bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry
Authors: Alfares Bader A , van der Doef Hubert P J , Wildhaber Barbara E , Casswall Thomas , Nowak Greg , Delle Martin , Aldrian Denise , Berchtold Valeria , Vogel Georg F , Kaliciński Piotr , Markiewicz-Kijewska Malgorzata , Kolesnik Adam , Bernabeu Jesús Q , Hally María Mercadal , Larrarte K Mauricio , Marra Paolo , Bravi Michela , Pinelli Domenico , Kasahara Mureo , Sakamoto Seisuke , Uchida Hajime , Mali Vidyadhar , Aw Marion , Franchi-Abella Stéphanie , Gonzales Emmanuel , Guérin Florent , Cervio Guillermo , Minetto Julia , Sierre Sergio , de Santibañes Martin , Ardiles Victoria , Uno Jimmy Walker , Evans Helen , Duncan David , McCall John , Hartleif Steffen , Sturm Ekkehard , Patel Jai , Mtegha Marumbo , Prasad Raj , Ferreira Cristina T , Nader Luiza S , Farina Marco , Jaramillo Catalina , Rodriguez-Davalos Manuel I , Feola Peter , Shah Amit A , Wood Phoebe M , Acord Michael R , Fischer Ryan T , Mullapudi Bhargava , Hendrickson Richard J , Khanna Rajeev , Pamecha Viniyendra , Mukund Amar , Sharif Khalid , Gupte Girish , McGuirk Simon , Porta Gilda , Spada Marco , Alterio Tommaso , Maggiore Giuseppe , Hardikar Winita , Beretta Marisa , Dierckx Rudi , de Kleine Ruben H J , Bokkers Reinoud P H
Published: July 2023

Introduction

Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO.

Methods and analysis

The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques.

Ethics and dissemination

Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences.

Trial registration number

Netherlands Trial Register (NL9261).
Randomised double-blind controlled trial of non-invasive preimplantation genetic testing for aneuploidy in in vitro fertilisation: a protocol paper
Authors: Cheng Hiu Yee Heidi , Chow Judy F C , Lam Kevin K W , Lai Shui Fan , Yeung William Shu Biu , Ng Ernest H Y
Published: July 2023

Introduction

The success rate of in vitro fertilisation (IVF) treatment for couples with infertility remains low due to lack of a reliable tool in selecting euploid embryos for transfer. This study aims to compare the efficacy in embryo selection based on morphology alone compared with non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) and morphology in infertile women undergoing IVF.

Methods and analysis

This is a randomised double-blind controlled trial conducted in two tertiary assisted reproduction centres. A total of 500 infertile women will be recruited and undergo IVF as indicated. They will be randomly assigned on day 6 after oocyte retrieval into two groups: the intervention group using morphology and niPGT-A and the control group based on morphology alone. In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of spent culture medium will be replaced first. The primary outcome is a live birth per the first embryo transfer. The statistical analysis will be performed with the intention to treat and per protocol.

Ethics and dissemination

Ethics approval was sought from the institutional review board of the two participating units. All participants will provide written informed consent before joining the study. The results of the study will be submitted to scientific conferences and peer-reviewed journals.

Trial registration number

NCT04474522.
Variation in daytime general practice services and association with out-of-hours use for older patients: protocol for a Danish cohort study
Authors: Olsen Jonas K , Wehberg Sonja , Waldorff Frans Boch , Henriksen Daniel Pilsgaard , Lykkegaard Jesper
Published: July 2023

Introduction

Out-of-hours primary care services cannot provide the same continuity and coordination of care as general practice. Thus, patients with high risk of complex care trajectories should, when possible, be treated by the general practitioner during daytime opening hours. This study aims to analyse the variation among general practices in the frequencies of daytime services for persons aged ≥75 years and how it relates to the patients’ use of out-of-hours services.

Methods and analysis

Register-based cohort study of all Danish citizens aged ≥75 years, of whom >98% are listed with a general practice. Using Poisson regression, we will estimate each practice’s excess variation in delivered daytime services compared with the expected based on the characteristics of its listed patients. Delivered daytime services will be analysed overall and separately for face-to-face, phone, email, home visit and preventive services. The association with the use of out-of-hours services will be analysed by Poisson regression.

Ethics and dissemination

Complying with European data protection rules, the legal services at University of Southern Denmark (Research & Innovation Organisation) approved the data processing activities regarding this project (journal number 11.593). According to section 14.2 of the Act on Research Ethics Review of Health Research Projects, because the study is based solely on register data, approval from the ethics committee and informed consent are not required. Results from the study will be disseminated as publications in peer-reviewed scientific journals and at international conferences.
Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
Authors: Karayama Masato , Inui Naoki , Inoue Yusuke , Yasui Hideki , Hozumi Hironao , Suzuki Yuzo , Furuhashi Kazuki , Fujisawa Tomoyuki , Enomoto Noriyuki , Asada Kazuhiro , Uto Tomohiro , Fujii Masato , Matsui Takashi , Matsuura Shun , Hashimoto Dai , Toyoshima Mikio , Ikeda Masaki , Matsuda Hiroyuki , Inami Nao , Kaida Yusuke , Funayama Satoshi , Ichikawa Shintaro , Goshima Satoshi , Suda Takafumi
Published: July 2023

Background

There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).

Methods

In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest.

Results

Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician’s decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death.

Conclusions

In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP.

Trial registration number

jRCT: 1041190029.
Palliative care needs and specialist services post stroke: national population-based study
Authors: Liu Huiqin , Cook Angus , Ding Jinfeng , Lu Hongwei , Jiao Jingjing , Bai Wenhui , Johnson Claire E
Published: July 2023

Objectives

(1) To compare palliative care needs of patients admitted primarily with stroke and (2) to determine how the care needs of these patients affect their use of different types of specialist palliative care services.

Methods

Observational study based on point-of-care data from the Australian Palliative Care Outcomes Collaboration. Multivariate logistic regression models were used to explore the association between patients’ palliative care needs and use of community versus inpatient specialist palliative care services.

Results

The majority of patients who had a stroke in this study population had mild or no symptom distress, but experienced a high degree of functional impairment and needed substantial help with basic tasks of daily living. A lower Australia-modiﬁed Karnofsky Performance Status score (OR=1.82, 95% CI 1.06 to 3.13) and occurrence of an ‘unstable’ palliative care phase (OR=28.34, 95% CI 9.03 to 88.94) were associated with use of inpatient versus community palliative care, but otherwise, no clear association was observed between the majority of symptoms and use of different care services.

Conclusions

Many people with stroke could potentially have been cared for and could have experienced the terminal phases of their condition in a community setting if more community support services were available for their families.
Oral clinical findings and intensive care unit prognostic scores
Authors: Quintanilha Renata de Moura Cruz , Pereira Mara Regina Rocha , Oliveira Silvia Paula de , Penoni Daniela Cia , Salgado Diamantino Ribeiro , Agostini Michelle , Torres Sandra R
Published: July 2023

Objective

Hospitalisation in intensive care unit (ICU) may cause changes in oral environment, which may influence patients’ health status. The aim of this study was to evaluate the frequency of intraoral and extraoral findings observed during ICU admission, and to verify if there is an association with clinical prognosis scores.

Methods

Data regarding clinical characteristics of patients hospitalised in an ICU were collected from medical records. The prognostic scores Sepsis Related Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS 3) were estimated with data collected from admission and SOFA on the day of the oral examination as well. Data on oral mucosa lesions, saliva, dental condition and oral hygiene were evaluated during oral examinations.

Results

The association of oral findings with prognostic scores was statistically verified. The majority (92.2%) of the 170 evaluated patients showed extraoral or intraoral findings during ICU admission. The most frequent findings were chapped and crusted lips, coated tongue, pale mucosa, haemorrhagic lesions, candidiasis, depapillated tongue and traumatic lesions. There were significant higher prognostic scores in the presence of the following extraoral and intraoral findings: crusted and ulcerated lips, haemorrhagic lesions, jaundice, spontaneous oral bleeding, coated and depapillated tongue. Median SAPS 3 was higher in patients with poor oral hygiene.

Conclusions

Oral findings were frequent in the population of patients hospitalised in the ICU and some of them were associated with worse prognostic scores. Routine oral examinations must be performed in hospitalised patients from ICUs for detection of oral markers of worse clinical prognosis.
Research on reducing flow shock of the digital hydraulic wind turbine
Authors: Liu Zengguang , Zhang Benguo , Wei Liejiang , Yue Daling , Ren Lu , Su Liqiang , Zhao Yuyang
Published: July 2023

The wind turbine with digital hydraulic transmission can make the corresponding hydraulic pump work according to the wind speed, so that the hydraulic wind turbine can maintain high efficiency at the whole working wind speed. However, the switching of different displacement hydraulic pumps will cause a large flow impact on the hydraulic system of the wind turbine, affecting its working characteristics and the absorption of wind energy. Based on the analysis of the working principle of the digital hydraulic wind turbine, the scheme of a 5 MW wind turbine is designed and the AMESim model is established. The dynamic characteristics of the digital hydraulic wind turbine under two switching modes are compared. An advance valve closing control strategy is proposed to reduce the instantaneous flow impact. Simulation results show that the control strategy diminished the system flow shock by about 50% when switching the hydraulic pump. Finally, a hardware-in-loop system with a 5.5 kW digital hydraulic turbine is built to verify the effectiveness of the proposed control strategy. The research results provide a theoretical basis and technical reference for the efficient utilization of wind energy and stable operation of the digital hydraulic wind turbines.
Fairness in Recommendation: Foundations, Methods, and Applications
Authors: Li Yunqi , Chen Hanxiong , Xu Shuyuan , Ge Yingqiang , Tan Juntao , Liu Shuchang , Zhang Yongfeng
Published: July 2023

As one of the most pervasive applications of machine learning, recommender systems are playing an important role on assisting human decision-making. The satisfaction of users and the interests of platforms are closely related to the quality of the generated recommendation results. However, as a highly data-driven system, recommender system could be affected by data or algorithmic bias and thus generate unfair results, which could weaken the reliance of the systems. As a result, it is crucial to address the potential unfairness problems in recommendation settings. Recently, there has been growing attention on fairness considerations in recommender systems with more and more literature on approaches to promote fairness in recommendation. However, the studies are rather fragmented and lack a systematic organization, thus making it difficult to penetrate for new researchers to the domain. This motivates us to provide a systematic survey of existing works on fairness in recommendation. This survey focuses on the foundations for fairness in recommendation literature. It first presents a brief introduction about fairness in basic machine learning tasks such as classification and ranking to provide a general overview of fairness research, as well as introduce the more complex situations and challenges that need to be considered when studying fairness in recommender systems. After that, the survey will introduce fairness in recommendation with a focus on the taxonomies of current fairness definitions, the typical techniques for improving fairness, as well as the datasets for fairness studies in recommendation. The survey also talks about the challenges and opportunities in fairness research with the hope of promoting the fair recommendation research area and beyond.
Learning Hierarchical Spatial Tasks with Visiting Relations for Next POI Recommendation
Authors: Lim Nicholas , Hooi Bryan , Ng See-Kiong , Goh Yong Liang , Weng Renrong , Tan Rui
Published: July 2023

Sparsity is an established problem for the next Point-of-Interest (POI) recommendation task, where it hinders effective learning of user preferences from the User-POI matrix. However, learning multiple hierarchically related spatial tasks, and visiting relations between users and POIs, can help to alleviate this sparsity problem. In this article, we propose our Hierarchical Multi-Task Graph Recurrent Network (HMT-GRN) approach, which alleviates the sparsity problem by learning different User-Region matrices of lower sparsities in a multi-task setting. We then perform a Hierarchical Beam Search (HBS) on the different region and POI distributions to hierarchically reduce the search space with increasing spatial granularity and predict the next POI. Our HBS provides efficiency gains by reducing the search space, resulting in speedups of 5 to 7 times over an exhaustive approach. In addition, we propose a selectivity layer to predict if the next POI has been visited before by the user to balance between personalization and exploration. Further, we propose a novel Joint Triplet Loss Learning (JTLL) module to learn visited and unvisited relations between users and POIs for the recommendation task. Experimental results on two real-world Location-Based Social Network (LBSN) datasets show that our proposed approach significantly outperforms baseline and the state-of-the-art methods.
Solutions on Establishing and Utilizing BIM for General Contractors in Key Scenarios of Digital Construction
Authors: Peng Yang , Yu Fangqiang , Zhang Ming , Xu Jinglin , Gao Shang
Published: July 2023

Nowadays, digital construction has become popular when bringing convenience and efficiency to the traditional building construction industry. The primary tool of digital construction is the building information model (BIM). However, from the perspective of general contractors, unresolved puzzles still hinder obtaining the benefits of digital construction. When establishing a unified BIM from submodels provided by subcontractors, there will possibly be incomplete or inconsistent data during model merging. But extracting submodels from unified BIM often includes redundant data, thus making models less usable for subcontractors. It is also difficult for general contractors to effectively and accurately utilize resource information and submodel changes. This paper proposed solutions that depend on the widely adopted industry foundation classes standard to ensure the universality of our methods. First, a model merging algorithm is proposed to support the continuous merge of submodels created by different subcontractors. Second, an instance-level model extraction method based on strongly related entities is proposed, which extracts model instances to the minimum submodel and meets the subcontractor requirements at the same time. Third, the new model storage and indexing method are designed to reduce the complexity of model data and support rapid data retrieval, and a new BIM change detection method based on object metadata is provided. The proposed methods were applied by the general contractor of a large airport project during the construction stage. The application results proved that the proposed methods could ensure the quality of established deepening design models and extracted submodels and significantly reduce human labor by improving efficiency when utilizing BIM, which in turn supported key scenarios throughout the digital construction workflow.
Neural Network Clustering and Swarm Intelligence‐Based Routing Protocol for Wireless Sensor Networks: A Machine Learning Perspective
Authors: Balobaid Awatef Salem , Ahamed Saahira Banu , Shamsudheen Shermin , Balamurugan S.
Published: July 2023

With no requirement for an established network infrastructure, wireless sensor networks (WSNs) are well suited for applications that call for quick network deployment. Military training and emergency rescue operations are two prominent uses of WSNs. The individual network nodes must carry out routing and intrusion detection because there is no predetermined routing or intrusion detection in a wireless network. WSNs can only manage a certain volume of data, and doing so requires a significant amount of energy to process, transmit, and receive. Since sensors have a modest energy source and a constrained bandwidth, they cannot transmit all of their data to a base station for processing and analysis. Therefore, machine learning (ML) techniques are needed for WSNs to facilitate data transmission. Other current solutions have drawbacks as well, such as being less reliable, more susceptible to environmental changes, converging more slowly, and having shorter network lifetimes. This study addressed problems with wireless sensor networks and devised an efficient clustering and routing algorithm based on machine learning. Results from simulations demonstrate that the proposed system beats previous state‐of‐the‐art models on a variety of metrics, including accuracy, specificity, and sensitivity (0.93, 0.93, and 0.92 respectively).
It Is All in the Genes: A Story of Unexpected Survival in a 67-Year-Old Male with Metastatic Pancreatic Cancer
Authors: Lee Patsy W. P. , Strum Scott W. , Tsvetkova Elena
Published: July 2023

Background. We describe a case report of a 67-year-old male with PDAC who experienced an exceptional survival outcome during systemic therapy and its implications in precision medicine. We hypothesize that his outcomes are attributable, in part, to a germline BRCA2 deletion and somatic GNAS substitution. Methods. Retrospective single-patient chart review was performed at the London Regional Cancer Program, as well as a structured literature search spanning all years in PubMed of BRCA and GNAS mutations in pancreatic cancer. Results. The case described herein represents a 67-year-old male who survived over 27 months after third-line treatment with gemcitabine, docetaxel, and capecitabine (GTX) chemotherapy for metastatic PDAC after progression on gemcitabine and Abraxane and then on FOLFIRINOX. His survival far exceeded the median overall survival metrics. Genetic testing revealed a pathogenic heterozygous germline BRCA2 6643delT p.(Tyr2215Thrfs

∗

14) frameshift mutation and somatic

GNAS
 
2531
G
>
A

p.(Arg844His) mutation. Conclusions. This case highlights the urgent need to expand our knowledge of cancer biology to advance personalized cancer treatment and therapy development.
Figure S3 from T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
Authors: Kilian Michael , Friedrich Mirco , Sanghvi Khwab , Green Edward , Pusch Stefan , Kawauchi Daisuke , Löwer Martin , Sonner Jana K. , Krämer Christopher , Zaman Julia , Jung Stefanie , Breckwoldt Michael O. , Willimsky Gerald , Eichmüller Stefan B. , von Deimling Andreas , Wick Wolfgang , Sahm Felix , Platten Michael , Bunse Lukas
Published: July 2023

Supplementary Figure 3: T cell effector functions of TCR-transgenic T cells targeting CICR215W. A. Venn diagram of shared TCR-Î² sequences in T cell lines generated from n = 4 CICR215W vaccinated mice. B. Normalized IFN-Î³ production of different Î{plus minus}-CICR215W TCR candidates transduced in A2.DR1 T cells and re-stimulated with the indicated peptides that were subsequently vaccinated with CICR215W or MOG. C. Normalized IFN-Î³ production of expanded CT2 TCR-transduced T cells incubated with 20 Âµg/ml Î{plus minus}PD-1 and Î{plus minus}CTLA-4 or isotypes and restimulated with CICR215W 27-mer peptide. D. Cell trace far red (CTFR) dilution of CT2 TCR-transduced T cells injected in A2.DR1 recipient mice. E. Representative GFP expression in CD3+ T cells isolated from tumor, contralateral hemisphere (cH), cervical lymph node (cLN) or deep cervical lymph node (dcLN) harvested from A2.DR1 glioma-bearing mice 10 days after adoptive transfer of CT2 Î{plus minus}-CICR215W TCR-transduced T cells. F. Kaplan-Meier curve of A2.DR1 glioma-bearing mice after 2 intraventricular adoptive transfers (AT) of Î{plus minus}CICR215W-TCR T cells and Î{plus minus}Flu-TCR T cells and four doses of ICB (250 Âµg Î{plus minus}PD-1 and 100 Âµg Î{plus minus}CTLA-4 or isotype). n = 9 for CIC, n = 8 for Flu, n = 8 for CIC+ICB and n = 8 for Flu+ICB.
Supplementary Data 1 from A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer
Authors: Pook David , Geynisman Daniel M. , Carles Joan , de Braud Filippo , Joshua Anthony M. , Pérez-Gracia José Luis , Llácer Pérez Casilda , Shin Sang Joon , Fang Bruno , Barve Minal , Maruzzo Marco , Bracarda Sergio , Kim Miso , Kerloeguen Yannick , Gallo Jorge Daniel , Maund Sophia L. , Harris Adam , Huang Kuan-Chieh , Poon Victor , Sutaria Dhruvitkumar S. , Gurney Howard
Published: July 2023

Supplement Figure 1 and Table
Supplementary Table S6B from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Enrichment analysis for genes Downregulated by Subasumstat
Supplementary Table S6A from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Enrichment analysis for genes upregulated by Subasumstat
Supplementary Table S3 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Secondary Antibody Information
Supplementary Figure S13 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

TME cell spatial distributions in Patient 7 and Patient 8
Supplementary Figure S12 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Correlation of Percentage of cell types in TME to Percent of Cells MIL113 Positive
Figure S1 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

Volcano plots and Hallmark gene set analyses showing pathways targeted by X15695.
FIGURE 5 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695 reactivates p53. A, Western blot analysis of mortalin and p53 in immunoprecipitated extracts of MCF-7 cells treated with 1 μmol/L X15695 for 48 hours and lysed. 50 μg of cell extract was used as input control while 1,000 μg was immunoprecipitated with anti-p53 or IgG antibodies immobilized on protein A/G agarose beads. B, Western blot analysis of mortalin and BAG1 in immunoprecipitated extracts of MCF-7 cells treated with 1 μmol/L X15695 for 48 hours. MCF-7 cells were treated and processed as in A with the exception that the immunoprecipitation was carried out with a mouse anti-BAG1 antibody. C, Western blot analysis of BAG2 and BAG5 in immunoprecipitated extracts of T47D cells treated with 1 μmol/L X15695 for 48 hours. A total of 70 μg of cell extracts was used as input control while 1,000 μg was immunoprecipitated with anti-p53 or IgG antibodies immobilized on protein A/G agarose beads. D, Western blot analysis of p53 protein after transfection of MCF-7 and T47D cells with control and p53 siRNA and treatment with vehicle or X15695 (1 μmol/L) for 24 hours. β-actin was used for the loading control. E, Cell viability determination using MTT assay in control and p53 siRNA transfected cells treated with vehicle or X15695 (1 μmol/L) for 72 hours (n ≥ 3; ***, P ≤ 0.001; *, P ≤ 0.05). Cell-cycle analysis of MCF-7 (F) and T47D (G) cells treated with vehicle or 1 μmol/L X15695 for 48 hours. A total of 1 × 106 cells were stained with 7-AAD and used for flow cytometry measurement. Data were analyzed by FlowJo software. Apoptosis assessment of MCF-7 (H) and T47D (I) cells treated with 1 μmol/L X15695 for 48 hours. The cells were double stained with 7-AAD and Annexin V. Cells stained with 7-AAD or Annexin V alone were used for compensation of double staining. A total of 1 × 106 cells were used for the flow cytometry measurement. The quantified results are the mean ± SEM (n = 3; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.0001; ns is non-significant).
Entre “terras viciosas” e “jardins odoríferos fermosos”: as imagens da Ásia nas edições ilustradas de Os Lusíadas
Authors: Araújo Filipa Medeiros
Published: July 2023

Este artigo reflete sobre a representação da Ásia nas edições ilustradas d’Os Lusíadas, numa perspetiva comparatista que coteja os versos de Camões e as opções artísticas das representações gráficas ao longo dos tempos. Entre o vasto corpus de impressões da epopeia camoniana que incluem ilustrações, procurar-se-á selecionar uma amostra de imagens relacionadas com a Índia e, em particular, com a chegada a Calecute, fixando um arco temporal que se estende da monumental edição comentada de Faria e Sousa, em 1639, até à mais recente edição de 2021. A partir desse conjunto, serão analisadas as formas de diálogo entre o texto de Camões e a produção visual dos artistas, procurando discutir as relações texto/imagem, tendo em conta a finalidade das edições ilustradas. Deste modo, visa-se demonstrar a relevância deste tipo de publicações que, pela sua componente pictórica, transmitem informação adicional sobre a receção da epopeia camoniana no contexto em que as edições foram produzidas.
O pensamento estético de Antônio Mora, Álvaro de Campos e Fernando Pessoa
Authors: Carvalho Tiago Cabral Vieira de
Published: July 2023

A proposta deste artigo consiste numa reflexão acerca de textos de Fernando Pessoa pouco explorados – cujas autorias pertencem a uma personalidade, Antônio Mora, um heterônimo, Álvaro de Campos, e a Fernando Pessoa, o ortônimo – sobre estética e teoria da literatura. Pretende-se mostrar que o pensamento de Mora (grosso modo, clássico) e Campos (grosso modo, moderno) são rigorosamente opostos, e o de Pessoa consiste, em parte, na conjugação das ideias dos outros dois autores.
Two new species and faunistic records of the genus Mannerheimia Mäklin, 1880 from India, Nepal and China, and additional notes on some eastern Palaearctic species of Omaliinae Macleay, 1825 (Coleoptera: Staphylinidae)
Authors: SHAVRIN ALEXEY V.
Published: July 2023

New taxonomic and faunistic data for four species of the genus Mannerheimia Mäklin, 1880 from India, Nepal and China are provided. Two new species from the Himalayan Region are described and illustrated: M. prolongata sp.n. (India, Uttarakhand) and M. punctatissima sp.n. (Eastern Nepal, Taplejung). The distribution map for both new species is given. Faunistic and diagnostic data for several species of Omaliinae Macleay, 1825 from the Eastern Palaearctic Region are also given. New diagnostic data for Acrolocha rogeri Shavrin, 2017 and Amphichroum telnovi Shavrin, 2021 are provided. Depositories of the type material for three species of the genus Anthobium Leach, 1819 are clarified. The modified distributional maps for Amphichroum pindarense Champion, 1920, A. telnovi and A. anthobioides Champion, 1925 are provided. Several species are recorded from the certain area for the first time: Acidota crenata (Fabricius, 1792) from Kyrgyzstan, Acrulia inflata (Gyllenhal, 1813) from Maritime Province of Russia, Amphichroum pindarense from Nepal, A. telnovi from India, and M. hartmanni Shavrin, 2018 from the eastern part of Nepal (Solukhumbu).
Circadian therapy interventions for glymphatic dysfunction in concussions injuries: A narrative review
Authors: Kureshi Sohaib , Stowe Caroline , Francis John , Djalilian Hamid
Published: July 2023

There are two primary threats to the brain after concussion. The first is a buildup of neurotoxic proteins in the brain. The second, a partial consequence of the first, is a sustained neuroinflammatory response that may lead to central sensitization and the development of persistent post-concussive symptoms. These threats make neurotoxin clearance a high clinical priority in the acute period after injury. The glymphatic system is the brain's primary mechanism for clearing neurotoxic waste. The glymphatic system is intimately tied to the sleep cycle and circadian dynamics. However, glymphatic dysfunction and sleep disturbances are nearly ubiquitous in the acute period after concussion injury. Because of this, sleep optimization via circadian therapy is a time-sensitive and critical tool in acute concussion management.
The Geography of Telework in Latin America: New Spatial Devices during the Pandemic
Authors: Palomino Pichihua Yeimis Milton , Ruiz Sánchez Javier
Published: July 2023

The pandemic has revived attention to several problems in Latin America, among them the labor gap. The rise of remote work has led to debates centered around the future of workers in the face of cognitive capitalism and data colonialism. In this connection, the health emergency is revealed as a process of reengineering that threatens to further precarize and polarize employment, erasing the physical boundary between work and the home. An examination of the devices that have given geographical meaning to this phenomenon, addressing their impact within and across urban space, and of the problems arising from the right to digital connection and disconnection in various Latin American countries reveals a complex process of virtualization/spatialization and the disappearance of the boundary between productive and reproductive tasks because of the dissemination of teleworking.

La pandemia ha redescubierto diversos problemas existentes en Latinoamérica, uno de ellos la brecha laboral. El auge del trabajo remoto ha animado debates en torno al futuro de los trabajadores en el horizonte del capitalismo cognitivo y el colonialismo de datos; en este sentido, la emergencia sanitaria se revela como un proceso de reingeniería que amenaza con precarizar y polarizar el empleo; estallando la frontera física entre trabajo y hogar. Un estudio sobre los dispositivos que dan sentido geográfico a este fenómeno, desvelando su impacto desde y sobre el espacio urbano, y de los problemas derivados del derecho a la conexión y desconexión digital revela un complejo proceso de virtualización-espacialización, así como la desaparición del límite entre labores productivas y reproductivas como consecuencia de la difusión del teletrabajo.
Colorism as Historical Trauma: Exploring School Racial Context, Peer Dynamics, and Counternarratives Among Black Women
Authors: Leath Seanna , Bart-Plange Diane-Jo , Moseley Saidi , Teklu Helen
Published: July 2023

In the current qualitative study, we draw upon the colorist-historical trauma framework and misogynoir theory to explore Black college women’s peer-based messages of skin tone bias in school settings. We analyzed individual interview data from 26 ethnically diverse Black women (18–22 years) with consensual qualitative research methods to explore their beliefs and perspectives on their peers’ colorist messages in K-16 education. We focused on three main themes from the women’s narratives, including the critical role of school racial context, the harmful nature of colorist comments from Black men and boys, and the affirming nature of counternarratives from Black girlfriends. Consistent with past studies, peers’ colorist messages reinforced racialized social hierarchies and Eurocentric notions of beauty by privileging lighter-toned women compared to darker-toned women. The young women described how colorist messages from peers contributed to body surveillance and physical insecurities during childhood, and how they cultivated personal and collective counternarratives on beauty and self-worth in adulthood. Authors discuss colorism as a form of trauma among Black women and girls, with particular attention to identity development.
Estimating Global Bilateral Refugee Migration Flows from 1990 to 2015
Authors: Schellerer Stefan
Published: July 2023

Comprehensive data on refugee migration flows over space and time only exists for a limited number of countries and is prone to various problems, including quality issues, completeness, and different collection methods. This paper addresses these obstacles by presenting global bilateral five-year refugee migration flows between 1990 and 2015 that are derived from available stock data. The estimates, which reflect short-term rather than long-term movements captured by stock data, provide valuable insights into past refugee migration patterns. The results suggest a substantial worldwide decline in refugee migration flows after the early 1990s and a focus shift from African to Asian countries. Furthermore, the data show that global refugee migration flows are highly spatially concentrated and fluctuate between 0.11 and 0.33 percent of the world's population.
Association of cannabis use with neurocognition in adolescents with bipolar disorder
Authors: Sultan Alysha A , Mio Megan , Dimick Mikaela K , Zou Yi , Karthikeyan Sudhir , Kolla Nathan , Lanctot Krista , Zack Martin , Goldstein Benjamin I
Published: July 2023

Background:

Bipolar disorder (BD) and cannabis use are each associated with neurocognitive deficits in adolescents. However, little is known regarding the association of neurocognition with cannabis use among adolescents with BD. Therefore, we examined this topic in a sample of adolescents with BD and healthy control (HC) adolescents.

Methods:

Participants included 121 adolescents ( n = 32 with BD and lifetime cannabis use (BDCB+), n = 31 with BD and no lifetime cannabis use (BDCB−), n = 58 HC with no lifetime cannabis use), aged 14–20 years. Five neurocognitive subtests of the computerized CANTAB battery were assessed. Groups were compared using an analysis of covariance (ANCOVA) covarying for age, sex, and intelligence quotient.

Results:

The three groups differed significantly on tests of visuospatial working memory ( F = 4.41, p = 0.014, [Formula: see text]) and sustained attention ( F = 5.15, p = 0.007, [Formula: see text]). Post hoc analyses revealed working memory scores were significantly worse in BDCB+ versus HC ( p = 0.04, d = 0.59), and sustained attention was significantly worse in BDCB− versus HC ( p = 0.006, d = 0.70).

Conclusion:

These preliminary findings suggest that cannabis use among adolescents with BD is associated with working memory deficits. Future studies in larger samples are warranted to evaluate causation versus predisposition to cannabis use, and to evaluate duration, quantity, and potency of cannabis on neurocognition among adolescents with BD.
The Effect of Subacute Oral Folic Acid Treatment on Growth of Porphyromonas gulae in Dogs
Authors: Shirahata So , Katayama Yumi , Kaneki Mao , Uchiyama Jumpei , Fukuyama Tomoki
Published: July 2023

Periodontitis is one of the most prevalent infectious diseases in humans and animals. It is a multifactorial disease resulting in attachment loss and tooth loss. Therefore, preventive dentistry, such as daily teeth cleaning or providing dental chews from puppyhood is essential. This study aimed to find an alternative option for preventive dentistry by examining both in vitro and clinically, the antibacterial, antihalitosis, and anti-inflammatory effects of folic acid (FA) in dogs with periodontal disease. The antibacterial and antihalitosis responses of FA were evaluated in vitro using Porphyromonas gulae, a bacterium that plays a significant role in the development of periodontal disease in dogs. Anti-inflammatory responses, such as secretion of IL-1β, IL-6, and IL-8 induced by P. gulae infection in human gingival epithelium have been studied. This study used dogs with P. gulae-associated periodontal diseases and was conducted by providing a dental chew containing 0.13% FA for 28 days. The viability and halitosis production (hydrogen sulfide and methyl mercaptan) of P. gulae was significantly inhibited by FA in a dose and time-dependent manner. IL-1β, IL-6, and IL-8 secretion were also significantly suppressed by FA treatment in a dose-dependent manner. In vitro bactericidal, antihalitosis, and anti-inflammatory effects of FA were confirmed in dogs with P. gulae-associated periodontal disease. One month of oral treatment with 0.13% FA-containing dental chews significantly reduced halitosis as well as P. gulae activity. This study suggests that oral treatment with FA can be a preventive option for periodontal disease in dogs as well as humans.
Effect of income, energy consumption, energy prices, political stability, and geopolitical risk on the environment: Evidence from GCC countries by novel quantile-based methods
Authors: Ulussever Talat , Kartal Mustafa Tevfik , Kılıç Depren Serpil
Published: July 2023

This research investigates the effects of income, total energy consumption (TEC), energy price index (EPI), crude oil price (COP), political risk index (PRI), and geopolitical risk (GPR) on environmental degradation. In this context, the study includes five Gulf Cooperation Council (GCC) countries, which are mainly oil-rich and have high fossil fuel energy consumption with increasing environmental degradation; considers monthly data from 2000/1 to 2021/12, and deploys novel quantile-based methods. The outcomes demonstrate that (i) an increase in income, TEC, and EPI stimulates environmental degradation in all GCC countries; (ii) PRI, COP, and GPR have mixed effects on environmental degradation; (iii) a causal effect from the regressors to CO2 emissions exists in all quantiles except for some middle (0.45–0.55) and higher quantiles (0.95); (iv) the power of effect and causal effect vary according to quantiles and countries; (v) the consistency of the results is validated based on robust model. The findings reveal that an increase in income, TEC, and EPI is generally harmful to the environment in the GCC countries; but, PRI, COP, and GPR have mixed effects. The results of novel quantile-based methods underline the significance of political stability and geopolitical risk effect as non-economic and non-energy factors on environment degradation by demonstrating quantile-based varying effects of the regressors on the environment in GCC countries. Accordingly, various policies, such as focusing on increasing political stability, benefitting from geopolitical risk as leverage, and enabling the transition to clean energy, are discussed.
Multidisciplinary approach to lupus nephritis: Clinical pearls, pitfalls, and positioning of newly-approved agents
Authors: Fanouriakis Antonis , Bertsias George , Liapis George , Marinaki Smaragdi , Papagianni Aikaterini , Stangou Maria , Garyfallos Alexandros , Lionaki Sophia , Tektonidou Maria G. , Boletis John N. , Boumpas Dimitrios T
Published: July 2023

Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. To this end, we gathered a group of rheumatologists, nephrologists and a nephropathologist to review current evidence regarding diagnosis and management of LN. In this consensus paper, we summarize the key points from this meeting and provide practice guidelines for the management of kidney involvement in SLE, in view of emerging new data concerning novel agents approved recently. Renal biopsy is indispensable for the management of LN. Yet, important pearls and pitfalls need to be considered regarding indications and interpretation, which are summarized in informative tables. In new-onset LN, experts agreed that, although belimumab may be added from disease onset, patients with moderate to severe proliferative nephritis (defined as: NIH activity index > 5 plus ≥ 1 of the following: (i) NIH chronicity index > 2, (ii) proteinuria > 3  g/24 h, and (iii) increase in serum creatinine > 20%) may be more likely to benefit the most. In all other patients who have already started standard-of-care treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CY), belimumab could be considered in cases with an inadequate clinical response by 3 months, or in cases that experience a nephritic flare following initial response, or have an inability to reduce the dose of glucocorticoids. In all circumstances, the drug should be given as add-on therapy, that is, in combination with a standard-of-care therapy (MMF or CY). Voclosporin could be considered for up to 3 years, in combination with MMF, in patients with heavy proteinuria (well above the nephrotic range), wherein a quick reduction of protein loss in urine is desirable to avoid the complications of the nephrotic syndrome, either as part of the initial regimen, or in cases of inadequate reduction of proteinuria with MMF. In view of the potential scarring effects, long-term administration beyond the first year requires further documentation.
Presence and Team Performance in Synchronous Collaborative Virtual Environments
Authors: Massey Anne , Montoya Mitzi , Samuel Binny M. , Windeler Jaime
Published: July 2023

Synchronous collaborative virtual environments (CVEs) allow distributed teams to interact and work. CVEs afford a sense of presence, or “being there” in the workspace, as well as the opportunity to “do there” via interactions within the environment. However, there has been limited empirical evidence to support the link of presence and team performance, especially for CVE work. We identified multiple dimensions of presence that reflect relationships known to be essential to collaborative work and conducted a CVE experiment with 80 teams. Our results suggest certain aspects of presence are more important than others in driving virtual team performance.