finally, we describe the challenges associated with PROTACs and the ongoing efforts to overcome these issues to streamline clinical translation. Ultimately, these efforts may lead to their routine clinical use, which is expected to revolutionize cancer treatment strategies, delay familial cancer onset, and ultimately improve the lives and outcomes of those living with cancer.
Data from p120-Catenin Is Transcriptionally Downregulated by FOXC2 in Non–Small Cell Lung Cancer Cells
Authors: Mortazavi Fariborz , An Jiabin , Dubinett Steven , Rettig Matthew
Published: January 2024

Abstract
p120-catenin (p120ctn) plays a major role in cell adhesion and motility through the regulation of E-cadherin and interaction with RhoGTPase and Rac1. p120ctn is downregulated in several malignancies including non–small cell lung cancer (NSCLC). Here, we investigated transcriptional regulation of p120ctn in NSCLC. We cloned a 1,400-bp amplicon of chromosome 11 from position −1,082 to +320 relative to the transcription start site into a firefly luciferase reporter vector and prepared serial deletion constructs to pinpoint cis-acting elements involved in the regulation of p120ctn. We transfected NSCLC cell lines and immortalized normal human respiratory epithelial cells with the abovementioned constructs. We found reduced p120ctn promoter activity, protein level, and mRNA message in lung cancer cells compared with noncancerous immortalized lung epithelial cells. Serial deletion analysis of p120ctn promoter identified a region between positions +267 and +282, which mediated the transcriptional repression of p120ctn. This region harbored putative binding sites for FOXC2 and FOXL1 transcription factors. Direct binding of FOXC2 to the p120ctn promoter between positions +267 and +282 was confirmed by electromobility shift assay. RNAi-mediated silencing of FOXC2 in A549, H157, and H358 cells resulted in increasing p120ctn promoter activity as well as mRNA and protein levels. Finally, silencing FOXC2 in these NSCLC cells enhanced E-cadherin level, which was reversed by simultaneous silencing of p120ctn. In summary, our data support the notion that FOXC2 mediates the transcriptional repression of p120ctn in NSCLC. Mol Cancer Res; 8(5); 762–74. ©2010 AACR.
Figure S2 from Weakly Supervised Deep Learning Predicts Immunotherapy Response in Solid Tumors Based on PD-L1 Expression
Authors: Ligero Marta , Serna Garazi , El Nahhas Omar S.M. , Sansano Irene , Mauchanski Siarhei , Viaplana Cristina , Calderaro Julien , Toledo Rodrigo A. , Dienstmann Rodrigo , Vanguri Rami S. , Sauter Jennifer L. , Sanchez-Vega Francisco , Shah Sohrab P. , Ramón y Cajal Santiago , Garralda Elena , Nuciforo Paolo , Perez-Lopez Raquel , Kather Jakob Nikolas
Published: January 2024

Visualization of PanCytokeratin IHC staining, PD-L1 IHC staining and model attention heatmaps of a high (top) and low (bottom) PD-L1 score patients pan-cancer-VHIO cohort. PanCytokeratin IHC stained images differentiate tumor tissue (A, D). PD-L1 IHC stained images highlight tumor cells with high PD-L1 expression (B, E). Attention heatmaps indicate that the model is considering tumor areas for evaluating TPS (C,F)
FIGURE 4 from Weakly Supervised Deep Learning Predicts Immunotherapy Response in Solid Tumors Based on PD-L1 Expression
Authors: Ligero Marta , Serna Garazi , El Nahhas Omar S.M. , Sansano Irene , Mauchanski Siarhei , Viaplana Cristina , Calderaro Julien , Toledo Rodrigo A. , Dienstmann Rodrigo , Vanguri Rami S. , Sauter Jennifer L. , Sanchez-Vega Francisco , Shah Sohrab P. , Ramón y Cajal Santiago , Garralda Elena , Nuciforo Paolo , Perez-Lopez Raquel , Kather Jakob Nikolas
Published: January 2024

Explainability for model performance in the pan-cancer-VHIO validation cohort. Overall performance of the model in the validation cohort (A). Distribution of true negative ratio (TNR), true positive ratio (TPR), false negative ratio (FNR), and false positive ratio (FPR) per tumor type in the pan-cancer-VHIO validation cohort (B). Distribution of predicted scores in the pan-cancer-VHIO cohort compared with continuous TPS (C) and CPS (D). Examples of false positives due to histologic differences from NSCLC: PD-L1–stained IHC image from melanoma tumor sample predicted as high PD-L1 by the model (predicted TPS ≥ 1%) with low PD-L1 expression in the tumor cells (TPS < 1%) and high PD-L1 expression in the immune component (CPS ≥ 1%). Magnification of areas with tumor cells with no PD-L1 expression (blue) and immune cells with PD-L1 expression (red), image magnification: 5× and 20× (E). Examples of false negative due to low cellularity samples: PD-L1–stained IHC image from gastrointestinal tumor sample predicted as low PD-L1 by the model (predicted TPS < 1%) with high PD-L1 expression in the tumor cells (TPS = 20%) and high PD-L1 expression in the immune component (CPS ≥ 35%). Magnification of regions with tumor cells, image magnification, 0.35× and 5× (F).
Exploring Co-occurring POLE Exonuclease and Non-exonuclease Domain Mutations and Their Impact on Tumor Mutagenicity
Authors: Shah Shreya M. , Demidova Elena V. , Ringenbach Salena , Faezov Bulat , Andrake Mark , Gandhi Arjun , Mur Pilar , Viana-Errasti Julen , Xiu Joanne , Swensen Jeffrey , Valle Laura , Dunbrack Roland L. , Hall Michael J. , Arora Sanjeevani
Published: January 2024

POLE driver mutations in the exonuclease domain (ExoD driver) are prevalent in several cancers, including colorectal cancer and endometrial cancer, leading to dramatically ultra-high tumor mutation burden (TMB). To understand whether POLE mutations that are not classified as drivers (POLE Variant) contribute to mutagenesis, we assessed TMB in 447 POLE-mutated colorectal cancers, endometrial cancers, and ovarian cancers classified as TMB-high ≥10 mutations/Mb (mut/Mb) or TMB-low <10 mut/Mb. TMB was significantly highest in tumors with “POLE ExoD driver plus POLE Variant” (colorectal cancer and endometrial cancer, P < 0.001; ovarian cancer, P < 0.05). TMB increased with additional POLE variants (P < 0.001), but plateaued at 2, suggesting an association between the presence of these variants and TMB. Integrated analysis of AlphaFold2 POLE models and quantitative stability estimates predicted the impact of multiple POLE variants on POLE functionality. The prevalence of immunogenic neoepitopes was notably higher in the “POLE ExoD driver plus POLE Variant” tumors. Overall, this study reveals a novel correlation between POLE variants in POLE ExoD-driven tumors, and ultra-high TMB. Currently, only select pathogenic ExoD mutations with a reliable association with ultra-high TMB inform clinical practice. Thus, these findings are hypothesis-generating, require functional validation, and could potentially inform tumor classification, treatment responses, and clinical outcomes.

Significance:

Somatic POLE ExoD driver mutations cause proofreading deficiency that induces high TMB. This study suggests a novel modifier role for POLE variants in POLE ExoD-driven tumors, associated with ultra-high TMB. These data, in addition to future functional studies, may inform tumor classification, therapeutic response, and patient outcomes.
International Online Survey on the Management of Patent Ductus Arteriosus
Authors: Woodford Sarah , Parmar Trisha , Leong Emily , Zhong Jiayue , Oei Ju Lee , Suzuki Keiji , Kumar Kishore , Yeo Kee Thai , Ma Li , De Luca Daniele , Hummler Helmut , Schmölzer Georg , Vento Maximo , Schindler Timothy
Published: January 2024

Introduction: There is uncertainty and lack of consensus regarding optimal management of patent ductus arteriosus (PDA). We aimed to determine current clinical practice in PDA management across a range of different regions internationally. Materials and Methods: We surveyed PDA management practices in neonatal intensive care units using a pre-piloted web-based survey, which was distributed to perinatal societies in 31 countries. The survey was available online from March 2018 to March 2019. Results: There were 812 responses. The majority of clinicians (54%) did not have institutional protocols for PDA treatment, and 42% reported variable management within their own unit. Among infants <28 weeks (or <1,000 g), most clinicians (60%) treat symptomatically. Respondents in Australasia were more likely to treat PDA pre-symptomatically (44% vs. 18% all countries [OR 4.1; 95% CI 2.6–6.5; p < 0.001]), and respondents from North America were more likely to treat symptomatic PDA (67% vs. 60% all countries [OR 2.0; 95% CI 1.5–2.6; p < 0.001]). In infants ≥28 weeks (or ≥1,000 g), most clinicians (54%) treat symptomatically. Respondents in North America were more likely to treat PDAs in this group of infants conservatively (47% vs. 38% all countries [OR 2.3; 95% CI 1.7–3.2; p < 0.001]), and respondents from Asia were more likely to treat the PDA pre-symptomatically (21% vs. 7% all countries [OR 5.5; 95% CI 3.2–9.8; p < 0.001]). Discussion/Conclusion: There were marked international differences in clinical practice, highlighting ongoing uncertainty and a lack of consensus regarding PDA management. An international conglomeration to coordinate research that prioritises and addresses these areas of contention is indicated.