bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of 1-allyloxy-4-propoxybenzene (3c{3,6}) against Varroa destructor mites in honey bee colonies from Maryland, USA
Authors: Cook Steven C , Johnson Josephine D , Rogers Curtis W , Sachs Ian E , Feng Xinyi , Plettner Erika
Published: May 2024

Varroa destructor Oud (Acari: Varroidae) is a harmful ectoparasite of Apis mellifera L. honey bees causing widespread colony losses in Europe and North America. To control populations of these mites, beekeepers have an arsenal of different treatments, including both chemical and nonchemical options. However, nonchemical treatments can be labor intensive, and Varroa has gained resistance to some conventional pesticides, and the use of other chemical treatments is restricted temporally (e.g., cannot be applied during periods of honey production). Thus, beekeepers require additional treatment options for controlling mite populations. The compound 1-allyloxy-4-propoxybenzene (3c{3,6}) is a diether previously shown to be a strong feeding deterrent against Lepidopteran larvae and a repellent against mosquitoes and showed promise as a novel acaricide from laboratory and early field trials. Here we test the effect of the compound, applied at 8 g/brood box on wooden release devices, on honey bees and Varroa in field honey bee colonies located in Maryland, USA, and using a thymol-based commercial product as a positive control. 3c{3,6} had minimal effect on honey bee colonies, but more tests are needed to determine whether it affected egg production by queens. Against Varroa3c{3,6} had an estimated efficacy of 78.5%, while the positive control thymol product showed an efficacy of 91.3%. 3c{3,6} is still in the development stage, and the dose or application method needs to be revisited.
Elevated nitrogen and co-evolution history with competitors shape the invasion process of Galinsoga quadriradiata
Authors: Zhang Wen-Gang , Song Xing-Jiang , Petri Laís , Liu Gang , Chen Xiao-Yan , Liu Rui-Ling , Huang Fang-Fang , Zou Jia-Bin , Zhu Zhi-Hong
Published: May 2024

Invasive plants usually experience population differentiation as they expand from their initial invasive range to the edge. Moreover, invasive plants usually encounter competitors which shared different co-evolutionary histories with them. These factors may lead to varying responses of invasive plant populations to elevated nitrogen deposition during expansion. However, this issue has received limited attention in prior research. To address these challenges, we conducted a greenhouse experiment to investigate how population differentiation of Galinsoga quadriradiata interacts with the presence of various competitors in response to increased nitrogen deposition. Competitor types (new or old that shared short or long co-evolutionary history with the invader, respectively) were set to compete with the invasive central and edge populations under different nitrogen addition treatments. Individuals from the central population of G. quadriradiata, originating from the initial invasion range, showed greater total mass, reproduction and interspecific competitiveness compared with the edge population. Nitrogen addition improved growth and reproductive performance in both populations, and the central population had a stronger response compared with the edge population. The performance of G. quadriradiata was inhibited more effectively by old competitors than new competitors. Our results indicate that population differentiation occurs in terms of growth and competitiveness during the range expansion of G. quadriradiata, with the central population exhibiting superior performance. Co-evolutionary history with competitors is considered unfavorable for invasive plants in this study. Our results highlight the combined effects of population differentiation in invasive species and their co-evolution history with competitors in the context of global change factors.
Systematic Implications of Palynomorph Diversity Using Microscopic Trends Among Asteraceous Flora From the Drylands of Baluchistan, Pakistan
Authors: Sadia Bibi , Ahmad Mushtaq , Ramadan Mohamed Fawzy , Zafar Muhammad , Sultana Shazia , Noor Wajia , Makhkamov Trobjon , Yuldashev Akramjon , Khaydarov Khislat , Pieroni Andrea
Published: May 2024

Pollen micromorphological traits with taxonomic implications are first reported from the study area for 50 Asteraceous taxa belonging to nine tribes. Cichorieae (21 taxa), Cardueae (11 taxa), Inuleae (six taxa), and Anthemideae (four taxa) are the leading tribes. The research included Cousinia haeckeliae, Himalaiella afghana, Pterachaenia stewartii (endemic to Afghanistan and Pakistan), and Xylanthemum macropodum (endemic to Baluchistan). Light and scanning electron microscopy were employed for the visualization of pollen photomicrographs. The data was analyzed statistically via SPSS, PAST, and Origin. Significant diagnostic qualitative and quantitative palynological traits were explored for discrimination down to the species level within the tribes. All the investigated taxa possessed radial symmetry, isopolarity, and monad form (characters for distinction at the subdivision level). The aperture types were trizonocolporate, tetrazonocolporate, and tricolporate with number position and character (NPC) formulas N3P4C5, N4P4C5, and N3P4C3. Goniotreme, peritreme, and ptychotreme types of amb were recognized. Echinate, echinate lophate, scabrate, and gemmate sculpturing were present with and without perforated surface patterns. Variations in the shapes in polar and equatorial views and lacuna shapes further assisted the separation of taxa. The observed shape classes were perprolate, prolate spheroidal, prolate, subprolate, oblate spheroidal, suboblate, and oblate. Principal component analysis, correlation, standard probability plots, and ridge line paired features plot for quantitative variables determined the positive correlation between the length and width of colpi in equatorial and polar view with polar axis and equatorial diameter and number of spines between colpi with the number of spines per pollen. The number of spines per pollen was negatively correlated with the width and length of colpi in the polar view. Multiple sample analysis of variance (ANOVA) concluded that a high statistically significant difference exists among the means of analyzed traits. The examined qualitative and quantitative palynological traits revealed noticeable variations, thus providing the source for species discrimination in Asteraceous tribes.
Hotspots and photon rings in spherically symmetric space–times
Authors: Kocherlakota Prashant , Rezzolla Luciano , Roy Rittick , Wielgus Maciek
Published: May 2024

Future black hole (BH) imaging observations are expected to resolve finer features corresponding to higher order images of hotspots and of the horizon-scale accretion flow. In spherical space–times, the image order is determined by the number of half-loops executed by the photons that form it. Consecutive-order images arrive approximately after a delay time of ≈π times the BH shadow radius. The fractional diameters, widths, and flux-densities of consecutive-order images are exponentially demagnified by the lensing Lyapunov exponent, a characteristic of the space–time. The appearance of a simple point-sized hotspot when located at fixed spatial locations or in motion on circular orbits is investigated. The exact time delay between the appearance of its zeroth and first-order images agrees with our analytic estimate, which accounts for the observer inclination, with $\lesssim 20~{{\ \rm per\ cent}}$ error for hotspots located about ≲ 5M from a Schwarzschild BH of mass M. Since M87⋆ and Sgr A⋆ host geometrically thick accretion flows, we also explore the variation in the diameters and widths of their first-order images with disc scale-height. Using a simple ‘conical torus’ model, for realistic morphologies, we estimate the first-order image diameter to deviate from that of the shadow by $\lesssim 30~{{\ \rm per\ cent}}$ and its width to be ≲ 1.3M. Finally, the error in recovering the Schwarzschild lensing exponent (π), when using the diameters or the widths of the first and second-order images is estimated to be $\lesssim 20~{{\ \rm per\ cent}}$. It will soon become possible to robustly learn more about the space–time geometry of astrophysical BHs from such measurements.
Alternative localization of HEME OXYGENASE 1 in plant cells regulates cytosolic heme catabolism
Authors: Chen Yingxi , Nishimura Kohji , Tokizawa Mutsutomo , Yamamoto Yoshiharu Y , Oka Yoshito , Matsushita Tomonao , Hanada Kousuke , Shirai Kazumasa , Mano Shoji , Shimizu Takayuki , Masuda Tatsuru
Published: May 2024

Heme, an organometallic tetrapyrrole, is widely engaged in oxygen transport, electron delivery, enzymatic reactions, and signal transduction. In plants, it is also involved in photomorphogenesis and photosynthesis. HEME OXYGENASE 1 (HO1) initiates the first committed step in heme catabolism, and it has generally been thought that this reaction takes place in chloroplasts. Here, we show that HO1 in both Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) has 2 transcription start sites (TSSs), producing long (HO1L) and short (HO1S) transcripts. Their products localize to the chloroplast and the cytosol, respectively. During early development or de-etiolation, the HO1L/HO1S ratio gradually increases. Light perception via phytochromes (Phys) and cryptochromes elevates the HO1L/HO1S ratio in the whole seedling through the functions of ELONGATED HYPOCOTYL 5 (HY5) and HY5 HOMOLOG and through the suppression of DE-ETIOLATED 1, CONSTITUTIVE PHOTOMORPHOGENESIS 1, and PHYTOCHROME INTERACTING FACTORs. HO1L introduction complements the HO1-deficient mutant; surprisingly, HO1S expression also restores the short hypocotyl phenotype and high pigment content and helps the mutant recover from the genomes uncoupled (gun) phenotype. This indicates the assembly of functional Phys within these lines. Furthermore, our findings support the hypothesis that a mobile heme signal is involved in retrograde signaling from the chloroplast. Altogether, our work clarifies the molecular mechanism of HO1 TSS regulation and highlights the presence of a cytosolic bypass for heme catabolism in plant cells.
The white lupin trehalase gene LaTRE1 regulates cluster root formation and function under phosphorus deficiency
Authors: Xia Tianyu , Zhu Xiaoqi , Zhan Yujie , Liu Bowen , Zhou Xiangxue , Zhang Qian , Xu Weifeng
Published: May 2024

Under phosphorus (P) deficiency, white lupin (Lupinus albus L.) forms a specialized root structure, called cluster root (CR), to improve soil exploration and nutrient acquisition. Sugar signaling is thought to play a vital role in the development of CR. Trehalose and its associated metabolites are the essential sugar signal molecules that link growth and development to carbon metabolism in plants; however, their roles in the control of CR are still unclear. Here, we investigated the function of the trehalose metabolism pathway by pharmacological and genetic manipulation of the activity of trehalase in white lupin, the only enzyme that degrades trehalose into glucose. Under P deficiency, validamycin A treatment, which inhibits trehalase, led to the accumulation of trehalose and promoted the formation of CR with enhanced organic acid production, whereas overexpression of the white lupin TREHALASE1 (LaTRE1) led to decreased trehalose levels, lateral rootlet density, and organic acid production. Transcriptomic and virus-induced gene silencing results revealed that LaTRE1 negatively regulates the formation of CRs, at least partially, by the suppression of LaLBD16, whose putative ortholog in Arabidopsis (Arabidopsis thaliana) acts downstream of ARF7- and ARF19-dependent auxin signaling in lateral root formation. Overall, our findings provide an association between the trehalose metabolism gene LaTRE1 and CR formation and function with respect to organic acid production in white lupin under P deficiency.
Heterogeneous distribution of mitochondria and succinate dehydrogenase activity in human airway smooth muscle cells
Authors: Mahadev Bhat Sanjana , Sieck Gary C.
Published: May 2024

Succinate dehydrogenase (SDH) is a key mitochondrial enzyme involved in the tricarboxylic acid cycle, where it facilitates the oxidation of succinate to fumarate, and is coupled to the reduction of ubiquinone in the electron transport chain as Complex II. Previously, we developed a confocal‐based quantitative histochemical technique to determine the maximum velocity of the SDH reaction (SDHmax) in single cells and observed that SDHmax corresponds with mitochondrial volume density. In addition, mitochondrial volume and motility varied within different compartments of human airway smooth muscle (hASM) cells. Therefore, we hypothesize that the SDH activity varies relative to the intracellular mitochondrial volume within hASM cells. Using 3D confocal imaging of labeled mitochondria and a concentric shell method for analysis, we quantified mitochondrial volume density, mitochondrial complexity index, and SDHmax relative to the distance from the nuclear membrane. The mitochondria within individual hASM cells were more filamentous in the immediate perinuclear region and were more fragmented in the distal parts of the cell. Within each shell, SDHmax also corresponded to mitochondrial volume density, where both peaked in the perinuclear region and decreased in more distal parts of the cell. Additionally, when normalized to mitochondrial volume, SDHmax was lower in the perinuclear region when compared to the distal parts of the cell. In summary, our results demonstrate that SDHmax measures differences in SDH activity within different cellular compartments. Importantly, our data indicate that mitochondria within individual cells are morphologically heterogeneous, and their distribution varies substantially within different cellular compartments, with distinct functional properties.
Parasite‐derived microRNA let‐7‐5p detection for metacestodiasis based on rolling circular amplification‐assisted CRISPR/Cas9
Authors: Wang Liqun , Pu Guiting , Liu Tingli , Chen Guoliang , Li Hong , Amuda Tharheer Oluwashola , Cao Shanling , Yan Hongbin , Yin Hong , Fu Baoquan , Luo Xuenong
Published: May 2024

Metacestodiasis is an infectious disease caused by the larval stage of cestode parasites. This disease poses a serious health hazard to wildlife, livestock, and humans, and it incurs substantial economic losses by impacting the safety of the livestock industry, the quality of meat production, and public health security. Unfortunately, there is currently no available molecular diagnostic method capable of distinguishing cysticercus‐ and Echinococcus‐derived microRNAs (miRNAs) from other helminthes and hosts in the plasma of metacestode‐infected animals. This study aims to develop a specific, sensitive, and cost‐efficient molecular diagnostic method for cysticercosis and echinococcosis, particularly for early detection. The study developed a rolling circular amplification (RCA)‐assisted CRISPR/Cas9 detection method based on parasite‐derived miRNA let‐7‐5p. Using a series of dilutions of the let‐7 standard, the limit of detection (LOD) of the qPCR, RCA, and RCA‐assisted CRISPR/Cas9 methods was compared. The specificity of qPCR and CRISPR/Cas9 was evaluated using four artificially synthesized let‐7 standards from different species. A total of 151 plasma samples were used to evaluate the diagnostic performance. Additionally, the study also assessed the correlation between plasma levels of let‐7‐5p, the number of Taenia pisiformis cysticerci, and the weight of Echinococcus multilocularis cysts. The results demonstrated that the RCA‐assisted CRISPR/Cas9 assay could significantly distinguish let‐7 from cestodes and other species, achieving a LOD of 10 aM; the diagnostic sensitivity and specificity for rabbit cysticercosis and mouse E. multilocularis were 100% and 97.67%, and 100% and 100%, respectively. Notably, let‐7‐5p gradually increased in the plasma of T. pisiformis‐infected rabbits from 15 days post infection (dpi), peaked at 60 dpi, and persisted until 120 dpi. In E. multilocularis‐infected mice, let‐7‐5p gradually increased from 15 dpi and persisted until 90 dpi. Furthermore, the expression of let‐7‐5p positively correlated with the number of cysticerci and cyst weight. These results indicated that the let‐7‐5p‐based RCA‐assisted CRISPR/Cas9 assay is a sensitive and specific detection method that can be used as a universal diagnostic method for metacestodiasis, particularly for early diagnosis (15 dpi).
What Happens to Youth Baseball Players Diagnosed With Little League Shoulder and Little League Elbow Syndrome?
Authors: Jensen Evan J. , Pennock Andrew T. , Hulbert Molly A. , Tadlock Joshua C. , Paranjape Chinmay S. , Bryan Tracey P.
Published: May 2024

Background:

The long-term prognosis of baseball and softball players diagnosed with Little League elbow (LLE) and Little League shoulder (LLS) is unknown. Many of these athletes are potentially at risk of developing future shoulder and elbow injuries that may require surgical intervention. This study’s purpose is to retrospectively assess 5-year patient-reported outcomes and career progression of a series of youth baseball and softball players diagnosed with LLE and LLS.

Methods:

This institutional review board-approved, single-center, retrospective study evaluated 5-year outcomes of a cohort of youth baseball and softball players diagnosed with LLE and LLS between 2013 and 2017. Demographic and clinical data was recorded including age, gender, primary position, and months played per year. A standardized phone survey was obtained approximately 5 years post-treatment to assess upper extremity function, career progression, and pain recurrence.

Results:

Sixty-one patients (44 LLE, 17 LLS) met the inclusion criteria and participated in a standardized phone survey. The mean age at the time of diagnosis was 13.2 years and all but one of the athletes were male. On average, about 80% (34/44 LLE, 15/17 LLS) played baseball 9 months or more per year. After diagnosis and nonoperative management, more than 80% (37/44 LLE, 14/17 LLS) were able to return to competition, but up to 40% of players changed positions (9/44 LLE, 7/17 LLS). Five years later, less than half (21/44 LLE, 8/17 LLS) were playing baseball actively. The recurrence rate was >20% (9/42 LLE, 6/17 LLS) with a mean time of recurrence of 8.8 months. Patients who experienced symptom recurrence were less likely to play baseball 5 years later and had lower patient-reported outcomes.

Conclusions:

A diagnosis of LLE and LLS in early adolescence can be a setback for a young athlete. Fortunately, most athletes will be able to return to competition with ∼50% still competing at 5 years. Very few will progress to future arm surgery, but recurrence rates are relatively high, and these athletes are less likely to participate in their sport 5 years later.

Level of Evidence:

Level IV—Retrospective cohort study.
Clinical Practice of Pre-Assembling and Storing of Extracorporeal Membrane Oxygenation Systems
Authors: Winnersbach Patrick , Wallraff Alexander , Schadow Marlene , Rossaint Rolf , Kopp Rüdger , Bleilevens Christian , Strudthoff Lasse J.
Published: May 2024

According to the Extracorporeal Life Support Organization (ELSO) guidelines, pre-assembled and already primed extracorporeal membrane oxygenation (ECMO) systems can be safely stored for up to 30 days under specific conditions. This study gives a detailed overview of existing pre-assembly practices. An anonymous online survey was conducted among chief perfusionists at German ECMO centers. Forty-four of a total of 83 ECMO centers (53%) completed the survey. Thirty-three percent do not preassemble ECMO systems. Seventy-seven percent (n = 34) reported having preassembled ECMO systems readily available (30% dry preassembly/20% wet preassembly/27% wet preassembly with circulation). Half of the participating centers (50%) reported having a standard operating procedure (SOP) and the majority (57%) of chief perfusionists expressed a need for an evidence-based SOP. A maximum storage time for wet preassembled ECMO systems is established in 88% of departments. On average, wet preassembled systems are discarded after 20 days, which is below the ELSO’s safe limit of 30 days. Overall, this survey reveals a heterogeneous approach regarding the practice of provisioning preassembled ECMO systems. The demand for an evidence-based SOP for the preassembly and storing of ECMO systems becomes evident, necessitating the determination of hygienic standards, regular training, and a reliable maximum storage period.
Non–chest pain symptoms and likelihood of coronary occlusion in emergency department patients with ST segment elevation undergoing emergent coronary angiography
Authors: Ma Zhiyuan , Antoine Marc Kervin , Vefali Huseng , Manda Yugandhar , Salen Philip , Shoemaker Melinda , Stoltzfus Jill , Puleo Peter
Published: May 2024

Objectives

Patients presenting with suspected ST segment elevation myocardial infarction frequently have symptoms in addition to chest pain, including dyspnea, nausea or vomiting, diaphoresis, and lightheadedness or syncope. These symptoms are often regarded as supporting the diagnosis of infarction. We sought to determine the prevalence of the non–chest pain symptoms among patients who were confirmed as having a critically diseased coronary vessel as opposed to those with no angiographic culprit lesion.

Methods

Data from 1393 consecutive patients with ST segment elevation who underwent emergent coronary angiography were analyzed. Records were reviewed in detail for symptoms, ECG findings, prior history, angiographic findings, and in-hospital outcomes.

Results

Dyspnea was present in 50.8% of patients, nausea or vomiting in 36.5%, diaphoresis in 51.2%, and lightheadedness/syncope in 16.8%. On angiography, 1239 (88.9%) patients had a culprit lesion and 154 (11.1%) were found not to have a culprit. Only diaphoresis had a higher prevalence among the patients with, as compared with those without a culprit, with an odds ratio of 2.64 (P < 0.001). The highest occurrence of diaphoresis was among patients with a totally occluded artery, with an intermediate frequency among patients with a subtotal stenosis, and the lowest prevalence among those with no culprit. These findings were consistent regardless of ECG infarct location, affected vessel, patient age, or sex. Among the subset of patients who presented without chest discomfort, none of the symptoms were associated with the presence of a culprit.

Conclusion

The presence of diaphoresis, but not dyspnea, nausea, or lightheadedness is associated with an increased likelihood that patients presenting with ST elevation will prove to have a culprit lesion. In patients who present with ST elevation but without chest discomfort, these symptoms should not be regarded as ‘chest pain equivalents’. Further objective data among patients with angiographic confirmation of culprit lesion status is warranted.
Insight into the potential of bone turnover biomarkers: integration in the management of osteoporosis and chronic kidney disease-associated osteoporosis
Authors: Brouwers Pauline , Bouquegneau Antoine , Cavalier Etienne
Published: May 2024

Purpose of review

Disturbances in mineral and bone metabolism occurring in osteoporosis and chronic kidney disease-associated osteoporosis place patients at high risk of fracture making these conditions a major public health concern. Due to the limited use of bone histomorphometry in clinical practice, the gold standard for assessing bone turnover, extensive efforts have been made to identify bone turnover markers (BTMs) as noninvasive surrogates. Since the identification of certain commonly used markers several decades ago, considerable experience has been acquired regarding their clinical utility in such bone disorders.

Recent findings

Mounting evidence suggested that BTMs represent a simple, low-risk, rapid and convenient way to obtain data on the skeletal health and that they may be useful in guiding therapeutic choices and monitoring the response to treatment.

BTMs could provide clinicians with useful information, independent from, and often complementary to bone mineral density (BMD) measurements. They have proven valuable for monitoring the effectiveness of osteoporosis therapy, as well as promising for discriminating low and high turnover states. Improved performance is observed when BTMs are combined, which may be useful for selecting treatments for chronic kidney disease-bone mineral disorders (CKD-MBD).
High Reliability in a Safety Net Hospital Leading to Operational Excellence
Authors: Didion Lisa , Whitfield Candice , Bishop Phyllis , Jones Alan E. , Henderson J. Michael
Published: May 2024

Objective

The objective of this work was to establish sustainable systems for quality improvement in an Academic Medical Center and Safety Net Hospital.

Method

High reliability principles of leadership engagement, a culture of safety, and sustainable performance improvement were used. Target areas for improvement were clinical outcomes for patients, public reputation scores, and lower cost of care. The system was based on annual focused goals with specific targets, improvement teams, transparent scorecards, and data driven work. Program visibility was championed by leaders. Consistent education on quality, safety, efficiency, and effectiveness for all employees created buy-in. Data review and accountability tracked progress, helped resource allocation, and defined next steps.

Results

In the first 5 years, all patient quality and safety metrics improved between 10% and 60%. This improvement resulted in higher CMS Star Ranking and Leapfrog patient safety grade. The next phase included maximizing value by expanding into hospital operations and finance with a focus on improved clinical documentation and reduced length of stay and cost of care. Clinical documentation improvement led to a 15% increase in comorbidity capture. This positively impacted reported outcomes and hospital payment by appropriate risk adjustment. Length of stay was addressed with a new care coordination program and physician-driven utilization review.

Conclusions

High reliability principles are applicable in a resource limited healthcare system. Improved clinical and operational results were achieved through goal setting, improvement teams, and data driven projects leading to creation of an office of operational excellence.
Multiple Synchronous Thoracoabdominal Duplication Cysts With Ectopic Gastric Mucosa Detected on 99mTc-Pertechnetate Scintigraphy and SPECT/CT
Authors: Wakankar Ritwik , Sagar Sambit , Khan Dikhra , Dhiman Ayan , Kumar Rakesh
Published: May 2024

Thoracoabdominal duplication cysts are a congenital malformation of the posterior primitive foregut with synchronous thoracic and abdominal duplication cysts being found in up to 15% of cases. The presentation of duplication cysts depends on their location, size, and other factors, like the presence of ectopic functioning gastric mucosa, which is reported in 20%–30% of duplication cysts. 99mTc-pertechnetate scintigraphy along with SPECT/CT helps in the preoperative localization of ectopic functioning gastric mucosa in these duplication cysts. We report the scintigraphic and SPECT/CT findings of one such case, which helped in the final diagnosis and management of the patient.
A safety and feasibility analysis on the use of cold-stored platelets in combat trauma
Authors: Fisher Andrew D. , Stallings Jonathan D. , Schauer Steven G. , Graham Brock A. , Stern Caryn A. , Cap Andrew P. , Gurney Jennifer M. , Shackelford Stacy A.
Published: May 2024

BACKGROUND

Damage-control resuscitation has come full circle, with the use of whole blood and balanced components. Lack of platelet availability may limit effective damage-control resuscitation. Platelets are typically stored and transfused at room temperature and have a short shelf-life, while cold-stored platelets (CSPs) have the advantage of a longer shelf-life. The US military introduced CSPs into the battlefield surgical environment in 2016. This study is a safety analysis for the use of CSPs in battlefield trauma.

METHODS

The Department of Defense Trauma Registry and Armed Services Blood Program databases were queried to identify casualties who received room-temperature–stored platelets (RSPs) or both RSPs and CSPs between January 1, 2016, and February 29, 2020. Characteristics of recipients of RSPs and RSPs-CSPs were compared and analyzed.

RESULTS

A total of 274 patients were identified; 131 (47.8%) received RSPs and 143 (52.2%) received RSPs-CSPs. The casualties were mostly male (97.1%), similar in age (31.7 years), with a median Injury Severity Score of 22. There was no difference in survival for recipients of RSPs (88.5%) versus RSPs-CSPs (86.7%; p = 0.645). Adverse events were similar between the two cohorts. Blood products received were higher in the RSPs-CSPs cohort compared with the RSPs cohort. The RSPs-CSPs cohort had more massive transfusion (53.5% vs. 33.5%, p = 0.001). A logistic regression model demonstrated that use of RSPs-CSPs was not associated with mortality, with an adjusted odds ratio of 0.96 (p > 0.9; 95% confidence interval, 0.41–2.25).

CONCLUSION

In this safety analysis of RSPs-CSPs compared with RSPs in a combat setting, survival was similar between the two groups. Given the safety and logistical feasibility, the results support continued use of CSPs in military environments and further research into how to optimize resuscitation strategies.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Characterization of the Clostridioides difficile 630Δerm putative Pro-Pro endopeptidase CD1597
Authors: Claushuis Bart , de Ru Arnoud , van Veelen Peter A , Hensbergen Paul , Corver Jeroen
Published: May 2024

Clostridioides difficile is the leading cause of antibiotic-associated infections worldwide. Within the host, C. difficile can transition from a sessile to a motile state by secretion of PPEP-1, which releases the cells from the intestinal epithelium by cleaving adhesion proteins. PPEP-1 belongs to the group of Pro-Pro endopeptidases, which are characterized by their unique ability to cleave proline-proline bonds. Interestingly, another putative member of this group, CD1597, is present in C. difficile. Although it possesses a domain similar to other PPEPs, CD1597 displays several distinct features that suggest a markedly different role for this protein.
We investigated the proteolytic activity of CD1597 by testing various potential substrates. In addition, we investigated the effect of the absence of CD1597 by generating an insertional mutant of the cd1597 gene. Using the cd1597 mutant, we sought to identify phenotypic changes through a series of in vitro experiments and quantitative proteomic analyses. Furthermore, we aimed to study the localization of this protein using a fluorogenic fusion protein.
Despite its similarities to PPEP-1, CD1597 did not show proteolytic activity. In addition, the absence of CD1597 caused an increase in various sporulation proteins during the stationary phase, yet we did not observe any alterations in the sporulation frequency of the cd1597 mutant. Furthermore, a promoter activity assay indicated a very low expression level of cd1597 in vegetative cells that was independent of the culture medium and growth stage. The low expression was corroborated by our comprehensive proteomics analysis of whole cell cultures, which failed to identify CD1597. However, an analysis of purified C. difficile spores identified CD1597 as part of the spore proteome. Hence, we predict that the protein is involved in sporulation, although we were unable to define a precise role for CD1597 in C. difficile
Comparison of conservation strategies for California Channel Island Oak (Quercus tomentella) using climate suitability predicted from genomic data
Authors: Mead Alayna , Fitz-Gibbon Sorel , Knapp John , Sork Victoria
Published: May 2024

Management strategies, such as assisted gene flow, could increase resilience to climate change in tree populations. Knowledge of evolutionary history and genetic structure of species is needed to assess the risks and benefits of different strategies.Quercus tomentella,or Island Oak, is a rare oak restricted to six Channel Islands in California, USA, and Baja California, Mexico. Previous work has shown that Island Oaks on each island are genetically differentiated, but it is unclear whether assisted gene flow could enable populations to tolerate future climates. We performed whole-genome sequencing on Island Oak individuals andQ. chrysolepis,a closely related species that hybridizes with Island Oak (127 total), to characterize genetic structure and introgression across its range and assess the relationship between genomic variation and climate. We introduce and assess three potential management strategies with different trade-offs between conserving historic genetic structure and enabling populations to survive changing climates: the status quo approach; ecosystem preservation approach, which conserves the trees and their associated biodiversity; and species preservation approach, which conserves the species. We compare the impact of these approaches on predicted maladaptation to climate using Gradient Forest. We also introduce a climate suitability index to identify optimal pairs of seed sources and planting sites for approaches involving assisted gene flow. We found one island (Santa Rosa) that could benefit from the ecosystem preservation approach and also serve as a species preservation site. Overall, we find that both the ecosystem and species preservation approaches will do better than the status quo approach. If preserving Island Oak ecosystems is the goal, assisted migration into multiple sites could produce adapted populations. If the goal is to preserve a species, the Santa Rosa population would be suitable. This case study both illustrates viable conservation strategies for Island Oak and introduces a framework for tree conservation.
Posteruptive Loss of Enamel Proteins Concurs with Gain in Enamel Hardness
Authors: Karaaslan Hakan , Walker Alejandro R. , Gil-Bona Ana , Depalle Baptiste , Bidlack Felicitas B.
Published: May 2024

Tooth enamel maturation requires the removal of proteins from the mineralizing enamel matrix to allow for crystallite growth until full hardness is reached to meet the mechanical needs of mastication. While this process takes up to several years in humans before the tooth erupts, it is greatly accelerated in in the faster developing pig. As a result, pig teeth erupt with softer, protein-rich enamel that is similar to hypomineralized human enamel but continues to harden quickly after eruption.Proteins, such as albumin, that bind to enamel crystals and prevent crystal growth and enamel hardening have been suggested as cause for hypomineralized human enamel that does not naturally harden after eruption. However, albumin is abundant in pig enamel. It is unclear whether fast posteruptive enamel hardening in pigs occurs despite the high protein content or requires a facilitated protein loss to allow for crystal growth.

This study asked how the protein content in porcine enamel changes after eruption in relation to saliva. Based on previous data demonstrating the high albumin content in erupted porcine enamel, we hypothesize that following pre-eruptive maturation, enamel and saliva derived enzymes facilitate protein removal from porcine enamel after eruption. We analyzed enamel and the saliva proteome at three critical timepoints: at the time of tooth eruption, 2 weeks after eruption, and enamel 6 weeks after eruption. We used only fourth deciduous premolars and saliva samples from animals sacrificed at the respective time points to determine the organic content in tooth enamel, saliva, and saliva proteins within enamel.

We found a decrease in the number of proteins and their abundancy in enamel with posteruptive time, including a decrease in serum albumin within enamel. The rapid decrease in the first two weeks is in line with previously reported rapid increase in mineral density of porcine enamel after eruption. In addition to the enamel proteases KLK-4 and MMP-20, we identified serine-, cysteine-, aspartic-, and metalloproteases. Some of these were only identified in enamel, while almost half of the enzymes are in common with saliva at all timepoints. Our findings suggest that the fast posteruptive enamel maturation in the porcine model coincides with saliva exchange and influx of saliva enzymes into porous enamel.
Realigning representational drift in mouse visual cortex by flexible brain-machine interfaces
Authors: Zhao Siyuan , Shen Hao , Qin Shanshan , Jiang Shouhao , Tang Xin , Lee Madeleine , Zhang Xinhe , Lee Jaeyong , Chen Juntao , Liu Jia
Published: May 2024

The ability to stably decode brain activity is crucial for brain-machine interfaces (BMIs), which are often compromised by recording instability due to immune responses and probe drifting. In addition, many brain regions undergo intrinsic dynamics such as “representational drift”, in which neural activities associated with stable sensation and action continually change over time. In this study, we employed tissue-like flexible electrode arrays for recording visual stimulus-dependent single-unit action potentials in the mouse visual cortex. The flexible electrode array enabled us to record action potentials from the same neurons over extended periods under visual stimuli, allowing us to characterize the representational drift during these stimuli. With this approach, we tested hypotheses about the origins and mechanisms of representational drift, tracked latent dynamics transformation, and modeled these dynamics with affine transformation. Our findings enabled the construction of a single, long-term stable, high-performance visual information decoder that accounts for representational drift, potentiating chronically stable flexible BMIs in brain regions experiencing representational drifts.
Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory Targets
Authors: Agoro Rafiou , Myslinski Jered , Marambio Yamil G. , Janosevic Danielle , Jennings Kayleigh N. , Liu Sheng , Hibbard Lainey M. , Fang Fang , Ni Pu , Noonan Megan L. , Solis Emmanuel , Chu Xiaona , Wang Yue , Dagher Pierre C. , Liu Yunlong , Wan Jun , Hato Takashi , White Kenneth E.
Published: May 2024

FGF23 via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in rare and very common syndromes, however the spatial-temporal mechanisms dictating renal FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution. Computational analysis identified distinct epithelial, endothelial, stromal, and immune cell clusters, with differential expressional analysis uniquely tracking FGF23 bioactivity at each time point. FGF23 actions were sex independent but critically relied upon constitutive KL expression mapped within proximal tubule (S1-S3) and distal tubule (DCT/CNT) cell sub-populations. Temporal KL-dependent FGF23 responses drove unique and transient cellular identities, including genes in key MAPK- and vitamin D-metabolic pathways via early- (AP-1-related) and late-phase (EIF2 signaling) transcriptional regulons. Combining ATACseq/RNAseq data from a cell line stably expressing KL with thein vivoscRNAseq pinpointed genomic accessibility changes in MAPK-dependent genes, including the identification of FGF23-dependent EGR1 distal enhancers. Finally, we isolated unexpected crosstalk between FGF23-mediated MAPK signaling and pro-inflammatory TNF receptor activation via NF-κB, which blocked FGF23 bioactivityin vitroandin vivo. Collectively, our findings have uncovered novel pathways at the single cell level that likely influence FGF23-dependent disease mechanisms.

Translational statement

Inflammation and elevated FGF23 in chronic kidney disease (CKD) are both associated with poor patient outcomes and mortality. However, the links between these manifestations and the effects of inflammation on FGF23-mediated mineral metabolism within specific nephron segments remain unclear. Herein, we isolated an inflammatory pathway driven by TNF/NF-κB associated with regulating FGF23 bioactivity. The findings from this study could be important in designing future therapeutic approaches for chronic mineral diseases, including potential combination therapies or early intervention strategies. We also suggest that further studies could explore these pathways at the single cell level in CKD models, as well as test translation of our findings to interactions of chronic inflammation and elevated FGF23 in human CKD kidney datasets.
Proteogenomics analysis of human tissues using pangenomes
Authors: Wang Dong , Bouwmeester Robbin , Zheng Ping , Dai Chengxin , Sanchez Aniel , Shu Kunxian , Bai Mingze , Umer Husen M. , Perez-Riverol Yasset
Published: May 2024

The genomics landscape is evolving with the emergence of pangenomes, challenging the conventional single-reference genome model. The new human pangenome reference provides an extra dimension by incorporating variations observed in different human populations. However, the increasing use of pangenomes in human reference databases poses challenges for proteomics, which currently relies on UniProt canonical/isoform-based reference proteomics. Including more variant information in human proteomes, such as small and long open reading frames and pseudogenes, prompts the development of complex proteogenomics pipelines for analysis and validation. This study explores the advantages of pangenomes, particularly the human reference pangenome, on proteomics, and large-scale proteogenomics studies. We reanalyze two large human tissue datasets using the quantms workflow to identify novel peptides and variant proteins from the pangenome samples. Using three search engines SAGE, COMET, and MSGF+ followed by Percolator we analyzed 91,833,481 MS/MS spectra from more than 30 normal human tissues. We developed a robust deep-learning framework to validate the novel peptides based on DeepLC, MS2PIP and pyspectrumAI. The results yielded 170142 novel peptide spectrum matches, 4991 novel peptide sequences, and 3921 single amino acid variants, corresponding to 2367 genes across five population groups, demonstrating the effectiveness of our proteogenomics approach using the recent pangenome references.
SaprotHub: Making Protein Modeling Accessible to All Biologists
Authors: Su Jin , Li Zhikai , Han Chenchen , Zhou Yuyang , He Yan , Shan Junjie , Zhou Xibin , Chang Xing , Jiang Shiyu , Ma Dacheng ,   The OPMC, Steinegger Martin , Ovchinnikov Sergey , Yuan Fajie
Published: May 2024

Training and deploying deep learning models pose challenges for users without machine learning (ML) expertise. SaprotHub offers a user-friendly platform that democratizes the process of training, utilizing, storing, and sharing protein ML models, fostering collaboration within the biology community—all without requiring extensive machine learning expertise. At its core, Saprot is an advanced, foundational protein language model. Through its ColabSaprot framework, it supports potentially hundreds of protein training and prediction applications, enabling the co-construction and co-sharing of these trained models. This enhances user engagement and drives community-wide innovation.
Transportability of patient outcomes from a US clinical trial to real-world populations - a case study using Lung-MAP S1400I (NCT02785952)
Authors: Gupta Alind , Chan Kelvin , Gomes Manuel , Duffield Stephen , Ramagopalan Sreeram , Kent Seamus , Subbiah Vivek , Cheung Winson , Bendavid Eran , Arora Paul
Published: May 2024

2.

Background

The external validity of results from clinical trials to routine clinical practice is often questioned. This is sometimes because certain real world patient groups are excluded or underrepresented in clinical trials, or because standards of care in trials are different from those in real-world populations globally. This lack of external validity of trial results manifests as an efficacy-effectiveness gap. In this study, we aim to address the question of whether it is possible to extend results from a clinical trial to real-world populations across different countries. To do this, we use the Lung-MAP nonmatch sub-study S1400I trial (NCT02785952) as a case study.

Setting

Squamous cell lung carcinoma is a subtype of non-small cell lung cancer (NSCLC) accounting for 25-30% of cases. Compared to other NSCLC subtypes such as adenocarcinoma, the presence of actionable genetic variants is less common and there are fewer targeted therapies available for advanced/metastatic NSCLC (aNSCLC) of squamous subtype. Patients with squamous aNSCLC who progress on front-line chemotherapy commonly receive immunotherapy using immune checkpoint inhibitors such as nivolumab. The Lung-MAP nonmatch sub-study S1400I (NCT02785952) compared overall survival (OS) in patients with recurrent/stage IV squamous NSCLC randomized to receive either nivolumab monotherapy or nivolumab + ipilimumab combination therapy and found no significant difference in mortality rates between these groups. The trial included patients from the United States only.

Objectives

The goal of this study is to evaluate the transportability of results fromNCT02785952in United States patients to real-world populations in the United States, Germany, France, England and Japan. Using individual-level data for OS fromNCT02785952, we will adjust for baseline characteristics from published studies of real-world populations in these countries and benchmark the predicted OS against Kaplan-Meier estimates reported by these studies for patients with squamous cell aNSCLC treated with nivolumab. Sensitivity analyses for unmeasured prognostic variables will be performed.
Evidence of varicella zoster virus (VZV) reactivation in children with arterial ischemic stroke: Results of the VIPS II Study
Authors: Fullerton Heather J. , Hills Nancy K. , Wintermark Max , Dlamini Nomazulu , Amlie-Lefond Catherine , Dowling Michael M. , Jordan Lori C. , Bernard Timothy J. , Friedman Neil R. , Elkind Mitchell S.V. , Grose Charles ,   the VIPS II Investigators
Published: May 2024

Background

Varicella zoster virus (VZV) has been associated with focal cerebral arteriopathy (FCA) and arterial ischemic stroke (AIS) in childhood. The Vascular effects of Infection in Pediatric Stroke (VIPS) II study aimed to examine this relationship in the modern era when most children in North America and Australia receive VZV vaccination with live, attenuated virus.

Methods

This 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022), collected baseline [hyperacute (≤72 hours; n=194) and acute (4-6 days; n=181)] and convalescent (1-6 weeks; n=74) serum samples. Sites enrolled 95 stroke-free controls with single serum samples. A virology research laboratory measured VZV IgM and IgG titers by an in-house enzyme-linked immunosorbent assay (ELISA). Baseline IgG seropositivity indicated prior exposure (vaccination/infection) and elevated IgM titers indicated recent reactivation.

Results

Median (IQR) age was 11.6 (5.5-15.6) years for cases and 11.8 (6.8-15.3) years for controls. Baseline serologies indicated prior VZV exposure in 198 cases (97%) and all controls. Parents of cases reported VZV vaccination in 160 (78%) and remote chicken pox in three (1.4%). Twenty cases (9.8%) and three controls (3.1%) had serologic evidence of recent VZV reactivation (p=0.06); all had remote VZV exposure (vaccination in 19 cases and all controls) and all were asymptomatic. Recent VZV reactivation was seen in similar proportions in arteriopathic, cardioembolic, and idiopathic stroke. Of 32 cases of FCA, 4 (12.5%) had recent VZV reactivation, versus no cases of arterial dissection (n=10) or moyamoya (n=16).

Conclusions

Serologic evidence of recent VZV reactivation (≈1-6 weeks prior to stroke) was present in one in 10 cases of childhood AIS, including those without arteriopathy. Clinically silent VZV reactivation may be a childhood stroke trigger despite widespread vaccination. These cases could represent waning immunity with reactivation of either vaccine virus or wild-type virus after an unrecognized secondary VZV infection.