bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of GREB1 in colorectal cancer ovarian metastases may be a potential therapeutic target.
Authors: Ruff Samantha M. , La Ferlita Alessandro , Palavalli Manoj , Chick Robert Connor , Beane Joal D. , Tsai Susan , Eng Oliver S. , Kim Alex 
Published: June 2024

e15596 Background: Classification of ovarian metastases (OM) in colorectal cancer (CRC) as peritoneal metastasis (PM) remains controversial. Moreover, OM demonstrate resistance to systemic therapy, suggesting distinct molecular tumorigenesis. Gene expression profiling and transcriptomic analysis was performed to distinguish OM, PM, and primary CRC (pCRC) and identify potential therapeutic targets. Methods: RNA sequencing was performed on tissue from the Total Cancer Care database. Raw counts were scaled in reads per million to filter out low-expressed genes. Afterward, raw counts of retained genes were normalized in trimmed mean of M-values and then log2-transformed using the Limma R package. Genes with a |Log2FC| > 0.58 and an adjusted p-value < 0.05 were considered dysregulated. In silico motif enrichment analysis of estrogen receptor 1 (ESR1) on growth regulating estrogen receptor binding 1 (GREB1) was conducted via the FIMO program. Results: There were 115 patients with tissue from OM (n = 6), PM (n = 4), and pCRC (n = 105). The average age was 58 years and most patients were male (57.4%), Caucasian (89.5%), and had microsatellite stable disease (69.6%). Most patients underwent cytotoxic chemotherapy (67%), while fewer underwent targeted therapy (38.3%) or radiation therapy (27.8%). The median overall survival for the pCRC, OM, and PM populations was 7.1, 3.4, and 4.0 months, respectively. Among upregulated genes, LAMC3, SCUBE1, and GREB1 had the highest differential expression in OM compared to PM and PEG3, C7, and GREB1 had the highest differential expression in OM compared to pCRC (all p < 0.001). Among downregulated genes, IGLC1, IGHG2, and IGHG1 had the greatest differential expression in OM compared to PM and IGHG1, IGKV4-1, and MMP12 had the greatest differential expression in OM compared to pCRC (all p < 0.001, Figure 1). GREB1 was upregulated in OM compared to both PM and pCRC. There are two estrogen response element (ERE) sites within the promoter region of GREB1. ESR1 transcription factor was shown to bind to these ERE (p < 0.001). Conclusions: Transcriptomic analysis demonstrated clear molecular distinction between OM, PM and pCRC. Differences in gene expression profiling suggest distinct underlying mechanisms of metastasis. We identified a significant upregulation of GREB1 in OM compared to PM and pCRC. GREB1 contains both ERE and ESR1 in the upstream promoter regions implying potential upstream transcription regulation mediated by ESR1. GREB1 is a potential novel, hormonal target in treatment of OM in CRC. Continued analysis is ongoing to identify other potential targets.
Phase 1b study evaluating the efficacy and safety of ABBV-400, a c-Met–targeting antibody-drug conjugate, in select advanced solid tumor indications.
Authors: Perets Ruth , Sharma Manish , Strickler John H , Golan Talia , Hollebecque Antoine , Henner William , Vasilopoulos Athanasios , Morrison Thiele Gladys , Burns Michael Charles , Harding James J. 
Published: June 2024

TPS3162 Background: c-Met (MET protein) is commonly overexpressed in a number of tumors, including hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), and head and neck squamous cell carcinoma (HNSCC). Patients with c-Met–overexpressing tumors represent an underserved population, with the need for more effective c-Met–targeting therapies to become available. ABBV-400 is an antibody-drug conjugate, consisting of the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. Initial results from the ongoing first-in-human study (NCT05029882) of ABBV-400 in patients with advanced solid tumors indicate a tolerable safety profile, with a maximum tolerated dose of 3 mg/kg once every 3 weeks (Q3W), and promising antitumor activity, with an overall response rate of 24.4% (1). Herein, we describe a signal-seeking study evaluating ABBV-400 treatment in patients with select solid tumors. Methods: Multicenter, open-label, phase 1 signal-seeking study(NCT06084481). Eligible patients (≥18 years) have confirmed locally advanced/metastatic disease measurable per RECIST v1.1 and Eastern Cooperative Oncology Group performance status ≤1. Approximately 220 patients are planned for enrollment across 7 cohorts (HCC, n=40; PDAC, n=40; BTC, n=20; ESCC, n=40; triple-negative BC, n=20; hormone receptor-positive/HER2-negative BC, n=20; HNSCC, n=40). The primary objectives are to assess efficacy and safety/tolerability of ABBV-400 in each tumor indication. Secondary objectives include the evaluation of pharmacokinetics (PK) and immunogenicity of ABBV-400. Pharmacodynamic (PD) and biomarker analyses are exploratory endpoints. Patients receive intravenous ABBV-400 at 3 mg/kg Q3W until disease progression, intolerable toxicity, or any other per-protocol discontinuation criteria. c-Met expression will be assessed retrospectively by immunohistochemistry. The maximum treatment duration is 2 years. Tumor assessments are performed at screening and every 6 weeks from the first dose of study drug, with objective response rate as primary efficacy endpoint and duration of response, clinical benefit rate, progression-free survival, and overall survival as secondary efficacy endpoints. Safety evaluations include adverse events monitoring (graded according to the NCI CTCAE, v5.0), physical examinations, vital sign measurements, ECG variables, and clinical laboratory testing. Blood samples for PK, PD, and biomarker analysis are collected at designated time points throughout the study. Enrollment started in November 2023. As of 19 January 2024, 24 patients have been enrolled. 1. Sharma et al. JCO 2023;41[16 suppl]:3015. Clinical trial information: NCT06084481 .
ASSOCIATION BETWEEN WEIGHTBEARING CT AND MRI FINDINGS IN PROGRESSIVE COLLAPSING FOOT DEFORMITY
Authors: Andres L.K. , Donners R. , Harder D. , Krähenbühl N. 
Published: June 2024

BackgroundWeightbearing computed tomography scans allow for better understanding of foot alignment in patients with Progressive Collapsing Foot Deformity. However, soft tissue integrity cannot be assessed via WBCT. As performing both WBCT and magnetic resonance imaging is not cost effective, we aimed to assess whether there is an association between specific WBCT and MRI findings.MethodsA cohort of 24 patients of various stages of PCFD (mean age 51±18 years) underwent WBCT scans and MRI. In addition to signs of sinus tarsi impingement, four three-dimensional measurements (talo-calcaneal overlap, talo-navicular coverage, Meary's angle axial/lateral) were obtained using a post processing software (DISIOR 2.1, Finland) on the WBCT datasets. Sinus tarsi obliteration, spring ligament complex and tibiospring ligament integrity, as well as tibialis posterior tendon degeneration were evaluated with MRI. Statistical analysis was performed for significant (P<0.05) correlation between findings.ResultsNone of the assessed 3D measurements correlated with spring ligament complex or tibiospring ligament tears. Age, body mass index, and TCO were associated with tibialis posterior tendon tears. 75% of patients with sinus tarsi impingement on WBCT also showed signs of sinus tarsi obliteration on MRI. Of the assessed parameters, only age and BMI were associated with sinus tarsi obliteration diagnosed on MRI, while the assessed WBCT based 3D measurements were, with the exception of MA axial, associated with sinus tarsi impingement.ConclusionWhile WBCT reflects foot alignment and indicates signs of osseous impingement in PCFD patients, the association between WBCT based 3D measurements and ligament or tendon tears in MRI is limited. Partial or complete tears of the tibialis posterior tendon were only detectable in comparably older and overweight PCFD patients with an increased TCO. WBCT does not replace MRI in diagnostic value. Both imaging options add important information and may impact decision-making in the treatment of PCFD patients.
A INEVITÁVEL DOSE DE FICÇÃO DA LINGUAGEM
Authors: SANTAELLA MARIA LUCIA 
Published: June 2024

RESUMO: A concepção de Flusser, de que a distinção entre o ficcional e o não ficcional não é ontologicamente fundamental, é uma concepção original, mas, ao mesmo tempo, enigmática. Diante disso, por meio de uma metodologia semiótica-cognitiva, este artigo visa explorar esse enigma ao tomar como foco de discussão o modo como essa concepção se comporta na ciência, então, na fotografia, seguida das perplexidades da filosofia. Por fim, o artigo pretende resgatar a especificidade da ficção que é própria das obras literárias em que a criação humana expõe seus poderes da imaginação.
PALAVRAS-CHAVE: Ficção, Ciência, Fotografia, Filosofia, Literatura.

ABSTRACT: Flusser's conception that the distinction between the fictional and the non-fictional is not ontologically fundamental is an original conception, but, at the same time, it is enigmatic. Given this, through a cognitive-semiotic methodology, this article aims to explore this enigma by taking as focus of discussion the way this conception behaves in science, then in photography, followed by the perplexities of philosophy. Finally, the article aims to rescue the specificity of fiction that is characteristic of literary works in which human creation exposes its powers of imagination.
KEYWORDS: Fiction, Science, Photography, Philosophy, Literature.
Umdenken beim Verkauf von Business-to-Business-Lösungen: Integration von Marketing, Vertrieb und Customer Success Management
Authors: Durst Carolin , Pöppelbuß Jens 
Published: June 2024

ZusammenfassungDie Vermarktung und der Vertrieb von komplexen Produkt- und Dienstleistungsbündeln in Business-to-Business-Märkten wird als Solution Selling bezeichnet. Dieser Verkaufsansatz vermarktet keine einzelnen Produkte oder Dienstleistungen, sondern maßgeschneiderte Lösungen. Die Komplexität und Individualität der verkauften Lösungen erzeugt einen erhöhten Bedarf an relevanter und genauer Information auf beiden Seiten: Potenzielle Käufer recherchieren bereits vorab nach potenziellen Lösungen und die Anbieter müssen wiederum die Situation des Käufers verstanden haben. Für dieses tiefgreifende Verständnis der Kundenanforderungen sowie die passgenaue Distribution notwendiger Informationen ist eine enge Zusammenarbeit von Marketing, Vertrieb und Customer Success Management notwendig. Traditionelle Unternehmensstrukturen weisen jedoch oft eine Trennung zwischen Abteilungen auf, was zu Effizienzverlusten in der Kundenansprache und -bindung führen kann. Besonders in mittelständischen Unternehmen dominiert häufig der Vertrieb, während das Marketing unterrepräsentiert ist und das Customer Success Management in der Entwicklung hinterherhinkt. Dieser Beitrag stellt einen integrierten Verkaufsansatz vor und zeigt strategische Maßnahmen zur Förderung der Integration auf. Diese umfassen u. a. die Dezentralisierung von Entscheidungsprozessen, die Bildung funktionsübergreifender Teams oder die Einführung integrativer Rollen wie die eines Chief Revenue Officer (CRO).
Spatio—Temporal distribution of a vector of cutaneous leishmaniasis: Pintomyia longiflocosa, in a population from the Colombian Andean Mountains
Authors: Muñoz-Ortiz Astrid , Beltrán Miguel , Vargas Durango Jennifer , Mestre Gelys , Santamaria Herreño Erika , Escovar Jesús E. 
Published: June 2024

Background
Leishmaniasis, a neglected disease and public health concern, is associated with various factors such as biological, social, economical conditions and climate, increasing the risk of human infection. Understanding the population dynamics of the vectors, like Pintomyia longiflocosa, and its relationship with ecological variables is crucial for developing effective strategies to control sand fly populations and combat cutaneous leishmaniasis in a tropical country like Colombia.

Methodology
Adult sand flies were collected in three different sample locations: outdoor, indoor, and peri-domestic areas in three houses located in the rural settlement of Campoalegre (Huila) between February 2020 and February 2021, using the CDC light traps. The sand fly density was quantified and associated with the sample locations and the sampling months using Analysis of Variance and Pearson correlations.

Principal findings
In the period of the sample, 98.86% of sand fly collected was identified as Pi. longiflocosa. The density of this species was significantly different between males and females, the latter contributing more to density in all sample locations (P<0.0001). The outdoor was the sample location with the highest and most significative density in this study (70%, P = 0.04). The density of these sand flies is related to the seasonality of Campoalegre, revealing a density peak from February and June to October (P < 0.05). Finally, precipitation is the environmental variable prominently linked to the density pattern, showing a negative correlation with it. Months with the highest precipitations show the lowest values of Pi. longiflocosa abundance.

Conclusions/Signicance
Our investigation reveals a inverse correlation between precipitation levels and the abundance of Pi. longiflocosa in Campoalegre (Huila), particularly in outdoor areas. This suggests that vector control strategies to periods of reduced precipitation in outdoor settings could offer an effective approach to minimizing cases of cutaneous leishmaniasis in the region.
Fusarioid keratitis and other superficial infections: A 10-years prospective study from Northeastern Brazil
Authors: Ferreira da Cunha Neto Jose , da Silva Rocha Walicyranison Plinio , Makris Georgios , Sandoval-Denis Marcelo , Hagen Ferry , Crous Pedro Willem , Chaves Guilherme Maranhão 
Published: June 2024

BackgroundFusariumand allied genera (fusarioid) species are common colonizers of roots and aerial plant parts, or act as phytopathogens in forestry and horticultural or grain crops. However, they can also cause a wide range of infections in humans, including onychomycosis, cutaneous and invasive infections. Fusarioid keratitis is characterized by an infection of the cornea with a suppurative and ulcerative appearance, which may cause damage to vision and permanent blindness. The aim of the present study was to investigate the prevalence of fusarioid species, biofilm formation and antifungal susceptibility profiling of clinical isolates recovered from patients with keratitis and dermatomycoses.Methodology/Principal findingsThe study was performed between March, 2012-December, 2022. Demographic, clinical and epidemiological data of patients were also collected. In the present study, most of the patients with keratitis were male (74%), had a median age of 42 years old, worked with plant material or debris and 26% of them reported eye trauma. Regarding dermatomycosis, most of patients were female and exhibited toenail lesions. Forty-seven isolates belonged to the genusNeocosmospora(78.33%), nine to theFusarium fujikuroi(15%) and four to theFusarium oxysporum(6.66%) species complexes. Several strains were moderate biofilm producers, specifically amongFusarium annulatum. Most strains showed increased MICs to amphotericin B and ketoconazole and low MICs to itraconazole. MICs ranged from 0.25 to 16 μg/mL for amphotericin B, 0.0625 to >16 μg/mL for ketoconazole and 0.125 to 8 for itraconazole.Conclusions/SignificanceIt is possible to conclude that fusarioid keratitis in Northeastern Brazil is an important and neglected disease, given the high number of cases, increased need for keratoplasty and poor outcome of the disease.
Examining associations between mental health and Chronic Non-Communicable Diseases (C-NCDs) among older adults in Wakiso, Uganda
Authors: Bulamba Robert M. , Nalugoda Fred , Nkale James , Kigozi Godfrey , Ochieng A. Malachi , Kyasanku Emmanuel , Watya Stephen , Olwa Vitalis Ofumbi , Daama Alex , Nkwanzi Violet , Kiwanuka Deusdedit , Mugamba Stephen , Kigozi Grace , Wagman Jennifer , Ekström Anna Mia , Nakigozi Gertrude , Miller Amanda P. 
Published: June 2024

Background
Globally, the prevalence of chronic non-communicable diseases (C-NCDs) and occurrence of multi-morbidity specifically, has been increasing and will continue to rise as life expectancy increases. The burden of mental health disorders has also been rising globally. In sub-Saharan Africa (SSA), literature on these health issues, which are interrelated, is scarce. This study assesses the prevalence of C-NCDs, and depressive and anxiety symptomology and examines the relationship between these issues among a sample of older adults in Uganda.

Methods
Between 2021–2022, 604 consenting adults aged 35 years and older were surveyed on a broad range of health issues for the ongoing AMBSO Population Health Surveillance (APHS) cohort study in Wakiso district. Descriptive analyses were performed to characterize the burden of C-NCDs (e.g. diabetes, hypertension), depression (PHQ-9 using a cutoff of <5 scores for minimal/no and 5+ for mild to severe symptomology) and anxiety (GAD-7 using a cutoff of 5+ scores for mild to severe symptomology). Bivariate analysis and multivariable logistic regression models were built using STATA software version 16.0 to examine associations between mental health disorders and having at least one C-NCD. Our exposures of interest were depressive and anxiety symptoms and our outcomes of interest was presence of C-NCDs.

Results
Majority of participants were females (63.6%), median age was 46 (IQR: 39–54). Any C-NCDs prevalence was 18.7%, while 18.9% and 11.4%, had screening scores indicative of depressive and anxiety symptomology, respectively. Three percent (3.2%) had PHQ-9 scores indicative of moderate to severe depressive symptomology. In models adjusted for sociodemographic characteristics, there was 12% increased odds of suffering from C-NCDs for every unit increase in PHQ-9 score (AOR = 1.12, 95% CI: 1.10–1.20). Participants with any anxiety symptoms had 2.1 greater odds of suffering from C-NCD compared to those who did not have anxiety symptoms (AOR = 2.10, 95% CI: 1.21–3.70).

Conclusion
C-NCDs were prevalent in older adults, particularly among those experiencing mental health symptoms. Screening for C-NCDs and mental health disorders should be integrated into routine health care for older adults in the country. Early screening and identification of these health issues through primary health care could significantly reduce the public health burden attributable to mental health disorders and the incidence of multi-morbidity in Uganda.
Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial
Authors: Pottecher Julien , Raffi Francois , Jandrot-Perrus Martine , Binay Sophie , Comenducci Andrea , Desort-Henin Violaine , François Déborah , Gharakhanian Shahin , Labart Marilyn , Meilhoc Adeline , Toledano Elie , Pletan Yannick , Avenard Gilles , Sato Victor H. ,   the GARDEN Investigators
Published: June 2024

Background
Glenzocimab is a novel antithrombotic agent which targets platelet glycoprotein VI (GPVI) and does not induce haemorrhage. SARS-CoV-2 triggers a prothrombotic state and lung injury whose mechanisms include coagulopathy, endothelial dysfunction, and inflammation with dysregulated platelets.

Methods and patients
GARDEN was a randomised double-blind, exploratory phase II study of glenzocimab in SARS-CoV-2 respiratory failure (NCT04659109). PCR+ adults in Brazil and France (7 centres) were randomized to standard-of-care (SOC) plus glenzocimab (1000 mg/dayx3 days) or placebo, followed for 40 days. Primary efficacy endpoint was clinical progression at Day 4. All analyses concerned the intention-to-treat population.

Results
Between December 2020 and August 2021, 61 patients received at least one dose (30 glenzocimab vs 32 placebo) and 58 completed the study (29 vs 29). Clinical progression of COVID-19 ARDS was not statistically different between glenzocimab and placebo arms (43.3% and 29.0%, respectively; p = 0.245). Decrease in the NEWS-2 category at D4 was statistically significant (p = 0.0290) in the glenzocimab arm vs placebo. No Serious Adverse Event (SAE) was deemed related to study drug; bleeding related events were reported in 6 patients (7 events) and 4 patients (4 events) in glenzocimab and placebo arms, respectively.

Conclusions
Therapeutic GPVI inhibition assessment during COVID-19 was conducted in response to a Public Health emergency. Glenzocimab in coagulopathic patients under therapeutic heparin was neither associated with increased bleeding, nor SAE. Clinical impact of glenzocimab on COVID-19 ARDS was not demonstrated. A potential role for GPVI inhibition in other types of ARDS deserves further experimentation. Glenzocimab is currently studied in stroke (ACTISAVE: NCT05070260) and cardiovascular indications.
Exploring road safety using alignment perspective features in real driving images: A case study on mountain freeways
Authors: He Shijian , Fu Hongmei , Wang Jie , Yang Jiacheng , Yao Yanqing , Kuang Jiaojiao , Xiao Xiangliang 
Published: June 2024

Introduction
While driving, drivers frequently adapt their driving behaviors according to their perception of the road’s alignment features. However, traditional two-dimensional alignment methods lack the ability to capture these features from the driver’s perspective.

Method
This study introduces a novel method for road alignment recognition, employing image recognition technology to extract alignment perspective features, namely alignment perspective skewness (APS) and alignment perspective kurtosis (APK), from in-real driving images. Subsequently, the K-means clustering algorithm is utilized for road segment classification based on APS and APK indicators. Various sliding step length for clustering are employed, with step length ranging from 100m to 400m. Furthermore, the accident rates for different segment clusters are analyzed to explore the relationship between alignment perspective features and traffic safety. A 150 km mountain road section of the Erlianhaote-Guangzhou freewway from Huaiji to Sihui is selected as a case study.

Results
The results demonstrate that using alignment perspective features as classification criteria produces favorable clustering outcomes, with superior clustering performance achieved using shorter segment lengths and fewer cluster centers. The road segment classification based on alignment perspective features reveals notable differences in accident rates across categories; while traditional two-dimensional parameters-based classification methods fail to capture these differences. The most significant differences in accident rates across categories are observed with segment length of 100m, with the significance gradually diminishing as segment length increases and disappearing entirely when the length exceeds 300m.

Implication
These findings validate the reliability of using alignment perspective features (APS and APK) for road alignment classification and road safety analysis, providing valuable insights for road safety management.