bluuebunny/crossref_metadata_2025 huggingface dataset:
The loss of DNA polymerase epsilon accessory subunits POLE3–POLE4 leads to BRCA1-independent PARP inhibitor sensitivity
Authors: Mamar Hasan , Fajka-Boja Roberta , Mórocz Mónika , Jurado Eva Pinto , Zentout Siham , Mihuţ Alexandra , Kopasz Anna Georgina , Mérey Mihály , Smith Rebecca , Sharma Abhishek Bharadwaj , Lakin Nicholas D , Bowman Andrew James , Haracska Lajos , Huet Sébastien , Timinszky Gyula
Published: June 2024

The clinical success of PARP1/2 inhibitors (PARPi) prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARPi. We show that the sensitivity of POLE4 knockouts is not due to compromised response to DNA damage or homologous recombination deficiency. Instead, POLE4 loss affects replication speed leading to the accumulation of single-stranded DNA gaps behind replication forks upon PARPi treatment, due to impaired post-replicative repair. POLE4 knockouts elicit elevated replication stress signaling involving ATR and DNA-PK. We find POLE4 to act parallel to BRCA1 in inducing sensitivity to PARPi and counteracts acquired resistance associated with restoration of homologous recombination. Altogether, our findings establish POLE4 as a promising target to improve PARPi driven therapies and hamper acquired PARPi resistance.
Leveraging murine models of the neurofibromatosis type 1 cancer predisposition syndrome to elucidate the cellular circuits that drive pediatric low-grade glioma formation and progression
Authors: Gutmann David H
Published: June 2024

Brain tumors are the leading cause of cancer-related death in children, where low-grade gliomas (LGGs) predominate. One common hereditary cause for LGGs involves neurofibromatosis-1 (NF1) gene mutation, as seen in individuals with the NF1 cancer predisposition syndrome. As such, children with NF1 are at increased risk of developing LGGs of the optic pathway, brainstem, cerebellum, and midline brain structures. Using genetically engineered mouse models, studies have revealed both cell-intrinsic (MEK signaling) and stromal dependencies that underlie their formation and growth. Importantly, these dependencies represent vulnerabilities against which targeted agents can be used for preclinical investigation prior to clinical translation.
Petrogenesis and Geodynamic Evolution of the Archean Shawmere Anorthosite Complex and Associated Gneisses, Kapuskasing Uplift, Superior Province, Canada
Authors: Polat Ali , Frei Robert , Deng Hao , Longstaffe Fred J , Sotiriou Paul
Published: June 2024

In this study, we integrated extensive field, petrographic, whole-rock major and trace element, and Nd–Pb–Sr–O isotope, and zircon U–Pb ages, trace element and Lu–Hf isotope data from the Neoarchean Shawmere Anorthosite Complex and surrounding gneisses to unravel their petrogenetic origin and tectonic history. The ~2765 Ma Shawmere Anorthosite Complex is interpreted to have been emplaced into a sequence of interlayered greywacke and basalt deposited in an intra-continental arc rift system above a north-dipping subduction zone. The complex consists mainly of anorthosite, leucogabbro, gabbro, and hornblendite that were emplaced as several batches of magmas and crystal mushes originating from sub-arc mantle sources. In contrast to the previous studies, our field and petrographic data suggest an igneous origin for the most hornblende in the complex, implying hydrous parental magmas. A hydrous magma origin is also consistent with the high-anorthite content (mostly 70–90%) of the plagioclase in the complex. Percolation of hydrous basaltic melts through gabbroic cumulates in crustal magma chambers led to extensive (>50%) replacement of igneous clinopyroxene by igneous hornblende. Continued subduction resulted in the closure of the intra-arc rift system and the intrusion of the complex by tonalite, granodiorite and diorite between 2765 and 2680 Ma in an Andean-type margin. The complex and surrounding gneisses underwent hornblende granulite-facies metamorphism mainly between 2680 and 2620 Ma, overlapping with mid-crustal east-west extension between 2660 and 2640 Ma. The granulite-facies metamorphism is recorded by the replacement of hornblende, plagioclase and clinopyroxene by garnet and the development of a garnet-orthopyroxene-plagioclase metamorphic assemblage with a granoblastic texture. Tectonic rebounding of mid-crustal rocks to upper crustal levels after 2620 Ma led to the formation of an extensive network of extensional fractures and retrograde metamorphism. Migration of CO2-rich hydrous fluids along the extensional fractures and grain boundaries resulted in the precipitation of many metasomatic minerals mainly at the expense of hornblende and plagioclase, including epidote, clinozoisite, tremolite, actinolite, paragonite, margarite, titanite, quartz, calcite, sillimanite, dolomite, and chlorite. Prevalent replacement of hornblende by garnet during prograde metamorphism and metasomatic replacement of hornblende and plagioclase by retrograde mineral assemblages disturbed the Sm–Nd, U–Th–Pb, and Rb–Sr isotope systems.
RING/U-box E3 protein BIR1 interacts with and ubiquitinates barley growth repressor BROAD LEAF1
Authors: Soltani Ouad , Jöst Moritz , Hoffie Iris , Hensel Götz , Kappel Christian , Prag Gali , McKim Sarah , Kumlehn Jochen , Lenhard Michael
Published: June 2024

Establishment of final leaf size in plants relies on the precise regulation of 2 interconnected processes, cell division and cell expansion. The barley (Hordeum vulgare) protein BROAD LEAF1 (BLF1) limits cell proliferation and leaf growth in the width direction. However, how the levels of this potent repressor of leaf growth are controlled remains unclear. Here, we used a yeast 2-hybrid screen to identify the BLF1-INTERACTING RING/U-BOX 1 (BIR1) E3 ubiquitin ligase that interacts with BLF1 and confirmed the interaction of the 2 proteins in planta. Inhibiting the proteasome caused overaccumulation of a BLF1-eGFP fusion protein when co-expressed with BIR1, and an in vivo ubiquitination assay in bacteria confirmed that BIR1 can mediate ubiquitination of BLF1 protein. Consistent with regulation of endogenous BLF1 in barley by proteasomal degradation, inhibition of the proteasome in BLF1-vYFP–expressing barley plants caused an accumulation of the BLF1 protein. The BIR1 protein co-localized with BLF1 in nuclei and appeared to reduce BLF1 protein levels. Analysis of bir1-1 knockout mutants suggested the involvement of BIR1 in leaf growth control, although mainly on leaf length. Together, our results suggest that proteasomal degradation, in part mediated by BIR1, helps fine-tune BLF1 protein levels in barley.
A quadrilemma for theories of consciousness
Authors: List Christian
Published: June 2024

In this paper, I argue that no theory of consciousness can simultaneously respect four initially plausible metaphysical claims—namely ‘first-person realism’, ‘non-solipsism’, ‘non-fragmentation’, and ‘one world’—but that any three of the four claims are mutually consistent. So, theories of consciousness face a ‘quadrilemma’. Since it will be hard to achieve a consensus on which of the four claims to retain and which to give up, we arrive at a landscape of competing theories, all of which have pros and cons. I will briefly indicate which kinds of theories correspond to the four horns of the quadrilemma.
Trace Conservation Laws in T2/Zm Orbifold Gauge Theories
Authors: Takeuchi Kota , Inagaki Tomohiro
Published: June 2024

Gauge theory compactified on an orbifold is defined by gauge symmetry, matter contents, and boundary conditions (BCs). There are equivalence classes (ECs), each of which consists of physically equivalent BCs. We propose the powerful necessary conditions, trace conservation laws (TCLs), which achieve a sufficient classification of ECs in U(N) and SU(N) gauge theories on T2/Zm orbifolds (m = 2, 3, 4, 6). The TCLs yield the equivalent relations between the diagonal BCs without relying on an explicit form of gauge transformations. The TCLs also show the existence of off-diagonal ECs, which consist only of off-diagonal matrices, on T2/Z4 and T2/Z6. After the sufficient classification, the exact numbers of ECs are obtained.
Deep learning in the precise assessment of primary Sjögren’s syndrome based on ultrasound images
Authors: Niu Xinyue , Zhou Yujie , Xu Jin , Xue Qin , Xu Xiaoyan , Li Jia , Wang Ling , Tang Tianyu
Published: June 2024

Objectives

This study aimed to investigate the value of a deep learning (DL) model based on greyscale ultrasound (US) images for precise assessment and accurate diagnosis of primary Sjögren’s syndrome (pSS).

Methods

This was a multicentre prospective analysis. All pSS patients were diagnosed according to 2016 ACR/EULAR criteria. A total of 72 pSS patients and 72 sex- and age-matched healthy controls recruited between January 2022 and April 2023, together with 41 patients and 41 healthy controls recruited from June 2023 to February 2024 were used for DL model development and validation, respectively. The DL model was constructed based on the ResNet 50 input with preprocessed all participants’ bilateral submandibular glands (SMGs), parotid glands (PGs), and lacrimal glands (LGs) greyscale US images. Diagnostic performance of the model was compared with two radiologists. The accuracy of prediction and identification performance of DL model were evaluated by calibration curve.

Results

A total of 864 and 164 greyscale US images of SMGs, PGs, and LGs were collected for development and validation of the model. The area under the ROC (AUCs) of DL model in the SMGs, PGs, and LGs were 0.92, 0.93, 0.91 in the model cohort, and were 0.90, 0.88, 0.87 in the validation cohort, respectively, outperforming both radiologists. Calibration curves showed the prediction probability of the DL model was consistent with the actual probability in both model cohort and validation cohort.

Conclusion

The DL model based on greyscale US images showed diagnostic potential in the precise assessment of pSS patients in the SMGs, PGs and LGs, outperforming conventional radiologist evaluation.
Advancing the Measurement of Social Functioning in Schizophrenia: Applications of Egocentric Social Network Analysis
Authors: Abplanalp Samuel J , Catalano Lauren T , Green Michael F
Published: June 2024

People with schizophrenia face challenges with forming and maintaining social relationships, often resulting in poor social functioning. Commonly used measures of social functioning provide broad information relating to social relationships, but they do not adequately capture information regarding network structure and characteristics of network members. One method that can assess these more detailed aspects of social networks and provide a more comprehensive understanding of social functioning deficits is egocentric social network analysis (SNA). SNA is a scientific discipline that uses principles of network science and graph theory to analyze social relations quantitatively. Even though some types of SNA have been applied in prior schizophrenia studies, its application as a framework to measure social functioning has been extremely limited. Therefore, this article aims to formally introduce SNA and select quantitative SNA metrics, including measures of network composition, structure, homophily, and centrality, to schizophrenia researchers as novel ways of measuring components of social functioning. To demonstrate the application of SNA, we provide illustrative examples of the SNA metrics and graphical diagrams of social networks for two individuals with schizophrenia.
Institutional implications for science and industrial capacity: policy lessons from the UK’s pandemic response
Authors: Watkins Andrew , Srinivas Smita , Wield David
Published: June 2024

Global shortages of critical equipment and supplies induced by COVID-19 forced countries to rapidly build and ramp up their indigenous testing and production capacities. However, the many ways in which institutional and organizational change occurred has not been sufficiently captured. Building domestic capacity requires the leveraging and repurposing of existing domestic scientific and technological capabilities, coupled with intensified global outreach to new and existing partners and suppliers. Using the framework of institutional variety, this paper looks at two facets of the UK’s COVID emergency industrial response: (1) building its laboratory testing capabilities and (2) for increasing production of personal protective equipment; assessing the institutional capacities and relations that were leveraged in this regard. It uses these findings together with observations of ‘innovation processes under emergency conditions’ and the potential uses of a ‘critical equipment policy’ to sharpen some of the recommendations made in the UK’s post-COVID Research and Development Roadmap.
Developmental PFOS exposure alters lung inflammation and barrier integrity in juvenile mice
Authors: Lucas Joseph H , Wang Qixin , Meehan-Atrash Jiries , Pang Cortney , Rahman Irfan
Published: June 2024

Emerging epidemiological evidence indicates perfluorooctane sulfonic acid (PFOS) is increasingly associated with asthma and respiratory viral infections. Animal studies suggest PFOS disrupts lung development and immuno-inflammatory responses, but little is known about the potential consequences on respiratory health and disease risk. Importantly, PFOS exposure during the critical stages of lung development may increase disease risk later in life. Thus, we hypothesized that developmental PFOS exposure will affect lung inflammation and alveolar/airway development in a sex-dependent manner. To address this knowledge gap, timed pregnant Balb/cJ dams were orally dosed with a PFOS (1.0 or 2.0 mg/kg/d) injected mealworm or a vehicle control daily from gestational day (GD) 0.5 to postnatal day (PND) 21, and offspring were sacrificed at PND 22-23. PFOS-exposed male offspring displayed increased alveolar septa thickness. Occludin was also downregulated in the lungs after PFOS exposure in mice, indicative of barrier dysfunction. BALF macrophages were significantly elevated at 2.0 mg/kg/d PFOS in both sexes compared with vehicles, whereas BALF cytokines (TNF-α, IL-6, KC, MIP-1α, MIP-1β, and MCP-1) were suppressed in PFOS-exposed male offspring compared with vehicle controls. Multiplex nucleic acid hybridization assay showed male-specific downregulation of cytokine gene expression in PFOS-exposed mice compared with vehicle mice. Overall, these results demonstrate PFOS exposure exhibits male-specific adverse effects on lung development and inflammation in juvenile offspring, possibly predisposing them to later-in-life respiratory disease. Further research is required to elucidate the mechanisms underlying the sex-differentiated pulmonary toxicity of PFOS.
The Bacterial and Viral Communities Associated with Onion Bacterial Bulb Rot
Authors: Liakos Christopher , Ibanez Verushka , Lebre Pedro H. , Derie Mike L. , van der Waals Jacquie , du Toit Lindsey , Dutta Bhabesh , Kvitko Brian , Cowan Don A. , Coutinho Teresa A.
Published: June 2024

Microbes occur in complex communities within plants as endophytes and establish a network of interactions that can influence plant health positively or negatively. Positive interactions may be synergistic and confer abiotic and biotic stress tolerance. The aim of this study was to identify bacteria and viruses present in storage onion bulbs that were symptomatic and asymptomatic for bacterial bulb rot from crops grown in Georgia and Washington states, and to assess their potential role in the bulbs based on the functions of bacterial and viral genes detected. DNA was extracted from nine asymptomatic bulbs and nine bulbs displaying symptoms of bacterial bulb rot and subjected to 16S rRNA amplicon sequencing and metagenome-assembled genome analysis. The Illumina platform was used to sequence the hypervariable region (V3-V4) of the 16S rRNA gene. The 16S rRNA amplicon profiling revealed the presence of numerous bacteria, including potential onion pathogens in the genera Pantoea and Burkholderia. Metagenome-assembled genome assembly identified P. agglomerans, B. gladioli, and B. cepacia, known bulb rot pathogens, including genes linked to fitness and those involved in both type II and III secretion systems. Eighty-nine unique viral genomes were identified, of which 67 could be classified taxonomically. The bacterial and viral genomes differed significantly in asymptomatic versus symptomatic bulbs. Viral genomes showed evidence of auxiliary metabolic genes, including genes involved in fitness and pathogenicity to bacterial hosts. The onion bulbs hosted endophytic bacteria and viruses, some of which were potentially beneficial and others potentially pathogenic to onion or as hosts to bacteriophages.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Prevalence of Hip Dysplasia on Radiographs for Adolescent Idiopathic Scoliosis
Authors: Fowler Hayley , Prior Anjali , Gregoski Mathew J. , Van Nortwick Sara S. , Jones Richard , Ashy Cody , Dow Matthew A. , Galasso Annemarie C. , Mooney James F. , Murphy Robert F.
Published: June 2024

Background:

During radiographic assessment of adolescent idiopathic scoliosis (AIS), upright images frequently capture the hip. The purpose of this study was to assess the prevalence of radiographic hip dysplasia on postero-anterior (PA) scoliosis radiographs, as defined as a lateral center edge angle (LCEA) ≤25 degrees.

Methods:

All patients with upright PA scoliosis radiographs over a one-year study period at a single tertiary academic medical center (2020 to 2021) were included in the study. Radiographs containing the hip joints were annotated by 3 reviewers for left and right LCEA, and triradiate cartilage (TRC) status. Inter-rater reliability was determined among the 3 reviewers.

Results:

Two hundred fifty patients {500 hips, 75.6% female, median age 14 [interquartile range (IQR)=3]} had PA scoliosis radiographs that captured the hip, which qualified for analysis. Seventy-four hips (14.8%) demonstrated evidence of dysplasia (LCEA ≤25 deg) in 55/250 patients (22%). The median LCEA was significantly lower in the dysplastic hip cohort (23.9 deg, IQR=4.8 deg), compared with those without dysplasia (33 deg IQR=7.3 deg; P=0.001). A higher percentage of dysplastic hip patients were female than male (72.7% vs. 27.3%). Patients with bilateral dysplasia had a similar LCEA ( 22.9 deg) [to those with unilateral dysplasia (22.9 deg left, 23.9 deg right, P=0.689)].

Conclusions:

In a cohort of 250 AIS patients, 22% demonstrated evidence of hip dysplasia, as defined as an LCEA ≤2 degrees. The dysplastic patients were more likely to be female. Screening for hip symptomatology in AIS patients may be of benefit, considering the frequency of radiographic hip dysplasia in this population.

Level of Evidence:

III. Type of Evidence: diagnostic.
Financial burden in a US cohort of patients with HCC
Authors: Desai Ruchi , Jiang Yue , VanWagner Lisa B. , Singal Amit G. , Lieber Sarah R.
Published: June 2024

Background:

High financial burden for patients has been reported for multiple types of cancer, but there are limited data in those with HCC. We aimed to describe the financial burden for patients diagnosed with HCC and identify correlates of high financial burden.

Methods:

We used the IQVIA PharMetrics Plus for Academics database to identify commercially insured patients diagnosed with HCC between 2006 and 2021. Patient financial liability was defined as the difference between allowed and paid amounts from adjudicated insurance claims. We reported total and HCC-related financial liabilities (i.e., cost for HCC-related claims), with high total financial liability defined as ≥$3000 annually and high HCC–related financial liability as ≥$1000 annually. We used multivariable logistic regression modeling to identify factors associated with high total and HCC-related financial liability.

Results:

Among 11,609 patients with HCC, the median total financial liability during the year after HCC diagnosis was $2955 (Q1–Q3: $972–$6293). Nearly half (45%) of patients experienced high total financial liability, with the greatest liability incurred in the 3-month period immediately following HCC diagnosis. Older age, increased comorbidity, and cirrhosis-related complications were associated with higher total patient liability. Patient liability also varied by type of HCC treatment, with systemic therapy and liver transplantation having the highest financial liability in multivariable analysis. However, only 66.7% of the patients experienced HCC-related liability.

Conclusions:

Patients with HCC experience significant financial liability underscoring a need for price transparency as well as financial counseling in this population.
Corneal Backscatter, Pachymetric Indices, and Ectasia Indices for the Assessment of Fuchs Endothelial Corneal Dystrophy
Authors: Patel Sanjay V. , Hodge David O. , Baratz Keith H.
Published: June 2024

Purpose:

To determine whether corneal backscatter, pachymetric indices, and ectasia indices derived from Scheimpflug tomography can identify Fuchs endothelial corneal dystrophy (FECD) corneas with abnormal tomography, the relationships between these parameters and tomographic edema in FECD, and if these parameters help predict improvement in central corneal thickness (CCT) after Descemet membrane endothelial keratoplasty (DMEK).

Methods:

Tomography maps of 132 eyes of 80 subjects with FECD were analyzed to determine how backscatter, pachymetric, and ectasia parameters compared with the instrument's normative database and if any predicted tomographic edema. Tomography maps from a separate group undergoing DMEK were split into derivation (48 eyes of 39 subjects) and validation (45 eyes of 41 subjects) subgroups to derive a predictive model of improvement in CCT after DMEK. Backscatter, pachymetric, and ectasia parameters were incorporated to determine if the model could be enhanced.

Results:

Among all ectasia, pachymetric, and backscatter parameters, at best only 65% of FECD corneas with definite tomographic edema could be identified based on the instrument's normative database. Among all parameters individually, the highest sensitivity for detecting tomographic edema was 77%. Anterior and mid-corneal backscatter featured in a model predicting improvement in CCT after DMEK with high performance in derivation (R2 = 0.79; 95% confidence interval, 0.65–0.87) and validation (R2 = 0.72; 95% confidence interval, 0.52–0.83) subgroups.

Conclusions:

The Scheimpflug camera software program could not reliably detect abnormal tomography in FECD from corneal backscatter, pachymetric indices, or ectasia indices. Corneal backscatter contributes to, but does not enhance, a predictive model of improvement in CCT after DMEK.
High-Resolution Ocular Surface Imaging: Real-Time Visualization of Tear Film Dysfunction
Authors: Coroneo Minas T. , Kokkinakis Jim , Lee Brendon W.H. , Chen Helen , Tat Lien
Published: June 2024

Purpose:

Recent advancements in infrared sensing technology have made it possible to visualize tear film dynamics in real time, enabling evaluation of tear film quality during blinking. A retrospective clinical evaluation was conducted to explore this by grading videos of the tear film and comparing grading data with dry eye diagnostic results using the OCULUS keratograph (K5M).

Methods:

Videos were used to grade patients’ tear film perturbations as compared with healthy control subjects. The grading was then correlated with the ocular surface disease index (OSDI) scores, tear film breakup time (TFBUT), tear meniscus height (TMH), corneal staining, redness, and meibography data.

Results:

Infrared imaging of the ocular surface revealed instantaneous and recurring dynamic characteristics of the tear film, allowing for the differentiation between normal and abnormal tear films. Abnormal features included a complete absence of a spreading tear film, hindered spreading of the tear film after blinking, areas of tear film instability, or a combination of the latter 2. Some of these features show a resemblance to the tear film appearance after fluorescein staining. The grading of these features correlated with TFBUT and, to a lesser extent, with TMH but did not show significant correlation with any other diagnostic data from the K5M. Furthermore, the speed of tear film spreading after blinking showed a positive correlation with TMH.

Conclusions:

Direct visualization of the tear film across the entire palpebral aperture using infrared sensing offers a noninvasive, reproducible, and rapid method for assessing the health and quality of the tear film.
Scholarly analytics for nurse practitioners
Authors: Hicks Rodney W.
Published: June 2024

Nurse practitioners who publish contribute to the profession's body of knowledge. Today's digitally inclined environment easily allows for the tracking of contributing to knowledge and impact. Four popular measures for tracking include Altmetric, Google Scholar, Scopus, and Web of Science. Authors should understand each tracking source's purpose, process, and value. The strengths and limitations of the tracking sources are reviewed. Awareness of the tracking sources and knowing how to influence the tools will bring additional attention to the authors.
Importance of provoked spasms at the sites of nonobstructive stenosis as well as at the sites of obstructive stenosis in patients with obstructive coronary arteries and coronary spasm
Authors: Sueda Shozo , Hayashi Yutaka
Published: June 2024

Objectives

There are few reports regarding the prognosis in patients with obstructive coronary artery disease (OCAD) and vasospastic angina (VSA). This study investigated the clinical characteristics and clinical outcomes in patients with VSA and OCAD, especially regarding provoked spasm phenotypes and sites.

Methods

This was a retrospective, observational, single-center study of 403 patients with typical or atypical angina-like chest pain undergoing acetylcholine (ACH) spasm provocation testing and OCAD. An obstructed coronary artery was defined as ≥50% luminal narrowing. We defined positive epicardial spasm as ≥90% transient stenosis and usual chest symptoms or ischemic ECG changes.

Results

Among these 403 patients with OCAD, positive spasm by intracoronary ACH testing was observed in 196 patients (49%), whereas negative spasm was found in the remaining 207 patients (51%). The clinical outcomes in the patients with OCAD and provoked spasm were not different according to the provoked-spasm phenotypes. Furthermore, the clinical outcomes were unsatisfactory in the patients with spasm at the site of nonobstructive lesion alone compared with those with spasm at the site of obstructive and nonobstructive lesions.

Conclusion

We should precisely diagnose patients with OCAD who have provoked spasm by using intracoronary ACH testing and medicate the nonobstructive vessels in patients with OCAD and VSA under optimal coronary vasodilators.
Factors Predicting Loss of Remission in Crohn’s Disease Patients in Endoscopic Remission in the Real World
Authors: Ahmad Harris , Click Benjamin , Morris Heather L. , Crawford Julie M. , Choi Jiyoon , Long Millie D. ,   on behalf of TARGET-IBD Investigators
Published: June 2024

Background:

There is limited evidence that histologic remission improves outcomes in Crohn’s disease (CD). We aimed to characterize a cohort of patients with CD in endoscopic remission and explore factors associated with subsequent loss of remission (LOR).

Methods:

In total, 4474 patients were enrolled in TARGET-IBD, a longitudinal, observational cohort study. Patients with a normal steroid-free colonoscopy (index) were defined as “in endoscopic remission” and were followed for LOR, defined as presence of inflammation, erosion, ulceration, or stricturing on a subsequent colonoscopy or commencement of steroids. Histologic activity was dichotomized using standard of care reports for active inflammation. Unadjusted and multivariable-adjusted Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of LOR in relation to independent variables.

Results:

Of 658 patients with CD with steroid-free endoscopic remission, the majority were female (57%), white (83%), non-Hispanic (93%); 20% had ileal and 20% isolated colonic disease. Inflammatory (B1) disease was the most common phenotype (43%). Of these 658 patients, 257 (39%) had histologic inflammation on index colonoscopy. Histologic inflammation at index colonoscopy was associated with nearly twice the LOR risk (HR 1.96, 95% CI: 1.50-2.57) with median time to relapse of 1.20 years. Biologic use at index was associated with lower LOR risk (monotherapy, HR 0.61, 95% CI: 0.45-0.82; combination therapy, HR 0.43, 95% CI: 0.28-0.66).

Conclusions:

Active histologic inflammation despite endoscopic remission, and lack of biologic use were independently associated with risk of subsequent LOR, providing evidence that histologic remission may impart improved outcomes in patients with CD.
Metabolic dysfunction-associated steatotic liver disease related cirrhosis and incidence of portal vein thrombosis
Authors: Amjad Waseem , Jiang Zhenghui G. , Lai Michelle
Published: June 2024

Background

There is heterogeneous data on whether metabolic-associated steatohepatitis is an independent risk factor for portal vein thrombosis (PVT). We aim to compare the incidence of PVT in patients with cirrhosis with and without metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods

This is a single-center retrospective study of patients with cirrhosis seen between 1 January 2016 and 31 January 2021. Patients with a history of hepatocellular cancer, liver transplant, Budd-Chiari syndrome, and intra-abdominal malignancies were excluded. Patients with cirrhosis were followed from their first hepatology visit for 180 days to determine the incidence of PVT. Cox proportional hazard regression was used to determine the relationship between MASLD with PVT.

Results

We analyzed data from 2785 patients with cirrhosis who met inclusion and exclusion criteria [mean age: 61.0 ± 12.3 years, 44.3% female, 63.8% Whites and mean model for end-stage liver disease-sodium (MELD-Na) score: 11.7 ± 6.1]. MASLD was present in 21.7% of patients. A total of 89 patients developed PVT during the follow-up, which was fewer in patients with MASLD [2.0% vs. 3.5%, P = 0.04, unadjusted heart rate (HR): 0.60, 95% confidence interval (CI): 0.27–0.96, P = 0.04]. After adjusting for the demographics, MASLD-related comorbid conditions and MELD-Na score, MASLD was associated with a lower incidence of PVT as compared to non-MASLD cirrhosis (HR: 0.44, 95% CI: 0.21–0.92, P = 0.03). After adjusting for the indicators of Child-Pugh Turcotte score, the risk of PVT in patients with MASLD compared to non-MASLD was not statistically significant (HR: 0.50, 95% CI: 0.22–1.13, P = 0.096).

Conclusion

PVT incidence was lower in patients with MASLD cirrhosis as compared to non-MASLD cirrhosis. However, the difference was not significantly different after adjusting for liver decompensation.
Apixaban versus low molecular weight heparin in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis
Authors: Amin Anam , Naeem Muhammad Omar , Amin Laraib , Khaliq Saad Ul , Ahmad Athar , Vohra Rimsha Rahim , Jawad Sayed
Published: June 2024

Background:

The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE.

Methods:

MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non-major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding-related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs.

Results:

The analysis included 12 011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding [RR 0.67 (95% CI 0.54, 0.83); P=0.0003, I2=0%] without significantly changing the risk of clinically relevant non-major bleeding [RR 0.96 (95% CI 0.64, 0.1.45); P=0.85, I2=57%]. Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis [RR 0.56 (95% CI 0.32, 0.99); P=0.05, I2=0%]. There was no discernible difference between apixaban and LMWH in bleeding-related mortality events [RR 0.20 (95% CI 0.01, 4.18); P=0.30, I2=NA%], and recurrence of DVT [RR 0.60 (95% CI 0.22, 1.59); P=0.23, I2=32%],

Conclusion:

Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.
Geriatric oral health neglect: calculus on the attached gingiva: a case report
Authors: Okereke Udohchukwu Promise , Offurum Chimeremeze , Eze Victor Anezi , Okpechukwu Chidubem Peter , Ifedibar Wisdom Chisom , Akaji Ezi Abigail
Published: June 2024

Introduction and importance:

Aging exerts various effects on and causes changes to the oral tissues. It is often difficult to distinguish between what is caused by the physiological process of aging itself and what is caused by the individual’s lifestyle or diseases. The elderly face peculiar health challenges and require special dental care. It is therefore vital that greater attention be given to the oral health needs of this rapidly population. In this article, the authors present the case of an elderly female patient with a rare case of calculus on the attached gingiva.

Case presentation:

A 90-year-old retired teacher with a history of hypertension, presented with a small, painless, grayish-brown growth on her attached gingiva, noticed by her daughter-in-law. Examination revealed signs of gingivitis and significant dental issues including missing teeth, fractures, and calculus buildup. Diagnosis of chronic generalized marginal gingivitis and calculus deposition was made, and scaling and polishing were performed. Perforation of the attached gingiva was observed during scaling thus exposing the root, which facilitated the calculus accumulation. Post-procedure care included medication and oral hygiene instructions. Follow-up after 1 week showed satisfactory healing, but subsequent assessment at 3 months revealed plaque accumulation, with the patient declining further treatment.

Clinical discussion:

The patient shows relative neglect in oral healthcare given the subpar oral health features she exhibited and decline of further treatment options presented to her. This is common in the population as some abnormal oral presentations and features are perceived as normal in the population, which can be attributed to poor knowledge of oral health practices, which affects the illness seeking behaviour of individual.

Conclusion:

Calculus deposition in the oral cavity requires a hard surface for formation, and proper oral hygiene practices are essential to mitigate its adverse effects, particularly among the elderly who may require additional attention due to their unique physiological changes.
Consensus Building to Identify Nursing Research Priorities Among Oncology Nurses: A Delphi Study in a National Cancer Institute–Designated Comprehensive Cancer Center
Authors: Hacker Eileen Danaher , Forbes Sheryl , Martinez Ashley , Fadol Anecita , Vaughn Jessica , Shelton Valerie , Dains Joyce
Published: June 2024

Background

To advance oncology nursing science and clinical practice, researchers and clinicians must understand the important real-world concerns of nurses who provide direct care to people with cancer or manage processes that support patient care.

Objective

This study developed a comprehensive compendium of real-world concerns among oncology nurses and built consensus regarding their importance.

Methods

Using Delphi survey methodology, this prospective, descriptive study was performed in 3 phases: (1) identification of experts, defined as registered nurses (RNs) employed within a comprehensive cancer center; (2) qualitative content analysis of 353 responses from 267 RNs who responded to the question, “What do you see as nursing research concerns, problems, and/or issues on your unit or in your work environment that needs to be studied?”; and (3) rating the importance of 62 research themes identified from the qualitative content analysis (n = 247 RNs).

Results

The top research priority was patient safety followed by patient education, oncologic emergencies, patient expectations and adherence with care, team communication, patient psychosocial needs, patient-reported outcomes and quality of life, healthcare team burnout, workload, and nurse burnout.

Conclusions

The findings support the nursing discipline’s fundamental focus on patient safety, the top-rated nursing research priority, along with other patient-related and work environment issues.

Implications for Practice

Oncology nursing is complex and complicated. This study identified and prioritized the real-world concerns, issues, and problems of oncology RNs who provide direct care or manage the processes that support care, supporting the need to focus on patient-related and work environment research.
Using Machine Learning to Identify Patients at Risk of Acquiring HIV in an Urban Health System
Authors: Nethi Arun Kumar , Karam Albert George , Alvarez Kristin S. , Luque Amneris Esther , Nijhawan Ank E. , Adhikari Emily , King Helen Lynne
Published: June 2024

Background:

Effective measures exist to prevent the spread of HIV. However, the identification of patients who are candidates for these measures can be a challenge. A machine learning model to predict risk for HIV may enhance patient selection for proactive outreach.

Setting:

Using data from the electronic health record at Parkland Health, 1 of the largest public healthcare systems in the country, a machine learning model is created to predict incident HIV cases. The study cohort includes any patient aged 16 or older from 2015 to 2019 (n = 458,893).

Methods:

Implementing a 70:30 ratio random split of the data into training and validation sets with an incident rate <0.08% and stratified by incidence of HIV, the model is evaluated using a k-fold cross-validated (k = 5) area under the receiver operating characteristic curve leveraging Light Gradient Boosting Machine Algorithm, an ensemble classifier.

Results:

The light gradient boosting machine produces the strongest predictive power to identify good candidates for HIV PrEP. A gradient boosting classifier produced the best result with an AUC of 0.88 (95% confidence interval: 0.86 to 0.89) on the training set and 0.85 (95% confidence interval: 0.81 to 0.89) on the validation set for a sensitivity of 77.8% and specificity of 75.1%.

Conclusions:

A gradient boosting model using electronic health record data can be used to identify patients at risk of acquiring HIV and implemented in the clinical setting to build outreach for preventative interventions.
Odontogenic Cutaneous Fistula: A Zombie Diagnosis
Authors: Taylor Ruby R. , Mirsky Nicholas , Jabori Sinan , Verling Samantha , Coelho Paulo G. , Thaller Seth R.
Published: June 2024

Background:

Odontogenic cutaneous fistula (OCF) is a pathologic communication between the cutaneous surface of the face and oral cavity. Majority of oral cutaneous fistulas are reported to arise from chronic dental infection. Delay in treatment may result in chronic tissue injury as well as cosmetic deformities. Lesions are often misdiagnosed, leading to delayed management. Misdiagnosis may be the result of the variability of clinical morphological presentation and location of lesions compounded by the lack of knowledge that these lesions can have dental etiology. It is estimated that half of patients with OCF undergo multiple dermatologic surgical operations, antibiotic regimens, and other excisions and biopsies before a correct diagnosis is made. Herein, we present a systematic review to detail cases of odontogenic cutaneous lesions that had been previously misdiagnosed or managed inappropriately. In addition, we include a case report from our own institution. The aims are to demonstrate various presentations of OCF, increase awareness of plastic surgeons and oral maxillofacial surgeons to this pathological condition, and reinforce the importance of prompt diagnosis and treatment.

Methods:

The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A literature search was conducted in PubMed, Web of Science, and Cochrane databases from January 1, 2013 to July 24, 2023. The following search terms were utilized: “odontogenic cutaneous fistula” OR “odontogenic cutaneous sinus.”

Results:

Twenty-three articles published between 2013 and 2023 were included in this review. In addition, we report a case from our own institution. A total of 28 cases were included in the review.

Conclusions:

Diagnosis of OCF is challenging for numerous reasons. Misdiagnosis can lead to multiple trials of antibiotics and surgical procedures as well as reoccurrence of the lesion. Cases summarized highlight the importance of communication between oral maxillofacial surgery, plastic surgery, other medical subspecialists, and dentists in the evaluation of patients with head and neck lesions. Physicians should consider dental etiology in the differential diagnosis of orofacial skin lesions, even if teeth appear normal on oral examination.
Is Muscle Pain in Temporomandibular Disorder a Hyperactivity Problem? A Clinical, Thermographic, and Electromyographic Analysis
Authors: Catunda Ivson Souza , Lima Junior Miqueias Oliveira de , Costa Araujo Fábio Andrey da , Fontan Soares Cauê , Ferreira Jessica Caroline Afonso , Kosminsky Maurício , Vasconcelos Belmiro Cavalcanti do Egito , Vasconcellos Ricardo José de Holanda
Published: June 2024

This study aimed to report clinical data on muscle pain in temporomandibular disorders using thermography, algometry, and surface electromyography (EMG). This was done to support or rule out the hypothesis that painful muscles are always related to muscular hyperactivity. This cross-sectional, analytical study included 50 participants who underwent clinical examination and evaluation of anterior temporal muscles and bilateral masseters using thermography, algometry, and EMG. The muscles with greater pain symptoms had hyporadiation and a lower temperature compared with both contralateral muscles and muscles in the asymptomatic group. There was no muscle hyperactivity at rest on EMG analysis; however, there was a greater capacity for muscle recruitment of these symptomatic muscles after a joint decompression test with cotton rolls, suggesting hypoactivity of the affected muscles in the symptomatic patient group. Muscle pain may be related to hypoactivity of the musculature when there is neurological inhibition of the recruitment of muscle fibers, and treatment must consider these neurophysiological alterations.

Level of Evidence:

Level IV.
Use of Titanium Mesh During Frontal Sinus Setback in Facial Feminization Surgery: Clinical Outcomes and Perspectives
Authors: Moghadam Shahrzad , Khetpal Sumun , Ozaki Wayne
Published: June 2024

Brow position, hairline shape, and forehead projection may confer cis-feminine identity, and facial feminization surgery (FFS) can improve gender dysphoria among transfeminine patients. Depending on the Ousterhout classification, burring, osteotomy, anterior frontal sinus setback, and augmentation, with subsequent fixation via metal or bioabsorbable plates, can address forehead projection. However, titanium mesh, often used in frontal sinus fracture repair, has not been described for forehead contouring in FFS. The purpose of this study was to study clinical outcomes associated with the use of titanium mesh for the stabilization of bone following anterior frontal sinus setback. A retrospective cohort study of trans-female and nonbinary patients undergoing primary FFS by our senior author between January 2021 and February 2023 was performed. Variables collected include demographics, Ousterhout classification, operative details, complications, and follow-up duration. Patients with prior FFS or facial trauma were excluded. Data were analyzed using SPSS, (IBM, Armonk, NY). Forty-three transfeminine patients were included for analysis. The cohort had an average age of 33.0±8.7 years and a median follow-up time of 3.0 months (IQR = 1.0–7.0). Among our cohort, 26 patients (60.5%) received titanium mesh and 17 patients (39.5%) underwent burring only for forehead contouring. There were no reported complications (ie, infection, hardware extrusion, or mucocele formation) or a need for forehead revisions among the entire cohort regardless of the frontal sinus reconstruction material utilized. Clinical outcomes were favorable among patients receiving titanium mesh anterior table fixation during FFS. Titanium mesh can be considered as an additional technique for frontal bossing reduction and anterior table fixation in FFS.
Congenital Infiltrating Lipomatosis of Face-Induced Temporomandibular Joint Ankylosis
Authors: Rattan Vidya , Singh Apoorva , Malik Priyanka , Jolly Satnam Singh
Published: June 2024

Temporomandibular joint ankylosis (TMJA) secondary to congenital infiltrating lipomatosis of the face (CILF) is an exceptionally uncommon condition which is characterized by the involvement of unilateral facial soft tissues and bones. In some cases, the extensive exophytic bony growth in the temporomandibular joint region often extends toward the skull base and lies near adjacent vital structures. Only very few cases of TMJA associated with CILF have been reported in the literature. The authors report a case of a 36-year-old female with right TMJA secondary to CILF. The bony overgrowth in the right temporomandibular joint region was arising from a deformed right mandibular condyle, extending towards the ipsilateral temporal bone, greater wing of the sphenoid, skull base, and approaching the lateral limit of foramen ovale, and foramen spinosum. To prevent any damage to the skull base and adjacent vital structures and to achieve adequate mouth opening, the authors have performed a unique technique of subankylotic osteotomy for the release of TMJA, instead of conventional gap arthroplasty.