bluuebunny/crossref_metadata_2025 huggingface dataset:
Microalbuminuria in Perinatally HIV-Infected Children and Adolescents in the United States
Authors: Al Hammoud Roukaya , Kalaskar Anupama , Rodriguez Gilhen , Del Bianco Gabriela , Bell Cynthia , Murphy James R , Heresi Gloria P
Published: July 2023

Background

The kidney is a common target for human immunodeficiency virus (HIV), making renal disease a common noninfectious complication of HIV. Microalbuminuria is an important marker that can detect early renal damage. Timely detection of microalbuminuria is important to initiate renal management and stop the progression of renal dysfunction in people with HIV. Limited data are available about renal abnormalities in people with perinatal HIV infection. The objective of this study was to determine the prevalence of microalbuminuria in a cohort of perinatally HIV-infected children and young adults receiving combination antiretroviral therapy and investigate correlations between microalbuminuria and clinical and laboratory findings.

Methods

This was a retrospective study of 71 patients with HIV followed in an urban pediatric HIV clinic in Houston, Texas, between October 2007 and August 2016. Demographic, clinical, and laboratory data were compared between subjects with persistent microalbuminuria (PM) and those without. PM is defined as a microalbumin-to-creatinine ratio ≥30 mg/g on at least 2 occasions separated by at least 1 month.

Results

Sixteen of 71 patients (23%) met the definition of PM. In univariate analysis, patients with PM had significantly higher CD8+ T-cell activation and lower CD4+ T-cell nadir. Multivariate analysis demonstrated increased microalbuminuria to be independently associated with older age and CD8+ T-cell activation measured as CD8+HLA-DR+ T-cell percentage.

Conclusions

Older age and increased activation of CD8+HLA-DR+ on T cells correlate with presence of microalbuminuria in this cohort of HIV-infected patients.
Long-term Safety and Tolerability of Omadacycline for the Treatment of Mycobacterium abscessus Infections
Authors: Mingora Christina M , Bullington Wendy , Faasuamalie Paige E , Levin Adrah , Porter Gabriella , Stadnik Ryan , Varley Cara D , Addrizzo-Harris Doreen , Daley Charles L , Olivier Kenneth N , Winthrop Kevin L , Dorman Susan E , Flume Patrick A
Published: July 2023

Background

Mycobacterium abscessus is a virulent human pathogen. Treatment is complex and often poorly tolerated with suboptimal rates of eradication, highlighting the need for improved therapeutics. This study reports clinical experience with omadacycline for treatment of M abscessus infections at five large nontuberculous mycobacterial (NTM) disease clinics across the United States to better understand long-term safety and tolerability.

Methods

We conducted a multicenter retrospective chart review of adults with M abscessus infections. All patients treated with omadacycline as part of a multidrug therapeutic regimen through December 2021 were included. Clinical data from time of omadacycline initiation and up to 12 months of follow-up were collected. Descriptive statistics were performed.

Results

Analysis included 117 patients. Among patients with M abscessus isolate subspeciation, 58 of 71 (81.7%) were M abscessus spp abscessus. In isolates with reported drug susceptibility testing, 15 of 70 (21.4%) had confirmed susceptibility to macrolides. The most common site of infection was lungs. Median duration omadacycline treatment was 8 months (range, 0.25–33 months; interquartile range, 4–15 months). Omadacycline was discontinued in 60 patients (51.3%); 20 completed planned treatment course, 23 experienced intolerance or adverse event leading to drug cessation, and 17 stopped due to cost, death (unrelated to NTM infection or therapy), or another reason. In those with pulmonary disease, 44 of 95 (46%) had 1 or more negative cultures at time of final microbiological assessment, with 17 of 95 (18%) achieving culture conversion.

Conclusions

This study reports data supporting long-term safety and tolerability of omadacycline along with signal of effectiveness in treatment of M abscessus infections.
Identification of Immune Subtypes and Candidate mRNA Vaccine Antigens in Small Cell Lung Cancer
Authors: Wei Yuanfeng , Zheng Lingnan , Yang Xi , Luo Yong , Yi Cheng , Gou Hongfeng
Published: July 2023

Background

Immune checkpoint inhibitors (ICIs) have demonstrated promising outcomes in small cell lung cancer (SCLC), but not all patients benefit from it. Thus, developing precise treatments for SCLC is a particularly urgent need. In our study, we constructed a novel phenotype for SCLC based on immune signatures.

Methods

We clustered patients with SCLC hierarchically in 3 publicly available datasets according to the immune signatures. ESTIMATE and CIBERSORT algorithm were used to evaluate the components of the tumor microenvironment. Moreover, we identified potential mRNA vaccine antigens for patients with SCLC, and qRT-PCR were performed to detect the gene expression.

Results

We identified 2 SCLC subtypes and named Immunity High (Immunity_H) and Immunity Low (Immunity_L). Meanwhile, we obtained generally consistent results by analyzing different datasets, suggesting that this classification was reliable. Immunity_H contained the higher number of immune cells and a better prognosis compared to Immunity_L. Gene-set enrichment analysis revealed that several immune-related pathways such as cytokine-cytokine receptor interaction, programmed cell death-Ligand 1 expression and programmed cell death-1 checkpoint pathway in cancer were hyperactivated in the Immunity_H. However, most of the pathways enriched in the Immunity_L were not associated with immunity. Furthermore, we identified 5 potential mRNA vaccine antigens of SCLC (NEK2, NOL4, RALYL, SH3GL2, and ZIC2), and they were expressed higher in Immunity_L, it indicated that Immunity_L maybe more suitable for tumor vaccine development.

Conclusions

SCLC can be divided into Immunity_H and Immunity_L subtypes. Immunity_H may be more suitable for treatment with ICIs. NEK2, NOL4, RALYL, SH3GL2, and ZIC2 may be act as potential antigens for SCLC.
Application of new breeding techniques in fruit trees
Authors: Campa Manuela , Miranda Simón , Licciardello Concetta , Lashbrooke Justin Graham , Dalla Costa Lorenza , Guan Qingmei , Spök Armin , Malnoy Mickael
Published: July 2023

Climate change and rapid adaption of invasive pathogens pose a constant pressure on the fruit industry to develop improved varieties. Aiming to accelerate the development of better-adapted cultivars, new breeding techniques have emerged as a promising alternative to meet the demand of a growing global population. Accelerated breeding, cisgenesis, and CRISPR/Cas genome editing hold significant potential for crop trait improvement and have proven to be useful in several plant species. This review focuses on the successful application of these technologies in fruit trees to confer pathogen resistance and tolerance to abiotic stress and improve quality traits. In addition, we review the optimization and diversification of CRISPR/Cas genome editing tools applied to fruit trees, such as multiplexing, CRISPR/Cas-mediated base editing and site-specific recombination systems. Advances in protoplast regeneration and delivery techniques, including the use of nanoparticles and viral-derived replicons, are described for the obtention of exogenous DNA-free fruit tree species. The regulatory landscape and broader social acceptability for cisgenesis and CRISPR/Cas genome editing are also discussed. Altogether, this review provides an overview of the versatility of applications for fruit crop improvement, as well as current challenges that deserve attention for further optimization and potential implementation of new breeding techniques.
Overexpression of REDUCED WALL ACETYLATION C increases xylan acetylation and biomass recalcitrance in Populus
Authors: Zhang Jin , Wang Xiaqin , Wang Hsin-Tzu , Qiao Zhenzhen , Yao Tao , Xie Meng , Urbanowicz Breeanna R , Zeng Wei , Jawdy Sara S , Gunter Lee E , Yang Xiaohan , Czarnecki Olaf , Regan Sharon , Seguin Armand , Rottmann William , Winkeler Kimberly A , Sykes Robert , Lipzen Anna , Daum Chris , Barry Kerrie , Lu Meng-Zhu , Tuskan Gerald A , Muchero Wellington , Chen Jin-Gui
Published: July 2023

Plant lignocellulosic biomass, i.e. secondary cell walls of plants, is a vital alternative source for bioenergy. However, the acetylation of xylan in secondary cell walls impedes the conversion of biomass to biofuels. Previous studies have shown that REDUCED WALL ACETYLATION (RWA) proteins are directly involved in the acetylation of xylan but the regulatory mechanism of RWAs is not fully understood. In this study, we demonstrate that overexpression of a Populus trichocarpa PtRWA-C gene increases the level of xylan acetylation and increases the lignin content and S/G ratio, ultimately yielding poplar woody biomass with reduced saccharification efficiency. Furthermore, through gene coexpression network and expression quantitative trait loci (eQTL) analysis, we found that PtRWA-C was regulated not only by the secondary cell wall hierarchical regulatory network but also by an AP2 family transcription factor HARDY (HRD). Specifically, HRD activates PtRWA-C expression by directly binding to the PtRWA-C promoter, which is also the cis-eQTL for PtRWA-C. Taken together, our findings provide insights into the functional roles of PtRWA-C in xylan acetylation and consequently saccharification and shed light on synthetic biology approaches to manipulate this gene and alter cell wall properties. These findings have substantial implications for genetic engineering of woody species, which could be used as a sustainable source of biofuels, valuable biochemicals, and biomaterials.
Online data resource for exploring transposon insertion polymorphisms in public soybean germplasm accessions
Authors: Yin Zhiyuan , Yang Qingjie , Shen Danyu , Liu Jinding , Huang Wen , Dou Daolong
Published: July 2023

Soybean (Glycine max L. Merrill) is one of the most important economical crops. A large number of whole-genome resequencing datasets have been generated and are increasingly expanded for exploring genetic diversity and mining important quantitative trait loci. Most genome-wide association studies have focused on single-nucleotide polymorphisms, short insertions, and deletions. Nevertheless, structure variants mainly caused by transposon element mobilization are not fully considered. To fill this gap, we uniformly processed the publicly available whole-genome resequencing data from 5,521 soybean germplasm accessions and built an online soybean transposon insertion polymorphisms database named Soybean Transposon Insertion Polymorphisms Database (SoyTIPdb) (https://biotec.njau.edu.cn/soytipdb). The collected germplasm accessions derived from more than 45 countries and 160 regions representing the most comprehensive genetic diversity of soybean. SoyTIPdb implements easy-to-use query, analysis, and browse functions to help understand and find meaningful structural variations from TE insertions. In conclusion, SoyTIPdb is a valuable data resource and will help soybean breeders/researchers take advantage of the whole-genome sequencing datasets available in the public depositories.
Identification of blood metabolites linked to the risk of intervertebral disc diseases: a comprehensive Mendelian randomization study
Authors: Ji Linsong , Wang Yanping , Lu Tingsheng , Yang Jianwen , Luo Chunshan , Qiu Bing
Published: July 2023

Background

Intervertebral disc degeneration (IVDD) has affected millions of people worldwide and dramatically affects human beings’ quality of life. Observational studies hypothesize that metabolites play key roles as markers and effectors of IVDD, but their causality has not yet been illustrated.

Methods

We conducted comprehensive Mendelian randomization (MR) to determine the causal relationship between 249 plasma metabolites and IVDD. Inverse-variance weighting was used as the primary estimate, whereas MR-Egger and weighed median were used to detect robustness. A series of sensitivity analyses including Cochran Q test, leave one out, and MR-Egger intercept analysis were also conducted.

Results

In total, we found 13 blood metabolites significantly associated with IVDD, including phospholipids in very large high-density lipoprotein (HDL), free cholesterol to total lipids ratio in very large HDL, average diameter for HDL particles, cholesteryl esters to total lipids ratio in large HDL, free cholesterol to total lipids ratio in medium HDL, creatinine, free cholesterol to total lipids ratio in large HDL, phospholipids to total lipids ratio in very large HDL, cholesterol to total lipids ratio in very large HDL, cholesteryl esters to total lipids ratio in large HDL, phospholipids in large HDL, total lipids in very large HDL, and total lipids in large HDL. No pleiotropy was detected. Heterogeneity existed in several estimates and random-effect inverse-variance weighting was applied.

Conclusions

Our study highlighted the causal association of blood metabolites with the risk of IVDD. Our results provide new insights into possible treatment protocols controlling the concentration of specific blood metabolites in IVDD patients.

Key messages What is already known on this topic Low back pain is the most common symptom for patients with intervertebral disc degeneration (IVDD) and influences the quality of life of large populations. Observational studies have indicated the association between metabolites and IVDD. However, causality has not been determined yet. What this study adds We conducted a comprehensive Mendelian randomization study to reveal the causal effect from 249 blood metabolites on low back pain. A total of 13 metabolites were found to causally affect the risk of IVDD, among which 11 were negatively associated and 2 were positively asscociated. How this study might affect research, practice, or policy These 13 significant metabolites could serve as biomarkers for IVDD and our results provide new insights into possible treatment protocols for IVDD patients.
Development of a method of evaluating PuO2 particle diameters using an alpha-particle imaging detector
Authors: Morishita Yuki , Sagawa Naoki , Takada Chie , Momose Takumaro , Takasaki Koji
Published: July 2023

It is very important to evaluate the diameters (activity median aerodynamic diameter) of plutonium dioxide (PuO2) particles for internal exposure dose evaluation. In this study, a method of evaluating PuO2 particle diameters using an alpha-particle imaging detector was developed. PuO2 particles with different diameters were modeled by Monte Carlo simulation, and the change in the shape of the energy spectrum for each particle diameter was evaluated. Two different patterns were modeled, namely, the case of 239PuO2 and the case of PuO2 (including isotopic composition of Pu). Multiple regression analysis was performed to determine the PuO2 particle diameter from the obtained parameters. The simulated diameters and the diameters obtained with the regression model were in good agreement. The advantage of using the alpha-particle imaging detector is to measure the alpha energy spectrum for individual particle, and this allows accurate measurement of particle diameter distribution.
The study of virtual source position with the geometric convergent ratio errors prevention management method of spot scanning beam in carbon ion therapy
Authors: Zhang Wen-Hua , Luo Bing-Zhi , Ye Yan-Cheng , Wu Jia-Ming
Published: July 2023

Introduction: We developed a technique including preventing errors management method capable of dealing with the virtual source position delivered by different carbon ion energies from the pattern of spot scanning beam in this study. Materials and Methods: A homemade large-format complementary metal-oxide-semiconductor (CMOS) sensor and Gaf Chromic EBT3 films were used for the virtual source position measurement. The Gaf films were embedded in a self-designed rectangular plastic frame to tighten the films and set up on a treatment couch for irradiation in the air with the film perpendicular to the carbon ion beam at the nominal source-axis-distance (SAD) as well as upstream and downstream from the SAD. The horizontal carbon ion beam with five energies at a machine opening field size was carried out in this study. The virtual source position was determined mainly with a linear regression by back projecting the full width half maximum (FWHM) to zero at a distance upstream from the various source-film-distance and double checks additionally with a geometric convergent method to avoid any mistakes caused by manual measurement on FWHM. Results: The virtual source position for higher carbon ion energy has an obvious longer distance from the SAD since the more carbon ion beam energy, the less spreading affected by the horizontal and vertical magnetism, therefore, the distance of virtual source positions is decreased from SAD with high to low energy. Conclusion: The method for investigating the virtual source position in the carbon ion beam in this study can also be used for electrons and the proton. We have developed a technique capable of dealing with the virtual source position with a geometric convergent method to avoid any mistakes in spot scanning carbon ion beam.
IL33-mediated NPM1 promotes fibroblast-to-myofibroblast transition via ERK/AP-1 signaling in silica-induced pulmonary fibrosis
Authors: Wang Yue , Cheng Demin , Li Ziwei , Sun Wenqing , Zhou Siyun , Peng Lan , Xiong Haojie , Jia Xinying , Li Wei , Han Lei , Liu Yi , Ni Chunhui
Published: July 2023

Silicosis is a global occupational pulmonary disease due to the accumulation of silica dust in the lung. Lacking effective clinical drugs makes the treatment of this disease quite challenging in clinics largely because the pathogenic mechanisms remain obscure. Interleukin 33 (IL33), a pleiotropic cytokine, could promote wound healing and tissue repair via the receptor ST2. However, the mechanisms governing the involvement of IL33 in silicosis progression remain to be further explored. Here, we demonstrated that the IL33 levels in the lung sections were significantly overexpressed after bleomycin and silica treatment. Chromatin immunoprecipitation assay, knockdown, and reverse experiments were performed in lung fibroblasts to prove gene interaction following exogenous IL33 treatment or cocultured with silica-treated lung epithelial cells. Mechanistically, we illustrated that silica-stimulated lung epithelial cells secreted IL33 and further promoted the activation, proliferation, and migration of pulmonary fibroblasts by activating the ERK/AP-1/NPM1 signaling pathway in vitro. And more, treatment with NPM1 siRNA-loaded liposomes markedly protected mice from silica-induced pulmonary fibrosis in vivo. In conclusion, the involvement of NPM1 in the progression of silicosis is regulated by the IL33/ERK/AP-1 signaling axis, which is the potential therapeutic target candidate in developing novel antifibrotic strategies for pulmonary fibrosis.
Machine learning reveals common transcriptomic signatures across rat brain and placenta following developmental organophosphate ester exposure
Authors: Newell Andrew J , Jima Dereje , Reading Benjamin , Patisaul Heather B
Published: July 2023

Toxicogenomics is a critical area of inquiry for hazard identification and to identify both mechanisms of action and potential markers of exposure to toxic compounds. However, data generated by these experiments are highly dimensional and present challenges to standard statistical approaches, requiring strict correction for multiple comparisons. This stringency often fails to detect meaningful changes to low expression genes and/or eliminate genes with small but consistent changes particularly in tissues where slight changes in expression can have important functional differences, such as brain. Machine learning offers an alternative analytical approach for “omics” data that effectively sidesteps the challenges of analyzing highly dimensional data. Using 3 rat RNA transcriptome sets, we utilized an ensemble machine learning approach to predict developmental exposure to a mixture of organophosphate esters (OPEs) in brain (newborn cortex and day 10 hippocampus) and late gestation placenta of male and female rats, and identified genes that informed predictor performance. OPE exposure had sex specific effects on hippocampal transcriptome, and significantly impacted genes associated with mitochondrial transcriptional regulation and cation transport in females, including voltage-gated potassium and calcium channels and subunits. To establish if this holds for other tissues, RNAseq data from cortex and placenta, both previously published and analyzed via a more traditional pipeline, were reanalyzed with the ensemble machine learning methodology. Significant enrichment for pathways of oxidative phosphorylation and electron transport chain was found, suggesting a transcriptomic signature of OPE exposure impacting mitochondrial metabolism across tissue types and developmental epoch. Here we show how machine learning can complement more traditional analytical approaches to identify vulnerable “signature” pathways disrupted by chemical exposures and biomarkers of exposure.
The shape of water: adaptations of cochlea morphology in seals and otters
Authors: Taszus Roxana , del Rio Joaquin , Stoessel Alexander , Nowotny Manuela
Published: July 2023

Seals (Pinnipedia) and otters (Lutrinae) are two major taxa of the mammalian order Carnivora that independently adapted to a semi-aquatic lifestyle. Their sensory capabilities, including hearing, are still not fully understood. Notably, the functional morphology of amphibious hearing presents an interesting example for studying convergent evolution. We therefore investigated the shape and dimensions of morphological traits of the inner ear and the surrounding structures involved in sound perception using Micro-Computer Tomography (µCT) data of 52 skulls belonging to 38 species of the carnivoran subgroup Caniformia. Principal component analysis (PCA) of cochlea shape variables revealed that 82% of shape variation is explained by PC1 and PC2. A number of traits (e.g. cochlea shape, reduction in cochlea turns, flattening of the cochlea, relative size of tympanum and round window) are significantly different from terrestrial Caniformia. We also found an external cochlea foramen in all Pinnipedia, which is likely related to coping with pressure compensation during diving. Finally, we demonstrate that hearing parameters, such as characteristic hearing frequency, correlate with changes in the morphological traits that separate seals and otters from other Caniformia. Our data suggest that large parts of the morphology of ear region of these semi-aquatic carnivorans have independently adapted to allow hearing in air and water.
Pyricularia Are Mostly Host-Specialized with Limited Reciprocal Cross-Infection Between Wheat and Endemic Grasses in Minas Gerais, Brazil
Authors: Ascari João P. , Cazón Luis I. , Rahnama Mostafa , Lamour Kurt , Fernandes José M. C. , Farman Mark L. , Ponte Emerson M. Del
Published: July 2023

Wheat blast, caused by Pyricularia oryzae Triticum (PoT), is an emerging threat to global wheat production. The current understanding of the population biology of the pathogen and epidemiology of the disease has been based on phylogenomic studies that compared the wheat blast pathogen with isolates collected from grasses that were invasive to Brazilian wheat fields. In this study, we performed a comprehensive sampling of blast lesions in wheat crops and endemic grasses found in and away from wheat fields in Minas Gerais. A total of 1,368 diseased samples were collected (976 leaves of wheat and grasses and 392 wheat heads), which yielded a working collection of 564 Pyricularia isolates. We show that, contrary to earlier implications, PoT was rarely found on endemic grasses, and, conversely, members of grass-adapted lineages were rarely found on wheat. Instead, most lineages were host-specialized, with constituent isolates usually grouping according to their host of origin. With regard to the dominant role proposed for signalgrass in wheat blast epidemiology, we found only one PoT member in 67 isolates collected from signalgrass grown away from wheat fields and only three members of Urochloa-adapted lineages among hundreds of isolates from wheat. Cross-inoculation assays on wheat and a signalgrass used in pastures ( U. brizantha) suggested that the limited cross-infection observed in the field may be due to innate compatibility differences. Whether or not the observed level of cross-infection would be sufficient to provide an inoculum reservoir, or serve as a bridge between wheat growing regions, is questionable and, therefore, deserves further investigation.
Evaluation of Plant Defense Inducers and Plant Growth Regulators for Fire Blight Management Using Transcriptome Studies and Field Assessments
Authors: Yuan Xiaochen , Gdanetz Kristi , Outwater Cory A. , Slack Suzanne M. , Sundin George W.
Published: July 2023

Fire blight, caused by Erwinia amylovora, is a destructive disease of pome fruit trees. In the United States, apple and pear growers rely on applications of copper and antibiotics during bloom to control fire blight, but such methods have already led to regional instances of resistance. In this study, we used transcriptome analyses and field trials to evaluate the effectiveness of three commercially available plant defense elicitors and one plant growth regulator for fire blight management. Our data indicated that foliar applications of acibenzolar- S-methyl (ASM; Actigard 50WG) triggered a strong defense-related response in apple leaves, whereas applications of Bacillus mycoides isolate J (LifeGard WG) or Reynoutria sachalinensis extract (Regalia) did not. Genes upregulated by ASM were enriched in the biological processes associated with plant immunity, such as defense response and protein phosphorylation. The expression of several pathogenesis-related (PR) genes was induced by ASM as well. Surprisingly, many differentially expressed genes in ASM-treated apple leaves overlapped with those induced by treatment with prohexadione-calcium (ProCa; Apogee), a plant growth regulator that suppresses shoot elongation. Further analysis suggested that ProCa likely acts similarly to ASM to stimulate plant immunity because genes involved in plant defense were shared and significantly upregulated (more than twofold) by both treatments. Our field trials agreed with the transcriptome study, demonstrating that ASM and ProCa exhibit the best control performance relative to the other biopesticides. Taken together, these data are pivotal for the understanding of plant response and shed light on future improvements of strategies for fire blight management.
Long Saphenous Vein Harvesting: Reviewing Various Techniques
Authors: Raja Momna Sajjad , Duric Bea , Khashkhusha Arwa , Abbasi Hannah , Goyal Kartik , Harky Amer
Published: July 2023

Ischemic heart disease is the leading cause of mortality and morbidity in the Western world. Thus, coronary artery bypass graft is the most common cardiac procedure performed as it remains the gold standard for multiple vessel disease and left main disease. Long saphenous vein is the conduit of choice for coronary artery bypass graft as it is accessible and easy to harvest. Over the previous 4 decades, several techniques have emerged to optimize harvesting and reducing adverse clinical outcomes. The most cited techniques are open vein harvesting, no-touch technique, endoscopic vein harvesting, and standard bridging technique. In this literature review, we aim to summarize current literature for each of the 4 techniques in terms of: (A) graft patency and attrition, (B) myocardial infarction and revascularization, (C) wound infections, (D) postoperative pain, and (E) patient satisfaction.
The Comparative Dermal Stimulation Potential of Constant-Volume and Constant-Amount Diluted Calcium Hydroxylapatite Injections Versus the Concentrated Form
Authors: Botsali Aysenur , Erbil Hakan , Eşme Pelin , Gamsızkan Mehmet , Aksoy Ali Okan , Caliskan Ercan
Published: July 2023

INTRODUCTION

Biostimulation properties of diluted and hyperdiluted calcium hydroxylapatite (CaHA) injections have become increasingly popular. However, the existing data are insufficient to certify a particular dose–response pattern.

OBJECTIVE

To assess and compare the dermal stimulation potentials of different concentrations of CaHA injections.

MATERIALS AND METHODS

Two independent experiments (Experiment-1: constant injection volume vs Experiment-2: constant CaHA amount) included 4 study groups each, and these experimental groups were placed consecutively on the abdominal skin of a juvenile Yorkshire pig. Histopathological and immunohistochemical stainings were performed on punch biopsy materials collected 4 months after the injection day.

RESULTS

The fibroblast count significantly decreased upon dilution from 1:3 to 1:19 in experiment 1 (p = .000) but still higher than the control group. In experiment 1, the collagen density of the concentrated form was more elevated than the 1:19 dilution and the negative control groups (p = .034 and .000, respectively) but similar to the 1:3 dilution (p = .123). No significant difference was observed between the groups regarding collagen density with a standard amount of CaHA (0.2 mL, 30%) (p > .05).

CONCLUSION

Despite the efficacy being more pronounced till 1:3 dilution, hyperdiluted CaHA at any dilution ratio up to 1:19 can provide a higher fibroblast count than the negative control group.
Arterial partial pressure of oxygen as a marker of airway closure does not correlate with the efficacy of pre-oxygenation
Authors: Larsson Alexander , Östberg Erland , Edmark Lennart
Published: July 2023

BACKGROUND

The prerequisites for the early formation of anaesthesia-related atelectasis are pre-oxygenation with its resulting high alveolar oxygen content, and airway closure. Airway closure increases with age, so it seems counterintuitive that atelectasis formation during anaesthesia does not. One proposed explanation is that pre-oxygenation is impaired in the elderly by airway closure present in the waking state. The extent of airway closure cannot be assessed at the bedside, but arterial partial pressure of oxygen (P
aO2) as a surrogate variable of the resulting ventilation to perfusion mismatch can.

OBJECTIVE

The primary aim was to test the hypothesis that a decreased efficacy of pre-oxygenation, measured as the fraction of end-tidal oxygen (FE’O2) after 3 min of pre-oxygenation, correlates with decreased P
aO2 on room air. We also re-investigated the influence on FE’O2 by age.

DESIGN

Prospective observational study.

SETTING

Two regional hospitals, Västerås and Köping County Hospitals, Västmanland, Sweden, between 30 October 2018 and 17 September 2021.

PARTICIPANTS

We included 120 adults aged 40 to 79 years presenting for elective noncardiac surgery.

INTERVENTION

An arterial blood gas was sampled before commencing pre-oxygenation.

RESULTS

No linear correlation was found between FE’O2 at 3 min and P
aO2 or age (Pearson's r = −0.038, P = 0.684; and Pearson's r = −0.113, P = 0.223, respectively). The mean ± SD FE’O2 at 3 min for the population studied was 0.87 ± 0.05.

CONCLUSION

The lack of correlation between FE’O2 at 3 min and P
aO2 or age during pre-oxygenation has implications for further studies concerning the interaction between airway closure and atelectasis. After 3 min of pre-oxygenation, FE’O2, even in the elderly, indicated a high enough alveolar oxygen concentration to promote atelectasis after induction, therefore, it is still unclear why atelectasis formation diminishes after middle age.

TRIAL REGISTRATION

ClinicalTrials.gov NCT03395782
Current State of Entry-level Physical Therapy Oncology Curricula in the United States: A Faculty Survey
Authors: Harrington Shana E. , VanHoose Lisa , Westlake Frances
Published: July 2023

Introduction.

The purpose of this study was to determine the extent of oncology rehabilitation education in current physical therapist educational programs in the United States, including oncology rehabilitation content characteristics, delivery, and instructional resources.

Review of Literature.

By 2030, more than 21 million survivors of cancer in the United States (US) will be living with multisystem side effects depending on the treatment delivered. In addition, the sociopsychological factors associated with cancer treatment require that physical therapists are equipped with a unique body of knowledge, skills, and abilities. Insufficient cancer rehabilitation education is problematic across the health care spectrum.

Subjects.

Program directors at 235 US physical therapist educational programs.

Methods.

An online survey was developed in REDCap using the American Board of Physical Therapy Specialist's Description of Specialty Practice: Oncology Physical Therapy as a guide. An electronic link to the survey was sent to the email of the chair/program director at 235 Commission for the Accreditation of Physical Therapy Education–accredited programs.

Results.

The overall response rate was 40.4% (95/235) and represented 36 of the 50 states. Private universities represented 54.3% of the responses, and 65% of the surveys were completed by core faculty. Four programs reported having an independent oncology course, ranging from 1 to 3 credit hours. Integrated content hours averaged 14.8 contact hours (range: 1–60) in the 69 reporting programs. Fifty-four percent of respondents were aware of published rehabilitation cancer guidelines. The majority of respondents (62%) felt their students received adequate instruction related to oncology rehabilitation. Certified lymphedema therapists (68%) were primarily responsible for teaching the oncology content. Goodmans' Pathophysiology text was most reported (87%), whereas 38% used evidence-based research in Rehabilitation Oncology Journal. About half of the respondents (52%) reported offering students full-time clinical experiences in oncology rehabilitation.

Discussion and Conclusions.

This survey demonstrated how oncology rehabilitation education is incorporated into physical therapist educational programs and highlights areas for improvement. The results from this study lay the groundwork for developing core competencies for prelicensure education in oncology rehabilitation.
Challenges and Opportunities for Physical Therapist Education Research: Results From an American Council of Academic Physical Therapy Needs Assessment Survey
Authors: Dickson Tara , Eckert Jody , Pabian Patrick , Greco Jamie
Published: July 2023

Introduction.

The physical therapy (PT) profession has cited a need for education research, yet the needs of researchers are not fully understood. Furthermore, there continues to be a limited understanding of where resources are most needed to support and advance education research. The purpose of this study was to identify barriers and opportunities for education research to support PT faculty.

Review of Literature.

Scholarly productivity may be related to the attainment of an academic doctoral degree, research culture within an institution, and faculty time devoted to research. There is a lack of knowledge about what factors relate to the production of education research and the types of support needed for education researchers.

Subjects.

Two hundred sixteen PT education researchers.

Methods.

An open survey invitation was sent through email through the American Council of Academic Physical Therapy newsletter. A multiple regression analysis was used to determine factors that were associated with scholarly productivity of education researchers in PT. Open responses to a question regarding needed resources for engagement in education research were qualitatively analyzed.

Results.

The multiple regression analysis yielded a large effect (R2 = 0.31), demonstrating that faculty years of experience, faculty rank, and having an academic doctoral degree were correlated with scholarly productivity. “Faculty time/workload” was considered “very important” or higher to the production of education research by 87% of respondents. This item was rated of highest importance on the survey. Mentorship was considered the most important external resource, with 69% of respondents rating it as “very important” or higher, whereas “other personal commitments (ie, family care, household management, other community-related volunteer commitments)” was the most important personal factor (rated by 70% of the respondents as “very important” or higher). Open-ended responses further suggest that institution logistics, appropriate dissemination venues, and funding are areas of need to foster success in engaging in education research.

Discussion and Conclusion.

Results highlight challenges and opportunities for resource investment in education research. Among these are time and funding. Existing professional networking and educational opportunities need to be continually evaluated for their effectiveness. Further development should focus on mitigating these barriers while considering the logistics of the researcher's institution.
Using Cardiohelp, Quadrox, and Nautilus Extracorporeal Membrane Oxygenators as Vascular Access for Hemodialysis, Continuous Renal Replacement Therapy, and Plasmapheresis: A Brief Technical Report
Authors: Odish Mazen F. , Garimella Pranav S. , Crisostomo Hermogenes , Yi Cassia , Owens Robert L. , Pollema Travis
Published: July 2023

The use of intermittent hemodialysis (iHD), and continuous renal replacement therapy (CRRT), along with extracorporeal membrane oxygenation (ECMO) in patients with acute kidney injury (AKI) and end-stage renal disease (ESRD) is very common. In this technical report, we describe the methods to perform these dialytic therapies safely and effectively using the ECMO circuit in lieu of a separate dialysis catheter. Specifically, we describe in detail how to connect these kidney replacement therapy modalities to a Quadrox, Nautilus, and Cardiohelp HLS (combined oxygenator and pump) oxygenator. The dialysis (iHD or CRRT) inlet is attached to the post-oxygenators Luer-Lock, whereas the return is attached to the pre-oxygenator Luer-Lock, both with a dual lumen pigtail. We also discuss the technical aspects of performing plasmapheresis in conjunction with ECMO and iHD or CRRT. Finally, we highlight the fact that the reported technique does not require modifying the ECMO cannulas/tubing which helps maximize safety.
Fibrinolytic drugs induced hemorrhage: mechanisms and solutions
Authors: Tang Mingqing , Hu Chengjia , Lin Hongjun , Yan Hui
Published: July 2023

Thrombosis has been emerging as a major global life-threatening issue with high mortality and serious complications, especially in the post-COVID-19 era. Compared with the commonly used plasminogen activators thrombolytic drugs, fibrinolytic drugs are no longer heavily dependent on the patients’ own plasminogen, which are poorly expressed in most patients. As a novel “direct acting” thrombolytic agent, fibrinolytic drugs are considered to have stronger thrombolytic efficacy and safety than the widely used plasminogen activators. However, the risk of their hemorrhage remains a major concern. Herein, the molecular mechanisms and solutions were summarized for the first time based on the systematic review of the latest developments, which could shed new light on the development of novel safety fibrinolytic drugs in the future.
Management of patients with idiopathic pulmonary fibrosis and lung cancer: challenges in clinical practice
Authors: Karampitsakos Theodoros , Sampsonas Fotios , Herazo-Maya Jose D. , Tzouvelekis Argyris
Published: July 2023

Purpose of review

Idiopathic pulmonary fibrosis (IPF) is the nonmalignant, chronic lung disease with the worst prognosis. Prevalent comorbidities including lung cancer exert a negative impact on patients’ survival. However, there is considerable lack of knowledge on the diagnostic and therapeutic management of patients diagnosed with both clinical entities. This review article presents the main challenges in the management of patients with IPF and lung cancer and highlights future perspectives.

Recent findings

Recent registries for patients with IPF demonstrated that approximately 10% of patients developed lung cancer. Importantly, incidence of lung cancer was increasing remarkably over time in patients with IPF. Patients with IPF and otherwise technically operable lung cancer who underwent surgical resection had improved survival compared with those who did not undergo surgery. However, specific precautions perioperatively are crucial. Finally, the first randomized-controlled, phase 3 trial (J-SONIC trial) showed no significant difference in exacerbation-free survival for chemotherapy-naive patients with IPF and advanced nonsmall cell lung cancer that were allocated to receive carboplatin and nab-paclitaxel every 3 weeks with or without nintedanib.

Lung cancer is prevalent in IPF. Management of patients with IPF and lung cancer is challenging. A consensus statement aiming to attenuate confusion is greatly anticipated.
Pulmonary alveolar proteinosis – current and future therapeutical strategies
Authors: Jehn Lutz-Bernhard , Bonella Francesco
Published: July 2023

Purpose of review

We discuss the most recent advances in the treatment of pulmonary alveolar proteinosis (PAP), an ultra-rare syndrome.

Recent findings

Whole lung lavage (WLL) remains the gold standard of treatment for PAP syndrome. For the autoimmune form, recent trials with inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) confirmed the efficacy in up to 70% of cases, especially under continuous administration. In patients with hereditary PAP with underlying GM-CSF receptor mutations, ex vivo autologous hematopoietic stem-cell gene therapy and reimplantation of autologous ex vivo gene-corrected macrophages are promising approaches.

There are no drugs approved for PAP at present, but cause-based treatments such as GM-CSF augmentation and pulmonary macrophage transplantation are paving the way for targeted therapy for this complex syndrome.
Lessons learned in developing a chronic thromboembolic pulmonary hypertension program
Authors: Bair Nancy D. , Heresi Gustavo A.
Published: July 2023

Purpose of review

Chronic thromboembolic pulmonary hypertension (CTEPH) is a deadly underdiagnosed form of pulmonary hypertension, traditionally treated with surgical extraction of thrombo-fibrotic lesions via pulmonary thrombendarterectomy (PTE) surgery. More recently, treatment options have expanded to pulmonary vasodilator medical therapy and balloon pulmonary angioplasty (BPA). This has led to increased awareness and detection of CTEPH, as well as growing interest in performing PTE and BPA. This review will describe the steps required to build a successful CTEPH team in the context of the rapidly evolving treatment of CTEPH.

Recent findings

CTEPH care requires a multidisciplinary team, including a Pulmonologist or Cardiologist expert in Pulmonary Hypertension, a PTE surgeon, a BPA interventionalist, a dedicated radiologist, cardiothoracic anesthesia and Vascular Medicine or Hematology. Careful assessment of precise imaging and hemodynamic data is needed for operability assessment in the context of the experience of the CTEPH team and surgeon. Medical therapy and BPA are indicated for inoperable CTEPH and residual CTEPH after PTE. Increasingly, multimodality approaches, including surgery, BPA and medical therapy are utilized for best outcomes.

An expert CTEPH center requires a multidisciplinary team with dedicated specialists, and time to develop the experience and expertise to achieve high volumes and good outcomes.
Pulmonary hypertension in interstitial lung disease and in chronic obstructive pulmonary disease: different entities?
Authors: Piccari Lucilla , Aguilar-Colindres Ricardo , Rodríguez-Chiaradía Diego A.
Published: July 2023

Purpose of review

Pulmonary hypertension (PH) is a common complication of both chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), classified as Group 3 PH. To which extent PH presents and behaves similarly in COPD and ILD is unclear. This review examines the similarities and differences in pathogenesis, clinical presentation, natural history and treatment response of PH in COPD and ILD.

Recent findings

The latest studies on PH in chronic lung disease have re-evaluated the role of traditionally held etiopathogenetic factors such as tobacco exposure and hypoxia, although new ones such as airborne pollutant and genetic mutations are increasingly recognized. We examine common and diverging factors involved in PH development in COPD and ILD, as well as common and diverging clinical features of presentation, natural history and response to treatment and highlight areas for future research.

The development of PH in lung disease significantly worsens the morbidity and mortality of patients with COPD and ILD. However, recent findings show importance of recognizing distinct patterns and behaviors of pulmonary vascular disease, taking into account the specific underlying lung disease and severity of the hemodynamic involvement. Further studies are needed to build evidence on these aspects, especially in early disease.
Twenty versus 40 back-and-forth needle movements for endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic masses: a prospective, crossover, randomized study
Authors: Hu Xinyi , Yu Fang , Cao Tingting , Chen Xiaojia , Nie Haihang , Zhang Zhang , Wang Fan , Wang Hongling , Fang Jun , Zhao Qiu
Published: July 2023

Background and aims

In endoscopic ultrasound (EUS)-fine-needle biopsy (FNB) of solid pancreatic mass lesions, the number of times the needle moves back and forth within the lesion might affect the collection of the sample and the subsequent diagnostic accuracy. Thus, this study was designed to compare the diagnostic adequacy between different numbers of back-and-forth movements in EUS-FNB.

Methods

Fifty-five patients with solid pancreatic masses underwent EUS-FNB sampling with the needle (22-gauge) moved 20 times (MTT) and 40 times (MFT) randomly and sequentially for a total of four alternating passes. We compared the acquisition rate of appropriate and adequate specimens for histologic assessment and diagnostic accuracy.

Results

Finally, 55 patients (35 men and 20 women) were included in the study. We found that 56.4% (31/55) and 60% (33/55) of the specimens obtained using MTT and MFT, respectively, could be adequately diagnosed histologically (P = 0.815, McNemar test). The diagnostic accuracy of MTT and MFT was 72.7% (40/55) and 80% (44/55), respectively (P = 0.289, McNemar test). The overall diagnostic accuracy was 89.1%.

Conclusion

There was no significant statistical difference between the histopathological diagnostic samples obtained in MTT and those obtained in MFT. Therefore, a large number of back-and-forth movements of the needle should be avoided during EUS-FNB, which can help reduce the operation time and may reduce the risk of intraoperative and postoperative complications (Clinical trial registration number: ChiCTR2000031106).