bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of alkaline phosphatase cytochemistry in canine neoplastic and non‐neoplastic pulmonary mass aspirates
Authors: O'Day Jack , Seelig Davis , Emanuelli Mauren , Heinrich Daniel
Published: August 2023

Background

Distinguishing primary and secondary pulmonary neoplasms can be challenging via cytology, and a rapid, inexpensive diagnostic tool to differentiate these neoplasms is unavailable. Alkaline phosphatase cytochemistry (ALP‐CC) has been used to identify primary pulmonary carcinomas in human patients, and we hypothesized it could be applied to canine lung aspirates.

Objective

We aimed to characterize ALP‐CC expression in fine‐needle aspirate (FNA) samples of canine pulmonary neoplastic and non‐neoplastic tumors.

Methods

A retrospective case search was conducted to identify cases with contemporaneous cytology and histopathology reports from pulmonary lesions, including neoplastic and non‐neoplastic etiologies. Slides prepared from pulmonary aspirates were stained for ALP‐CC activity, and the percentage of ALP‐CC‐positive primary pulmonary epithelial tumors was determined. To characterize the ALP‐CC expression in non‐neoplastic cellular constituents of pulmonary FNA samples, mesothelial cells were also evaluated.

Results

Forty‐eight canine cases met the inclusion criteria. ALP‐CC–positive cells were seen in both neoplastic and non‐neoplastic lesions. In non‐neoplastic lesions, pulmonary epithelial cells were ALP‐CC positive. Eighty‐nine percent of primary pulmonary epithelial neoplasms were ALP‐CC positive, and no ALP‐CC positivity was noted in mesothelial cells. ALP‐CC–positive neoplastic cells were seen in a metastatic amelanotic melanoma.

Conclusions

Primary pulmonary epithelial neoplasms are frequently ALP‐CC positive, but such positivity is not restricted to this tumor type. Non‐neoplastic pulmonary epithelial cells can be ALP‐CC positive, whereas mesothelial cells are negative.
Comparing 3 mm and 5 mm laparoscopic liver biopsy samples in dogs
Authors: Larose Philippe Chagnon , Brisson Brigitte A. , Foster Robert A. , Monteith Gabrielle
Published: August 2023

Objective

To determine whether 3 mm cup biopsy forceps (CBF) provide equivalent diagnostic samples to 5 mm CBF for histopathologic diagnosis, bacterial culture, and copper quantification.

Study design

Clinical prospective study.

Animals

Ten client‐owned dogs, presenting for laparoscopic liver biopsy (LLB).

Methods

Dogs underwent LLB, and paired samples were collected using 3 and 5 mm CBF. Portal triad and hepatic lobule counts, crush and fragmentation artifacts, copper concentration, bacterial culture results, and agreement on histopathologic diagnosis were compared.

Results

Both CBF sizes allowed for easy sample collection and resulted in minimal hemorrhage. An average of 12.13 (confidence limit (CL): 9.4–14.9) and 17.84 (CL: 15.1–20.6) portal triads were obtained using a 3 and 5 mm CBF, respectively (p = .0003). A portal triad count of 11 or more was achieved in 73.3% of the 3 mm and 93.3% of the 5 mm samples. Gwets AC1 coefficient showed a high level of agreement (0.8) for overall histopathologic diagnosis (p < .0001). The 3 mm CBF crush scores were higher (median of the differences: −1; range: −1 to 1) (p = .035). There was no difference in fragmentation scores (p = .935).

Conclusion

The 3 mm CBF yielded smaller samples in terms of size and portal triad count compared with the 5 mm CBF. However, the portal triad count was sufficient in a majority of samples and histologic agreement with the 5 mm CBF was excellent.

Clinical significance

In dogs, a 3 mm CBF yields adequate samples for histopathologic interpretation, copper quantification, and bacterial culture.
Impact of secondary amenorrhea on cardiovascular disease risk in physically active women: a systematic review protocol
Authors: Tegg Nicole L. , Myburgh Caitlynd , Kennedy Megan , Norris Colleen M.
Published: August 2023

Objective:

The objective of this review is to assess the association between secondary amenorrhea in physically active women and cardiovascular disease risk.

Introduction:

It is well established that a woman’s risk of cardiovascular disease greatly increases after menopause. The sharp decline in estrogen is seen as a causal factor. Exercise-induced secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen’s cardioprotective pathways. Further, estrogen may be essential in a woman’s endothelial adaptations to exercise. The impact of secondary amenorrhea on cardiovascular disease risk in premenopausal women is not well established.

Inclusion criteria:

This review will consider studies that include physically active women experiencing amenorrhea in any country. Only studies that present evidence of cardiovascular disease, alterations to cardiovascular physiology, or data on cardiovascular risk factors (eg, lipid profile changes) will be considered. The review will consider experimental or observational epidemiological study designs.

Methods:

Searches will be conducted in CINAHL (EBSCOhost), Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Two independent reviewers will screen titles, abstracts, and full texts, appraise methodological quality, and extract data from studies. Where possible, studies will be pooled in a statistical meta-analysis in addition to subgroup analyses. Where pooling is not possible, the findings will be presented in narrative format. Certainty of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Systematic review registration number:

PROSPERO CRD42023360781
Public health interventions preventing adolescent vaping: a scoping review protocol
Authors: DiCasmirro Jamie , Tranmer Joan , Davison Colleen , Woo Kevin , Ross-White Amanda , Hubeny Michael , Goldie Catherine
Published: August 2023

Objective:

The objective of the review is to systematically examine the emerging literature related to public health interventions aimed at preventing adolescent vaping.

Introduction:

The prevalence of vaping behaviors among adolescents is a rising concern worldwide. A thorough investigation of existing public health interventions to prevent vaping among adolescents is imperative to reduce serious and avoidable vaping-related health risks for this cohort. Many vaping-prevention interventions have been described in the literature, but their key components and outcomes have not been summarized.

Inclusion criteria:

All English literature related to public health interventions preventing adolescent (aged 10 to 18 years) vaping from all countries will be included.

Methods:

This scoping review will follow the JBI methodology for scoping reviews. A comprehensive search of academic and gray literature using MEDLINE (Ovid), CINAHL (EBSCO), Embase (Ovid), PubMed, PsycINFO (Ovid), ProQuest (Health and Medicine and Sociology Collections), and Web of Science Core Collection will be performed. Articles will be screened for inclusion by 2 independent reviewers. Results will be extracted using customized tools and summarized in a final report using narrative synthesis and presented in table format.
La responsabilidad civil como fundamento de la mediación en seguros
Authors: Sánchez García Mateo
Published: August 2023

El presente texto tiene como finalidad el estudio de algunos aspectos del régimen de responsabilidad civil en accidentes de circulación con el objetivo de analizar algunos temas sobre la mediación en seguros tales como: ¿Quién puede solicitar la mediación?, la elección del Mediador, aspectos relacionados con la cuantificación del daño, la manera en que debe desarrollarse las sesiones de mediación, entre otras.  Para tal finalidad se tendrá como fuentes jurídicas la normatividad comunitaria y en específico la legislación española.
Reticencia, omisión, información incorrecta y la eficacia del contrato de seguro
Authors: Arbache Henrique Pires
Published: August 2023

En esta investigación, buscamos esbozar supuestos importantes para examinar el tratamiento legal adecuado de la información presentado por el asegurado, a favor de la eficiencia de los contratos de seguro.

Partiendo del examen de las principales características de los contratos de seguro, el mutualismo, los cálculos actuariales, su función social, llegamos a la importancia de la información proporcionada por el asegurado, para la adecuada y equilibrada tarificación del servicio.

En este escenario, buscamos evaluar las consecuencias atribuidas por los ordenamientos jurídicos argentino y brasileño, destacando los puntos positivos de cada uno y los que podrían sufrir aportes.
Behavioral Modeling of Collaborative Problem Solving in Multiplayer Virtual Reality Manufacturing Simulation Games
Authors: Kim Haedong , Hartleb Tyler , Bello Khalid , Aqlan Faisal , Zhao Richard , Yang Hui
Published: August 2023

Engineering is an inherently creative and collaborative endeavor to solve real-world problems, in which collaborative problem solving (CPS) is considered one of the most critical professional skills. Hands-on practices and assessment methods are essential to promote deeper learning and foster the development of professional skills. However, most existing approaches are based on out-of-process procedures such as surveys, tests, or interviews that measure the effectiveness of learning activity in an aggregated way. It is desirable to quantify CPS dynamics during the learning process. Advancements in virtual reality (VR) provide great opportunities to realize digital learning environments to facilitate a learning-by-doing curriculum. In addition, sensors in VR systems allow us to collect in-process user behavioral data. This paper presents a multiplayer VR manufacturing simulation game for virtual hands-on learning experiences, as well as a behavioral modeling method for monitoring the CPS skills of participants. First, we developed the Virtual Learning Factory, where users play simulation games of various manufacturing paradigms. Second, we collected action logs from a sample of participants and used the same pattern to generate more data. Third, the behavioral data are modeled as dynamic networks for each player. Last, network features are calculated, and a CPS scoring method is driven from them. Experimental results show that the proposed behavioral modeling successfully captures different patterns of CPS dynamics according to manufacturing paradigms and individuals. This detailed assessment contributes to the development of appropriate student-specific interventions to improve learning outcomes.
Manufacturing Multi-Matrix Composites: Out-of-Vacuum Bag Consolidation
Authors: Radhakrishnan Arjun , Georgillas Ioannis , Hamerton Ian , Shaffer Milo S. P. , Ivanov Dmitry S.
Published: August 2023

The formation of porosity is a major challenge in any composite manufacturing process, particularly in the absence of vacuum assistance. Highly localized injection of polymer matrix into regions of interest in a dry preform is a route to manufacturing multi-matrix fiber-reinforced composites with high filler concentrations, which are otherwise difficult to achieve. Unlike traditional composites, such multi-matrix fiber-reinforced composite systems, which combine multiple resins in continuous form, offer improved structural performance around stress concentrators and multifunctional capabilities. As the process lacks vacuum assistance, porosity becomes a primary issue to be addressed. This paper presents a rheo-kinetic coupled rapid consolidation procedure for optimizing the quality of localized matrix patches. The procedure involves manufacturing trials and analytical consolidation models to determine the best processing program for minimal voidage in the patch. The results provide a step toward an efficient manufacturing process for the optimal design of multi-matrix composites without the need for complex vacuum bag arrangements, thus reducing cost and time while opening avenues to improve overall composite performance.
Accurate measurement of the loss rate of cold atoms due to background gas collisions for the quantum-based cold atom vacuum standard
Authors: Barker Daniel S. , Fedchak James A. , Kłos Jacek , Scherschligt Julia , Sheikh Abrar A. , Tiesinga Eite , Eckel Stephen P.
Published: August 2023

We present the measurements of thermalized collisional rate coefficients for ultra-cold 7Li and 87Rb colliding with room-temperature He, Ne, N2, Ar, Kr, and Xe. In our experiments, a combined flowmeter and dynamic expansion system, a vacuum metrology standard, is used to set a known number density for the room-temperature background gas in the vicinity of the magnetically trapped 7Li or 87Rb clouds. Each collision with a background atom or molecule removes a 7Li or 87Rb atom from its trap, and the change in the atom loss rate with background gas density is used to determine the thermalized loss rate coefficients with fractional standard uncertainties better than 1.6% for 7Li and 2.7% for 87Rb. We find consistency—a degree of equivalence of less than one—between the measurements and recent quantum-scattering calculations of the loss rate coefficients [Kłos and Tiesinga, J. Chem. Phys. 158, 014308 (2023)], with the exception of the loss rate coefficient for both 7Li and 87Rb colliding with Ar. Nevertheless, the agreement between theory and experiment for all other studied systems provides validation that a quantum-based measurement of vacuum pressure using cold atoms also serves as a primary standard for vacuum pressure, which we refer to as the cold-atom vacuum standard.
Effects of lexical frequency on the post-exposure magnitude of recalibration in lexically guided perceptual learning: An explorative analysis
Authors: Koo Hahn , Kataoka Reiko , Swan Julia Thomas , Tzeng Christina Y.
Published: August 2023

Listeners use lexical information to guide the mapping between acoustic signals and representations of speech sound. This process is known as perceptual learning and results in recalibration of phonetic categories. The current work examines the effect of lexical frequency of exposure words on the magnitude of recalibration. Results showed comparable levels of perceptual learning for listeners exposed to high-frequency vs low-frequency critical words, in line with empirical findings that suggest that if frequency affects recalibration, such effects may be difficult to detect. These findings warrant further empirical probing and theoretical characterization of the role of lexical frequency in perceptual learning.
Interaction Between Coaches and Athletes in African Nations During the Lockdown Period of COVID-19
Authors: Luguterah Austin W. , Abonyi Usman , Yeboah Rita , Kubayi Alliance
Published: August 2023

The lockdown period of the COVID-19 pandemic has created several innovative methods of interaction at workplaces and, more importantly, within the sports industry. The COVID-19 pandemic has affected the usual training procedures and further challenged coaches and athletes to find ways of interaction. The researchers combined both qualitative and quantitative approaches and descriptive statistics in this article. This article attempts to find out the means, media, experiences, and source of interaction between coaches and athletes in five African countries during the COVID-19 lockdown period. Data were gathered from 127 coaches and 212 athletes from five African countries. The article reveals that coaches and athletes made use of phone calls, emails, text messages, and internet videos to interact during the lockdown period. The athletes benefited from the interactions, and the coaches achieved their coaching goals. The finding of this study, apart from triggering research on the use of technology in sports coaching in Africa, further creates a new path of distant coaching in Africa.
Predicting Gait Patterns of Children With Spasticity by Simulating Hyperreflexia
Authors: Veerkamp Kirsten , Carty Christopher P. , Waterval Niels F.J. , Geijtenbeek Thomas , Buizer Annemieke I. , Lloyd David G. , Harlaar Jaap , van der Krogt Marjolein M.
Published: August 2023

Spasticity is a common impairment within pediatric neuromusculoskeletal disorders. How spasticity contributes to gait deviations is important for treatment selection. Our aim was to evaluate the pathophysiological mechanisms underlying gait deviations seen in children with spasticity, using predictive simulations. A cluster analysis was performed to extract distinct gait patterns from experimental gait data of 17 children with spasticity to be used as comparative validation data. A forward dynamic simulation framework was employed to predict gait with either velocity- or force-based hyperreflexia. This framework entailed a generic musculoskeletal model controlled by reflexes and supraspinal drive, governed by a multiobjective cost function. Hyperreflexia values were optimized to enable the simulated gait to best match experimental gait patterns. Three experimental gait patterns were extracted: (1) increased knee flexion, (2) increased ankle plantar flexion, and (3) increased knee flexion and ankle plantar flexion when compared with typical gait. Overall, velocity-based hyperreflexia outperformed force-based hyperreflexia. The first gait pattern could mostly be explained by rectus femoris and hamstrings velocity-based hyperreflexia, the second by gastrocnemius velocity-based hyperreflexia, and the third by gastrocnemius, soleus, and hamstrings velocity-based hyperreflexia. This study shows how velocity-based hyperreflexia from specific muscles contributes to different spastic gait patterns, which may help in providing targeted treatment.
PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma
Authors: Peng Song , Wang Ze , Tang Peng , Wang Shuo , Huang Yiqiang , Xie Qiubo , Wang Yapeng , Tan Xintao , Tang Tang , Yan Xuzhi , Xu Jing , Lan Weihua , Wang Luofu , Zhang Dianzheng , Wang Bin , Pan Tiejun , Qin Jun , Jiang Jun , Liu Qiuli
Published: August 2023

For clear cell renal cell carcinoma (ccRCC), lipid deposition plays important roles in the development, metastasis, and drug resistance. However, the molecular mechanisms underlying lipid deposition in ccRCC remain largely unknown. By conducting an unbiased CRISPR-Cas9 screening, we identified the epigenetic regulator plant homeodomain finger protein 8 (PHF8) as an important regulator in ccRCC lipid deposition. Moreover, PHF8 is regulated by von Hippel–Lindau (VHL)/hypoxia-inducible factor (HIF) axis and essential for VHL deficiency–induced lipid deposition. PHF8 transcriptionally up-regulates glutamate-ammonia ligase (GLUL), which promotes the lipid deposition and ccRCC progression. Mechanistically, by forming a complex with c-MYC, PHF8 up-regulates TEA domain transcription factor 1 (TEAD1) in a histone demethylation–dependent manner. Subsequently, TEAD1 up-regulates GLUL transcriptionally. Pharmacological inhibition of GLUL by
l
-methionine sulfoximine not only repressed ccRCC lipid deposition and tumor growth but also enhanced the anticancer effects of everolimus. Thus, the PHF8-GLUL axis represents a potential therapeutic target for ccRCC treatment.
Illuminating the inner workings of a natural protein switch: Blue-light sensing in LOV-activated diguanylate cyclases
Authors: Vide Uršula , Kasapović Dženita , Fuchs Maximilian , Heimböck Martin P. , Totaro Massimo G. , Zenzmaier Elfriede , Winkler Andreas
Published: August 2023

Regulatory proteins play a crucial role in adaptation to environmental cues. Especially for lifestyle transitions, such as cell proliferation or apoptosis, switch-like characteristics are desirable. While nature frequently uses regulatory circuits to amplify or dampen signals, stand-alone protein switches are interesting for applications like biosensors, diagnostic tools, or optogenetics. However, such stand-alone systems frequently feature limited dynamic and operational ranges and suffer from slow response times. Here, we characterize a LOV-activated diguanylate cyclase (LadC) that offers precise temporal and spatial control of enzymatic activity with an exceptionally high dynamic range over four orders of magnitude. To establish this pronounced activation, the enzyme exhibits a two-stage activation process in which its activity is inhibited in the dark by caging its effector domains and stimulated upon illumination by the formation of an extended coiled-coil. These switch-like characteristics of the LadC system can be used to develop new optogenetic tools with tight regulation.
Quantifying the impact of SARS-CoV-2 temporal vaccination trends and disparities on disease control
Authors: Larsen Sophie L. , Shin Ikgyu , Joseph Jefrin , West Haylee , Anorga Rafael , Mena Gonzalo E. , Mahmud Ayesha S. , Martinez Pamela P.
Published: August 2023

SARS-CoV-2 vaccines have been distributed at unprecedented speed. Still, little is known about temporal vaccination trends, their association with socioeconomic inequality, and their consequences for disease control. Using data from 161 countries/territories and 58 states, we examined vaccination rates across high and low socioeconomic status (SES), showing that disparities in coverage exist at national and subnational levels. We also identified two distinct vaccination trends: a rapid initial rollout, quickly reaching a plateau, or sigmoidal and slow to begin. Informed by these patterns, we implemented an SES-stratified mechanistic model, finding profound differences in mortality and incidence across these two vaccination types. Timing of initial rollout affects disease outcomes more substantially than final coverage or degree of SES disparity. Unexpectedly, timing is not associated with wealth inequality or GDP per capita. While socioeconomic disparity should be addressed, accelerating initial rollout for all over focusing on increasing coverage is an accessible intervention that could minimize the burden of disease across socioeconomic groups.
The
Chlamydia
effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35
Authors: Meier Karsten , Jachmann Lana H. , Türköz Gözde , Babu Sait Mohammed Rizwan , Pérez Lucía , Kepp Oliver , Valdivia Raphael H. , Kroemer Guido , Sixt Barbara S.
Published: August 2023

The obligate intracellular bacterium
Chlamydia trachomatis
inserts a family of inclusion membrane (Inc) proteins into the membrane of its vacuole (the inclusion). The Inc CpoS is a critical suppressor of host cellular immune surveillance, but the underlying mechanism remained elusive. By complementing a
cpoS
mutant with various natural orthologs and variants of CpoS, we linked distinct molecular interactions of CpoS to distinct functions. Unexpectedly, we found CpoS to be essential for the formation of inclusion membrane microdomains that control the spatial organization of multiple Incs involved in signaling and modulation of the host cellular cytoskeleton. While the function of CpoS in microdomains was uncoupled from its role in the suppression of host cellular defenses, we found the ability of CpoS to interact with Rab GTPases to be required not only for the manipulation of membrane trafficking, such as to mediate transport of ceramide-derived lipids (sphingolipids) to the inclusion, but also for the inhibition of Stimulator of interferon genes (STING)-dependent type I interferon responses. Indeed, depletion of Rab35 phenocopied the exacerbated interferon responses observed during infection with CpoS-deficient mutants. Overall, our findings highlight the role of Inc–Inc interactions in shaping the inclusion microenvironment and the modulation of membrane trafficking as a pathogenic immune evasion strategy.

IMPORTANCE

Chlamydia trachomatis
is a prevalent bacterial pathogen that causes blinding ocular scarring and urogenital infections that can lead to infertility and pregnancy complications. Because
Chlamydia
can only grow within its host cell, boosting the intrinsic defenses of human cells may represent a novel strategy to fight pathogen replication and survival. Hence, CpoS, a
Chlamydia
protein known to block host cellular defenses, or processes regulated by CpoS, could provide new opportunities for therapeutic intervention. By revealing CpoS as a multifunctional virulence factor and by linking its ability to block host cellular immune signaling to the modulation of membrane trafficking, the present work may provide a foundation for such rationale targeting and advances our understanding of how intracellular bacteria can shape and protect their growth niche.
New reference genomes of honey bee-associated bacteria
Paenibacillus melissococcoides, Paenibacillus dendritiformis,
and
Paenibacillus thiaminolyticus
Authors: Dainat Benjamin , Oberhaensli Simone , Ory Florine , Dietemann Vincent
Published: August 2023

We sequenced the genomes of recently discovered
Paenibacillus melissococcoides
(CCOS 2000) and of the type strains of closely related
P. thiaminolyticus
(DSM 7262) and
P. dendritiformis
(LMG 21716). The three genomes set the basis to unambiguous diagnostic of these honey bee associated
Paenibacillus
bacteria.
Magma mingling and ascent in the minutes to hours before an explosive eruption as recorded by banded pumice
Authors: Shamloo Hannah I. , Grunder Anita L.
Published: August 2023

High-threat explosive silicic eruptions commonly contain banded pumice, reflecting magma mingling in the conduit prior to or during eruption. Heterogeneities in tuffs have been attributed to the draw-up of compositionally distinct magmas, in which low-viscosity magmas ascend more quickly than high-viscosity magmas. The Rattlesnake Tuff of the High Lava Plains in Oregon (northwestern United States) represents a zoned magma reservoir where at least five different rhyolite compositions are preserved in banded pumice samples in variable mingled combinations. Geochemical gradients recorded across band boundaries in pumice were modeled using a Monte Carlo least-square minimization procedure to find the complementary error function that best fit observed Si and Ba diffusion profiles by iteratively varying the concentration of each plateau (i.e., the concentration on either side of the band boundary), the center and spacing of the diffusion profile, diffusion length scale, and temperature. Modeling indicates maximum time scales between mingling and conduit ascent from minutes to hours. Viscosity calculations for each rhyolite composition confirm that highly viscous rhyolites have longer ascent times than low-viscosity magmas, strongly supporting a model of sequential tapping of a zoned chamber controlled by viscosity.
Supplemental Material: Large Si isotope fractionation reveals formation mechanism of quartz in silicon-poor carbonatite
Authors: Huang Yong-shu , Li Qiuli , al. et
Published: August 2023

Large Si isotope fractionation reveals formation mechanism of quartz in silicon-poor carbonatite 
Diabetic Retinopathy Screening at the Point of Care (DR SPOC): detecting undiagnosed and vision-threatening retinopathy by integrating portable technologies within existing services
Authors: Weerasinghe Lakni Shahanika , Dunn Hamish Paul , Fung Adrian T , Maberly Glen , Cheung Ngai Wah , Weerasinghe Daminda P , Liew Gerald , Do Helen , Hng Tien-Ming , Pryke Alison , Marks Samuel I , Nguyen Helen , Jayaballa Rajini , Gurung Seema , Ford Belinda , Bishay Ramy H , Girgis Christian M , Meyerowitz-Katz Gideon , Keay Lisa , White Andrew J
Published: August 2023

Introduction

The aim of this study was to determine the prevalence of diabetic retinopathy (DR) in a low socioeconomic region of a high-income country, as well as determine the diagnostic utility of point-of-care screening for high-risk populations in tertiary care settings.

Research design and methods

This was a cross-sectional study of patients with diabetes attending foot ulcer or integrated care diabetes clinics at two Western Sydney hospitals (n=273). DR was assessed using portable, two-field, non-mydriatic fundus photography and combined electroretinogram/ pupillometry (ERG). With mydriatic photographs used as the reference standard, sensitivity and specificity of the devices were determined. Prevalence of DR and vision-threatening diabetic retinopathy (VTDR) were reported, with multivariate logistic regression used to identify predictors of DR.

Results

Among 273 patients, 39.6% had any DR, while 15.8% had VTDR, of whom 59.3% and 62.8% were previously undiagnosed, respectively. Non-mydriatic photography demonstrated 20.2% sensitivity and 99.5% specificity for any DR, with a 56.7% screening failure rate. Meanwhile, mydriatic photography produced high-quality images with a 7.6% failure rate. ERG demonstrated 72.5% sensitivity and 70.1% specificity, with a 15.0% failure rate. The RETeval ERG was noted to have an optimal DR cut-off score at 22. Multivariate logistic regression identified an eGFR of ≤29 mL/min/1.73 m2, HbA1c of ≥7.0%, pupil size of <4 mm diameter, diabetes duration of 5–24 years and RETeval score of ≥22 as strong predictors of DR.

Conclusion

There is a high prevalence of vision-threatening and undiagnosed DR among patients attending high-risk tertiary clinics in Western Sydney. Point-of-care DR screening using portable, mydriatic photography demonstrates potential as a model of care which is easily accessible, targeted for high-risk populations and substantially enhances DR detection.
Evaluation of Ebola virus disease surveillance system capability to promptly detect a new outbreak in Liberia
Authors: Shannon, Fulton Quincy , Bawo Luke L , Crump John A , Sharples Katrina , Egan Richard , Hill Philip C
Published: August 2023

Introduction

Liberia was heavily affected by the 2014–2016 Ebola virus disease (EVD) outbreak. With substantial investments in interventions to combat future outbreaks, it is hoped that Liberia is well prepared for a new incursion. We assessed the performance of the current EVD surveillance system in Liberia, focusing on its ability to promptly detect a new EVD outbreak.

Methods

We integrated WHO and US Centers for Disease Control and Prevention guidelines for public health surveillance system evaluation and used standardised indicators to measure system performance. We conducted 23 key informant interviews, 150 health facility assessment surveys and a standardised patient (SP) study (19 visits) from January 2020 to January 2021. Data were summarised and a gap analysis conducted.

Results

We found basic competencies of case detection and reporting necessary for a functional surveillance system were in place. At the higher (national, county and district) levels, we found performance gaps in 2 of 6 indicators relating to surveillance system structure, 3 of 14 indicators related to core functions, 1 of 5 quality indicators and 2 of 8 indicators related to support functions. The health facility assessment found performance gaps in 9 of 10 indicators related to core functions, 5 of 6 indicators related to support functions and 3 of 7 indicators related to quality. The SP simulations revealed large gaps between expected and actual practice in managing a patient warranting investigation for EVD. Major challenges affecting the system’s operations across all levels included limited access to resources to support surveillance activities, persistent stock out of sample collection materials and attrition of trained staff.

Conclusion

The EVD surveillance system in Liberia may fail to promptly detect a new EVD outbreak. Specific improvements are required, and regular evaluations recommended. SP studies could be crucial in evaluating surveillance systems for rarely occurring diseases that are important to detect early.
Association between HIV and treatment-resistant hypertension in Malawian adults: a protocol for a case–control study
Authors: Gondwe Josephine , Ndovie Maclean , Khuluza Felix , Banda Clifford George
Published: August 2023

Introduction

Treatment-resistant hypertension (RH), defined as uncontrolled blood pressure (≥140/90 mm Hg) despite treatment with ≥3 medications of different classes (including diuretics) at optimal doses, is associated with poor prognosis and an elevated risk of end-organ damage. In areas where HIV is endemic, such as sub-Saharan Africa, the risk of hypertension is high in people living with HIV. It remains unknown if HIV infection further increases the risk of RH. This study seeks to determine the association between HIV and RH as well as investigate other factors associated with RH in hypertensive Malawian adults.

Methods and analysis

A case–control study will be conducted among adult hypertensive patients attending a clinic at a referral hospital in Malawi. The cases will be hypertensive patients with a confirmed diagnosis of RH. For each case, two controls (hypertensive patients without RH), frequency matched for age group and sex, will be selected from among hospital clients attending the same hypertension clinic as the case. In both groups, HIV status will be ascertained. Additionally, information on other potential risk factors of RH, such as chronic kidney disease, obesity, hypercholesteraemia, diabetes, smoking, alcohol use, antiretroviral therapy regimen and duration, will be collected in both cases and controls. For each of the potential risk factors, ORs will be calculated to quantify the strength of their association with RH. In a multivariate analysis, conditional logistic regression will be used to assess the independent association between HIV and RH as well as the influence of the other potential drivers of RH.

Ethics and dissemination

This protocol has been approved by the College of Medicine Research Ethics Committee (COMREC) in Malawi (P.05/22/3637). Findings from this study will be disseminated through a peer-reviewed publication in an open-access international journal. Furthermore, anonymised data will be available on request from the authors.
School performances in children with cataract: results from a population-based cohort study
Authors: Al-Bakri Moug , Skovgaard Anne Mette , Bach-Holm Daniella , Larsen Dorte Ancher , Siersma Volkert , Kessel Line
Published: August 2023

Objectives

Childhood cataract is a chronic condition that may interfere with the child’s learning capacities. We aimed to investigate whether childhood cataract influences academic development by comparing school performance in reading and mathematics in children with cataract to a matched control group.

Design

Nationwide registry-based cohort study.

Settings

Two surgical centres that perform all treatments for childhood cataract in Denmark.

Participants

Children born between 2000 and 2009 diagnosed with cataract before 10 years of age (n=275) and an age-matched and sex-matched control group (n=2473).

Main outcome measures

School performance was assessed as test scores in national tests performed at regular intervals from grade 2 to grade 8 in reading and mathematics. Analyses were corrected for birth origin, child somatic and mental disorder and parental socioeconomic status and mental disorders.

Results

Of 275 children, 85 (30.9%) were operated for bilateral cataract, 79 (28.7%) unilateral cataract and 111 (40,4%) were not operated. We found that children with cataract have lower participation rate in the tests (62.5%) compared with the control cohort (77.2%) (p value=0.0001). After adjusting the pooled analyses for birth origin, somatic and mental disease in the child and parental socioeconomic status and mental disorders, we found that the children with cataract scored significantly lower in mathematics compared with those without cataract (mean difference=−4.78, 95% CI: −8.18 to −1.38, p value=0.006), whereas no difference was found regarding scores in reading (p=0.576). The lower score in mathematics was driven by children who had been operated for bilateral cataract (p-value=0.004).

Conclusion

Children with cataract without somatic or neurodevelopmental comorbidities or psychosocial adversities seem to do well in school, whereas children operated for bilateral cataract have higher frequencies of difficulties in mathematical tasks.
Improving outpatient clinic experience: the future of chronic kidney disease care and associated multimorbidity
Authors: Al-Chalabi Saif , Alderson Helen , Garratt Natalie , Green Darren , Kalra Philip A , Ritchie James , Santhirasekaran Schanhave , Poulikakos Dimitrios , Sinha Smeeta
Published: August 2023

Background

Chronic kidney disease (CKD) is estimated to affect more than 2.5 million adults in England, and this is expected to rise to 4.2 million by 2036 (1). Population-level digital healthcare systems have the potential to enable earlier detection of CKD providing an opportunity to introduce interventions that attenuate progression and reduce the risk of end-stage kidney disease (ESKD) and cardiovascular diseases (CVD). Services that can support patients with CKD, CVD, and diabetes mellitus (DM) have the potential to reduce fragmented clinical care and optimise pharmaceutical management.

Methods and results

The Salford renal service has established an outpatient improvement programme which aims to address these issues via two projects. Firstly, the development of a CKD dashboard that can stratify patients by their kidney failure risk equation (KFRE) risk. High-risk patients would be invited to attend an outpatient clinic if appropriate. Specialist advice and guidance would be offered to primary care providers looking after patients with medium risk. Patients with lower risk would continue with standard care via their primary care provider unless there was another indication for a nephrology referral. The CKD dashboard identified 11546 patients (4.4% of the total adult population in Salford) with T2DM and CKD. The second project is the establishment of the Metabolic CardioRenal (MRC) clinic. It provided care for 209 patients in the first 8 months of its establishment with a total of 450 patient visits. Initial analysis showed clustering of cardiorenal metabolic diseases with 85% having CKD stages 3 and 4 and 73.2% having DM. In addition, patients had a significant burden of CVD with 50.2% having hypertension and 47.8% having heart failure.

Conclusion

There is a pressing need to create new outpatient models of care to tackle the rising epidemic of cardio-renal metabolic diseases. This model of service has potential benefits at both organisational and patient levels including improving patient management via risk stratification, increased care capacity and reduction of variation of care. Patients will benefit from earlier intervention, appropriate referral for care, reduction in CKD-related complications, and reduction in hospital visits and cardiovascular events. In addition, this combined digital and patient-facing model of care will allow rapid translation of advances in cardio-renal metabolic diseases into clinical practice.
Cost analysis of archives in the pathology laboratories: from safety to management
Authors: Eccher Albino , Dei Tos Angelo Paolo , Scarpa Aldo , L'Imperio Vincenzo , Munari Enrico , Troncone Giancarlo , Naccarato Antonio Giuseppe , Seminati Davide , Pagni Fabio
Published: August 2023

Context

Despite the reluctance to invest and the challenging estimation of necessary supporting costs, optimising the archives seems to be one of the hottest topics in the future management of the pathology laboratories. Historically, archives were only partially designed to securely store and organise tissue specimens, and tracking systems were often flawed, posing significant risks to patients’ health and legal ramifications for pathologists.

Objective

The current review explores the available data from the literature on archives’ management in pathology, including comprehensive business plans, structure setup, outfit, inventories, ongoing conservation and functional charges.

Data sources

Electronic searches in PubMed-MEDLINE and Embase were made to extract pertinent articles from the literature. Works about the archiving process and storage were included and analysed to extract information. Prepublication servers were ignored. Italian Institutional Regional databases for public competitive bidding processes were queried too.

Conclusions

A new emergent feeling in the pathology laboratory is growing for archives management; the digital pathology era is a great opportunity to apply innovation to tracking systems and samples preservation. The main aim is a critical evaluation of the return of investment in developing automatic and tracked archiving processes for improving not only quality, efficacy and efficiency of the labs but also patients’ healthcare.
Carotid blowout into the trachea: unusual entity with unexpected management outcome
Authors: Awad Ahmed , Pal Koustav , Maniakas Anastasios , Zafereo Mark , Grosu Horiana , Cabanillas Maria , Chen Stephen R
Published: August 2023

We present a case report of a patient with a history of aggressive thyroid cancer managed by surgery, chemotherapy, and radiation to the neck. A year later, he presented with hemoptysis. Endobronchial ultrasound showed a pulsatile vessel; however, a CT scan and conventional angiogram were negative. Three days later, a repeat angiogram revealed a pseudoaneurysm arising from the right common carotid artery. Carotid sacrifice was performed after passing balloon test occlusion. Three years later the patient presented with coil herniation into the trachea. The carotid stump was closed with a vascular plug to prevent rebleeding from coil removal. Four months later the patient experienced an intractable cough and underwent laryngoscopy-assisted removal of the residual coil mass. This case report discusses the rare scenario of a carotid blowout into the trachea and the subsequent course of events.
Lyme neuroborreliosis presenting with urinary retention and spastic paraparesis
Authors: Iversen Lars , Boesen Magnus Spangsberg , Zibrandtsen Ivan Chrilles
Published: August 2023

Progressive myelopathy, urinary retention and gait problems are rare presenting features of Lyme neuroborreliosis. A 30-year-old man had 11 months of urinary retention and 3 months of spastic paraparesis. MR scans of the brain and the spinal cord showed leptomeningeal thickening with contrast enhancement. Cerebrospinal fluid showed mononuclear pleocytosis, decreased glucose, increased protein and chemokine ligand 13, with intrathecalBorrelia-specific IgM and IgG antibodies. He received 14 days of intravenous ceftriaxone followed by 14 days of oral doxycycline. Despite improvement at 6 months, he still had severe gait problems. Urinary retention in otherwise healthy people needs investigation, and Lyme neuroborreliosis is a rare cause.
Leflunomide/hydroxychloroquine combination therapy targets type I IFN-associated proteins in patients with Sjögren’s syndrome that show potential to predict and monitor clinical response
Authors: Hamkour Safae , van der Heijden Eefje HM , Lopes Ana P , Blokland Sofie L M , Bekker Cornelis P J , Van Helden-Meeuwsen Cornelia G , Versnel Marjan A , Kruize Aike A , Radstake Timothy RDJ , Leavis Helen L , Hillen Maarten R , van Roon Joel AG
Published: August 2023

Objectives

To assess to what extent leflunomide (LEF) and hydroxychloroquine (HCQ) therapy in patients with primary Sjögren’s syndrome (RepurpSS-I) targets type I IFN-associated responses and to study the potential of several interferon associated RNA-based and protein-based biomarkers to predict and monitor treatment.

Methods

In 21 patients treated with LEF/HCQ and 8 patients treated with placebo, blood was drawn at baseline, 8, 16 and 24 weeks. IFN-signatures based on RNA expression of five IFN-associated genes were quantified in circulating mononuclear cells and in whole blood. MxA protein levels were measured in whole blood, and protein levels of CXCL10 and Galectin-9 were quantified in serum. Differences between responders and non-responders were assessed and receiver operating characteristic analysis was used to determine the capacity of baseline expression and early changes (after 8 weeks of treatment) in biomarkers to predict treatment response at the clinical endpoint.

Results

IFN-signatures in peripheral blood mononuclear cell and whole blood decreased after 24 weeks of LEF/HCQ treatment, however, changes in IFN signatures only poorly correlated with changes in disease activity. In contrast to baseline IFN signatures, baseline protein concentrations of galectin-9 and decreases in circulating MxA and Galectin-9 were robustly associated with clinical response. Early changes in serum Galectin-9 best predicted clinical response at 24 weeks (area under the curve 0.90).

Conclusions

LEF/HCQ combination therapy targets type-I IFN-associated proteins that are associated with strongly decreased B cell hyperactivity and disease activity. IFN-associated Galectin-9 is a promising biomarker for treatment prediction and monitoring in pSS patients treated with LEF/HCQ.
To treat or not to treat? Current attitudes on treatment aimed at modifying the disease burden in clinically suspect arthralgia: a survey among participants of the TREAT EARLIER trial and healthcare professionals
Authors: Krijbolder Doortje I , Khidir Sarah J H , van der Helm-van Mil Annette HM
Published: August 2023

Objectives

While awaiting therapies accomplishing rheumatoid arthritis (RA)-prevention in individuals at-risk, recent evidence supports that a 1-year methotrexate treatment may lead to sustained reduction in disease burden and subclinical joint inflammation in patients with clinically suspect arthralgia (CSA). We aimed to study the previously unexplored attitudes of CSA patients and rheumatologists on 1-year DMARD treatment in the arthralgia phase to reduce the disease burden, while not preventing RA.

Methods

CSA patients who participated in the TREAT EARLIER trial, thus being expert by experience, were informed on the trial results. Thereafter they completed an anonymous questionnaire about their attitudes on treatment in the CSA phase. We used the same approach for Dutch healthcare professionals in rheumatology.

Results

The majority of trial participants (85%) considered the effects of the 1-year treatment as found in the TREAT EARLIER trial, beneficial in the symptomatic at-risk stage. 79% would recommend a 1-year methotrexate course to others with comparable joint complaints. Two-thirds indicated RA prevention and improving disease burden to be equally important treatment goals in the CSA phase. Most healthcare professionals (88%) were inclined to prescribe 1-year treatment to CSA patients aimed at long-term improvement of symptoms and functioning, while not preventing RA development. 59% believed the profits of a 1-year methotrexate course to outweigh disadvantages, for example, side effects.

Conclusions

A considerable willingness exists among CSA patients and rheumatologists to start a 1-year treatment resulting in long-term improvement of symptoms and functioning, while not preventing RA. This emphasises the need for more research optimising treatment regimens and disease monitoring in individuals at-risk to facilitate such treatment decisions in the future, while avoiding an intervention, either limited or for a prolonged period, which may have harms that outweigh benefits.

Trial registration number

The Netherlands Trials Registry (NTR4853-trial-NL4599). EudraCT number: NL2014-004472-35.