bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation fidelity to HIV assisted partner services (aPS) during scale-up in western Kenya: a convergent mixed methods study
Authors: Wamuti Beatrice , Owuor Mercy , Liu Wenjia , Katz David , Lagat Harison , Otieno George , Kariithi Edward , Macharia Paul , Masyuko Sarah , Mugambi Mary , Farquhar Carey , Weiner Bryan
Published: May 2023

Background

HIV assisted partner services (aPS) is an intervention to improve HIV status awareness among sex and drug-injecting partners of people newly diagnosed with HIV (index clients). Implementation fidelity—the degree to which an intervention is conducted as intended – is critical to effectiveness, but there are limited data about aPS fidelity when delivered by HIV testing service (HTS) providers. We explored factors affecting implementation fidelity to aPS in two high-HIV prevalence counties in western Kenya.

Methods

We used convergent mixed methods adapting the conceptual framework for implementation fidelity within the aPS scale-up project. This was an implementation study examining scale-up of APS within HTS programs in Kisumu and Homa Bay counties that recruited male sex partners (MSPs) of female index clients. We defined implementation fidelity as the extent to which HTS providers followed the protocol for phone and in-person participant tracing at six expected tracing attempts. Quantitative data were collected from tracing reports in 31 facilities between November 2018 and December 2020, and in-depth interviews (IDIs) were conducted with HTS providers. Descriptive statistics were used to describe tracing attempts. IDIs were analyzed using thematic content analysis.

Results

Overall, 3017 MSPs were mentioned of whom 98% (2969/3017) were traced, with most tracing attempts being successful (2831/2969, 95%). Fourteen HTS providers participated in the IDIs—mostly females (10/14, 71%) with a median age of 35 years (range 25–52), who all had post-secondary education (14/14, 100%). The proportion of tracing attempts occurring by phone ranged from 47 to 66%, with the highest proportion occurring on the first attempt and lowest on the sixth attempt. Contextual factors either enhanced or impeded implementation fidelity to aPS. Positive provider attitudes towards aPS and conducive work environment factors promoted implementation fidelity, while negative MSP responses and challenging tracing conditions impeded it.

Conclusion

Interactions at the individual (provider), interpersonal (client—provider), and health systems (facility) levels affected implementation fidelity to aPS. As policymakers prioritize strategies to reduce new HIV infections, our findings highlight the importance of conducting fidelity assessments to better anticipate and mitigate the impact of contextual factors during the scale-up of interventions.
Assessment of precision in growth inhibition assay (GIA) using human anti-PfRH5 antibodies
Authors: Miura Kazutoyo , Diouf Ababacar , Fay Michael P. , Barrett Jordan R. , Payne Ruth O. , Olotu Ally I. , Minassian Angela M. , Silk Sarah E. , Draper Simon J. , Long Carole A.
Published: May 2023

Background

For blood-stage malaria vaccine development, the in vitro growth inhibition assay (GIA) has been widely used to evaluate functionality of vaccine-induced antibodies (Ab), andPlasmodium falciparumreticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage antigen. However, precision, also called “error of assay (EoA)”, in GIA readouts and the source of EoA has not been evaluated systematically.

Methods

In the Main GIA experiment, 4 different cultures ofP. falciparum3D7 parasites were prepared with red blood cells (RBC) collected from 4 different donors. For each culture, 7 different anti-RH5 Ab (either monoclonal or polyclonal Ab) were tested by GIA at two concentrations on three different days (168 data points). To evaluate sources of EoA in % inhibition in GIA (%GIA), a linear model fit was conducted including donor (source of RBC) and day of GIA as independent variables. In addition, 180 human anti-RH5 polyclonal Ab were tested in a Clinical GIA experiment, where each Ab was tested at multiple concentrations in at least 3 independent GIAs using different RBCs (5,093 data points). The standard deviation (sd) in %GIA and in GIA50(Ab concentration that gave 50%GIA) readouts, and impact of repeat assays on 95% confidence interval (95%CI) of these readouts was estimated.

Results

The Main GIA experiment revealed that the RBC donor effect was much larger than the day effect, and an obvious donor effect was also observed in the Clinical GIA experiment. Both %GIA and log-transformed GIA50data reasonably fit a constant sd model, and sd of %GIA and log-transformed GIA50measurements were calculated as 7.54 and 0.206, respectively. Taking the average of three repeat assays (using three different RBCs) reduces the 95%CI width in %GIA or in GIA50measurements by ~ half compared to a single assay.

Conclusions

The RBC donor effect (donor-to-donor variance on the same day) in GIA was much bigger than the day effect (day-to-day variance using the same donor’s RBC) at least for the RH5 Ab evaluated in this study; thus, future GIA studies should consider the donor effect. In addition, the 95%CI for %GIA and GIA50shown here help when comparing GIA results from different samples/groups/studies; therefore, this study supports future malaria blood-stage vaccine development.
Healthy Nordic diet and associations with plasma concentrations of metabolites in the choline oxidation pathway: a cross-sectional study from Northern Sweden
Authors: Hesselink André , Winkvist Anna , Lindahl Bernt , Ueland Per M. , Schneede Jörn , Johansson Ingegerd , Karlsson Therese
Published: May 2023

Background

The choline oxidation pathway and metabolites involved have been linked to diseases including cardiovascular disease, type 2 diabetes and cancer. A healthy Nordic diet is a recently defined dietary pattern associated with decreased risk for these diseases. Our aim was to explore associations between adherence to a healthy Nordic diet and plasma concentrations of metabolites of the choline oxidation pathway.

Methods

The Healthy Nordic Food Index (HNFI) and Baltic Sea Diet Score (BSDS) were applied to cross-sectional data (n = 969) from the Västerbotten Intervention Programme in Northern Sweden to score adherence to a healthy Nordic diet. Data included responses to a dietary questionnaire and blood sample analyses (1991–2008). Associations of diet scores with plasma concentrations of metabolites of the choline oxidation pathway and total homocysteine (tHcy), seven metabolites in total, were evaluated with linear regression, adjusting for age, BMI, education and physical activity.

Results

HNFI scores showed linear relationships with plasma choline (β = 0.11), betaine (β = 0.46), serine (β = 0.98) and tHcy (β =  − 0.38), and BSDS scores with betaine (β = 0.13) and tHcy (β =  − 0.13); unstandardized beta coefficients, all significant at P < 0.05. The regression models predicted changes in plasma metabolite concentrations (± 1 SD changes in diet score) in the range of 1–5% for choline, betaine, serine and tHcy. No other statistically significant associations were observed.

Conclusions

A healthy Nordic diet was associated with plasma concentrations of several metabolites of the choline oxidation pathway. Although relationships were statistically significant, effect sizes were moderate. Further research is warranted to explore the underlying mechanisms and associations with health outcomes.
Ocular images-based artificial intelligence on systemic diseases
Authors: Tan Yuhe , Sun Xufang
Published: May 2023

Purpose

To provide a summary of the research advances on ocular images-based artificial intelligence on systemic diseases.

Methods

Narrative literature review.

Results

Ocular images-based artificial intelligence has been used in a variety of systemic diseases, including endocrine, cardiovascular, neurological, renal, autoimmune, and hematological diseases, and many others. However, the studies are still at an early stage. The majority of studies have used AI only for diseases diagnosis, and the specific mechanisms linking systemic diseases to ocular images are still unclear. In addition, there are many limitations to the research, such as the number of images, the interpretability of artificial intelligence, rare diseases, and ethical and legal issues.

Conclusion

While ocular images-based artificial intelligence is widely used, the relationship between the eye and the whole body should be more clearly elucidated.
Characterization of blaAFM-1-positive carbapenem-resistant strains isolated in Guangzhou, China
Authors: Qin Yingcheng , Peng Yuan , Duan Xiaonv , Song Zhenli , Huang Rong , Rui Yongyu
Published: May 2023

Background

Carbapenemase-producing makes a great contribution to carbapenem resistance in Gram-negative bacilli. BlaAFM-1 gene was first discovered by us in Alcaligenes faecalis AN70 strain isolated in Guangzhou of China and, was submitted to NCBI on 16 November 2018.

Methods

Antimicrobial susceptibility testing was performed by broth microdilution assay using BD Phoenix 100. The phylogenetic tree of AFM and other B1 metallo-β-lactamases was visualized by MEGA7.0. Whole-genome sequencing technology was used to sequence carbapenem-resistant strains including the blaAFM-1 gene. Cloning and expressing of blaAFM-1 were designed to verify the function of AFM-1 to hydrolyze carbapenems and common β-lactamase substrates. Carba NP and Etest experiments were conducted to evaluate the activity of carbapenemase. Homology modeling was applied to predict the spatial structure of AFM-1. A conjugation assay was performed to test the ability of horizontal transfer of AFM-1 enzyme. The genetic context of blaAFM-1 was performed by Blast alignment.

Results

Alcaligenes faecalis strain AN70, Comamonas testosteroni strain NFYY023, Bordetella trematum strain E202, and Stenotrophomonas maltophilia strain NCTC10498 were identified as carrying the blaAFM-1 gene. All of these four strains were carbapenem-resistant strains. Phylogenetic analysis revealed that AFM-1 shares little nucleotide and amino acid identity with other class B carbapenemases (the highest identity (86%) with NDM-1 at the amino acid sequence level). The spatial structure of the AFM-1 enzyme was predicted to be αβ/βα sandwich structure, with two zinc atoms at its active site structure. Cloning and expressing of blaAFM-1 verified AFM-1 could hydrolyze carbapenems and common β-lactamase substrates. Carba NP test presented that the AFM-1 enzyme possesses carbapenemase activity. The successful transfer of pAN70-1(plasmid of AN70) to E.coli J53 suggested that the blaAFM-1 gene could be disseminated by the plasmid. The genetic context of blaAFM indicated that the downstream of the blaAFM gene was always adjacent to trpF and bleMBL. Comparative genome analysis revealed that blaAFM appeared to have been mobilized by an ISCR27-related mediated event.

Conclusions

The blaAFM-1 gene is derived from chromosome and plasmid, and the blaAFM-1 gene derived from the pAN70-1 plasmid can transfer carbapenem resistance to susceptible strains through horizontal transfer. Several blaAFM-1-positive species have been isolated from feces in Guangzhou, China.
Long-term exposure and health risk assessment from air pollution: impact of regional scale mobility
Authors: Gilardi Lorenza , Marconcini Mattia , Metz-Marconcini Annekatrin , Esch Thomas , Erbertseder Thilo
Published: May 2023

Background

The negative effect of air pollution on human health is widely reported in recent literature. It typically involves urbanized areas where the population is concentrated and where most primary air pollutants are produced. A comprehensive health risk assessment is therefore of strategic importance for health authorities.

Methods

In this study we propose a methodology to perform an indirect and retrospective health risk assessment of all-cause mortality associated with long-term exposure to particulate matter less than 2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3) in a typical Monday to Friday working week. A combination of satellite-based settlement data, model-based air pollution data, land use, demographics and regional scale mobility, allowed to examine the effect of population mobility and pollutants daily variations on the health risk. A Health Risk Increase (HRI) metric was derived on the basis of three components: hazard, exposure and vulnerability, utilizing the relative risk values from the World Health Organization. An additional metric, the Health Burden (HB) was formulated, which accounts for the total number of people exposed to a certain risk level.

Results

The effect of regional mobility patterns on the HRI metric was assessed, resulting in an increased HRI associated with all three stressors when considering a dynamic population compared to a static one. The effect of diurnal variation of pollutants was only observed for NO2 and O3. For both, the HRI metric resulted in significantly higher values during night. Concerning the HB parameter, we identified the commuting flows of the population as the main driver in the resulting metric.

Conclusions

This indirect exposure assessment methodology provides tools to support policy makers and health authorities in planning intervention and mitigation measures. The study was carried out in Lombardy, Italy, one of the most polluted regions in Europe, but the incorporation of satellite data makes our approach valuable for studying global health.
Detoxified synthetic bacterial membrane vesicles as a vaccine platform against bacteria and SARS-CoV-2
Authors: Park Kyong-Su , Svennerholm Kristina , Crescitelli Rossella , Lässer Cecilia , Gribonika Inta , Andersson Mickael , Boström Jonas , Alalam Hanna , Harandi Ali M , Farewell Anne , Lötvall Jan
Published: May 2023

The development of vaccines based on outer membrane vesicles (OMV) that naturally bud off from bacteria is an evolving field in infectious diseases. However, the inherent inflammatory nature of OMV limits their use as human vaccines. This study employed an engineered vesicle technology to develop synthetic bacterial vesicles (SyBV) that activate the immune system without the severe immunotoxicity of OMV. SyBV were generated from bacterial membranes through treatment with detergent and ionic stress. SyBV induced less inflammatory responses in macrophages and in mice compared to natural OMV. Immunization with SyBV or OMV induced comparable antigen-specific adaptive immunity. Specifically, immunization with Pseudomonas aeruginosa-derived SyBV protected mice against bacterial challenge, and this was accompanied by significant reduction in lung cell infiltration and inflammatory cytokines. Further, immunization with Escherichia coli-derived SyBV protected mice against E. coli sepsis, comparable to OMV-immunized group. The protective activity of SyBV was driven by the stimulation of B-cell and T-cell immunity. Also, SyBV were engineered to display the SARS-CoV-2 S1 protein on their surface, and these vesicles induced specific S1 protein antibody and T-cell responses. Collectively, these results demonstrate that SyBV may be a safe and efficient vaccine platform for the prevention of bacterial and viral infections.
Is there any role of staging laparoscopy in pancreatic adenocarcinoma?
Authors: Soni Theresa , Singh Jaiveer , Nagarajan Bharath , Velmurugan Priyadarshini , Sundaramurthi Sudharsanan
Published: May 2023

This is a letter to the editor on a study by Jambor et al. on the role of staging laparoscopy in identifying occult and distant metastases in pancreatic adenocarcinoma patients. In this study, inclusion of staging laparoscopy as an adjunct to computed tomography resulted in an absolute risk reduction of 12.5% for non-therapeutic laparotomy. The study found no correlation between the presence of occult and distant metastases, and serum CA 19-9 level, tumour size or location, which was in significant contrast to a number of other studies. This was likely due to the smaller sample size of the study and restriction to a single high-volume referral centre. It is also noted that staging laparoscopy cannot detect vascular invasion, lymph node involvement and deep hepatic metastases. The sensitivity of peritoneal lavage cytology in detecting occult metastases is low as well. Inclusion of biomarkers like peritoneal lavage tumour DNA may improve sensitivity. Hence, even as this study adds to the evidence supporting staging laparoscopy, further studies on improving the sensitivity of staging laparoscopy are warranted.
The methods for removal of direct oral anticoagulants and heparins to improve the monitoring of hemostasis: a narrative literature review
Authors: Frackiewicz Aleksandra , Kalaska Bartlomiej , Miklosz Joanna , Mogielnicki Andrzej
Published: May 2023

The assessment of hemostasis is necessary to make suitable decisions on the management of patients with thrombotic disorders. In some clinical situations, for example, during thrombophilia screening, the presence of anticoagulants in sample makes diagnosis impossible. Various elimination methods may overcome anticoagulant interference. DOAC-Stop, DOAC-Remove and DOAC Filter are available methods to remove direct oral anticoagulants in diagnostic tests, although there are still reports on their incomplete efficacy in several assays. The new antidotes for direct oral anticoagulants – idarucizumab and andexanet alfa – could be potentially useful, but have their drawbacks. The necessity to remove heparins is also arising as heparin contamination from central venous catheter or therapy with heparin disturbs the appropriate hemostasis assessment. Heparinase and polybrene are already present in commercial reagents but a fully-effective neutralizer is still a challenge for researchers, thus promising candidates remain in the research phase.
Pyroptosis, ferroptosis, and autophagy cross-talk in glioblastoma opens up new avenues for glioblastoma treatment
Authors: Wan Sicheng , Zhang Guanghui , Liu Ruochen , Abbas Muhammad Nadeem , Cui Hongjuan
Published: May 2023

Glioma is a common primary tumor of the central nervous system (CNS), with glioblastoma multiforme (GBM) being the most malignant, aggressive, and drug resistant. Most drugs are designed to induce cancer cell death, either directly or indirectly, but malignant tumor cells can always evade death and continue to proliferate, resulting in a poor prognosis for patients. This reflects our limited understanding of the complex regulatory network that cancer cells utilize to avoid death. In addition to classical apoptosis, pyroptosis, ferroptosis, and autophagy are recognized as key cell death modalities that play significant roles in tumor progression. Various inducers or inhibitors have been discovered to target the related molecules in these pathways, and some of them have already been translated into clinical treatment. In this review, we summarized recent advances in the molecular mechanisms of inducing or inhibiting pyroptosis, ferroptosis, or autophagy in GBM, which are important for treatment or drug tolerance. We also discussed their links with apoptosis to better understand the mutual regulatory network among different cell death processes.
Characterization of the seed virome of alfalfa (Medicago sativa L)
Authors: Nemchinov Lev G. , Irish Brian M. , Grinstead Sam , Postnikova Olga A.
Published: May 2023

Background

Seed transmission of plant viruses can be important due to the role it plays in their dissemination to new areas and subsequent epidemics. Seed transmission largely depends on the ability of a virus to replicate in reproductive tissues and survive during the seed maturation process. It occurs through the infected embryo or mechanically through the contaminated seed coat. Alfalfa (Medicago sativa L.) is an important legume forage crop worldwide, and except for a few individual seedborne viruses infecting the crop, its seed virome is poorly known. The goal of this research was to perform initial seed screenings on alfalfa germplasm accessions maintained by the USDA ARS National Plant Germplasm System in order to identify pathogenic viruses and understand their potential for dissemination.

Methods

For the detection of viruses, we used high throughput sequencing combined with bioinformatic tools and reverse transcription-polymerase chain reactions.

Results

Our results suggest that, in addition to common viruses, alfalfa seeds are infected by other potentially pathogenic viral species that could be vertically transmitted to offspring.

Conclusions

To the best of our knowledge, this is the first study of the alfalfa seed virome carried out by HTS technology. This initial screening of alfalfa germplasm accessions maintained by the NPGS showed that the crop’s mature seeds contain a broad range of viruses, some of which were not previously considered to be seed-transmitted. The information gathered will be used to update germplasm distribution policies and to make decisions on the safety of distributing germplasm based on viral presence.
Headache following vaccination against COVID-19 among healthcare workers with a history of COVID-19 infection: a cross-sectional study in Iran with a meta-analytic review of the literature
Authors: Nasergivehchi Somayeh , Togha Mansoureh , Jafari Elham , Sheikhvatan Mehrdad , Shahamati Donya
Published: May 2023

Background

There is evidence of the occurrence of headache after vaccination against COVID-19. However, only a few studies have examined the headache characteristics and related determinants, especially among healthcare workers with a history of COVID-19 infection.

Methods

We evaluated the incidence of headaches after injection of different types of COVID-19 vaccine to determine factors relating to the incidence of headache after vaccination among the Iranian healthcare workers who had previously contracted COVID-19. A group of 334 healthcare workers with a history of COVID-19 infection were included and vaccinated (at least one month after recovery without any COVID-19 related symptoms) with different COVID-19 vaccines. The baseline information, headache characteristics and vaccine specifications were recorded.

Results

Overall, 39.2% reported experiencing a post-vaccination headache. Of those with a previous history of headache, 51.1% reported migraine-type, 27.4% tension-type and 21.5% other types. The mean time between vaccination and headache appearance was 26.78 ± 6.93 h, with the headache appearing less than 24 h after vaccination in most patients (83.2%). The headaches reached its peak within 8.62 ± 2.41 h. Most patients reported a compression-type headache. The prevalence of post-vaccination headaches was significantly different according to the type of vaccine used. The highest rates were reported for AstraZeneca, followed by Sputnik V. In regression analysis, the vaccine brand, female gender and initial COVID-19 severity were the main determinants for predicting post-vaccination headache.

Conclusion

Participants commonly experienced a headache following vaccination against COVID-19. Our study results indicated that this was slightly more common in females and in those with a history of severe COVID-19 infection.
Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcer healing: a systematic review and meta-analysis of randomized controlled trials
Authors: Deng Juan , Yang Mei , Zhang Xingyu , Zhang Hongmin
Published: May 2023

Background

The occurrence of a diabetic foot ulcer (DFU) is a significant complication of diabetes that often precedes the need for amputation. Autologous platelet-rich plasma (Au-PRP), a substance abundant in various growth factors and cytokines, is increasingly being recognized as a promising method for promoting ulcer healing due to its potential similarities to the physiological wound healing process.

Methods

The databases Medline, EMBASE, PubMed, and the Cochrane Library were systematically accessed on January 26, 2023, without any consideration for the date of publication. The selection and assessment of research studies were conducted autonomously, based on predetermined criteria and methodological standards. Two researchers gathered data and evaluated the potential for bias separately. We utilize the Stata 17.0 software to conduct data analysis and generate relevant visual representations.

Results

The results of the meta-analysis indicate that autologous PRP has a significant positive effect on the healing rate (RR = 1.42, 95% CI 1.30–1.56, P < 0.001), reduces the healing time (MD = − 3.13, 95% CI − 5.86 to − 0.39, P < 0.001), accelerates the reduction of ulcer area (MD = 1.02, 95% CI 0.51–1.53, P < 0.001), decreases the rate of amputation (RR = 0.35, 95% CI 0.15–0.83, P < 0.001), and does not increase the incidence of adverse events (RR = 0.96, 95% CI 0.57–1.61, P > 0.05) when compared to conventional therapy.

Conclusions

Au-PRP therapy has been shown to facilitate the process of wound healing and represents a viable and secure therapeutic alternative for individuals with DFU.
Quick Epidural Top-up with Alkalinized Lidocaine for emergent caesarean delivery (QETAL study): protocol for a randomized, controlled, bicentric trial
Authors: Lechat Thomas , d’Aprigny Thomas , Henriot Jérémy , Arthur Jill , Sylla Dienabou , Bénard Antoine , Nouette-Gaulain Karine
Published: May 2023

Background

General anesthesia in pregnant women can be associated with significant maternal and fetal morbidity. Emergency caesarean section can be performed by converting labor epidural analgesia to surgical anesthesia by injecting high-dose short-acting local anesthetics through the epidural catheter. The effectiveness and the delay to obtain surgical anesthesia depends upon the protocol used. Data indicate that alkalinization of local anesthetics may shorten their onset of action and increase their effectiveness. This study investigates whether alkalinization of adrenalized lidocaine could increase the efficacy and decrease the delay of onset of surgical anesthesia via an indwelling epidural catheter, thus decreasing the necessity to resort to general anesthesia for emergency caesarean deliveries.

Methods

This study will be a bicentric, double-blind, randomized, controlled trial with two parallel groups of 66 women who require emergency caesarian deliveries and who have been receiving epidural labor analgesia. The number of subjects in groups will be unbalanced with a 2:1 ratio of experimental:control. In both groups, all eligible patients will have had an epidural catheter placed for labor analgesia with levobupicaine or ropivacaine. Patient randomization will occur when the decision is made by the surgeon that an emergency caesarean delivery is indicated. Surgical anesthesia will be obtained by injecting 20 mL of 2% lidocaine with epinephrine 1:200,000, or 10 mL 2% lidocaine with epinephrine 1:200,000 plus 2 mL sodium bicarbonate 4.2% (total of 12 mL). The primary outcome will be the rate of conversion to general anesthesia for failure of the epidural to provide adequate analgesia. This study will be powered to detect a 50% reduction in the incidence of general anesthesia, from 80 to 40%, with a confidence ratio of 90%.

Discussion

Sodium bicarbonate could be used to avoid general anesthesia for emergency caesarean deliveries by providing reliable and effective surgical anesthesia in women with pre-existing labor epidural catheters is promising. This randomized controlled trial seeks to determine the optimal local anesthetic mixture for converting epidural analgesia to surgical anesthesia for emergency caesarean sections. This may decrease the need for general anesthesia for emergency caesarian section, shorten the time to fetal extraction, and improve safety and patient satisfaction.

Trial registration

ClinicalTrials.gov NCT05313256. Registered on 6 April 2022
Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure
Authors: de Bakker Marie , Petersen Teun B. , Akkerhuis K. Martijn , Harakalova Magdalena , Umans Victor A. , Germans Tjeerd , Caliskan Kadir , Katsikis Peter D. , van der Spek Peter J. , Suthahar Navin , de Boer Rudolf A. , Rizopoulos Dimitris , Asselbergs Folkert W. , Boersma Eric , Kardys Isabella
Published: May 2023

Background

Studies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.

Methods

In 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13–31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.

Results

In 104 women and 278 men (mean age 62 and 64 years, respectively) cumulative PEP incidence at 30 months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (Pinteraction < 0.001) and somatostatin (Pinteraction = 0.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p < 0.001) compared to women (1.14 [1.01, 1.29], p = 0.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p < 0.001), but inversely associated in women (0.33 [0.12, 0.93], p = 0.036).

Conclusion

Baseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.
The costs associated with stroke care continuum: a systematic review
Authors: Lucas-Noll Jorgina , Clua-Espuny José L. , Lleixà-Fortuño Mar , Gavaldà-Espelta Ester , Queralt-Tomas Lluïsa , Panisello-Tafalla Anna , Carles-Lavila Misericòrdia
Published: May 2023

Stroke, a leading cause of death and long-term disability, has a considerable social and economic impact. It is imperative to investigate stroke-related costs. The main goal was to conduct a systematic literature review on the described costs associated with stroke care continuum to better understand the evolution of the economic burden and logistic challenges. This research used a systematic review method. We performed a search in PubMed/MEDLINE, ClinicalTrial.gov, Cochrane Reviews, and Google Scholar confined to publications from January 2012 to December 2021. Prices were adjusted using consumer price indices of the countries in the studies in the years the costs were incurred to 2021 Euros using the World Bank and purchasing power parity exchange rate in 2020 from the Organization for Economic Co-operation and Development with the XE Currency Data API. The inclusion criteria were all types of publications, including prospective cost studies, retrospective cost studies, database analyses, mathematical models, surveys, and cost-of-illness (COI) studies. Were excluded studies that (a) were not about stroke, (b) were editorials and commentaries, (c) were irrelevant after screening the title and abstract,(d) grey literature and non-academic studies, (e) reported cost indicators outside the scope of the review, (f) economic evaluations (i.e., cost-effectiveness or cost–benefit analyses); and (g) studies not meeting the population inclusion criteria. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 724 potential abstracts were identified of which 25 articles were pulled for further investigation. The articles were classified into the following categories: 1)stroke primary prevention, 2) expenditures related to acute stroke care, 3) expenditures for post-acute strokes, and 4) global average stroke cost. The measured expenditures varied considerably among these studies with a global average cost from €610-€220,822.45. Given the great variability in the costs in different studies, we can conclude that we need to define a common system for assessing the costs of strokes. Possible limitations are related to clinical choices exposed to decision rules that trigger decisions alerts within stroke events in a clinical setting. This flowchart is based on the guidelines for acute ischemic stroke treatment but may not be applicable to all institutions.
Thermoluminescence and radiocarbon dating of pre-colonial ceramics and organic midden material from the US Virgin Islands: outline for a revised chronology
Authors: Torres Joshua , Toftgaard Casper Jacobsen , Delbey Thomas , Brewer David , Farchette John , de La Fuente Guillermo , Rasmussen Kaare Lund
Published: May 2023

A sample of 128 pottery shards curated by the National Museum of Denmark, from seven archaeological sites in the US Virgin Islands, has been dated using the thermoluminescence dating (TL) technique with the purpose of refining local pre-colonial pottery chronology. The results of the TL-dating generally confirm chronologies offered by Wild for St. John and there is considerable variation identified in traditional frameworks due to overlap in distributions of various pottery styles. The results of this study show that the Virgin Islands offer a viable space for the application of TL-dating, and that TL-dating offer a reliable addition to the traditional radiometric radiocarbon technique in pre-colonial midden contexts. Using the TL-technique for dating of pottery assemblages allows for a nuanced chronology and better understanding of settlement timing, socio-cultural interaction, and information transmission.

Graphical Abstract
Unified platform for storing, retrieving, and analysing biomechanical applications data using graph database
Authors: Hribernik Matevž , Tomažič Sašo , Umek Anton , Kos Anton
Published: May 2023

Sensors and smart equipment are frequently used in biomechanical systems and applications in sports and rehabilitation to measure various physical quantities. Various sensors, measuring different parameters, can produce a large amount of data at high speeds and volumes that must be stored for real-time or post-processing and analysis. In addition to sensor data, metadata is an important component and can vary between biomechanical applications. Currently however, each application typically has its own unique data flow and storage solution. In this research, we present a universal data model solution that can be applied to any sensor-based biomechanical application in sport and physical rehabilitation. Our proposed cloud platform architecture allows for the manipulation of sensor data and metadata using a combination of Big Data and conventional techniques. The main idea of this research is to develop a platform that allows a universal way for any biomechanical application to handle its data regardless of the type of data and metadata. This is achieved by creating a universal data model, and implementing this data model in a generalized architecture using a graph database. We demonstrate the benefits of this approach using examples from existing biomechanical systems and describe the development of the cloud platform architecture and the underlying data model. We also provide an example of the use of this platform in a sport shooting application. This approach is unique in that it allows data from different sources and applications to be stored and processed using the same procedures and techniques, facilitating data analysis and application development. We envision this system will expand to multiple different biomechanical applications in the future. We expect that in time, the ability to compare various data and store different biomechanical datasets will become necessity. With the advantages of modern recommender systems and utilization of artificial intelligence, huge amounts of relevant and well-prepared data with useful metadata are required thus having such system is an important advantage for future biomechanical systems development. With the increase of people’s awareness and usage of devices that increase well-being and quality of life, presented platform and similar systems will play a pivotal role in shaping the future lifestyle.
Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non–Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy
Authors: Shepherd Frances A. , Dancey Janet , Ramlau Rodryg , Mattson Karin , Gralla Richard , O’Rourke Mark , Levitan Nathan , Gressot Laurent , Vincent Mark , Burkes Ronald , Coughlin Susan , Kim Yong , Berille Jocelyne
Published: May 2023

PURPOSE

To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non–small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life.

PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non–small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m2 (49 patients) or 75 mg/m2 (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks.

RESULTS

One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was more significant for docetaxel 75 mg/m2 patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m2, three of whom died, and in one patient treated with docetaxel 75 mg/m2. Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups.

CONCLUSION

Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy outweigh the risks.
MLH1 Loss in Primary Prostate Cancer
Authors: Nourmohammadi Abadchi Sanaz , Sena Laura A. , Antonarakis Emmanuel S. , Pritchard Colin C. , Eshleman James R. , Konnick Eric Q. , Salipante Stephen J. , Shenderov Eugene , Lotan Tamara L.
Published: May 2023

PURPOSE

Among mismatch repair-deficient (MMRd) prostate cancers, loss of MLH1 is relatively uncommon and few cases have been reported in detail.

METHODS

Here, we describe the molecular features of two cases of primary prostate cancer with MLH1 loss detected by immunohistochemistry, and in one case, confirmed via transcriptomic profiling.

RESULTS

Both cases were microsatellite stable on standard polymerase chain reaction (PCR)–based microsatellite instability (MSI) testing, but showed evidence of MSI on a newer PCR-based long mononucleotide repeat (LMR) assay and by next-generation sequencing. Germline testing was negative for Lynch syndrome–associated mutations in both cases. Targeted or whole-exome tumor sequencing using multiple commercial/academic platforms (Foundation, Tempus, JHU, and UW-OncoPlex) showed modestly elevated, though variable, tumor mutation burden estimates (2.3-10 mutations/Mb) consistent with MMRd, but without identifiable pathogenic single-nucleotide or indel mutations in MLH1. Copy-number analysis confirmed biallelic MLH1 loss in one case and monoallelic MLH1 loss in the second case, without evidence of MLH1 promoter hypermethylation in either. The second patient was treated with single-agent pembrolizumab and demonstrated a short-lived prostate-specific antigen response.

CONCLUSION

These cases highlight the challenges in identifying MLH1-deficient prostate cancers using standard MSI testing and commercial sequencing panels, and support the utility of immunohistochemical assays and LMR- or sequencing-based MSI testing for detection of MMRd prostate cancers.
Marginal Geography: Pedagogical Design in Medieval Commentaries on Classical Poems
Authors: Gerber Amanda
Published: May 2023

This article explores the nature and significance of geographical diagrams in medieval commentaries on classical Roman poems. It situates these diagrams within larger conversations about cartographic traditions and the pedagogical contexts for which these diagrams were originally designed. Modern scholars have only begun to address these geographical diagrams in histories of cartography, but not in textual studies. In surveying a range of ninth- to fifteenth-century manuscripts especially of Lucan's poetry, the article uncovers the sources of geographical diagrams that recur in cartography, encyclopedias, and other pedagogical tools, illustrating how medieval academics developed paratexts to shape an extensive program of geographical explication. Geographical diagrams and other textual annotations accompanying classical poems established a distinct pedagogical strand of cartography that served medieval students’ training in Latin composition and understanding of the ancient world.
Scrollwork: Visual Cultures of Musical Notation and Graphic Materiality in the English Renaissance
Authors: Chan Eleanor
Published: May 2023

Early modern English musical notation bears a fleeting resemblance to that of its modern counterpart. This superficial similarity conceals the markedly different manner in which early music notation functioned and the clues that it offers for an older and more dynamic way of reading music. This form of notation was not a transcription for future performance but rather a provocation to performance. As a result, musical notation frequently “leaked” into decorative margins. The musical pages of this period display evident delight in melding, blending, and blurring the distinction between decorative and notational elements in an effort to forge musical meaning. This article explores how far the curled lines of musical notation and ornamentation can be thought of as visual prompts to think about music and its continuation beyond the space of the page, testament to an older, more playful understanding of how to read music.
Attending to the Passion in Early Modern England: Lancelot Andrewes's Good Friday Sermons
Authors: Ashmore Joseph
Published: May 2023

This article investigates writing about the Passion in late sixteenth- and early seventeenth-century England. It examines the sermons preached on Good Friday by Lancelot Andrewes (1555 – 1626). Like many Protestants, Andrewes hoped to minimize the idolatrous potential of the Passion. Rather than problematizing the sensuality of the Crucifixion, however, Andrewes's sermons cultivate an interpretive disposition that can read it correctly. Drawing on Bernardine and Augustinian models, he treats the attention of his listeners as a vital resource for negotiating the outward materiality of the Crucifixion: reading the Passion “with due attention” reveals through its carnality an eternal message of divine love and integrates it within a broader pattern of scriptural reading. Andrewes's openness to the roles of mental and ocular sight in worship commits him to explaining how outward surfaces reveal inner truths. His theorization of attention in these sermons sheds new light on post-Reformation readings of the Passion's iconography.
Visual environment of rearing sites affects larval response to perceived risk in poison frogs
Authors: Fouilloux Chloe A. , Stynoski Jennifer L. , Yovanovich Carola A. M. , Rojas Bibiana
Published: May 2023

Turbidity challenges the visual performance of aquatic animals. Here, we use the natural diversity of ephemeral rearing sites occupied by tadpoles of two poison frog species to explore the relationship between environments with limited visibility and individual response to perceived risk. To compare how species with diverse natural histories respond to risk after developing in a range of photic environments, we sampled wild tadpoles of (1) Dendrobates tinctorius, a rearing-site generalist with facultatively cannibalistic tadpoles and (2) Oophaga pumilio, a small-pool specialist dependent on maternal food-provisioning. Using experimental arenas, we measured tadpole activity and space use first on a black and white background, and then on either black or white backgrounds where tadpoles were exposed to potentially predatory visual stimuli. The effects of rearing environment on D. tinctorius tadpoles were clear: tadpoles from darker pools were less active than tadpoles from brighter pools and did not respond to the visual stimuli, whereas tadpoles from brighter pools swam more when paired with conspecifics versus predatory insect larvae, suggesting that tadpoles can visually discriminate between predators. For O. pumilio, tadpoles were more active on experimental backgrounds that more closely matched the luminosity of their rearing sites, but their responses to the two visual stimuli did not differ. Larval specialisation associated with species-specific microhabitats may underlie the observed responses to visual stimuli. Our findings demonstrate that light availability in wild larval rearing conditions influences risk perception in novel contexts, and provides insight into how visually guided animals may respond to sudden environmental disturbances.
Imaging of the septum pellucidum: normal, variants and pathology
Authors: Siala Selima , Homen Dean , Smith Benjamin , Guimaraes Carolina
Published: May 2023

The septum pellucidum is a largely neglected anatomical midline structure during post-natal neuroimaging interpretation. Conversely, it is one of the anatomical landmarks used on pre-natal ultrasound to access normal midline formation. Because of its importance during the pre-natal period, the awareness of its primary malformative abnormalities is much higher than its disruptive acquired pathologies, often leading the misinterpretation. In this article, we will review the normal septum pellucidum formation, anatomy, and anatomical variants and will describe the imaging findings in primary malformative and secondary disruptive abnormalities affecting the septum pellucidum.