bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of concentration parameters for maximizing bacteriophage recovery value using response surface methodology: A case study on determining the optimal concentration parameters for Erwinia amylovoraEA1T1.B3 phage
Authors: Guven Kubra , Ekiz Esra , Evran Eylul , Tayyarcan Emine Kubra , Boyaci Ismail Hakki
Published: February 2024

Bacteriophages have emerged as effective antimicrobial agents in combating pathogenic bacteria. To successfully apply phages in real‐life scenarios, it is crucial to optimize their large‐scale production, concentration and purification processes. In this study, our objective was to optimize the phage concentration parameters with a high recovery rate within a shorter time and minimum chemical consumption. We isolated and characterized a specific Erwinia amylovora phage. Subsequently, we employed response surface methodology (RSM) combined with a three‐factor central composite design to optimize the phage recovery. The factors considered were polyethylene glycol (PEG) concentration, NaCl concentration and incubation time. The optimized values for PEG, NaCl and incubation time, which resulted in a maximum recovery rate of 85.37%, were determined as 18%, 2.38 M and 0 h, respectively. This finding indicates that the concentration step, which traditionally took up to 18 h with a recovery rate of 65%, can now be accomplished in a significantly shorter time with an improved recovery rate. Our study demonstrates the effectiveness of RSM to identify the optimum conditions for phage precipitation. This approach allows for the rapid and efficient design of precipitation protocols tailored to specific bacteriophages, resulting in shorter processing times and higher recovery rates.
Diversity, Variance, and Stability of Root Phenes of Peanut (Arachis hypogaea L.)
Authors: Li Lijie , Li Qian , Liu Yanli , Xue Huiyun , Zhang Xiaotian , Wang Bin , Pan Xiaoping , Zhang Zhiyong , Zhang Baohong
Published: February 2024

Root phenes are associated with the absorptive efficiency of water and fertilizers. However, there are few reports on the genetic variation and stability of peanut (Arachis hypogaea L.) root architecture under different environments. In this study, the diversity, variance and stability of root phenes of 89 peanut varieties were investigated with shovelomics (high throughput phenotyping of root system architecture) for two years in both field and laboratory experiments. The root phenes of these peanut genotypes presented rich diversity; for example, the value of total root length (TRL) ranged from 347.84 cm to 1013.80 cm in the field in 2018, and from 55.14 cm to 206.22 cm in the laboratory tests. The root phenes of different genotypes varied differently; for example, the coefficient of variation (CV) of TRL ranged from 24.0 to 83.5 across the two‐year field test. Field and laboratory evaluations were highly correlated, especially on lateral root density (LRD) and root angle (RA), and the quadrant graph analysis of LRD and RA implied that 69.7% of the roots belong to the same type. These not only further reflect root phenes stability through different environment but also demonstrate that some root phenes identified at early stage can indicate their status at later growth stage. In addition, root phenes showed a strong correlation with shoot growth, especially root dry weight (RDW), TRL and（nodule number）NN. Thus, laboratory tests in combination with field shovelomics can efficiently screen and select genotypes with contrasting root phenes to optimize water and nutrient management.
Immigrant selectivity at school entry
Authors: Lanuza Yader R.
Published: February 2024

Immigrant educational selectivity—immigrant parents' educational attainment relative to their peers who did not migrate—is associated with better schooling outcomes for children at later stages of the educational pipeline in the United States. Less is known, however, about its influence on early education‐related outcomes. Using Early Childhood Longitudinal Study data from three different cohorts and quantitative analyses, I examine the relationship between immigrant selectivity and school readiness at school entry (proxied through math skills and approaches to learning evaluations). I find that immigrant selectivity is positively associated with school readiness, but it does not generate a widespread immigrant advantage at school entry, contrary to findings related to schooling outcomes later in the schooling pipeline. Notably, among most Asian groups, immigrant selectivity partly accounts for school readiness advantages compared to their White peers with native‐born parentage, whenever they emerge. By contrast, accounting for immigrant selectivity reveals the full extent of the immigrant disadvantage at school entry among most Latino groups. These results suggest that immigrant selectivity is an important factor in shaping racial/ethnic stratification early in the schooling pipeline.
Donor complication rates in whole blood, plasma and platelet donors: Age versus experience
Authors: Paalvast Yared , Díaz Padilla Niubel , Bruijns Sanne , Wiersum‐Osselton Johanna , Molenaar Ties
Published: February 2024

Background

Many blood banks use upper age limits for donors out of concern for a higher donor complication rate in older donors. Experienced donors are known to have lower donor complication rates, and older donors are often more experienced, confounding the effect of age on donor complication rate.

Study Design and Methods

We studied donor complication rates in whole blood, plasma, and plateletpheresis donors from 2012 to 2022. Donor complication rates were compared between age groups in inexperienced (<20th donation) and experienced (≥20th donation) donors. In addition to this direct comparison, we made use of logistic regression with finer‐grained experience groups, to further quantify the effects of age, experience and other factors on donor complication rate.

Results

While overall rate of vasovagal reaction was lower, rate of moderate/severe vasovagal syncope was highest in 70–79 year donors, however, only reached significance for plasma donors. Furthermore, rates of failed stab were highest in this age group. Hematoma rate showed a U‐shaped pattern with regard to age, where the rate was not higher in the 70–79 year age group than in the 18–23 year age group. Pain decreased with age, however, rates were higher in the 70–79 year age group than in the 65–69 year age group.

Discussion

When properly accounting for donor experience, donor complication rate profiles clearly change with age. The increased risk for moderate/severe vasovagal syncope in older donors should be clearly communicated. Extra caution is needed if these donors are accepted for first‐time donations.
A tight interplay between platelet activation and mitochondrial DNA release promotes platelet storage lesion in platelet concentrates
Authors: Haeri Kamand , Samiee Shahram , Beigi Peyman , Hajati Smerdis , Deyhim Mohammad Reza
Published: February 2024

Background and Objectives

Platelet storage lesion (PSL) adversely affects the quality of platelet concentrates (PCs). Platelets are prone to activation during storage. Moreover, elevated free mitochondrial DNA (mtDNA) levels in PCs are associated with a higher risk of adverse transfusion reactions. Therefore, we aimed to evaluate the correlation between platelet activation markers and mtDNA release during PC storage.

Materials and Methods

Six PCs prepared by the platelet‐rich plasma method were assessed for free mtDNA copy number using quantitative real‐time PCR and CD62P (P‐selectin) expression by flow cytometry on days 0 (PC collection day), 3, 5 and 7 of storage. Lactate dehydrogenase (LDH) activity, pH, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) were measured as well. The correlation between free mtDNA and other PSL parameters, and the correlation between all parameters, was determined.

Results

Significant increases in free mtDNA, MPV and PDW, and a significant decrease in platelet count and pH were observed. CD62P expression and LDH activity elevated significantly, particularly on storage days 5–7 and 0–3, respectively. Moreover, a moderate positive correlation (r = 0.61) was observed between free mtDNA and CD62P expression. The r values between free mtDNA and LDH, pH, platelet count, MPV and PDW were 0.81, −0.72, −0.49, 0.81 and 0.77, respectively.

Conclusion

The interplay between platelet activation and mtDNA release in promoting PSL in PCs may serve as a promising target for future research on applying additive solutions and evaluating the quality of PCs to improve transfusion and clinical outcomes.
The Impact of Online Negative Hotel Reviews and Merchant Response Strategies on Potential Consumers’ Purchase Intentions: A Perceived Trust Perspective
Authors: Lin Xia , Zhu Jiali
Published: February 2024

Based on online negative reviews, the paper explores the influence mechanism of emotional and attributive reviews on potential customers’ purchase intentions. Against the background of online hotel booking, using ability, benevolence, and integrity in perceived trust as intermediary variables, we constructed a two-factor group experiment with 2 (types of online negative reviews) × 5 (merchant response strategies). This study was conducted by randomly recruiting participants from a university, utilizing a questionnaire-based experimental approach. Two hundred fifty valid questionnaires were collected for statistical analysis, including t-test, analysis of variance, and structural equation model. This paper reveals the influence of online negative reviews and merchant response strategies on ability, integrity, and benevolence. It verifies the mechanism of three factors and potential customers’ purchase intention. Concurrently, this study provides crucial inspiration for hotel managers to focus on addressing the service quality issues in the reviews and develop tailored response strategies to enhance customers’ perception and trust.
An oxidative photocyclization approach to the synthesis of
Securiflustra securifrons
alkaloids
Authors: Alexander Brandon W. , Bartfield Noah M. , Gupta Vaani , Mercado Brandon Q. , Del Campo Mark , Herzon Seth B.
Published: February 2024

Securines and securamines are cytotoxic alkaloids that contain reactive alkene and heterocyclic residues embedded in skeletons comprising four to six oxidized rings. This structural complexity imparts a rich chemistry to the isolates but has impeded synthetic access to the structures in the nearly three decades since their isolation. We present a flexible route to eight isolates that exemplify the three skeletal classes of metabolites. The route proceeds by the modular assembly of the advanced azides
38
and
49
(13 steps, 6 to 10% yield), sequential oxidative photocyclizations, and late-stage functional group manipulations. With this approach, the targets were obtained in 17 to 19 steps, 12 to 13 purifications, and 0.5 to 3.5% overall yield. The structure of an advanced intermediate was elucidated by microcrystal electron diffraction (MicroED) analysis. The route will support structure-function and target identification studies of the securamines.
Altitudinal patterns of alpine soil ammonia-oxidizing community structure and potential nitrification rate
Authors: Zhao Yuwei , Ling Ning , Liu Xiang , Li Chao , Jing Xin , Hu Jingjing , Rui Junpeng
Published: February 2024

Nitrogen availability limits the net primary productivity in alpine meadows on the Qinghai–Tibetan Plateau, which is regulated by ammonia-oxidizing microorganisms. However, little is known about the elevational patterns of soil ammonia oxidizers in alpine meadows. Here, we investigated the potential nitrification rate (PNR), abundance, and community diversity of soil ammonia-oxidizing microorganisms along the altitudinal gradient between 3,200 and 4,200 m in Qinghai–Tibetan alpine meadows. We found that both PNR and
amoA
gene abundance declined from 3,400 to 4,200 m but lowered at 3,200 m, possibly due to intense substrate competition and biological nitrification inhibition from grasses. The primary contributors to soil nitrification were ammonia-oxidizing archaea (AOA), and their proportionate share of soil nitrification increased with altitude in comparison to ammonia-oxidizing bacteria (AOB). The alpha diversity of AOA increased by higher temperature and plant richness at low elevations, while decreased by higher moisture and low legume biomass at middle elevations. In contrast, the alpha diversity of AOB increased along elevation. The elevational patterns of AOA and AOB communities were primarily driven by temperature, soil moisture, and vegetation. These findings suggest that elevation-induced climate changes, such as shifts in temperature and water conditions, could potentially alter the soil nitrification process in alpine meadows through changes in vegetation and soil properties, which provide new insights into how soil ammonia oxidizers respond to climate change in alpine meadows.

IMPORTANCE

The importance of this study is revealing that elevational patterns and nitrification contributions of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) communities were primarily driven by temperature, soil moisture, and vegetation. Compared to AOB, the relative contribution of AOA to soil nitrification increased at higher elevations. The research highlights the potential impact of elevation-induced climate change on nitrification processes in alpine meadows, mediated by alterations in vegetation and soil properties. By providing new insights into how ammonia oxidizers respond to climate change, this study contributes valuable knowledge to the field of microbial ecology and helps predict ecological responses to environmental changes in alpine meadows.
Clinical validation of loop-mediated isothermal amplification for the detection of
Escherichia coli
sequence type complex 131
Authors: Peirano Gisele , Castellanos L. Ricardo , Matsumura Yasufumi , Chaffee Ryan , Castañeda-Mogollón Daniel , Pillai Dylan R. , Pitout Johann D. D.
Published: February 2024

The dissemination of
Escherichia coli
multidrug-resistant (MDR) STc131 is related to its persistence in the human gastrointestinal tract as efficient gut colonizers. Infection and prevention measures are the cornerstones for preventing STc131 spread. Oral decolonization therapies that target ST131 are being developed. There are no rapid methods available to identify STc131 in human specimens. A loop-mediated isothermal amplification (LAMP) assay (named LAMP-ST131) was developed for the detection of STc131 on well-characterized
E. coli
isolates and then compared to culture and PCR for urines and stool swabs. With
E. coli
isolates (
n
= 720), LAMP-ST131 had a sensitivity (sens) of 100% [95% confidence interval (C.I.) = 98.1–100%)] and a specificity (spec) of 98.9% (95% C.I. = 97.5–99.5%). On urines (
n
= 550), LAMP-ST131 had a sens of 97.6% (95% C.I. = 89.68–94.33%) and a spec of 92.3% (95% C.I. = 87.68–99.88%), while on stool swabs (
n
= 278), LAMP-ST131 had a sens of 100% (95% C.I. = 88.7–100%) and a spec of 83.9% (95% C.I. = 78.8–87.9%). LAMP-ST131 detected 10 (urines) and 100 (stool swabs) gene copies/μL. LAMP-ST131 accurately identified STc131 within
E. coli
isolates and human specimens. The implementation of LAMP-ST131 will aid genomic surveys, enable the rapid implementation of effective infection prevention measures, and identify patients suitable for ST131 decolonization therapies. Such approaches will curb the spread of STc131 and decrease incidence rates of global MDR
E. coli
infections.

IMPORTANCE

We developed an accurate non-culture-based loop-mediated isothermal amplification (LAMP) methodology for the detection of (sequence type) STc131 among
Escherichia coli
isolates and human specimens. The use of LAMP-ST131 for global genomic surveillance studies and to identify patients that are suitable for ST131 decolonization therapies will be important for decreasing multidrug-resistant
E. coli
infections across the globe.
Mental health of caregivers of children with medical complexity: group-based trajectory modelling
Authors: Nathwani Apsara Ali , Fayed Nora , Grandi Sonia M , Orkin Julia , Cohen Eyal
Published: February 2024

Objective

To describe the mental health trajectories of caregivers of children with medical complexity (CMC) and explore child characteristics associated with below-average caregiver mental health.

Design

A secondary analysis of prospectively collected data from 123 caregivers of children aged <16 years with medical complexity from a multicentre randomised trial conducted from December 2016 to June 2021.

Main outcome measure

The Patient-Reported Outcomes Measurement Information System Global Mental Health Scale was used to measure caregivers' self-reported mental health well-being. Group-based trajectory analysis was used to identify clusters of caregivers with similar changes in mental health across 24 months. Logistic regression was used to identify child-related predictors of mental health among caregivers.

Results

A final model with three distinct groups was selected, corresponding to caregivers with average (n=39), moderately below-average (n=65) and severely below-average (n=19) mental health scores, all with stable trajectories and high posterior probabilities (>90%). Moderately and severely below-average caregiver mental health groups, merged into one group, were associated with a greater number of child medical technology devices (adjusted OR (aOR) 1.44, 95% CI 1.01 to 2.04), gross motor difficulties (aOR 3.51, 95% CI 1.02 to 12.05) and worse child emotional (aOR 0.93, 95% CI 0.87 to 0.99) and psychological well-being (aOR 0.93, 95% CI 0.88 to 0.99).

Conclusion

Most caregivers of CMC reported persistently below-average mental health. The intensity of caregiving, as indicated by medical technology and child functional needs, is a potential risk factor for below-average caregiver mental health. Future design and evaluation of interventions focused on support for caregivers of CMC are warranted.
Optimal timing of influenza vaccination in young children: population based cohort study
Authors: Worsham Christopher M , Bray Charles F , Jena Anupam B
Published: February 2024

Objective

To assess optimal timing of influenza vaccination in young children.

Design

Population based cohort study.

Setting

United States.

Participants

Commercially insured children aged 2-5 years who were vaccinated against influenza during 2011-18.

Main outcome measure

Rates of diagnosis of influenza among children who were vaccinated against influenza, by birth month.

Results

Overall, 819 223 children aged 2-5 received influenza vaccination. Children vaccinated in November and December were least likely to have a diagnosis of influenza, a finding that may be confounded by unmeasured factors that influence the timing of vaccination and risk of influenza. Vaccination commonly occurred on days of preventive care visits and during birth months. Children born in October were disproportionately vaccinated in October and were, on average, vaccinated later than children born in August and earlier than those born in December. Children born in October had the lowest rate of influenza diagnosis (for example, 2.7% (6016/224 540) versus 3.0% (6462/212 622) for those born in August; adjusted odds ratio 0.88, 95% confidence interval 0.85 to 0.92).

Conclusions

In a quasi-experimental analysis of young children vaccinated against influenza, birth month was associated with the timing of vaccination through its influence on the timing of preventive care visits. Children born in October were most likely to be vaccinated in October and least likely to have a diagnosis of influenza, consistent with recommendations promoting October vaccination.
Factors influencing deceased organ donation rates in OECD countries: a panel data analysis
Authors: Qu Zhi , Oedingen Carina , Bartling Tim , Schrem Harald , Krauth Christian
Published: February 2024

Objectives

This study aims to investigate factors with a significant influence on deceased organ donation rates in Organisation for Economic Co-operation and Development (OECD) countries and determine their relative importance. It seeks to provide the necessary data to facilitate the development of more efficient strategies for improving deceased organ donation rates.

Design

Retrospective study.

Setting

Publicly available secondary annual data.

Participants

The study includes 36 OECD countries as panel members for data analysis.

Outcome measures

Multivariable panel data regression analysis was employed, encompassing data from 2010 to 2018 for all investigated variables in the included countries.

Results

The following variables had a significant influence on deceased organ donation rates: ‘opt-in’ system (β=−4.734, p<0.001, ref: ‘opt-out’ system), only donation after brain death (DBD) donors allowed (β=−4.049, p=0.002, ref: both DBD and donation after circulatory death (DCD) donors allowed), number of hospital beds per million population (pmp) (β=0.002, p<0.001), total healthcare employment pmp (β=−0.00012, p=0.012), World Giving Index (β=0.124, p=0.008), total tax revenue as a percentage of gross domestic product (β=0.312, p=0.009) and percentage of population aged ≥65 years (β=0.801, p<0.001) as well as high education population in percentage (β=0.118, p=0.017).

Conclusions

Compared with the promotion of socioeconomic factors with a positive significant impact on deceased organ donation rates, the following policies have been shown to significantly increase rates of deceased organ donation, which could be further actively promoted: the adoption of an ‘opt-out’ system with presumed consent for deceased organ donation and the legal authorisation of both DBD and DCD for transplantation.
Adoption of technology enabled care to support the management of children and teenagers in rheumatology services: a protocol for a mixed-methods systematic review
Authors: Rostron Heather , Wright Judy M , Gilbert Anthony W , Dillon Beth , Pini Simon , Redmond Anthony C , Livermore Polly
Published: February 2024

Introduction

COVID-19 catalysed a rapid move to provide care away from the hospital using online communication platforms. Technology enabled care (TEC) continues to be an important driver in progressing future healthcare services. Due to the complex and chronic nature of conditions seen within paediatric rheumatology, TEC may lead to better outcomes. Despite some growth in published literature into the adoption of TEC in paediatric rheumatology, there is limited synthesis. The aim of this review is to provide a comprehensive understanding and evaluation of the adoption of TEC by patients in paediatric rheumatology services, to establish best practices.

Methods and analysis

This proposed mixed-methods systematic review will be conducted by searching a wide variety of healthcare databases, grey literature resources and associated charities and societies, for articles reported in English language. Data extraction will include population demographics, technology intervention, factors affecting adoption of intervention and consequent study outcomes. A parallel-results convergent synthesis design is planned, with independent syntheses of quantitative and qualitative data, followed by comparison of the findings of each synthesis using a narrative approach. Normalisation process theory will be used to identify, characterise and explain implementation factors. The quality of included articles will be assessed using the Mixed Methods Appraisal Tool for research papers and the Authority, Accuracy, Coverage, Objectivity, Date, Significance checklist for grey literature. Overall confidence in quality and strength of evidence will be assessed using the Confidence in the Evidence from Reviews of Qualitative Research tool.

Ethics and dissemination

Ethical approval is not required due to the nature of this mixed-methods systematic review. The findings will be disseminated via a peer-reviewed journal, relevant conferences and any other methods (eg, via NHS Trust or NIHR YouTube channels) as advised by paediatric rheumatology patients.

PROSPERO registration number

CRD42023443058.
Does the implementation of a trauma system affect injury-related morbidity and economic outcomes? A systematic review
Authors: Bath Michael F , Hobbs Laura , Kohler Katharina , Kuhn Isla , Nabulyato William , Kwizera Arthur , Walker Laura E , Wilkins Tom , Stubbs Daniel , Burnstein RM , Kolias Angelos , Hutchinson Peter John , Clarkson P John , Halimah Sara , Bashford Tom
Published: February 2024

Background

Trauma accounts for a huge burden of disease worldwide. Trauma systems have been implemented in multiple countries across the globe, aiming to link and optimise multiple aspects of the trauma care pathway, and while they have been shown to reduce overall mortality, much less is known about their cost-effectiveness and impact on morbidity.

Methods

We performed a systematic review to explore the impact the implementation of a trauma system has on morbidity, quality of life and economic outcomes, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All comparator study types published since 2000 were included, both retrospective and prospective in nature, and no limits were placed on language. Data were reported as a narrative review.

Results

Seven articles were identified that met the inclusion criteria, all of which reported a pre-trauma and post-trauma system implementation comparison in high-income settings. The overall study quality was poor, with all studies demonstrating a severe risk of bias. Five studies reported across multiple types of trauma patients, the majority describing a positive impact across a variety of morbidity and health economic outcomes following trauma system implementation. Two studies focused specifically on traumatic brain injury and did not demonstrate any impact on morbidity outcomes.

Discussion

There is currently limited and poor quality evidence that assesses the impact that trauma systems have on morbidity, quality of life and economic outcomes. While trauma systems have a fundamental role to play in high-quality trauma care, morbidity and disability data can have large economic and cultural consequences, even if mortality rates have improved. The sociocultural and political context of the surrounding healthcare infrastructure must be better understood before implementing any trauma system, particularly in resource-poor and fragile settings.

PROSPERO registration number

CRD42022348529

Level of evidence

Level III.
Association of pulmonary hypertension with the outcome in patients undergoing edge-to-edge mitral valve repair
Authors: Ubben Timm , Frerker Christian , Fujita Buntaro , Rosenkranz Stephan , Pfister Roman , Baldus Stephan , Alessandrini Hannes , Kuck Karl-Heinz , Willems Stephan , Eitel Ingo , Schmidt Tobias
Published: February 2024

Objectives

The association of pulmonary hypertension (PH) with the outcome after mitral transcatheter edge-to-edge repair (M-TEER) focusing on the new ESC/ERS guidelines definition for PH.

Background

PH is frequently found in patients with mitral regurgitation and is associated with lower survival rates. Recent studies were based on echocardiographic parameters, but results based on invasive haemodynamics differentiating distinct types of PH using the new definition for PH are missing.

Methods

449 consecutive M-TEER-treated patients from December 2009 to February 2015 were included in this retrospective analysis. All patients were stratified by the distinct types of PH (no PH, precapillary PH, isolated postcapillary PH, combined post-PH and precapillary PH) according to the definitions of the ESC/ERS guidelines for the diagnosis of PH from 2015 (meanPA cut-off <25 mm Hg, pulmonary capillary wedge pressure (PCWP) cut-off ≤15 mm Hg, diastolic pulmonary gradient cut-off ≥7 mm Hg or pulmonary vascular resistance (PVR) >3 WU) and 2022 (meanPA cut-off ≤20 mm Hg, PCWP cut-off ≤15 mm Hg, PVR cut-off ≥3 WU).

Results

Patients with any type of PH (2015: meanPA cut-off 25 mm Hg; 2022: meanPA cut-off >20 mm Hg) showed a higher risk of death after M-TEER compared with patients with no PH (2015: HR 1.61 (95% CI 1.25 to 2.07); p<0.001 and 2022: HR 2.09 (95% CI 1.54 to 2.83); p<0.001). Based on the new PH definition, each PH subgroup showed a lower survival after M-TEER compared with patients with no PH. Echocardiographic estimated systolic PAP showed a correlation with invasively measured mean pulmonary artery pressure (mPAP) (r=0.29, p<0.001) and systolic pulmonary arterial pressure (r=0.34,p<0.001). Cox-regression analysis showed higher invasive diastolic, systolic and mean pulmonary pressures were associated with higher all-cause mortality (p<0.001). In addition, invasive measured higher right atrial pressure, lower pulmonary arterial compliance, higher PVR and higher wedge pressure were identified as predictors of all-cause mortality after M-TEER.

Conclusions

The new PH definition discriminates PH groups and mortality better than the old definition. The lower threshold of mPAP of 20mmHg improved prognostication in this cohort of patients.
Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS)
Authors: Mangone Laura A. , Taylor Beth A. , Schmelzer Robert , Noh Sung Gi , White Michael C , Kwon Oh Sung , Thompson Paul D
Published: February 2024

Objective

The objective of this article is to evaluate near-infrared spectroscopy (NIRS), a non-invasive technique to assess tissue oxygenation and mitochondrial function, as a diagnostic tool for statin-associated muscle symptoms (SAMS).

Methods

We verified SAMS in 39 statin-treated patients (23 women) using a double-blind, placebo-controlled, cross-over protocol. Subjects with suspected SAMS were randomised to simvastatin 20 mg/day or placebo for 8 weeks, followed by a 4-week no treatment period and then assigned to the alternative treatment, either simvastatin or placebo. Tissue oxygenation was measured before and after each statin or placebo treatment using NIRS during handgrip exercise at increasing intensities of maximal voluntary contraction (MVC).

Results

44% (n=17) of patients were confirmed as having SAMS (11 women) because they reported discomfort only during simvastatin treatment. There were no significant differences in percent change in tissue oxygenation in placebo versus statin at all % MVCs in all subjects. The percent change in tissue oxygenation also did not differ significantly between confirmed and unconfirmed SAMS subjects on statin (−2.4% vs −2.4%, respectively) or placebo treatment (−1.1% vs −9%, respectively). The percent change in tissue oxygenation was reduced after placebo therapy in unconfirmed SAMS subjects (−10.2%) (p≤0.01) suggesting potential measurement variability.

Conclusions

NIRS in the forearm cannot differentiate between confirmed and unconfirmed SAMS, but further research is needed to assess the usability of NIRS as a diagnostic tool for SAMS.

Trial registration number

NCT03653663.
About this title - Carbonate Reservoirs: Applying Current Knowledge to Future Energy Needs
Authors: Garland J. , Barnett A.J. , Burchette T.P. , Wright V.P.
Published: February 2024

This Special Publication is a compendium of studies on carbonate petroleum reservoirs from several key areas, together with subsurface examples of renewable energy generation, storage and sequestration. It shows how the tools developed entirely for petroleum reservoir exploitation are now being utilized to enable aspects of our new low-carbon environment.
Plant Molecular Phenology and Climate Feedbacks Mediated by BVOCs
Authors: Satake Akiko , Hagiwara Tomika , Nagano Atsushi J. , Yamaguchi Nobutoshi , Sekimoto Kanako , Shiojiri Kaori , Sudo Kengo
Published: February 2024

Climate change profoundly affects the timing of seasonal activities of organisms, known as phenology. The impact of climate change is not unidirectional; it is also influenced by plant phenology as plants modify atmospheric composition and climatic processes. One important aspect of this interaction is the emission of biogenic volatile organic compounds (BVOCs), which link the Earth's surface, atmosphere, and climate. BVOC emissions exhibit significant diurnal and seasonal variations and are therefore considered essential phenological traits. To understand the dynamic equilibrium arising from the interplay between plant phenology and climate, this review presents recent advances in comprehending the molecular mechanisms underpinning plant phenology and its interaction with climate. We provide an overview of studies investigating molecular phenology, genome-wide gene expression analyses conducted in natural environments, and how these studies revolutionize the concept of phenology, shifting it from observable traits to dynamic molecular responses driven by gene–environment interactions. We explain how this knowledge can be scaled up to encompass plant populations, regions, and even the globe by establishing connections between molecular phenology, changes in plant distribution, species composition, and climate.
Exploring the Multifaceted Influences of Social Media Motivation on Online Relationship Commitment among Young Adults in Jordan: An Empirical Study
Authors: Hatamleh Islam Habis Mohammad
Published: February 2024

In the context of a rapidly evolving global communication landscape, this study delves into the influence of social media motivation on online relationship commitment among young adults in Jordan. Utilizing a quantitative methodology, the research operationalizes and tests a conceptual model to assess the correlation between various motivational factors and online relationship commitment. Results reveal that social media exerts a significant influence on online relationship commitment, with information-seeking and trend-following emerging as the most salient contributing factors. Additionally, the study identifies that providing self-status information, social interaction, and entertainment are key motivators that positively impact and strengthen online relationship commitment.
Acquired Cross-Resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC Paralogs
Authors: Pal Choudhuri Shreoshi , Girard Luc , Lim Jun Yi Stanley , Wise Jillian F. , Freitas Braeden , Yang Di , Wong Edmond , Hamilton Seth , Chien Victor D. , Kim Yoon Jung , Gilbreath Collin , Zhong Jun , Phat Sarah , Myers David T. , Christensen Camilla L. , Mazloom-Farsibaf Hanieh , Stanzione Marcello , Wong Kwok-Kin , Hung Yin P. , Farago Anna F. , Meador Catherine B. , Dyson Nicholas J. , Lawrence Michael S. , Wu Sihan , Drapkin Benjamin J.
Published: February 2024

Small cell lung cancer (SCLC) presents as a highly chemosensitive malignancy but acquires cross-resistance after relapse. This transformation is nearly inevitable in patients but has been difficult to capture in laboratory models. Here, we present a preclinical system that recapitulates acquired cross-resistance, developed from 51 patient-derived xenograft (PDX) models. Each model was tested in vivo against three clinical regimens: cisplatin plus etoposide, olaparib plus temozolomide, and topotecan. These drug-response profiles captured hallmark clinical features of SCLC, such as the emergence of treatment-refractory disease after early relapse. For one patient, serial PDX models revealed that cross-resistance was acquired through MYC amplification on extrachromosomal DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC, and this was corroborated in tumor biopsies from relapsed patients. We conclude that ecDNAs with MYC paralogs are recurrent drivers of cross-resistance in SCLC.

Significance:

SCLC is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. We use a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC.

This article is featured in Selected Articles from This Issue, p. 695
Supplementary Figure S2 from Estrogen Receptor Mutations as Novel Targets for Immunotherapy in Metastatic Estrogen Receptor–positive Breast Cancer
Authors: Goldberg Jonathan , Qiao Na , Guerriero Jennifer L. , Gross Brett , Meneksedag Yagiz , Lu Yoshimi F. , Philips Anne V. , Rahman Tasnim , Meric-Bernstam Funda , Roszik Jason , Chen Ken , Jeselsohn Rinath , Tolaney Sara M. , Peoples George E. , Alatrash Gheath , Mittendorf Elizabeth A.
Published: February 2024

Expression of ESR1 in various Healthy and Malignant Tissues
Supplementary Figure S1 from Estrogen Receptor Mutations as Novel Targets for Immunotherapy in Metastatic Estrogen Receptor–positive Breast Cancer
Authors: Goldberg Jonathan , Qiao Na , Guerriero Jennifer L. , Gross Brett , Meneksedag Yagiz , Lu Yoshimi F. , Philips Anne V. , Rahman Tasnim , Meric-Bernstam Funda , Roszik Jason , Chen Ken , Jeselsohn Rinath , Tolaney Sara M. , Peoples George E. , Alatrash Gheath , Mittendorf Elizabeth A.
Published: February 2024

Kinetics of Overlapping peptide
FIGURE 5 from Estrogen Receptor Mutations as Novel Targets for Immunotherapy in Metastatic Estrogen Receptor–positive Breast Cancer
Authors: Goldberg Jonathan , Qiao Na , Guerriero Jennifer L. , Gross Brett , Meneksedag Yagiz , Lu Yoshimi F. , Philips Anne V. , Rahman Tasnim , Meric-Bernstam Funda , Roszik Jason , Chen Ken , Jeselsohn Rinath , Tolaney Sara M. , Peoples George E. , Alatrash Gheath , Mittendorf Elizabeth A.
Published: February 2024

Peptide-specific CTLs effectively kill ER+ breast tumor cells. MCF7 cells were pulsed with corresponding peptides and labeled with calcein-AM. Cytotoxicity was determined by a standard calcein-AM release assay. MCF7 cells were pulsed with corresponding peptides. CG1-pulsed MCF7 cells and non-pulsed MCF7 cells were used as negative controls. Statistical significance was determined via one-way ANOVA. Data show percent cytotoxicity at the 10:1 effector:target ratio, and represent the average cytotoxicity of five experiments (run in triplicate) from different healthy female donors. *, P < 0.05; ***, P < 0.001.
Supplementary Figure S1 from Discovery and Preclinical Activity of BMS-986351, an Antibody to SIRPα That Enhances Macrophage-mediated Tumor Phagocytosis When Combined with Opsonizing Antibodies
Authors: Chan Henry , Trout Christina V. , Mikolon David , Adams Preston , Guzman Roberto , Mavrommatis Konstantinos , Abbasian Mahan , Hadjivassiliou Haralambos , Dearth Lawrence , Fox Brian A. , Sivakumar Pallavur , Cho Ho , Hariharan Kandasamy
Published: February 2024

CD47 gene expression across all of TCGA, shown with a boxplot for each indication (A), and a scatterplot showing the expression of SIRPA compared to the average macrophage gene expression (mean of CD163, CSF1R, CD14 and CD68 gene expression) in TCGA cohorts (B).
FIGURE 4 from Discovery and Preclinical Activity of BMS-986351, an Antibody to SIRPα That Enhances Macrophage-mediated Tumor Phagocytosis When Combined with Opsonizing Antibodies
Authors: Chan Henry , Trout Christina V. , Mikolon David , Adams Preston , Guzman Roberto , Mavrommatis Konstantinos , Abbasian Mahan , Hadjivassiliou Haralambos , Dearth Lawrence , Fox Brian A. , Sivakumar Pallavur , Cho Ho , Hariharan Kandasamy
Published: February 2024

Effect of BMS-986351, alone or in combination with rituximab, on the proportion of phagocytic macrophages in ABC (A) and GCB (B) cell lines. ABC, activated B cell; GCB, germinal center B cell.
FIGURE 3 from Discovery and Preclinical Activity of BMS-986351, an Antibody to SIRPα That Enhances Macrophage-mediated Tumor Phagocytosis When Combined with Opsonizing Antibodies
Authors: Chan Henry , Trout Christina V. , Mikolon David , Adams Preston , Guzman Roberto , Mavrommatis Konstantinos , Abbasian Mahan , Hadjivassiliou Haralambos , Dearth Lawrence , Fox Brian A. , Sivakumar Pallavur , Cho Ho , Hariharan Kandasamy
Published: February 2024

Gene expression data from TCGA across four indications (COAD = colon adenocarcinoma, DLBC = diffuse large B-cell lymphoma, HNSC = head and neck cancer, READ = rectal adenocarcinoma) with each point from one patient and expression units shown as the log2(normalized counts+1). The left panel of (A) shows that the absolute level of SIRPα (x-axis) is comparable to and often correlated with CD163 gene expression (y-axis). The right panel of (A) shows that CD163 is a representative marker of myeloid cells as it is highly correlated to CD14 (x-axis), with many other macrophage marker genes showing a similar pattern (not shown). Validation by IHC in tumor samples from CRC, SCCHN, and DLBCL (B), showing overlapping expression of macrophage marker CD163 and SIRPα (data shown are example images from the tumor microarray). Proportion of phagocytic macrophages after exposure to BMS-986351 alone or in combination with cetuximab in samples derived from donors with CRC (C) and SCCHN (D). Immunofluorescence illustrating increased tumor cell phagocytosis with BMS-986351 plus cetuximab compared with cetuximab plus isotype matched control (anti-RSV) or control alone in GP5d (E) and FaDu (F) tumor cells. Arrows indicate phagocytic macrophages. CRC, colorectal cancer; IHC, immunohistochemistry; RSV, respiratory syncytial virus; SCCHN, squamous cell carcinoma of head and neck.
Data from Estrogen Receptor Mutations as Novel Targets for Immunotherapy in Metastatic Estrogen Receptor–positive Breast Cancer
Authors: Goldberg Jonathan , Qiao Na , Guerriero Jennifer L. , Gross Brett , Meneksedag Yagiz , Lu Yoshimi F. , Philips Anne V. , Rahman Tasnim , Meric-Bernstam Funda , Roszik Jason , Chen Ken , Jeselsohn Rinath , Tolaney Sara M. , Peoples George E. , Alatrash Gheath , Mittendorf Elizabeth A.
Published: February 2024

Abstract
Estrogen receptor–positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy. In this study, we investigated ESR1 mutations as novel targets for breast cancer immunotherapy. Using machine learning algorithms, we identified ESR1-derived peptides predicted to form stable complexes with HLA-A*0201. We then validated the binding affinity and stability of the top predicted peptides through in vitro binding and dissociation assays and showed that these peptides bind HLA-A*0201 with high affinity and stability. Using tetramer assays, we confirmed the presence and expansion potential of antigen-specific CTLs from healthy female donors. Finally, using in vitro cytotoxicity assays, we showed the lysis of peptide-pulsed targets and breast cancer cells expressing common ESR1 mutations by expanded antigen-specific CTLs. Ultimately, we identified five peptides derived from the three most common ESR1 mutations (D538G, Y537S, and E380Q) and their associated wild-type peptides, which were the most immunogenic. Overall, these data confirm the immunogenicity of epitopes derived from ESR1 and highlight the potential of these peptides to be targeted by novel immunotherapy strategies.
Significance:
Estrogen receptor (ESR1) mutations have emerged as a key factor in endocrine therapy resistance. We identified and validated five novel, immunogenic ESR1-derived peptides that could be targeted through vaccine-based immunotherapy.
Data from Discovery and Preclinical Activity of BMS-986351, an Antibody to SIRPα That Enhances Macrophage-mediated Tumor Phagocytosis When Combined with Opsonizing Antibodies
Authors: Chan Henry , Trout Christina V. , Mikolon David , Adams Preston , Guzman Roberto , Mavrommatis Konstantinos , Abbasian Mahan , Hadjivassiliou Haralambos , Dearth Lawrence , Fox Brian A. , Sivakumar Pallavur , Cho Ho , Hariharan Kandasamy
Published: February 2024

Abstract
In normal cells, binding of the transmembrane protein CD47 to signal regulatory protein-α (SIRPα) on macrophages induces an antiphagocytic signal. Tumor cells hijack this pathway and overexpress CD47 to evade immune destruction. Macrophage antitumor activity can be restored by simultaneously blocking the CD47-SIRPα signaling axis and inducing a prophagocytic signal via tumor-opsonizing antibodies. We identified a novel, fully human mAb (BMS-986351) that binds SIRPα with high affinity. BMS-986351 demonstrated broad binding coverage across SIRPα polymorphisms and potently blocked CD47-SIRPα binding at the CD47 binding site in a dose-dependent manner. In vitro, BMS-986351 increased phagocytic activity against cell lines from solid tumors and hematologic malignancies, and this effect was markedly enhanced when BMS-986351 was combined with the opsonizing antibodies cetuximab and rituximab. A phase I dose-escalation/-expansion study of BMS-986351 for the treatment of advanced solid and hematologic malignancies is underway (NCT03783403).
Significance:
Increasing the phagocytotic capabilities of tumor-associated macrophages by modulating macrophage–tumor cell surface signaling via the CD47-SIRPα axis is a novel strategy. Molecules targeting CD47 have potential but its ubiquitous expression necessitates higher therapeutic doses to overcome potential antigen sink effects. The restricted expression pattern of SIRPα may limit toxicities and lower doses of the SIRPα antibody BMS-986351 may overcome target mediated drug disposition while maintaining the desired pharmacology.
Occupation, Retirement Age, and 20-Year Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study
Authors: Liu Albert C. , Patel Mehul D. , Gross Alden L. , Mosley Thomas H. , Schneider Andrea L.C. , Kucharska-Newton Anna M. , Sharrett A. Richey , Gottesman Rebecca F. , Koton Silvia
Published: February 2024

Introduction: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. Methods: Current or most recent occupation at ARIC baseline (1987–1989; aged 45–64 years) was categorized based on 1980 US Census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n = 14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999–2007 was classified as occurring before or after age 70 (n = 7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990–1992) to visit 5 (2011–2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. Results: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in white women but slower decline in black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in white men and women and in black men. Results did not change substantially after accounting for attrition. Conclusion: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in white participants and in black men. Further research should explore reasons for the observed associations and race-sex differences.