bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of the Potato Virus Y Strain Composition Impacting Michigan Seed Potato Production
Authors: Satoh-Cruz Mio , Rhodes Stefanie , Kurzer Damen , Dorman Elizabeth , Willbur Jaime F.
Published: October 2024

Potato virus Y (PVY) is a complex of multiple strains that cause a variety of foliar and tuber symptoms. Several current strains have potential to result in variety-dependent yield and quality losses. Understanding the local PVY strain population and variety responses are critical for detection and management. From 2019 to 2023, PVY strain composition was monitored across seven Michigan seed potato-producing counties growing prevalent chip, russet, and tablestock market classes. Using multiplex reverse-transcriptase polymerase chain reaction (RT-PCR) methods, PVY strains were identified from potato tuber or leaf samples collected through the certification program ( n = 78 positive lots). PVYN-Wi remained most prevalent in Michigan, but tuber necrotic strains PVYNTN and PVYE also continued to be detected. These, as well as some PVYN-Wi isolates, are known to cause necrotic symptoms in tubers, causing yield and quality reductions for susceptible potato cultivars. As in other U.S. potato-growing regions, PVYN-Wi and PVYNTN were most prevalent in Michigan seed potato lots. Of note, mild to severe tuber necrosis was observed in diagnostic samples positive with local PVYN-Wi strains. Parental strain PVYO appeared to re-emerge in 2023 and should be considered in certification and management. Mild or asymptomatic reactions may still lead to yield or quality losses and may pose a risk to more susceptible cultivars. Due to the diversity of strains and varieties prevalent in the Great Lakes region, continued uniform certification is recommended. Information gathered from this and future survey efforts will be valuable for growers, inspectors, and future breeding and selection efforts.
Association of baseline neutrophil-to-lymphocyte ratio and prognosis in melanoma patients treated with PD-1/PD-L1 blockade: a systematic review and meta-analysis
Authors: Kreuz Michele , de Moraes Francisco Cezar Aquino , Sano Vitor Kendi Tsuchiya , Westphal Filho Fernando Luiz , Silva Ana Laura Soares , Kelly Francinny Alves
Published: October 2024

Immunotherapy treatments that target programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) have revolutionized the treatment of metastatic melanoma and currently represent the standard first-line treatment for this type of cancer. However, it is still not entirely clear which biomarkers are cost-effective, simple, and highly reliable. This systematic review and meta-analysis aims to analyze the predictive value of the baseline neutrophil-lymphocyte ratio (NLR) regarding disease progression and overall survival of patients with metastatic melanoma undergoing treatment with PD-1/PD-L1 blockade. PubMed, Scopus, and Web of Science were searched for studies comparing high versus low NLR. We performed the meta-analysis using RStudio v4.4.2 software. A total of 20 studies and 2691 patients were included, all with diagnoses of melanoma. The majority of the individuals were male 2278 (84, 65%). The median overall survival (OS) and progression-free survival (PFS) ranged from 5.0 to 44.4 and from 1.8 to 15.0 months, respectively. Compared with the high NLR ratio, the low exposure group achieved better rates of OS [hazard ratio (HR), 2.07; 95% CI, 1.73–2.48; P < 0.00001; I² = 47%]. Regarding PFS, there was a statistically significant difference between groups with tendencies toward the low NLR exposure group (HR, 1.59; 95% CI, 1.39–1.81; P < 0.00001; I²=31%]. This systematic review and meta-analysis revealed significant lower OS in melanoma patients treated with PD-1/PD-L1 blockade who had elevated baseline NLR values. Furthermore, an increased PFS was observed in patients with a lower baseline NLR value. This study highlights NLR as an important prognostic biomarker for patients with metastatic melanoma who are candidates for treatment with PD-1 and PD-L1.
Determination of positive end-expiratory pressure in COVID-19-related acute respiratory distress syndrome
Authors: Sachkova Alexandra , Andreas Marike , Heise Daniel , Golinski Martin , Stephani Caspar , Dickel Steffen , Grimm Clemens , Monsef Ina , Piechotta Vanessa , Skoetz Nicole , Laudi Sven , Moerer Onnen ,   CEOsys
Published: October 2024

BACKGROUND

The impact of high positive end-expiratory pressure (PEEP) ventilation and the optimization of PEEP titration in COVID-19-induced acute respiratory distress syndrome (ARDS) continues to be a subject of debate. In this systematic review, we investigated the effects of varying PEEP settings on patients with severe ARDS primarily resulting from COVID-19 (C-ARDS).

OBJECTIVES

Does higher or lower PEEP improve the outcomes in COVID-19 ARDS? Does individually titrated PEEP lead to better outcomes compared with PEEP set by standardised (low and high ARDS network PEEP tables) approaches? Does the individually set PEEP (best PEEP) differ from PEEP set according to the standardised approaches (low and high ARDS network PEEP tables)?

DESIGN

Systematic review of observational studies without metaanalysis.

DATA SOURCES

We performed an extensive systematic literature search in Cochrane COVID-19 Study Register (CCSR), PubMed, Embase.com, Web of Science Core Collection, World Health Organization COVID-19 Global literature on coronavirus disease, World Health Organization International Clinical Trials Registry Platform (ICTRP), medRxiv, Cochrane Central Register of Controlled Trials until 24/01/2024.

ELIGIBILITY CRITERIA

Ventilated adult patients (≧18 years) with C-ARDS.

RESULTS

We screened 16 026 records, evaluated 119 full texts, and included 12 studies (n = 1431 patients) in our final data synthesis, none of them being a randomised controlled trial. The heterogeneity of study procedures and populations did not allow conduction of a meta-analysis. The results of those studies that compared lower and higher PEEP strategies in C-ARDS were ambiguous pointing out either positive effects on oxygenation with high levels of PEEP, or negative changes in lung mechanics.

CONCLUSION

The available evidence does not provide sufficient guidance for recommendations on optimal PEEP settings in C-ARDS. In general, well designed platform studies are needed to answer the questions raised in this review and, in particular, to investigate the use of individualised PEEP titration techniques and the inclusion of patients with different ARDS entities, severities and disease stages.

TITLE REGISTRATION

Our systematic review protocol was registered with the international prospective register of systematic reviews (PROSPERO 2021: CRD42021260303).
RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Brosh Koby , Semionov Anastasia , Hanhart Joel , Goldberg Mordechai , Potter Michael J.
Published: October 2024

Purpose:

To report the characteristics of retinal detachment demarcation lines on infrared imaging together with retinal detachment progression analysis.

Methods:

We performed a retrospective case series of 25 eyes of 24 patients who underwent macula off rhegmatogenous retinal detachment (RRD) repair and demonstrated a postoperative demarcation line on in infrared imaging. All patients had an optical coherence tomography imaging at baseline capturing the extent of the RRD. Criteria for demarcation lines diagnosis on infrared imaging included a line parallel and with the same contour of the RRD edge. These lines were not observed on infrared imaging before RRD repair surgery.

Results:

Demarcation lines' hyperreflectivity was situated in the interdigitation-ellipsoid zone complex. These lines were more obvious on the early postoperative week but faded over time (average disappearance time 2.6 ± 2.9 months). The analysis of retinal detachment progression showed that superior RRDs progressed more than inferior RRDs (611 vs. 122 μ, P = 0.02). Among 13 cases with a superior RRD, the temporal border progressed more than the nasal side (697 vs. 426 μ, P = 0.01, Figure 1). The use of intraoperative perfluorocarbon was associated with less RRD progression (P = 0.01).

Conclusion:

The study concludes that demarcation lines are distinct findings on infrared imaging, appearing early but diminishing relatively quickly after RRD repair. It also revealed the characteristics of RRDs progression specifically that inferior RRDs and perfluorocarbon use were associated with less retinal progression.
Career Paths, Practice Location, and Scholarly Contributions of American Society of Ophthalmic Plastic and Reconstructive Surgery Fellowship Graduates, 2000–2021
Authors: Azzam Daniel B. , Meller Leo Li Tang , Oca Michael , Vagefi M. Reza , Tao Jeremiah P.
Published: October 2024

Purpose:

To characterize American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) fellowship graduates’ career paths and contributions to society missions, including trends across gender, time, and geography.

Methods:

In this retrospective cohort study, ASOPRS fellowship graduates from 2000 to 2021 were stratified by demographics, time, and geography. Main outcomes were career paths and contributions to ASOPRS missions of advancing education, research, and quality of clinical practice.

Results:

Among 474 ASOPRS graduates, women increased from 19% (2000–2005) to 47% (2016–2021). Women contributed equally to men in most ASOPRS missions but were underrepresented as fellowship directors (p = 0.03). Over time, graduates after 2005 had higher publication rates (adjusted p < 0.001). Geographically, Northeast fellows (adjusted p = 0.034) and Midwest employment (adjusted p = 0.003) correlated with academic careers, while West employment conferred community careers (adjusted p < 0.001). Geographic retention near fellowship directly correlated with academic careers (adjusted p = 0.006), educational roles (adjusted p < 0.001), and publications (adjusted p = 0.006). Forty-one percent practiced in the 5 most saturated states, with fewer in the Midwest. The attrition rate of United States ASOPRS fellows who left the national workforce was 2%.

Conclusions:

From 2000 to 2021, ASOPRS fellows entered diverse career paths with increasing gender parity, though women were underrepresented as fellowship directors. Career paths and contributions to the field varied geographically. Graduates frequently practice in saturated states, potentially exacerbating access disparities in underserved regions. These findings highlight opportunities to address geographic differences, promote workforce diversity, and align fellowships with society objectives.
A Longitudinal Analysis of Long Working Hours and the Onset of Psychological Distress
Authors: Ezekekwu Emmanuel , Johnson Christopher , Karimi Seyed , Lorenz Doug , Antimisiaris Demetra
Published: October 2024

Objectives

There is a paucity of longitudinal studies examining the relationship between working hours and the development of psychological distress (PD) among US workers. This study utilized a longitudinal approach to examine this relationship.

Methods

The 2010–2019 Medical Expenditure Panel Survey (MEPS) data was utilized. PD was analyzed among full-time US employees without PD at baseline using a fixed effect approach.

Results

The sample comprised 27,548 full-time workers. Individuals working 61 hours or more weekly had the highest risk of PD onset, at 9.9% (95% CI = 1.9%–17.8%, P < 0.05), compared to those working 30 to 35 hours weekly. Interestingly, an increased risk of PD onset was found among individuals working 36 to 40 hr/wk at 6.6% (CI = 1.5%–11.6%%, P < 0.05).

Conclusions

Long working hours were associated with the increased development of PD.
COVID-19 Vaccine Hesitancy and Uptake Among Firefighters
Authors: Hooker Stephanie A. , Ziegenfuss Jeanette Y. , Muegge Jule , Dinh Jennifer M. , Zabel Erik W. , Dabrowski Dominik , Nadeau Ashley M. , McKinney Zeke J.
Published: October 2024

Objective

The aim of this study was to assess COVID-19 vaccination prevalence and explore whether health beliefs were associated with vaccination among firefighters.

Methods

A cross-sectional online survey was distributed to Minnesota firefighters in March–April 2022. Survey questions included demographics, vaccination status, and beliefs about COVID-19 and vaccines.

Results

Of the survey respondents (n = 974, 91% male, 89% White), 76% were fully vaccinated and 53% were boosted. Firefighters were less likely to be vaccinated if they reported more perceived barriers (OR = 0.42, P < 0.001), greater decision-making ease (OR = 0.42, P < 0.001), and greater autonomy (OR = 0.65, P = 0.04). Greater perceived benefits (OR = 2.63, P < 0.001) and social norms (OR = 2.10, P < 0.001) were associated with a greater likelihood of being vaccinated. Similar results were seen predicting booster status.

Conclusions

Firefighters had similar vaccination rates as the general population, despite high exposure risks. Health beliefs are strongly related to vaccination status.
Flourine-18 Prostate-Specific Membrane Antigen-1007 Positron Emission Tomography Imaging in Staging of Primary and Secondary Prostate Cancer—A Retrospective Observational Cohort Study
Authors: Byrne Matthew H. V. , Ranasinha Nithesh , Sharma Abhishek , Mercader Claudia , Raslan Mutie , Sathanapally Ganesh , Lewis Francesca , Gorgoraptis Stefanos , Lopes Vieira Ana Catarina , Golebka Jedrzej , Peiris Bryony , Lopez J. Francisco , Leslie Tom , Bell Richard C. , Miah Saiful , Tuthill Mark , Protheroe Andrew , Camilleri Philip , Sabharwal Ami , Andrade Gerard , Hamdy Freddie C. , Macpherson Ruth , Gleeson Fergus , Bryant Richard J. , Lamb Alastair D.
Published: October 2024

Background:

Detection of metastatic disease is important to inform prostate cancer management.

Objectives:

Evaluate local and distant staging by initial 18F-PSMA-1007 PET in primary and secondary prostate cancer.

Design, Setting, and Participants:

We retrospectively identified a consecutive series of 18F-PSMA-1007 PET scans from the date of introduction of 18F-PSMA-1007 PET in September 2019 until April 2022 at a single UK tertiary referral center. Our protocol was registered in advance (OSF registration ID: KTE3R).

Results:

We identified 1335 PSMA-PET scans, from 1220 men. Across 623 initial scans for primary staging, we observed PSMA-PET avidity in 97.6% cases positive for local disease, 29.5% for nodal disease, and 26.5% for metastatic disease. PSMA-PET identified a 13.2% absolute increase in nodal lesions compared with MRI and a 24.0% absolute increase in metastatic lesions compared with MRI marrow. The sensitivity for detection of local disease among 79 patients who had radical prostatectomy was 96.2% for PSMA-PET vs 89.4% for multiparametric MRI. Across 612 scans for secondary staging, we observed PSMA-PET positive avidity in 51.2% of cases for local recurrence, 46.6% for nodal disease, and 43.0% for metastatic disease. When evaluated by the PSA range for patients receiving secondary staging, using the PSA values of 0.2 to 0.49, 0.5 to 0.99, 1 to 1.99, and ≥ 2 ng/mL, PSMA-PET scans were positive in 57.8%, 75.0%, 83.8%, and 95.5% of cases, respectively. PSMA-PET identified a 26.2% absolute increase in metastatic lesions compared with MRI marrow or other skeletal MRI (n = 61) and a 14.7% absolute increase in metastatic lesions compared with the bone scan (n = 42).

Conclusion:

18F-PSMA-1007 PET identifies a higher number of nodal and metastatic lesions compared with conventional cross-sectional imaging. However, the high number of indeterminate lesions and stage migration necessitates discussion of 18F-PSMA-1007 PET imaging within a multidisciplinary team and places a higher burden on these teams.
Pediatric Extracorporeal Membrane Oxygenation in Restrictive and Hypertrophic Cardiomyopathy: A Single Center Experience
Authors: Geisser Diana L. , Siegel Bryan D. , Kobayashi Ryan L. , VanderPluym Christina J. , Fynn-Thompson Francis , Thiagarajan Ravi R. , Moynihan Katie M.
Published: October 2024

Patients with restrictive cardiomyopathy (RCM) and hypertrophic cardiomyopathy (HCM) were previously considered poor candidates for mechanical circulatory support due to technical limitations related to restrictive ventricular physiology and small ventricular size, limiting the ability to provide adequate flows and decompress the heart. Literature examining use of extracorporeal membrane oxygenation (ECMO) in this population consists of a single case series reporting no survivors. We report our experience providing ECMO in children with RCM or HCM at a large pediatric quaternary cardiac center. Between 2012 and 2022, five patients (four RCM, one HCM) were supported with seven ECMO runs. All patients were cannulated to ECMO with ongoing cardiopulmonary resuscitation. Four patients survived decannulation from ECMO (median support time 209 hr, interquartile range [IQR]: 48–265), of which three (60%) survived to hospital discharge after transitioning to a ventricular assist device (VAD) and undergoing orthotopic heart transplant (OHT). Two remain alive at long-term follow-up with normal or mildly impaired functional status. These findings suggest that while RCM and HCM have traditionally been considered contraindications to ECMO due to adverse outcomes, this population may be successfully supported with ECMO with survival comparable to international registry outcomes in select centers where VAD as a bridge to OHT is available.
Gadopiclenol: A q = 2 Gadolinium-Based MRI Contrast Agent Combining High Stability and Efficacy
Authors: Maimouni Ilham , Henoumont Céline , De Goltstein Marie-Christine , Mayer Jean-François , Dehimi Anissa , Boubeguira Yamina , Kattenbeck Christina , Maas Torben J. , Decout Nathalie , Strzeminska Izabela , Bazin Gwénaëlle , Medina Christelle , Factor Cécile , Rousseaux Olivier , Karst Uwe , Laurent Sophie , Catoen Sarah
Published: October 2024

Objectives

Gadopiclenol is a q = 2 pyclen gadolinium-based contrast agent (GBCA) recently approved by the Food and Drug Administration, European Medicines Agency, and other European countries. The aim of this report is to demonstrate its stability in multiple stressed in vitro conditions and in vivo, in rat kidney, while maintaining its higher relaxivity compared with conventional GBCAs on the market.

Materials and Methods

Both gadopiclenol and its chemical precursor Pi828-Gd were characterized and compared with q = 1 gadolinium (Gd) complexes. The number of water molecules coordinated to the Gd (the hydration number, q) was determined by luminescence. 17O NMR (Nuclear Magnetic Resonance) measurements gave access to the water residence time τM. These parameters were used for the fitting of the nuclear magnetic relaxation dispersion profiles in water. Proton relaxivities of the complexes were determined in different media at 60 MHz (1.4 T), at different pH and temperature. The kinetic inertness was investigated in human serum, acidic media, under zinc competition in the presence of phosphate, and under ligand competition. The in vivo stability was evaluated in rat kidneys 12 months after repeated injections.

Results

The presence of 2 inner-sphere water molecules per Gd complex was confirmed for both pyclen derivatives. The high relaxivity of the complexes in water is maintained under physiological conditions, even under stressed conditions (ionic media, extreme pH, and temperature), which guarantees their efficiency in a large range of in vivo situations. Gd release from the q = 2 complexes was investigated in different potentially destabilizing conditions. Either no Gd release or a slower one than with “q = 1” stable macrocyclic GBCA (acidic conditions) was observed. Their kinetic inertness was demonstrated in physiological conditions, and the Gd release was below the lower limit of quantification of 0.1 μM after 12 days at 37°C in human serum. It was also demonstrated that gadopiclenol is stable in vivo in rat kidney 12 months after repeated injections.

Conclusions

Thanks to its optimized structural design, gadopiclenol is a highly stable and effective macrocyclic q = 2 GBCA.
Treatment of Late-onset Acute Graft-versus-host Disease Following Double Lung Transplantation Using a JAK2 Inhibitor
Authors: Alyamany Ruah , Alnughmush Ahmed , Albaiz Faisal , Aversa Meghan , Law Arjun
Published: October 2024

Acute graft-versus-host disease (aGVHD) is a rare but potentially life-threatening complication that can occur after solid organ transplantation, particularly in organs with abundant lymphoid tissue like the liver and intestines. While less common in lung transplants, the rising numbers of these procedures have brought more attention to aGVHD, usually appearing within the first 3-mo posttransplant. Given its relative rarity, a clear understanding of the pathophysiology, risk factors, diagnostic, and management strategies remain elusive. These knowledge gaps can lead to delays in diagnosis and the initiation of appropriate treatment leading to predictably inferior outcomes. Managing aGVHD following solid organ transplantation is challenging, and there is no standard approach. Current management involves high-dose steroids and other immunosuppressive drugs. However, these interventions are associated with serious complications, including potentially fatal infections, underscoring the urgent need for more research to refine both diagnostic methods and treatment approaches and ultimately improving patient outcomes. In this report, we aim to deepen our understanding of aGVHD following lung transplants and share our experience with a unique case of aGVHD occurring almost a year after lung transplantation that was successfully managed using ruxolitinib, describing a potential treatment approach modeled on the contemporary management of stem cell transplant associated aGVHD.
Cost-effectiveness of Dual Hypothermic Oxygenated Machine Perfusion Versus Static Cold Storage in DCD Liver Transplantation
Authors: Endo Chikako , van Rijn Rianne , Huurman Volkert , Schurink Ivo , van den Berg Aad , Murad Sarwa Darwish , van Hoek Bart , de Meijer Vincent E. , de Jonge Jeroen , van der Hilst Christian S. , Porte Robert J.
Published: October 2024

Background.

Ex situ machine perfusion of the donor liver, such as dual hypothermic oxygenated machine perfusion (DHOPE), is increasingly used in liver transplantation. Although DHOPE reduces ischemia/reperfusion-related complications after liver transplantation, data on cost-effectiveness are lacking. Our objective was to evaluate the cost-effectiveness of DHOPE in donation after circulatory death (DCD) liver transplantation.

Methods.

We performed an economic evaluation of DHOPE versus static cold storage (SCS) based on a multicenter randomized controlled trial in DCD liver transplantation (DHOPE-DCD trial; ClinicalTrials.gov number, NCT02584283). All patients enrolled in the 3 participating centers in the Netherlands were included. Costs related to the transplant procedure, hospital stay, readmissions, and outpatients treatments up to 1 y posttransplant were calculated. The cost for machine perfusion was calculated using 3 scenarios: (1) costs for machine perfusion, (2) machine perfusion costs plus costs for personnel, and (3) scenario 2 plus depreciation expenses for a dedicated organ perfusion room.

Results.

Of 119 patients, 60 received a liver after DHOPE and 59 received a liver after SCS alone. The mean total cost per patient up to 1 y posttransplant was €126 221 for the SCS group and €110 794 for the DHOPE group. The most significant reduction occurred in intensive care costs (28.4%), followed by nonsurgical interventions (24.3%). In cost scenario 1, DHOPE was cost-effective after 1 procedure. In scenarios 2 and 3, cost-effectiveness was achieved after 25 and 30 procedures per year, respectively.

Conclusions.

Compared with conventional SCS, machine perfusion using DHOPE is cost-effective in DCD liver transplantation, reducing the total medical costs up to 1 y posttransplant.
Robotic Repair of Ureteral Strictures After Kidney Transplantation
Authors: Sanz-Serra Pol , Etcheverry Begoña , Fiol Maria , Fábregas Maya , Lozano Víctor , Pérez-Reggeti José Ignacio , Buisan Óscar , Riera Lluís , Suárez José Francisco , Castells Manel , Vigués Francesc
Published: October 2024

Background.

Approximately 5% to 10% of patients who undergo kidney transplantation develop ureteral stricture, which can be treated endoscopically or by open surgery, which is more effective but complications are common and potentially severe. Robotic surgery has begun to emerge as an alternative in reconstructive procedures. However, few studies have evaluated the role of robotic surgery in this clinical setting. The aim of this study was to assess the efficacy and safety of robotic surgery in treating ureteral stricture after kidney transplantation.

Methods.

Single-center study of patients (n = 27), who developed ureteral stricture following kidney transplantation. All patients were treated from 2018 to 2023. We describe the patients’ baseline characteristics and clinical and surgical features. We determined the success rate as a measure of efficacy and complications to measure safety.

Results.

We perform 15 pyeloureterostomies to the native ureter and 12 ureteroneocystostomies. At a median follow-up of 15 mo, the success rate was 92.6%. Fourteen patients (52%) developed treatment-related complications, mainly grade II (Clavien-Dindo classification), except for one grade IVb complication. The median length of hospital stay was 3 d [interquartile range (2–6)].

Conclusions.

These data show that robotic surgery is a safe and effective procedure for the treatment of ureteral strictures after kidney transplantation. The success rate was high with a low complication rate. To our knowledge, this is the largest series to date to evaluate robotic surgery in this clinical setting.
Aggregation of adult parasitic nematodes in sex-mixed groups analysed by transient anomalous diffusion formalism
Authors: Leben Ruth , Rausch Sebastian , Elomaa Laura , Hauser Anja E. , Weinhart Marie , Fischer Sabine C. , Stark Holger , Hartmann Susanne , Niesner Raluca
Published: October 2024

Intestinal parasitic worms are widespread throughout the world, causing chronic infections in humans and animals. However, very little is known about the locomotion of the worms in the host gut. We studied the movement of
Heligmosomoides bakeri,
naturally infecting mice, and used as an animal model for roundworm infections. We investigated the locomotion of
H. bakeri
in simplified environments mimicking key physical features of the intestinal lumen, i.e. medium viscosity and intestinal villi topology. We found that the motion sequence of these nematodes is non-periodic, but the migration could be described by transient anomalous diffusion. Aggregation as a result of biased, enhanced-diffusive locomotion of nematodes in sex-mixed groups was detected. This locomotion is probably stimulated by mating and reproduction, while single nematodes move randomly (diffusive). Natural physical obstacles such as high mucus-like viscosity or villi topology slowed down but did not entirely prevent nematode aggregation. Additionally, the mean displacement rate of nematodes in sex-mixed groups of 3.0 × 10
−3
mm s
−1
in a mucus-like medium is in good agreement with estimates of migration velocities of 10
−4
to 10
−3
mm s
−1
in the gut. Our data indicate
H. bakeri
motion to be non-periodic and their migration random (diffusive-like), but triggerable by the presence of kin.
A systematic review to explore factors affecting participation in health research trials amongst underrepresented socio-economically disadvantaged populations in the UK and Ireland
Authors: Brandon Jakki , Bagnall Anne Marie
Published: October 2024

Background

Those with the greatest health inequalities and highest burden of poor-health have the lowest representation in health research. Meaning that diseases which are known to have higher prevalence in disadvantaged populations are being studied in healthier populations, so findings will be inappropriately applied to those that face the greatest challenges to their health. This systematic review is concerned with those defined as socioeconomic-deprived, gypsy/traveller/Roma communities, and homeless people.

Objectives

To understand the barriers or facilitators to research participation in specific underserved groups to inform how equality, diversity and inclusion in research trials can be improved.

Methods

A systematic review of etiology of quantitative and qualitative primary research conducted in the UK and Ireland in the previous 10 years, to produce a narrative synthesis of the themes identified.

Results

Key themes of barriers and facilitators were identified across the groups. All facilitators reported were common to all the groups. The value of peer-researchers, gatekeepers, community relationships and participatory approaches was a prominent feature within the facilitators. Reporting of barriers overall was lower, with fewer commonalities seen across the groups. The SE deprived group had the fewest barriers reported.

Conclusion

The lack of identified barriers suggests that more work should be done to learn what these may be for specific groups, particularly in the SE deprived group. It seems likely that barriers exist in this group. The fact that these were not reported may indicate lack of reach to the most deprived sections of this population. Therefore, more research needs to be done to fully explore the barriers in the most deprived groups. By developing engagement approaches in a way which is tailored to separate underserved groups this will address barriers and help to shape the future of research.
The G3BP Stress-Granule Proteins Reinforce the Translation Program of the Integrated Stress Response
Authors: Smith Jarrett , Bartel David P.
Published: October 2024

When mammalian cells are exposed to extracellular stress, they coordinate the condensation of stress granules (SGs) through the action of key nucleating proteins G3BP1 and G3BP2 (G3BPs) and, simultaneously, undergo a massive reduction in translation.1–5Although SGs and G3BPs have been linked to this translation response, their overall impact has been unclear. Here, we investigate the longstanding question of how, and indeed whether, G3BPs and SGs shape the stress translation response. We find that SGs are enriched for mRNAs that are resistant to the stress-induced translation shutdown. Although the accurate recruitment of these stress-resistant mRNAs does require the context of stress, a combination of optogenetic tools and spike-normalized ribosome profiling demonstrates that G3BPs and SGs are necessary and sufficient to both help prioritize the translation of their enriched mRNAs and help suppress cytosolic translation. Together these results support a model in which G3BPs and SGs reinforce the stress translation program by prioritizing the translation of their resident mRNAs.
Kidney Dialysis Service: Experiences of Consumer and Provider and Quality of Life of End Stage Kidney Disease Patients in Parbat, Nepal
Authors: Dhakal Mamta , Sharma Prabin , P.C. Anjali , Sharma Suman
Published: October 2024

Background/Objectives

The kidney dialysis patients and service providers possess a wide range of experience relating to the service, and quality of life is an important measure to evaluate holistic approach to chronic disease management such as kidney disease. This study was conducted to find out the experience of kidney dialysis patients and service providers and quality of life of end stage kidney disease patients.

Methods

A qualitative study was conducted, from March 2024 to August 2024, among 20 end stage kidney disease patients visiting Parbat hospital for dialysis and 7 dialysis service providers, doctor and nurses, using in-depth interview guidelines, kidney disease quality of life-36 instrument (for end stage kidney disease patients) and job satisfaction survey tool (for service providers). Thematic analysis was performed from the transcribed and translated recorded information to carry out the actual theme.

Result

Nine (9) themes were extracted for experiences of kidney dialysis patients. They were (i) perception on end-stage kidney disease, (ii) perception on free kidney dialysis service at the hospital, (iii) administrative process for free dialysis service, (iv) feasibility with the schedules of dialysis session, (v) quality of care and response of service providers (vi) duration of dialysis session (vii) desires and challenges towards kidney transplantation, (viii) on recommending the dialysis site and (ix) further expectations for improvement. The quality of life of end-stage kidney disease patients was found to be moderate. Similarly, nine (9) themes were extracted for experiences of service providers. They were (i) patient personalized care and understanding patients’ behavior (ii) addressing queries and concerns of the patients (iii) rewarding aspect of the job (iv) learning acceptance and witnessing positivity (v) availability of safety measures and protective protocols (vi) training and professional development experience (vii) reflection on job security (viii) challenging aspect of the job (ix) further expectations and requests. The kidney dialysis service providers were found to be ambivalent, neither satisfied nor dissatisfied with the job.

Conclusion

Patients share an overall good experience of free kidney dialysis service at Parbat hospital while the service providers also have a positive experience working in the dialysis section. However, expectations for provision of free medications and availability of nephrologist by the end stage kidney disease patients direct towards the reforms for improved service delivery. The doctor and nurses should be provided with more opportunities for professional development and safety should be a priority. These respective vigilance and actions for, shall address the quality of life and job satisfaction as well.
C-Reactive Protein Drives Potent Clearance of Blood Bacteria in the Liver by Activating the Complement System
Authors: Chen Danyu , Hu Jiao , Zhu Mengran , Xie Yufeng , Yao Hantian , An Haoran , Meng Yumin , Wang Juanjuan , Huang Xueting , Shao Zhujun , Xiang Ye , Qi Jianxun , Gao George Fu , Zhang Jing-Ren
Published: October 2024

Plasma C-reactive protein (CRP) is widely used as a biomarker for bacterial infections due to its massive induction during infections, however, the precise function of CRP in bacterial infections remains undefined. Here we show that CRP enables Kupffer cells (liver macrophages) to capture and eliminate a wide range of encapsulated bacteria from the bloodstream of mice and thereby provides rapid and effective immunity. Mechanistically, CRP binds to the structurally diverse capsular polysaccharides of major Gram-positive and -negative pathogens, and thereby activates complement C3 at the bacterial surface. The C3-opsonized microbes are in turn captured by C3 receptors on the surface of Kupffer cells, and eliminated in the liver sinusoids. Since CRP principally shares the functional features of antibodies in pathogen recognition/execution, CRP-based defense combines the broad spectrum of the innate immunity with the swiftness, potency and specificity of the adaptive immunity, which helps explain massive rise of CRP during systemic bacterial infections.
Shape analysis of biomimetic and plasma membrane vesicles
Authors: Kudawla Rajni , Kaur Harshmeet , Pandey Tanmay , Bhatia Tripta
Published: October 2024

Giant membrane vesicles (GUVs) and Giant plasma membrane vesicles (GPMVs) are models for examining membrane properties. We attempted to conduct a comparative study of reduced volume of vesicles with different lipid compositions, solution symmetry, solution asymmetry, and membrane charge. The vesicular morphology is studied using three-dimensional visualization techniques. The vesicles may not be exactly similar to spheres, but they may have some fluctuations resulting in changes in their shape. To understand these shape deformations, we visualize them as confocal image stacks. Our experimental observations indicate that the charge of the membrane affects the deflation of the GUVs in the presence of trans-bilayer sugar asymmetries. The lipid bilayers of our GUVs contain a uniform distribution of the lipids in the two leaflets, which implies that the two leaflets have the same lipid composition and there is no asymmetries in this composition. However, they obtain trans-bilayer asymmetries through asymmetric adsorption or desorption layers of different solution compositions adjacent to each leaflet. The deformation of the GPMVs shapes extracted from cells with trans-bilayer buffer asymmetries and the composition asymmetries is also estimated and compared with biomimetic membranes.
Predicting High Excess Risk of Hyponatremia Among Thiazide Users
Authors: Andersson Niklas Worm , Jakobsen Kim Daniel , Hviid Anders , Feenstra Bjarke , Melbye Mads , Wohlfahrt Jan , Lund Marie
Published: October 2024

Importance: Hyponatremia is a potential serious adverse drug reaction to treatment with thiazide diuretics. Whether individuals with a high risk of developing thiazide-induced hyponatremia can be predicted before treatment initiation is unknown. Objective: To identify patients with a high risk of thiazide-induced hyponatremia following treatment initiation. Design: Population-based cohort study, using national register data on demography, comorbidities, comedication, and blood test results to predict individual-level risk of thiazide-induced hyponatremia following treatment initiation based on models trained with the causal forest method. Models were validated in a separate cohort and compared by concordance-for-benefit (C-for-benefit) and calibration plots. Setting: Denmark, 1 January 2014 to 31 December 2020. Participants: Patients were ≥40 years old and new users of thiazide or non-thiazide antihypertensive drugs (renin-angiotensin-system inhibitors or calcium channel blockers) and split into a development (n=185,699; from 2014-2018) and a validation cohort (n=75,030; 2019-2020). Exposure: Thiazide or non-thiazide antihypertensive treatment. Main outcome and measure: Predicted excess risk of moderate-to-severe hyponatremia defined as plasma sodium levels <130 mmol/L, measured within the first 120 days of treatment. Results: Individual-level excess risk could be parsimoniously described by a four-covariate model that included information on age and plasma sodium, hemoglobin, and C-reactive protein levels at baseline with good calibration and C-for-benefit (0.66; 95% CI, 0.66-0.67) in the validation cohort. The average 120-day excess risk of hyponatremia among thiazide-treated patients was 1.8% (95% CI, 1.3% to 2.2%), with individual-level heterogeneity ranging from -1.6% to 15.9%. The 10% of thiazide-treated with the highest excess risk of hyponatremia had an average excess risk of 7.4% (95% CI, 4.4% to 10.5%). If this high-risk group were instead assigned a non-thiazide antihypertensive, the excess risk within the remaining thiazide-treated population would be reduced by 0.7% (95% CI, 0.1% to 1.2%), corresponding to a 38% relative reduction. Conclusion and relevance: The population-level burden of thiazide-induced hyponatremia can potentially be markedly reduced by assigning a small group of patients at highest risk, who would otherwise be assigned a thiazide, to an alternative antihypertensive drug. This high-risk group can be identified using a small set of simple baseline information.
Genetic Determinants of Bone Microarchitecture and its Association with Health Outcomes: A Genome-wide Association and Mendelian Randomization Study on Trabecular Bone Score
Authors: Guo Sijia , Zhang Jiping , Li Huiwu , Lin Guan Ning , Cheng Cheng-Kung , Zhang Jingwei
Published: October 2024

Background

Bone microarchitecture is a critical determinant of bone strength and fracture risk, yet its genetic basis and relationship to systemic health remain largely unexplored. This study aimed to identify genetic determinants of bone microarchitecture using trabecular bone score (TBS) and investigate the causal relationships between bone microarchitecture and various health outcomes.

Methods

We conducted a genome-wide association study (GWAS) of TBS in 25,268 UK Biobank participants to identify genetic loci associated with bone microarchitecture. Two-sample Mendelian randomization (MR) was employed to assess the causal relationships between systemic health risk factors and bone microarchitecture, as well as the impact of bone microarchitecture on musculoskeletal disorders.

Findings

The GWAS identified 75 significant single nucleotide polymorphisms (SNPs) across 19 genomic loci, with an estimated heritability of TBS at 24.5%. Many of these loci (18/19) were also associated with bone mineral density (BMD) and fractures, indicating a shared genetic basis for bone microarchitecture and bone mass. MR analysis revealed that rheumatoid arthritis has a significant causal effect on the deterioration of bone microarchitecture (β = -0.003, P = 1.14×10-4). Suggestive associations were found between bone microarchitecture deterioration and inflammatory bowel disease, cardiovascular disease, and depression (P < 0.05). Moreover, genetically predicted TBS was significantly associated with fracture risk (OR = 0.003, P = 1.89×10-8) and suggestively associated with osteonecrosis (OR = 0.002, P = 0.040).

Interpretation

This study identified novel genetic determinants of bone microarchitecture and demonstrated its association with various systemic diseases, highlighting the critical role of bone microarchitecture in skeletal health. The results advocate for the clinical use of TBS to better assess the risk of osteoporosis and fractures and to improve bone and overall health assessments. The causal effect of rheumatoid arthritis on microarchitectural deterioration underscores the need for increased monitoring of bone health in this population.

Funding

This work supported by Shanghai "Rising Stars of Medical Talent" Youth Development Program, Youth Medical Talents-Specialist Program (grant number SHHWRS 2023-62), the Fundamental Research Funds for the Central Universities (grant number AF0820060), Outstanding Research-oriented Doctor Cultivation Program at the Ninth People’s Hospital affiliated with the School of Medicine, Shanghai Jiao Tong University, National Natural Science Foundation of China (grant number 31900941).
Plant genotype and microbial strain combinations strongly influence the transcriptome under heavy metal stress conditions
Authors: Sharma Reena , Chakraborty Sanhita , Bhat Aditi , Clear Michael , Xie Meng , Pueyo José J. , Paape Timothy
Published: October 2024

Heavy metals such as cadmium (Cd) and mercury (Hg) pose significant threats to plant health and food safety as they are absorbed from the environment. Legumes are generally considered sensitive to heavy metals but possess standing genetic variation for accumulation and tolerance to toxic ions. We conducted a transcriptomic analysis on hydroponically and soil grownMedicago truncatulaplants to investigate gene expression responses to Cd and Hg exposure in roots, leaves, and nodules. By using plant genotypes with varying metal tolerance or accumulation levels, we observed distinct clustering of gene ontologies, indicating tissue-specific, genotype-specific, and metal-specific gene expression patterns. Considering the symbiotic relationship between legumes and nitrogen-fixing bacteria, we further examined plant phenotypes and transcriptomes of plant genotypes with contrasting Hg accumulation levels and inoculated them with high or low Hg-tolerantSinorhizobium medicaestrains that have presence-absence variation for a mercury reductase (Mer) operon. Host plants inoculated with the Hg-tolerant rhizobia strain possessing a Mer operon exhibited less reduction in nodule number and plant biomass. A smaller reduction in iron (Fe) distribution in nodules after Hg stress was measured using X-ray Fluorescence (XRF) imaging. Dual transcriptome (host plant and bacteria) analysis of nodules revealed a remarkable decrease in the number of differentially expressed genes (DEGs) and clustering of gene ontologies in plants inoculated with the Hg-tolerant rhizobia strain, including symbiosis related genes. This suggests the Hg-tolerant rhizobia strain has the potential to mitigate Hg stress in host plants. Furthermore, we observed genotype-by-genotype interactions between the high Hg accumulating plant genotype and the Hg-tolerant rhizobia strain. These findings provide insights into enhancing plant resilience in contaminated environments through optimizing legume-rhizobia interactions for heavy metal tolerance, as well as identification of genetic mechanisms that can reduce transport to edible plant parts.

Highlights

Genetic variation in tolerance to heavy metals affects responses in plant tissues

Symbiosis with Hg tolerant rhizobia strain reduced stress response in host plant

Dual-transcriptomics in nodules identified metal stress and symbiosis responses

Genotype by genotype interaction significantly affected symbiosis gene expression

Rhizobia strain possessing Mer operon suggests genetic basis affecting responses
A Novel Dataset for Nuclei and Tissue Segmentation in Melanoma with baseline nuclei segmentation and tissue segmentation benchmarks
Authors: Schuiveling Mark , Liu Hong , Eek Daniel , Breimer Gerben E. , Suijkerbuijk Karijn P.M. , Blokx Willeke A.M. , Veta Mitko
Published: October 2024

Background

Melanoma is an aggressive form of skin cancer in which tumor-infiltrating lymphocytes (TILs) are a biomarker for recurrence and treatment response. Manual TIL assessment is prone to interobserver variability, and current deep learning models are not publicly accessible or have low performance. Deep learning models, however, have the potential of consistent spatial evaluation of TILs and other immune cell subsets with the potential of improved prognostic and predictive value. To make the development of these models possible, we created the Panoptic Segmentation of nUclei and tissue in advanced MelanomA (PUMA) dataset and assessed the performance of several state-of-the-art deep learning models. In addition, we show how to improve model performance further by using heuristic post-processing in which nuclei classes are updated based on their tissue localization.

Results

The PUMA dataset includes 155 primary and 155 metastatic melanoma H&E stained regions of interest with nuclei and tissue annotations from a single melanoma referral institution. The Hover-NeXt model, trained on the PUMA dataset, demonstrated the best performance for lymphocyte detection, approaching human interobserver agreement. In addition, heuristic post-processing of deep learning models improve the detection of non-common classes, such as epithelial nuclei.

Conclusion

The PUMA dataset is the first melanoma specific dataset that can be used to develop melanoma-specific nuclei and tissue segmentation models. These models can, in turn, be used for prognostic and predictive biomarker development. Incorporating tissue and nuclei segmentation is a step towards improved deep learning nuclei segmentation performance. We will use this dataset to organize the PUMA challenge in which the goal is to further improve model performance.