bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma protein binding of ceftriaxone in critically ill patients: can we predict unbound fractions?
Authors: Ewoldt Tim M J , Bahmany Soma , Abdulla Alan , Muller Anouk E , Endeman Henrik , Koch Birgit C P
Published: February 2023

Background

Standard antibiotic dosing is not suitable for critically ill patients, due to altered pharmacokinetics (PK) in these patients. Knowledge of protein binding is important for optimizing antibiotic exposure because only the unbound fraction is pharmacologically active. If unbound fractions can be predicted, minimal sampling techniques and less costly methods can be routinely used.

Methods

Data from the DOLPHIN trial, a prospective randomized clinical trial that included critically ill patients, were used. Total and unbound ceftriaxone concentrations were determined using a validated UPLC-MS/MS method. A non-linear saturable binding model was made using 75% of the trough concentrations and validated on the remaining data. Our model and previously published models were tested for their performance for subtherapeutic (<1 mg/L) and high (>10 mg/L) unbound concentrations.

Results

In total, 113 patients were sampled [Acute Physiology And Chronic Health Evaluation version 4 (APACHE IV) score 71 (IQR 55–87), albumin 28 g/L (IQR 24–32)]. This resulted in 439 samples (trough = 224, peak = 215). Unbound fractions were significantly different between samples taken at trough and peak times [10.9% (IQR 7.9–16.4) versus 19.7% (IQR 12.9–26.6), P < 0.0001], which was not explained by concentration differences. Our model and most literature models showed good sensitivity and low specificity to determine high and subtherapeutic ceftriaxone trough concentrations using only the total ceftriaxone and albumin concentrations.

Conclusions

Ceftriaxone protein binding is not concentration related in critically ill patients. Existing models show good ability to predict high concentrations, but low specificity in predicting subtherapeutic concentrations.
The Hazel Stem Borer,Agrilus pseudocoryli(Coleoptera: Buprestidae), as a Pest of Hybrid Hazelnuts
Authors: Perish Patrick K , Shanovich Hailey N , Koch Alexa N , Lindsey Amelia R I , Aukema Brian H
Published: February 2023

Nuts from hybrid hazels (Corylus americana Walter × Corylus avellana L.) are a burgeoning, novel industry for the Great Lakes region of the United States. As such, scant information exists about the pest complex, although stem-boring beetles in the genus Agrilus Curtis (Coleoptera: Buprestidae) have been noted by growers as potential pests. Here, we report results of a comprehensive survey of 186 plants in a hybrid hazel planting consisting of nine cultivars in southeastern Minnesota affected by stem borers. Sixteen percent of the hybrid hazel plants exhibited between 25 and 100% buprestid associated dieback. Morphological and molecular identification of the adult and larval buprestids colonizing hybrid hazel plants revealed that the hazel stem borer, Agrilus pseudocoryli Fisher, was the only species present. Adult A. pseudocoryli were observed on plants between 8 June and 13 July 2021. Plants with higher damage ratings from the hazel stem borer were more likely to exhibit signs of eastern filbert blight (Anisogramma anomala Peck), a fungal pathogen virulent to C. avellana. Some hazel cultivars were more susceptible to damage from stem borers than others. Taken together, our findings suggest that the hazel stem borer has the potential to impact hybrid hazelnut yield. We speculate that a regional drought may have promoted increased populations of the hazel stem borer, as native Agrilus species are often secondary pests that become problematic when environmental stresses decrease host resistance. More research is needed to elucidate interactions between hazels, buprestid pests, and environmental conditions to predict impacts on crop yields.
Morphological Variation in Bumblebees (Bombus terrestris) (Hymenoptera:Apidae) After Three Decades of an Island Invasion
Authors: Kardum Hjort Cecilia , Smith Henrik G , Allen Andrew P , Dudaniec Rachael Y
Published: February 2023

Introduced social insects can be highly invasive outside of their native range. Around the world, the introduction and establishment of the eusocial bumblebee Bombus terrestris (L. 1758) (Hymenoptera: Apidae) has negatively impacted native pollinators and ecosystems. Understanding how morphological variation is linked to environmental variation across invasive ranges can indicate how rapidly species may be diverging or adapting across novel ranges and may assist with predicting future establishment and spread. Here we investigate whether B. terrestris shows morphological variation related to environmental variation across the island of Tasmania (Australia) where it was introduced three decades ago. We collected 169 workers from 16 sites across Tasmania and related relative abundance and morphology to landscape-wide climate, land use, and vegetation structure. We found weak morphological divergence related to environmental conditions across Tasmania. Body size of B. terrestris was positively associated with the percentage of urban land cover, a relationship largely driven by a single site, possibly reflecting high resource availability in urban areas. Proboscis length showed a significant negative relationship with the percentage of pasture. Wing loading and local abundance were not related to the environmental conditions within sites. Our results reflect the highly adaptable nature of B. terrestris and its ability to thrive in different environments, which may have facilitated the bumblebee’s successful invasion across Tasmania.
Testing the accuracy of likelihoods for cluster abundance cosmology
Authors: Payerne C , Murray C , Combet C , Doux C , Fumagalli A , Penna-Lima M
Published: February 2023

The abundance of galaxy clusters is a sensitive probe to the amplitude of matter density fluctuations, the total amount of matter in the Universe as well as its expansion history. Inferring correct values and accurate uncertainties of cosmological parameters requires accurate knowledge of cluster abundance statistics, encoded in the likelihood function. In this paper, we test the accuracy of cluster abundance likelihoods used in the literature, namely the Poisson and Gaussian likelihoods as well as the more complete description of the Gauss–Poisson Compound likelihood. This is repeated for a variety of binning choices and analysis setups. In order to evaluate the accuracy of a given likelihood, this work compares individual posterior covariances to the covariance of estimators over the 1000 simulated dark matter halo catalogues obtained from PINOCCHIO algorithm. We find that for Rubin/LSST and Euclid-like surveys the Gaussian likelihood gives robust constraints over a large range of binning choices. The Poisson likelihood, that does not account for sample covariance, always underestimates the errors on the parameters, even when the sample volume is reduced or only high-mass clusters are considered. We find no benefit in using the more complex Gauss–Poisson Compound likelihood as it gives essentially the same results as the Gaussian likelihood, but at a greater computational cost. Finally, in this ideal setup, we note only a small gain on the parameter error bars when using a large number of bins in the mass–redshift plane.
Substructure, supernovae, and a time-resolved star formation history for Upper Scorpius
Authors: Briceño-Morales Geovanny , Chanamé Julio
Published: February 2023

The improved astrometry precision of Gaia-eDR3 allows us to perform a detailed study of the Upper Scorpius OB association and revisit its spatial, kinematic, and age substructure. We achieve this by combining clustering techniques and complementing with age estimations based on Gaia photometry. Our census retrieves 3661 candidate members for Upper Scorpius with contamination ∼9 per cent. We also extract an astrometrically clean sample of 3004 sources with contamination ∼6 per cent. We show that Upper Scorpius can be divided into at least three main kinematic groups. We systematically investigate and characterize the Upper Scorpius’ internal structure, revealing that at least ∼34 per cent of its stellar populations are contained in seven spatial substructures, with well defined boundaries, kinematics, and relative ages with suggested names: π Scorpii (20 $^{\pm 2}_{\pm 1}$ Myr), α Scorpii (14$^{\pm 2}_{\pm 1}$ Myr), δ Scorpii (9$^{\pm 2}_{\pm 1}$ Myr), β Scorpii (8$^{\pm 1}_{\pm 1}$ Myr), ω Scorpii (8$^{\pm 1}_{\pm 1}$ Myr), ν Scorpii (7$^{\pm 1}_{\pm 1}$ Myr), after their brightest member, and the well known ρ Ophiuchi (4$^{\pm 1}_{\pm 1}$ Myr). We find a clear correlation in (1) density-age, providing an empirical expansion law to be tested in other associations, and (2) tangential velocity-age, providing constrains on the dynamics of these substructures and the position of potential past triggering events. We estimate the time at which four potential supernovae events occurred in Upper Scorpius. Based on these findings, we tie together previous work on the region and suggest a star formation history with unprecedented temporal resolution.
On the observability of recurrent nova super-remnants
Authors: Healy-Kalesh M W , Darnley M J , Harvey É J , Copperwheat C M , James P A , Andersson T , Henze M , O’Brien T J
Published: February 2023

The nova super-remnant (NSR) surrounding M 31N 2008-12a (12a), the annually erupting recurrent nova (RN), is the only known example of this phenomenon. As this structure has grown as a result of frequent eruptions from 12a, we might expect to see NSRs around other RNe; this would confirm the RN–NSR association and strengthen the connection between novae and type Ia supernovae (SN Ia) as NSRs centred on SN Ia provide a lasting, unequivocal signpost to the single degenerate progenitor type of that explosion. The only previous NSR simulation used identical eruptions from a static white dwarf (WD). In this Paper, we simulate the growth of NSRs alongside the natural growth/erosion of the central WD, within a range of environments, accretion rates, WD temperatures, and initial WD masses. The subsequent evolving eruptions create dynamic NSRs tens of parsecs in radius comprising a low-density cavity, bordered by a hot ejecta pile-up region, and surrounded by a cool high-density, thin, shell. Higher density environments restrict NSR size, as do higher accretion rates, whereas the WD temperature and initial mass have less impact. NSRs form around growing or eroding WDs, indicating that NSRs also exist around old novae with low-mass WDs. Observables such as X-ray and H α emission from the modelled NSRs are derived to aid searches for more examples; only NSRs around high accretion rate novae will currently be observable. The observed properties of the 12a NSR can be reproduced when considering both the dynamically grown NSR and photoionization by the nova system.
Functional analysis of polymorphism haplotypes of MGMT in residents of high background radiation area
Authors: Zhou Linqian , Zhang Sufen , Huang WeiXu , Zhang Lingyu , Cai Yashi , Ke Weiyi , Cai Lina , Zou Jianming , Chen Huifeng
Published: February 2023

To investigate the distribution of polymorphisms and their frequent haplotypes in the regulatory region of MGMT in residents of high background radiation area (HBRA) and their impacts on transcriptional activity, we collected DNA samples from 83 healthy Chinese residents in HBRA and searched for genetic polymorphisms in the regulatory region of MGMT. Haplotypes were characterized by Haploview analysis. Transcriptional activities of different polymorphism haplotypes were detected by using a dual-luciferase reporter assay. Six genetic polymorphisms were identified within the regulatory region (1024 bp) of MGMT. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic polymorphisms. These polymorphisms we found to be in high LD, with a Dʹ of 0.928 (r2 = 0.581) for −808 T>C and −19 C>T, 0.928 (r2 = 0.581) for −797 G>A and −19 C>T in Han Chinese HBRA residents. Complete LD with a Dʹ of 1.0 (r2 = 1.0) was observed between −808 T>C and −797 G>A. Haploview analysis revealed the existence of three polymorphism haplotypes in the core region of regulatory region of MGMT. Using serially truncated regulatory region of human MGMT luciferase reporter gene constructs, we found a 1002 bp (−637 nt to +365 nt) fragment in the MGMT gene was the core region. Dual-luciferase reporter assays showed that different polymorphism haplotypes bearing different variant alleles exhibit distinct transcriptional activities, especially the polymorphism haplotype carrying −19 T has the strongest transcriptional activity. In summary, the present study obtained genetic characteristics of the six polymorphisms in the regulatory region of the MGMT gene in HBRA residents, and the results suggest that different polymorphism haplotypes have significant effects on the transcriptional activity of the MGMT and that the −19 C>T polymorphism may be a functional variant involved in the transcriptional regulation of the MGMT gene.
Retreatment of Patients With Metastatic Cutaneous Melanoma Who Relapse After Elective Checkpoint Inhibitor Discontinuation After a Complete Remission
Authors: Sadrolashrafi Kaviyon , Samlowski Wolfram
Published: February 2023

Introduction

Checkpoint blockade has improved the response rate and survival in metastatic melanoma. Elective treatment discontinuation appears to be reasonable in most patients who have achieved a confirmed complete remission. It seems crucial to understand whether restarting immune checkpoint inhibitor therapy can induce additional responses or remissions in rare patients who relapse.

Methods

A retrospective analysis identified only 10 patients who relapsed after elective treatment discontinuation after a radiologically confirmed remission. These patients were retreated with single-agent PD-1 or combined CTLA-4 plus PD-1-directed monoclonal antibodies.

Results

We found an initial complete response rate of 20% (2 patients) following retreatment. With a median follow-up of 26 months, the addition of individualized salvage therapies converted an additional 4 patients to a 2nd remission. All 6 of these patients have again discontinued therapy. Three patients have died of metastatic melanoma, while another is receiving salvage therapy. Six of our 10 patients experienced grades 2-3 retreatment-related toxicity. There were no hospitalizations or fatalities.

Discussion

Retreatment of relapsing patients resulted in 20% complete responses with checkpoint inhibitors. The planned addition of other treatment modalities converted another 4 patients (40%) to a durable 2nd remission. This sequential approach merits further exploration in prospective clinical trials.
Loss of CpFTSY Reduces Photosynthetic Performance and Affects Insertion of PsaC of PSI in Diatoms
Authors: Nymark Marianne , Finazzi Giovanni , Volpe Charlotte , Serif Manuel , Fonseca Davi de Miranda , Sharma Animesh , Sanchez Nicolas , Sharma Amit Kumar , Ashcroft Felicity , Kissen Ralph , Winge Per , Bones Atle Magnar
Published: February 2023

The chloroplast signal recognition particle (CpSRP) receptor (CpFTSY) is a component of the CpSRP pathway that post-translationally targets light-harvesting complex proteins (LHCPs) to the thylakoid membranes in plants and green algae containing chloroplasts derived from primary endosymbiosis. In plants, CpFTSY also plays a major role in the co-translational incorporation of chloroplast-encoded subunits of photosynthetic complexes into the thylakoids. This role has not been demonstrated in green algae. So far, its function in organisms with chloroplasts derived from secondary endosymbiotic events has not been elucidated. Here, we report the generation and characterization of mutants lacking CpFTSY in the diatom Phaeodactylum tricornutum. We found that this protein is not involved in inserting LHCPs into thylakoid membranes, indicating that the post-translational part of the CpSRP pathway is not active in this group of microalgae. The lack of CpFTSY caused an increased level of photoprotection, low electron transport rates, inefficient repair of photosystem II (PSII), reduced growth, a strong decline in the PSI subunit PsaC and upregulation of proteins that might compensate for a non-functional co-translational CpSRP pathway during light stress conditions. The phenotype was highly similar to the one described for diatoms lacking another component of the co-translational CpSRP pathway, the CpSRP54 protein. However, in contrast to cpsrp54 mutants, only one thylakoid membrane protein, PetD of the Cytb6f complex, was downregulated in cpftsy. Our results point to a minor role for CpFTSY in the co-translational CpSRP pathway, suggesting that other mechanisms may partially compensate for the effect of a disrupted CpSRP pathway.
MEDIATOR SUBUNIT17 is required for transcriptional optimization of root system architecture in Arabidopsis
Authors: Agrawal Rekha , Singh Amrita , Giri Jitender , Magyar Zoltan , Thakur Jitendra Kumar
Published: February 2023

Sucrose and auxin are well-known determinants of root system architecture (RSA). However, the factors that connect the signaling pathways evoked by these two critical factors during root development are poorly understood. In this study, we report the role of MEDIATOR SUBUNIT17 (MED17) in RSA and its involvement in the transcriptional integration of sugar and auxin signaling pathways in Arabidopsis (Arabidopsis thaliana). Sucrose regulates root meristem activation through the TARGET OF RAPAMYCIN-E2 PROMOTER BINDING FACTOR A (TOR-E2FA) pathway, and auxin regulates lateral root (LR) development through AUXIN RESPONSE FACTOR-LATERAL ORGAN BOUNDARIES DOMAIN (ARF-LBDs). Both sucrose and auxin play a vital role during primary and LR development. However, there is no clarity on how sucrose is involved in the ARF-dependent regulation of auxin-responsive genes. This study establishes MED17 as a nodal point to connect sucrose and auxin signaling. Transcription of MED17 was induced by sucrose in an E2FA/B-dependent manner. Moreover, E2FA/B interacted with MED17, which can aid in the recruitment of the Mediator complex on the target promoters. Interestingly, E2FA/B and MED17 also occupied the promoter of ARF7, but not ARF19, leading to ARF7 expression, which then activates auxin signaling and thus initiates LR development. MED17 also activated cell division in the root meristem by occupying the promoters of cell–cycle genes, thus regulating their transcription. Thus, MED17 plays an important role in relaying the transcriptional signal from sucrose to auxin-responsive and cell–cycle genes to regulate primary and lateral root development, highlighting the role of the Mediator as the transcriptional processor for optimal root system architecture in Arabidopsis.
Autophagy and multivesicular body pathways cooperate to protect sulfur assimilation and chloroplast functions
Authors: Fu Yunting , Fan Baofang , Li Xifeng , Bao Hexigeduleng , Zhu Cheng , Chen Zhixiang
Published: February 2023

Autophagy and multivesicular bodies (MVBs) represent 2 closely related lysosomal/vacuolar degradation pathways. In Arabidopsis (Arabidopsis thaliana), autophagy is stress-induced, with deficiency in autophagy causing strong defects in stress responses but limited effects on growth. LYST-INTERACTING PROTEIN 5 (LIP5) is a key regulator of stress-induced MVB biogenesis, and mutation of LIP5 also strongly compromises stress responses with little effect on growth in Arabidopsis. To determine the functional interactions of these 2 pathways in Arabidopsis, we generated mutations in both the LIP5 and AUTOPHAGY-RELATED PROTEIN (ATG) genes. atg5/lip5 and atg7/lip5 double mutants displayed strong synergistic phenotypes in fitness characterized by stunted growth, early senescence, reduced survival, and greatly diminished seed production under normal growth conditions. Transcriptome and metabolite analysis revealed that chloroplast sulfate assimilation was specifically downregulated at early seedling stages in the atg7/lip5 double mutant prior to the onset of visible phenotypes. Overexpression of adenosine 5′-phosphosulfate reductase 1, a key enzyme in sulfate assimilation, substantially improved the growth and fitness of the atg7/lip5 double mutant. Comparative multi-omic analysis further revealed that the atg7/lip5 double mutant was strongly compromised in other chloroplast functions including photosynthesis and primary carbon metabolism. Premature senescence and reduced survival of atg/lip5 double mutants were associated with increased accumulation of reactive oxygen species and overactivation of stress-associated programs. Blocking PHYTOALEXIN DEFICIENT 4 and salicylic acid signaling prevented early senescence and death of the atg7/lip5 double mutant. Thus, stress-responsive autophagy and MVB pathways play an important cooperative role in protecting essential chloroplast functions including sulfur assimilation under normal growth conditions to suppress salicylic-acid-dependent premature cell-death and promote plant growth and fitness.
Safety profile and technical success rate of computed tomography–guided atlanto-axial lateral articulation injections
Authors: Liou Harris , Diehn Felix E , Lehman Vance T , Murthy Naveen S , Carr Carrie M , Madhavan Ajay A , Benson John C , Oien Michael P , Kim Dong Kun
Published: February 2023

Objective

To describe the technique, safety profile, and outcome of computed tomography (CT)–guided atlanto-axial lateral articulation injections performed at our institution.

Methods

Consecutive cases of all CT-guided atlanto-axial injections performed from January 2017 to April 2022 at our institution were searched in the electronic medical records. Patient charts were reviewed for demographics, characterization of pain, potential altered anatomy, pain level before and immediately after the procedure, procedure technique, complications, and follow-up outcomes, if available.

Results

Forty-five injections in 40 different patients were included. The average age was 67.4 years, and 28 (70%) of the patients were female. Of the 45 injections, 43 (96%) were technically successful. The average change in pain score (0–10) from immediately before to immediately after the injection was –3.36 (SD = 2.87, range = –8 to +3). Of all injections, 14 (31%) had a postprocedural pain score of zero. In 2 cases (4%), patients reported an increase in pain score immediately after the injection. In 3 cases (7%), transient non–vertebral artery vascular uptake of contrast was documented during the procedure, which could be cleared with needle repositioning. There were no complications.

Conclusion

CT-guided atlanto-axial lateral articulation injection is a safe procedure with a high technical success rate. It allows for direct visualization of vital structures and provides an alternative option to the traditional fluoroscopic guidance, especially in cases of prior technically unsuccessful fluoroscopically guided injection or altered anatomy.
A research on the effectiveness of innovation policy for regional innovation under Chinese long-range plan
Authors: Yang Boxu , Liu Xielin , Gao Yuchen , Zhu Langmei
Published: February 2023

By adopting a set of panel data from thirty provinces in China from 2007 to 2017, this paper examines how regional innovation efficiency is influenced by different types of innovation policies from a specific long-range plan (‘National Medium- and Long-Term Science and Technology Development Plan (2006–20)’). We incorporate public direct research and development (R&D) grants, R&D tax credits, and intellectual property rights (IPR) protection into our research. We also explore the heterogeneous influences of these factors at different stages in regional innovation development. The results indicate that public direct R&D grants have a significantly negative influence, especially in innovation-catching-up regions. Conversely, the R&D tax credit has a considerably positive impact on innovation-catching-up regions. IPR protection plays various roles according to different innovation development stages. Specifically, IPR protection has a positive impact on innovation-leading regions, while it negatively influences regional innovation efficiency in innovation-catching-up regions.
Chromatin accessibility dynamics insight into crosstalk between regulatory landscapes in poplar responses to multiple treatments
Authors: Wang Weiwei , Chen Kai , Chen Ningning , Gao Jinwen , Zhang Wenyan , Gong Jue , Tong Shaofei , Chen Yang , Li Yiling , Feng Yanlin , Jiang Yuanzhong , Ma Tao
Published: February 2023

Perennial trees develop and coordinate endogenous response signaling pathways, including their crosstalk and convergence, to cope with various environmental stresses which occur simultaneously in most cases. These processes are involved in gene transcriptional regulations that depend on dynamic interactions between regulatory proteins and corresponding chromatin regions, but the mechanisms remain poorly understood in trees. In this study, we detected chromatin regulatory landscapes of poplar under abscisic acid, methyl jasmonate, salicylic acid and sodium chloride (NaCl) treatment, through integrating ATAC-seq and RNA-seq data. Our results showed that the degree of chromatin accessibility for a given gene is closely related to its expression level. However, unlike the gene expression that shows treatment-specific response patterns, changes in chromatin accessibility exhibit high similarities under these treatments. We further proposed and experimentally validated that a homologous gene copy of RESPONSIVE TO DESICCATION 26 mediates the crosstalk between jasmonic acid and NaCl signaling pathways by directly regulating the stress-responsive genes and that circadian clock-related transcription factors like REVEILLE8 play a central role in response of poplar to these treatments. Overall, our study provides a chromatin insight into the molecular mechanism of transcription regulatory networks in response to different environmental stresses and raises the key roles of the circadian clock of poplar to adapt to adverse environments.
Critères de constitution des sociétés commerciales en droit OHADA et burundais
Authors: Nzohabonayo Anaclet , Clerson Iradukunda Olivier
Published: February 2023

Cette réflexion a examiné les critères de légalité et d’opérationnalité qui président à la constitution des sociétés commerciales dans le droit OHADA et burundais. Le code burundais des sociétés privées et à participation publique et l’Acte uniforme portant société commerciale et groupement d’intérêt économique ont servi de supports d’analyse. L’objectif consistait à examiner les critères qui régissent la formation des sociétés commerciales dans ces espaces juridiques afin d’en préciser le contenu pour après dégager les spécificités qui les caractérisent. Au seuil de la réflexion, l’étude conclut que les deux régimes juridiques partagent en commun les grands principes de formation des sociétés commerciales. Toutefois, à l’intérieur de ces principes se trouvent certaines spécificités qui font que ces régimes se démarquent l’un de l’autre. Les différences portent notamment sur la fixation du montant du capital minimum, la société anonyme unipersonnelle, la libération des apports en numéraire et la quotité des apports en industrie et bien d’autres.
Exploring the Relationship Between Pattern-Triggered Immunity and Quantitative Resistance to Xanthomonas vasicola pv. vasculorum in Maize
Authors: Mullens Alexander , Lipka Alexander E. , Balint-Kurti Peter , Jamann Tiffany
Published: February 2023

Bacterial leaf streak (BLS) of maize is an emerging foliar disease of maize in the Americas. It is caused by the gram-negative nonvascular bacterium Xanthomonas vasicola pv. vasculorum. There are no chemical controls available for BLS, and thus, host resistance is crucial for managing X. vasicola pv. vasculorum. The objective of this study was to examine the genetic determinants of resistance to X. vasicola pv. vasculorum in maize, as well as the relationship between other defense-related traits and BLS resistance. Specifically, we examined the correlations among BLS severity, severity for three fungal diseases, flg-22 response, hypersensitive response, and auricle color. We conducted quantitative trait locus (QTL) mapping for X. vasicola pv. vasculorum resistance using the maize recombinant inbred line population Z003 (B73 × CML228). We detected three QTLs for BLS resistance. In addition to the disease resistance QTL, we detected a single QTL for auricle color. We observed significant, yet weak, correlations among BLS severity, levels of pattern-triggered immunity response and leaf flecking. These results will be useful for understanding resistance to X. vasicola pv. vasculorum and mitigating the impact of BLS on maize yields.
A new approach to building a strong leadership bench
Authors: Lang Kathryn , Nash Alice
Published: February 2023

Planning for the nurse manager of the future
Predictors of the Need for Surgery in Cervical Ossification of the Posterior Longitudinal Ligament
Authors: Masuda Soichiro , Fukasawa Toshiki , Takeuchi Masato , Fujibayashi Shunsuke , Otsuki Bungo , Murata Koichi , Shimizu Takayoshi , Matsuda Shuichi , Kawakami Koji
Published: February 2023

Study Design:

Retrospective cohort study.

Objective:

The aim of this study was to determine predictors associated with the need

for cervical ossification of the posterior longitudinal ligament (cOPLL) surgery among

individuals with cOPLL.

Summary of Background Data:

cOPLL is a spinal disorder caused by ectopic ossification of the posterior longitudinal ligament. However, factors associated with a higher rate of surgery to treat the neurological symptoms of cOPLL are poorly understood.

Materials and Methods:

This retrospective population-based cohort study using a commercial administrative claims database from JMDC Inc. (Tokyo, Japan) enrolled patients newly diagnosed with cOPLL from April 2005 to October 2020 and followed to April 2021. A total of 1506 cOPLL patients aged 18 years or older with no history of cervical spine surgery and with a record of metabolic profiles obtained at general health checkups were included. Cox proportional hazards regression models identified patient characteristics and comorbidities associated with cOPLL surgery.

Results:

Of 1506 patients with cOPLL with a median of 1.8 years of follow-up after initial cOPLL diagnosis, 439 (29.2%) received cOPLL surgery. The 1-year cumulative incidence (95% CI) was 26.0% (23.7–28.2). In multivariable Cox proportional regression analysis, male (hazard ratio: 1.68; 95% CI: 1.26–2.24; P < 0.001) and obesity (body mass index: ≥25) (hazard ratio: 1.45; 95% CI: 1.10–1.89; P = 0.007) were associated with an increased risk of cOPLL surgery.

Conclusions:

In this large claims-based study of adults newly diagnosed with cOPLL, males and obesity were associated with a higher risk of cOPLL surgery. These findings may help clinicians to predict the future course of cOPLL in patients, although further research is needed to elucidate the biological role of these progression-associated factors.
Medial Locking Plate Can Increase the Fixation Stability of Vertical Femoral Neck Fracture in Young Adults?
Authors: Zanardi Vinícius Vieira , Guimarães João Antonio Matheus , Möller João Victor da Silveira , Roesler Carlos Rodrigo de Mello
Published: February 2023

Introduction:

Vertical femoral neck fractures in young adults are usually caused by high-energy trauma. These injuries are difficult to stabilize due to significant shear forces acting on the fracture site. Their treatment is challenging and with high risks of complications, such as fixation failure, malunion, nonunion, and avascular necrosis of the femoral head.

Material and Methods:

It compared the biomechanical stability provided by 3 different fixation methods: (1) dynamic hip screw with derotation screw, (2) cannulated screws with a conventional medial bone plate, and (3) cannulated screws with a locked medial bone plate. These fixation structures were applied on fourth-generation medium-sized synthetic bones, with a 17 pound per cubic foot cellular foam core and cervico-diaphyseal angle of 120 degrees were used. The comparison was performed through biomechanical tests under cyclic loading followed by an ultimate load. The interfragmentary movement at the fracture site was the main variable for the cyclical phase.

Results:

The biomechanical comparison showed no statistical differences (P > 0.05) in stiffness, micromovement level, and mechanical resistance among the fixation techniques evaluated.

Discussion:

To stabilize the vertical femoral neck fracture in young patients, the use of a medial bone plate associated with cannulated screws on a “tie-rod” assembly is an option that supports the mechanical demand until the fracture healing. The locked medial plate did not provide an advantage compared with the conventional bone plate.
Analysis of Wholesale Drug Acquisition and Laboratory Assessment Costs Between Heparin Compared With Bivalirudin-Based Systemic Anticoagulation Strategies in Adult Extracorporeal Membrane Oxygenation
Authors: Seelhammer Troy G. , Brokmeier Hannah M. , Hamzah Mohammed , Wieruszewski Patrick M.
Published: February 2023

OBJECTIVES:

To assess the wholistic costs of systemic anticoagulation delivery in heparin versus bivalirudin-based maintenance of adult patients supported on extracorporeal membrane oxygenation (ECMO).

DESIGN:

Single-center retrospective cohort study.

SETTING:

Large academic ECMO center.

PATIENTS:

Adults on ECMO receiving heparin or bivalirudin for primary maintenance systemic anticoagulation.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Electronic data were abstracted from a database maintained by our ECMO center, which transitioned to a preferred bivalirudin-based anticoagulation management in 2017. The pretransition group consisted of 126 patients (123 heparin and three bivalirudin), whereas the posttransition group included 275 patients (82 heparin and 193 bivalirudin). Drug costs were estimated using the wholesale acquisition cost, and laboratory assays costs were estimated using reimbursement fee schedules. Cost data were normalized to the duration of the ECMO run and reported in U.S. Dollar per ECMO day. Following the practice change, bivalirudin patients were less likely to receive AT supplementation (31.0 vs 12.4%; p < 0.0001) and had fewer coagulation assays ordered (6.1 vs 5.4 per ECMO day; p = 0.0004). After the transition, there was a dramatic decrease in costs related to AT assay assessments ($11.78 [interquartile range {IQR}, $9.48–$13.09] vs $1.03 [IQR, $0–$5.75]; p < 0.0001) and AT supplementation ($0 [IQR, $0–$312.82] vs $0 [IQR, $0–$0]; p < 0.0001) per ECMO day. Unadjusted survival at 28 days was higher posttransition (64.3 vs 74.9%; p = 0.0286).

CONCLUSIONS:

Antithrombin assays and supplementation compromise a significant proportion of heparin-based anticoagulation costs in ECMO patients and is substantially reduced when a bivalirudin-based anticoagulation strategy is deployed. A favorable association exists between the aggregate cost of administration of bivalirudin compared with heparin-based systemic anticoagulation in adults supported on ECMO driven by reductions in antithrombin activity assessments and the cost of antithrombin replacement.
Efficacy of Erbium YAG laser treatment in overactive bladder syndrome: a randomized controlled trial
Authors: Chiengthong Keerati , Bunyavejchevin Suvit
Published: February 2023

Objective

To evaluate the efficacy of vaginal Erbium YAG laser in postmenopausal women presenting with overactive bladder syndrome (OAB) and vaginal atrophy.

Methods

A single center, randomized sham-controlled study was conducted between July 2019 and August 2022. Thai postmenopausal women diagnosed with OAB and who complained of one or more of vaginal atrophy symptoms (VAS) were included. The participants received either one treatment session of vaginal Erbium YAG laser or the sham procedure. The primary outcome was the Thai version Overactive Bladder Symptom Score. The secondary outcomes included results from the Thai version Overactive Bladder questionnaire (OAB-q), Patient Perception of Bladder Condition Questionnaire, bladder diary, VAS score, and Vaginal Health Index score (VHI). Outcome measurements were assessed between groups at 12 weeks after treatment.

Results

Fifty participants were included and randomized. Twenty-five participants were assigned to the vaginal laser group, and 25 to the sham group. At 12-week follow-up, vaginal Erbium YAG laser demonstrated improvement compared with sham group in total Overactive Bladder Symptom Score (6.03 ± 3.36 vs 8.44 ± 3.39, P = 0.015), nocturia (1.71 ± 0.74 vs 2.32 ± 0.70, P = 0.004), and urgency (2 [3] vs 3 [4], P = 0.008). Coping and social subscale of OAB-q, daytime micturition frequency, urgency and maximum urine volume, VAS and VHI scores also significantly improved in the vaginal laser group.

Conclusions

This study showed the efficacy of the vaginal Erbium YAG laser in treatment of OAB and vaginal atrophy in postmenopausal women. The improvement of OAB symptoms scores was confirmed by the bladder diary.
The association between hormone therapy and the risk of lung cancer in postmenopausal women: a 16-year nationwide population-based study
Authors: Wu Chia-Chen , Chung Chi-Hsiang , Tzeng Nian-Sheng , Wu Min-Jung , Tsao Chang-Huei , Wu Ti-Hui , Chien Wu-Chien , Chen Hsin-Chien
Published: February 2023

Objective

Although an association between hormone therapy (HT) and the risk of developing lung cancer has been reported, the results on the topic are inconsistent. Our study objective was to investigate whether postmenopausal women who undergo HT exhibit a risk of developing lung cancer.

Methods

In this matched cohort study, we obtained the data of 38,104 postmenopausal women older than 45 years who were treated using HT between 2000 and 2015 from Taiwan's National Health Insurance Research Database, and 152,416 matched participants who were not treated using HT were enrolled as controls at a 1:4 ratio.

Results

We used a Cox proportional hazards regression model to identify the risk of developing lung cancer during 16 years of follow-up, and the results indicate no significant difference in the proportion of postmenopausal women treated using HT (P = 0.129) who developed lung cancer and that of those not treated using HT (0.866% [330 of 38,104] vs 0.950% [1,449 of 152,416]). After adjustment for age and other variables, the adjusted hazard ratio was 0.886 (95% CI, 0.666-1.305, P = 0.433), indicating no association between HT and lung cancer development in postmenopausal women. In a subgroup analysis, the risk of lung cancer was significantly lower in the women who were treated using HT when the HT cumulative dosage was ≥401 mg or when the therapy duration was ≥5 years compared with in those not treated using HT; the adjusted hazard ratios were 0.633 (95% CI, 0.475-0.930; P < 0.001) and 0.532 (95% CI, 0.330-0.934; P < 0.001), respectively, after adjustment.

Conclusions

Our results indicate that HT is not associated with the risk of lung cancer development in postmenopausal women; furthermore, a higher cumulative dosage and the long-term effects of HT reduce the risk of developing lung cancer.
Successful removal of heavy metals and environmental toxins using modern Mayr chelating detoxication in a patient: a model for prefertility treatment screening
Authors: Ogunsola Oluwole I. , Adeyi Atinuke , Ashiru Oladapo A.
Published: February 2023

Introduction:

Heavy metals are naturally existing constituents of the earth that have a high specific density (above 5 g/cm3) and atomic weights (>40.4 Da). Once taken into the body, heavy metals are distributed in the blood and deposited in tissues. The contamination chain follows a cyclic order: from industry, to the atmosphere, soil, water, and foods, then humans. At Martlife detox clinic, a comprehensive treatment plan based on the Mayr method of detoxification designed for the removal of heavy metals is available. To begin with, a bio-energetic test which reveals the types of heavy metals present in the patient’s body is conducted. Thereafter, therapies targeted at extracting the heavy metals and neutralizing their effect on the reproductive organs are commenced.

Methods:

Patient A underwent a metal toxicity test using urine samples at Genova Diagnostics laboratory in the United States. Patient A afterward underwent a bioenergetics test followed by a detoxification plan during the following month at the Martlife Detox Clinic. We performed a repeat test after detoxication at the Genova Diagnostics laboratory to know the outcome of the detoxication.

Results:

Genova Diagnostics laboratory’s first metal toxicity test revealed significantly high values of copper, manganese, vanadium, rubidium, gadolinium, and cesium. It also revealed similar outcomes with the bioenergetics testing before the detoxication process began at Martlife Detox Clinic. The repeat test showed that the detoxication process was successful.

Conclusion(s):

Our findings conclude that the modern Mayr method effectively reduces toxic levels of heavy metals. The bioenergetics test, which is less invasive, cheaper, and faster than the urine test, can also be used to check for toxins in the body.
Influence of Foreign Versus US Nativity on the Trajectory of Functional Independence Over the 10 Years After Traumatic Brain Injury: A Model Systems Study
Authors: Ohayagha Chimdindu , Perrin Paul B. , Arango-Lasprilla Juan Carlos , Jones Shawn C. T.
Published: February 2023

Objective:

Although racial/ethnic disparities have been documented in numerous outcomes after traumatic brain injury (TBI), research has yet to explore differences in rehabilitation outcomes based upon nativity (foreign-born vs US-born individuals). The purpose of this study was to compare the functional outcomes over the first 10 years after TBI for individuals born in the United States with those who were foreign-born.

Setting/Participants:

A sample of 10 695 individuals in the TBI Model Systems database with a coding for country of birth the United States (n = 9435) versus other than the United States (n = 1260) was used.

Design/Main Measures:

Outcome measures at 1, 2, 5, and 10 years after TBI included the Motor and Cognitive subscales of the Functional Independence Measure and the Supervision Rating Scale.

Results:

Foreign-born individuals exhibited lower motor functional independence trajectories than those born in the United States, even after controlling for demographic and injury-related covariates. However, foreign-born individuals generally showed a stronger upward quadratic trajectory in motor functional independence with the greatest gains between the 5- and 10-year time points, whereas those born in the United States improved more quickly but then plateaued between the 5- and 10-year time points; these differential effects over time dissipated with the addition of demographic and injury-related covariates. Foreign-born individuals also exhibited lower cognitive functional independence trajectories, as well as greater supervision needs trajectories, than those born in the United States, even after controlling for demographic and injury-related covariates.

Conclusion:

These findings dovetail with literature suggesting that racially/ethnically diverse groups exhibit reduced functional independence after TBI. The findings may also suggest potential systematic barriers such as healthcare access and language barriers that may influence the frequency, rate, and quality of care received. The results highlight the importance of uncovering cultural distinctions and can aid in facilitating research examining foreign nativity-based disparities following TBI.
Toward Uniform Insurer Coverage for Functional MRI Following Severe Brain Injury
Authors: Young Michael J. , Bodien Yelena G. , Freeman Holly J. , Fecchio Matteo , Edlow Brian L.
Published: February 2023

Functional magnetic resonance imaging (fMRI) now promises to improve diagnostic and prognostic accuracy for patients with disorders of consciousness, and accordingly has been endorsed by professional society guidelines, including those of the American Academy of Neurology, American College of Rehabilitation Medicine, National Institute on Disability, Independent Living, and Rehabilitation Research, and the European Academy of Neurology. Despite multiple professional society endorsements of fMRI in evaluating patients with disorders of consciousness following severe brain injury, insurers have yet to issue clear guidance regarding coverage of fMRI for this indication. Lack of insurer coverage may be a rate-limiting barrier to accessing this technique, which could uncover essential diagnostic and prognostic information for patients and their families. The emerging clinical and ethical case for harmonized insurer recognition and reimbursement of fMRI for vulnerable persons following severe brain injury with disorders of consciousness is explained and critically evaluated.
Differences in Risk of Alzheimer's Disease Following Later-Life Traumatic Brain Injury in Veteran and Civilian Populations
Authors: Yashkin Arseniy P. , Gorbunova Galina A. , Tupler Larry , Yashin Anatoliy I. , Doraiswamy Murali , Akushevich Igor
Published: February 2023

Objective:

To directly compare the effect of incident age 68+ traumatic brain injury (TBI) on the risk of diagnosis of clinical Alzheimer's disease (AD) in the general population of older adults, and between male veterans and nonveterans; to assess how this effect changes with time since TBI.

Setting and Participants:

Community-dwelling traditional Medicare beneficiaries 68 years or older from the Health and Retirement Study (HRS).

Design:

Fine-Gray models combined with inverse-probability weighting were used to identify associations between incident TBI, post-TBI duration, and TBI treatment intensity, with a diagnosis of clinical AD dementia. The study included 16 829 older adults followed over the 1991-2015 period. For analyses of veteran-specific risks, 4281 veteran males and 3093 nonveteran males were identified. Analysis of veteran females was unfeasible due to the age structure of the population. Information on occurrence(s) of TBI, and onset of AD and risk-related comorbidities was constructed from individual-level HRS-linked Medicare claim records while demographic and socioeconomic risk factors were based on the survey data.

Results:

Later-life TBI was strongly associated with increased clinical AD risk in the full sample (pseudo-hazard ratio [HR]: 3.22; 95% confidence interval [CI]: 2.57-4.05) and in veteran/nonveteran males (HR: 5.31; CI: 3.42-7.94), especially those requiring high-intensity/duration care (HR: 1.58; CI: 1.29-1.91). Effect magnitude decreased with time following TBI (HR: 0.72: CI: 0.68-0.80).

Conclusion:

Later-life TBI was strongly associated with increased AD risk, especially in those requiring high-intensity/duration care. Effect magnitude decreased with time following TBI. Univariate analysis showed no differences in AD risk between veterans and nonveterans, while the protective effect associated with veteran status in Fine-Gray models was largely due to differences in demographics, socioeconomics, and morbidity. Future longitudinal studies incorporating diagnostic procedures and documentation quantifying lifetime TBI events are necessary to uncover pathophysiological mediating and/or moderating mechanisms between TBI and AD.