bluuebunny/crossref_metadata_2025 huggingface dataset:
General Hydrography of the Beagle Channel, a Subantarctic Interoceanic Passage at the Southern Tip of South America
Authors: Giesecke Ricardo , Martín Jacobo , Piñones Andrea , Höfer Juan , Garcés-Vargas Jose , Flores-Melo Ximena , Alarcón Emilio , Durrieu de Madron Xavier , Bourrin François , González Humberto E.
Published: October 2021

The Beagle Channel (BC) is a long and narrow interoceanic passage (∼270 km long and 1–12 km wide) with west-east orientation and complex bathymetry connecting the Pacific and Atlantic oceans at latitude 55°S. This study is the first integrated assessment of the main oceanographic features of the BC, using recent oceanographic observations from cruises, moored instruments and historical observations. The waters transported into the BC are supplied mainly by the Cape Horn Current, which carries Subantarctic Water (SAAW) at depth (100 m below surface) along the Pacific Patagonian continental shelf break. SAAW enters the continental shelf via a submarine canyon at the western entrance of the BC. The SAAW is diluted by fresh, nutrient depleted (nitrate, phosphate and silicic acid) Estuarine Water (EW) from Cordillera Darwin Ice Field (CDIF) forming modified SAAW (mSAAW). Freshwater inputs from the CDIF generate a two-layer system with a sharp pycnocline which delimits the vertical distribution of phytoplankton fluorescence (PF). Two shallow sills (<70 m) along the BC contribute to EW and mSAAW mixing and the homogenization of the entire water column east of the sills, coherent with Bernoulli aspiration. The central section of the BC, extending ∼100 km toward the east, is filled by a salty (31–32) variety of EW. In winter, this central section is nearly vertically homogeneous with low nutrient concentrations (0.9–1.1 μM PO4 and 7.5–10 μM NO3) and PF. The temporal variability of seawater temperature from 50 to 195 m in the central section of the BC was found to be mostly dominated by the annual and semiannual cycles and influenced by tidal forcing. The middle section of the BC was less influenced by oceanic inputs and its basin-like structure most likely favors retention, which was observed from the weakly stratified water column at the mooring site. Toward the east, the central section bathymetry is disrupted at Mackinlay Strait where another shallow sill separates the middle channel from the shallow eastern entrance that connects to the Atlantic Ocean. In this section, a weakly stratified two-layer system is formed when the eastward surface outflow (salty-EW) flows over a deeper, denser tongue of oceanic mSAAW.
Sediment Exchange Between the Created Saltmarshes of Living Shorelines and Adjacent Submersed Aquatic Vegetation in the Chesapeake Bay
Authors: Vona Iacopo , Palinkas Cindy M. , Nardin William
Published: October 2021

Rising sea levels and the increased frequency of extreme events put coastal communities at serious risk. In response, shoreline armoring for stabilization has been widespread. However, this solution does not take the ecological aspects of the coasts into account. The “living shoreline” technique includes coastal ecology by incorporating natural habitat features, such as saltmarshes, into shoreline stabilization. However, the impacts of living shorelines on adjacent benthic communities, such as submersed aquatic vegetation (SAV), are not yet clear. In particular, while both marshes and SAV trap the sediment necessary for their resilience to environmental change, the synergies between the communities are not well-understood. To help quantify the ecological and protective (shoreline stabilization) aspects of living shorelines, we presented modeling results using the Delft3D-SWAN system on sediment transport between the created saltmarshes of the living shorelines and adjacent SAV in a subestuary of Chesapeake Bay. We used a double numerical approach to primarily validate deposition measurements made in the field and to further quantify the sediment balance between the two vegetation communities using an idealized model. This model used the same numerical domain with different wave heights, periods, and basin slopes and includes the presence of rip-rap, which is often used together with marsh plantings in living shorelines, to look at the influences of artificial structures on the sediment exchange between the plant communities. The results of this study indicated lower shear stress, lower erosion rates, and higher deposition rates within the SAV bed compared with the scenario with the marsh only, which helped stabilize bottom sediments by making the sediment balance positive in case of moderate wave climate (deposition within the two vegetations higher than the sediment loss). The presence of rip-rap resulted in a positive sediment balance, especially in the case of extreme events, where sediment balance was magnified. Overall, this study concluded that SAV helps stabilize bed level and shoreline, and rip-rap works better with extreme conditions, demonstrating how the right combination of natural and built solutions can work well in terms of ecology and coastal protection.
Plethysmographic Peripheral Perfusion Index: Could It Be a New Vital Sign?
Authors: Elshal Mamdouh M. , Hasanin Ahmed M. , Mostafa Maha , Gamal Reham M.
Published: October 2021

The plethysmographic peripheral perfusion index (PPI) is a very useful parameter with various emerging utilities in medical practice. The PPI represents the ratio between pulsatile and non-pulsatile portions in peripheral circulation and is mainly affected by two main determinants: cardiac output and balance between sympathetic and parasympathetic nervous systems. The PPI decreases in cases of sympathetic predominance and/or low cardiac output states; therefore, it is a useful predictor of patient outcomes in critical care units. The PPI could be a surrogate for cardiac output in tests for fluid responsiveness, as an objective measure of pain especially in un-cooperative patients, and as a predictor of successful weaning from mechanical ventilation. The PPI is simple to measure, easy to interpret, and has continuously displayed variables, making it a convenient parameter for detecting the adequacy of blood flow and sympathetic-parasympathetic balance.
Toward the Treatment of Inherited Diseases of the Retina Using CRISPR-Based Gene Editing
Authors: Hernández-Juárez Jennifer , Rodríguez-Uribe Genaro , Borooah Shyamanga
Published: October 2021

Inherited retinal dystrophies [IRDs] are a common cause of severe vision loss resulting from pathogenic genetic variants. The eye is an attractive target organ for testing clinical translational approaches in inherited diseases. This has been demonstrated by the approval of the first gene supplementation therapy to treat an autosomal recessive IRD, RPE65-linked Leber congenital amaurosis (type 2), 4 years ago. However, not all diseases are amenable for treatment using gene supplementation therapy, highlighting the need for alternative strategies to overcome the limitations of this supplementation therapeutic modality. Gene editing has become of increasing interest with the discovery of the CRISPR-Cas9 platform. CRISPR-Cas9 offers several advantages over previous gene editing technologies as it facilitates targeted gene editing in an efficient, specific, and modifiable manner. Progress with CRISPR-Cas9 research now means that gene editing is a feasible strategy for the treatment of IRDs. This review will focus on the background of CRISPR-Cas9 and will stress the differences between gene editing using CRISPR-Cas9 and traditional gene supplementation therapy. Additionally, we will review research that has led to the first CRISPR-Cas9 trial for the treatment of CEP290-linked Leber congenital amaurosis (type 10), as well as outline future directions for CRISPR-Cas9 technology in the treatment of IRDs.
Evaluation of Macular and Retinal Ganglion Cell Count Estimates for Detecting and Staging Glaucoma
Authors: Wu Yali , Cun Qing , Tao Yijin , Yang Wenyan , Wei Jia , Fan Daoqing , Zhang Ying , Chen Qin , Zhong Hua
Published: October 2021

Purpose: To investigate the clinical significance of macular estimated retinal ganglion cell (mRGC) and estimated retinal ganglion cell (eRGC) in the diagnosis and staging of glaucoma.

Methods: This is a cross-section study. All enrolled subjects underwent standard automated perimetry (SAP) and optical coherence tomography (OCT) examination. Swedish Interactive Threshold Algorithm (SITA)-FAST detection strategy and 24-2, 10-2 detection programs were employed in SAP assessment. The visual-field parameters and OCT parameters were calculated according to three formulas to obtain the eRGC and mRGC1 or mRGC2. The efficiency of eRGC, mRGC1, and mRGC2 estimates for the staging of glaucoma was compared. The sensitivity and specificity of each parameter for diagnosis of glaucoma were analyzed using the receiver operating characteristic (ROC) curve.

Results: A total of 119 eyes were included in the analysis. Compared with the healthy controls, eRGC, mRGC1, and mRGC2 estimates were significantly decreased in patients with glaucoma. As glaucoma progressed, eRGC, mRGC1, and mRGC2 estimates were gradually reduced. In preperimetric glaucoma, mRGC1, mRGC2, and eRGC were reduced by 13.2, 14.5, and 18%, respectively. In the mild stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 28, 34, and 38%, respectively. In the advanced stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 81, 85, and 92% respectively. The proportion of retinal ganglion cell (RGC) loss in the macula was close to that outside the macula. The specificity at 95% gave a sensitivity of 95.51, 86.52, and 87.64% for eRGC, mRGC1, and mRGC2, respectively. The sensitivity of structural parameters macular ganglion cell complex thickness and retinal nerve fiber layer (RNFL) were 98.88 and 95.51%, respectively. The sensitivity of functional parameters mean deviation (24-2) and visual field index (VFI) were 80.90 and 73.03%, respectively. The area under ROC curve of mRGC1, mRGC2, and eRGC were 0.982, 0.972, and 0.995 (P < 0.0001), respectively.

Conclusion: Estimated retinal ganglion cell, mRGC1, and mRGC2 provide value to the staging of glaucoma and better diagnostic performance. Macular RGC estimatesthat integration of both structural and functional damages in macular may serve as a sensitive indicator for assessing macular damage in glaucoma and are of importance for the diagnosis and progression management of glaucoma.
Diversity of the Bacterial Microbiome Associated With the Endosphere and Rhizosphere of Different Cassava (Manihot esculenta Crantz) Genotypes
Authors: Ha Jingwen , Gao Yu , Zhang Rui , Li Ke , Zhang Yijie , Niu Xiaolei , Chen Xin , Luo Kai , Chen Yinhua
Published: October 2021

Root-associated microbial communities play important roles in plant growth and development. However, little attention has been paid to the microbial community structures associated with cassava, which is a staple food for approximately 800 million people worldwide. Here, we studied the diversity and structure of tuber endosphere and rhizosphere bacterial communities in fourteen cassava genotypes: SC5, SC8, SC9, SC205, KU50, R72, XL1, FX01, SC16, 4612, 587, 045, S0061, and 1110. The results of bacterial 16S rDNA sequencing showed that the richness and diversity of bacteria in the rhizosphere were higher than those in the tuber endosphere across the 14 cassava genotypes. After sequencing, 21 phyla and 310 genera were identified in the tuberous roots, and 36 phyla and 906 genera were identified in the rhizosphere soils. The dominant phylum across all tuber samples was Firmicutes, and the dominant phyla across all rhizosphere samples were Actinobacteria, Proteobacteria, and Acidobacteria. The numbers of core bacterial taxa within the tuber endospheres and the rhizospheres of all cassava genotypes were 11 and 236, respectively. Principal coordinate analysis and hierarchical cluster analysis demonstrated significant differences in the compositions of rhizosphere soil microbiota associated with the different cassava genotypes. Furthermore, we investigated the metabolic changes in tuber roots of three genotypes, KU50, SC205, and SC9. The result showed that the abundances of Firmicutes, Proteobacteria, and Actinobacteria in tuber samples were positively correlated with organic acids and lipids and negatively correlated with vitamins and cofactors. These results strongly indicate that there are clear differences in the structure and diversity of the bacterial communities associated with different cassava genotypes.
Lulworthinone, a New Dimeric Naphthopyrone From a Marine Fungus in the Family Lulworthiaceae With Antibacterial Activity Against Clinical Methicillin-Resistant Staphylococcus aureus Isolates
Authors: Jenssen Marte , Rainsford Philip , Juskewitz Eric , Andersen Jeanette H. , Hansen Espen H. , Isaksson Johan , Rämä Teppo , Hansen Kine Ø.
Published: October 2021

The emergence of drug-resistant bacteria is increasing rapidly in all parts of the world, and the need for new antibiotics is urgent. In our continuous search for new antimicrobial molecules from under-investigated Arctic marine microorganisms, a marine fungus belonging to the family Lulworthiaceae (Lulworthiales, Sordariomycetes, and Ascomycota) was studied. The fungus was isolated from driftwood, cultivated in liquid medium, and studied for its potential for producing antibacterial compounds. Through bioactivity-guided isolation, a novel sulfated biarylic naphtho-α-pyrone dimer was isolated, and its structure was elucidated by spectroscopic methods, including 1D and 2D NMR and HRMS. The compound, named lulworthinone (1), showed antibacterial activity against reference strains of Staphylococcus aureus and Streptococcus agalactiae, as well as several clinical MRSA isolates with MICs in the 1.56–6.25 μg/ml range. The compound also had antiproliferative activity against human melanoma, hepatocellular carcinoma, and non-malignant lung fibroblast cell lines, with IC50 values of 15.5, 27, and 32 μg/ml, respectively. Inhibition of bacterial biofilm formation was observed, but no eradication of established biofilm could be detected. No antifungal activity was observed against Candida albicans. During the isolation of 1, the compound was observed to convert into a structural isomer, 2, under acidic conditions. As 1 and 2 have high structural similarity, NMR data acquired for 2 were used to aid in the structure elucidation of 1. To the best of our knowledge, lulworthinone (1) represents the first new bioactive secondary metabolite isolated from the marine fungal order Lulworthiales.
Shedding Light on Primary Donors in Photosynthetic Reaction Centers
Authors: Gorka Michael , Baldansuren Amgalanbaatar , Malnati Amanda , Gruszecki Elijah , Golbeck John H. , Lakshmi K. V.
Published: October 2021

Chlorophylls (Chl)s exist in a variety of flavors and are ubiquitous in both the energy and electron transfer processes of photosynthesis. The functions they perform often occur on the ultrafast (fs–ns) time scale and until recently, these have been difficult to measure in real time. Further, the complexity of the binding pockets and the resulting protein-matrix effects that alter the respective electronic properties have rendered theoretical modeling of these states difficult. Recent advances in experimental methodology, computational modeling, and emergence of new reaction center (RC) structures have renewed interest in these processes and allowed researchers to elucidate previously ambiguous functions of Chls and related pheophytins. This is complemented by a wealth of experimental data obtained from decades of prior research. Studying the electronic properties of Chl molecules has advanced our understanding of both the nature of the primary charge separation and subsequent electron transfer processes of RCs. In this review, we examine the structures of primary electron donors in Type I and Type II RCs in relation to the vast body of spectroscopic research that has been performed on them to date. Further, we present density functional theory calculations on each oxidized primary donor to study both their electronic properties and our ability to model experimental spectroscopic data. This allows us to directly compare the electronic properties of hetero- and homodimeric RCs.
Cold-Active Shewanella glacialimarina TZS-4T nov. Features a Temperature-Dependent Fatty Acid Profile and Putative Sialic Acid Metabolism
Authors: Qasim Muhammad Suleman , Lampi Mirka , Heinonen Minna-Maria K. , Garrido-Zabala Berta , Bamford Dennis H. , Käkelä Reijo , Roine Elina , Sarin Leif Peter
Published: October 2021

Species of genus Shewanella are among the most frequently identified psychrotrophic bacteria. Here, we have studied the cellular properties, growth dynamics, and stress conditions of cold-active Shewanella strain #4, which was previously isolated from Baltic Sea ice. The cells are rod-shaped of ~2μm in length and 0.5μm in diameter, and they grow between 0 and 25°C, with an optimum at 15°C. The bacterium grows at a wide range of conditions, including 0.5–5.5% w/v NaCl (optimum 0.5–2% w/v NaCl), pH 5.5–10 (optimum pH 7.0), and up to 1mM hydrogen peroxide. In keeping with its adaptation to cold habitats, some polyunsaturated fatty acids, such as stearidonic acid (18:4n-3), eicosatetraenoic acid (20:4n-3), and eicosapentaenoic acid (20:5n-3), are produced at a higher level at low temperature. The genome is 4,456kb in size and has a GC content of 41.12%. Uniquely, strain #4 possesses genes for sialic acid metabolism and utilizes N-acetyl neuraminic acid as a carbon source. Interestingly, it also encodes for cytochrome c3 genes, which are known to facilitate environmental adaptation, including elevated temperatures and exposure to UV radiation. Phylogenetic analysis based on a consensus sequence of the seven 16S rRNA genes indicated that strain #4 belongs to genus Shewanella, closely associated with Shewanella aestuarii with a ~97% similarity, but with a low DNA–DNA hybridization (DDH) level of ~21%. However, average nucleotide identity (ANI) analysis defines strain #4 as a separate Shewanella species (ANI score=76). Further phylogenetic analysis based on the 92 most conserved genes places Shewanella strain #4 into a distinct phylogenetic clade with other cold-active marine Shewanella species. Considering the phylogenetic, phenotypic, and molecular characterization, we conclude that Shewanella strain #4 is a novel species and name it Shewanella glacialimarina sp. nov. TZS-4T, where glacialimarina means sea ice. Consequently, S. glacialimarina TZS-4T constitutes a promising model for studying transcriptional and translational regulation of cold-active metabolism.
A Conserved Structural Role for the Walker-A Lysine in P-Loop Containing Kinases
Authors: Hajredini Fatlum , Ghose Ranajeet
Published: October 2021

Bacterial tyrosine kinases (BY-kinases) and shikimate kinases (SKs) comprise two structurally divergent P-loop containing enzyme families that share similar catalytic site geometries, most notably with respect to their Walker-A, Walker-B, and DxD motifs. We had previously demonstrated that in BY-kinases, a specific interaction between the Walker-A and Walker-B motifs, driven by the conserved “catalytic” lysine housed on the former, leads to a conformation that is unable to efficiently coordinate Mg2+•ATP and is therefore incapable of chemistry. Here, using enhanced sampling molecular dynamics simulations, we demonstrate that structurally similar interactions between the Walker-A and Walker-B motifs, also mediated by the catalytic lysine, stabilize a state in SKs that deviates significantly from one that is necessary for the optimal coordination of Mg2+•ATP. This structural role of the Walker-A lysine is a general feature in SKs and is found to be present in members that encode a Walker-B sequence characteristic of the family (Coxiella burnetii SK), and in those that do not (Mycobacterium tuberculosis SK). Thus, the structural role of the Walker-A lysine in stabilizing an inactive state, distinct from its catalytic function, is conserved between two distantly related P-loop containing kinase families, the SKs and the BY-kinases. The universal conservation of this element, and of the key characteristics of its associated interaction partners within the Walker motifs of P-loop containing enzymes, suggests that this structural role of the Walker-A lysine is perhaps a widely deployed regulatory mechanism within this ancient family.
Enriched Environment Prevents Surgery-Induced Persistent Neural Inhibition and Cognitive Dysfunction
Authors: Yang Shana , Zhang Song , Tang Wenting , Fang Shunchang , Zhang Hongyang , Zheng Jieyan , Liu Xia , Zhang Ying , Zhao Liang , Huang Lianyan , Li Boxing
Published: October 2021

Perioperative neurocognitive disorders (PND) encompass short-term delirium and long-term cognitive dysfunction. Aging increases the susceptibility to PND, yet the neural mechanism is not known. In this study, we monitored the dynamic changes of neuronal activity in the prelimbic cortex before and after surgery. We found that anesthesia combined with surgery, but not anesthesia alone, induced a prolonged decrease in neuronal activity during the post-operation period in the aged mice, but not in the adult mice. The prolonged decrease in neuronal activity was accompanied by surgery-induced microglial activation and proinflammatory cytokines expression. Importantly, we found that the enriched environment (EE) completely prevented both the prolonged neural inhibition and neuroinflammation, and improved cognitive function in the aged mice. These results indicate that the prolonged neural inhibition correlated to PND and that EE before the surgery could effectively alleviate the surgery- induced cognitive dysfunction.
Acetylation Profiles in the Metabolic Process of Glioma-Associated Seizures
Authors: Xu Ya-Wen , Lin Peng , Zheng Shu-Fa , Huang Wen , Lin Zhang-Ya , Shang-Guan Huang-Cheng , Lin Yuan-Xiang , Yao Pei-Sen , Kang De-Zhi
Published: October 2021

Objective: We test the hypothesis that lysine acetylation is involved in the metabolic process of glioma-associated seizures (GAS).

Methods: We used label-free mass spectrometry-based quantitative proteomics to quantify dynamic changes of protein acetylation between gliomas with seizure (CA1 group) and gliomas without seizure (CA2 group). Furthermore, differences of acetyltransferase and deacetylase expression between CA1 and CA2 groups were performed by a quantitative proteomic study. We further classified acetylated proteins into groups according to cell component, molecular function, and biological process. In addition, metabolic pathways and protein interaction networks were analyzed. Regulated acetyltransferases and acetylated profiles were validated by PRM and Western blot.

Results: We detected 169 downregulated lysine acetylation sites of 134 proteins and 39 upregulated lysine acetylation sites of 35 proteins in glioma with seizures based on acetylome. We detected 407 regulated proteins by proteomics, from which ACAT2 and ACAA2 were the differentially regulated enzymes in the acetylation of GAS. According to the KEGG analysis, the upregulated acetylated proteins within the PPIs were mapped to pathways involved in the TCA cycle, oxidative phosphorylation, biosynthesis of amino acids, and carbon metabolism. The downregulated acetylated proteins within the PPIs were mapped to pathways involved in fatty acid metabolism, oxidative phosphorylation, TCA cycle, and necroptosis. Regulated ACAT2 expression and acetylated profiles were validated by PRM and Western blot.

Conclusions: The data support the hypothesis that regulated protein acetylation is involved in the metabolic process of GAS, which may be induced by acetyl-CoA acetyltransferases.
Case Report: Hypopituitarism Presenting With Nonconvulsive Status Epilepticus
Authors: Li Huimin , Xu Lina , Yang Fengbing , Jia Longbin , Cheng Hongjiang , Liu Wei
Published: October 2021

Introduction: Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies. Nonconvulsive status epilepticus (NCSE) refers to a state of continuous or repetitive seizures without convulsions. In this paper, we review a case of an old female patient with hypopituitarism who presented with NCSE, which is rare in the clinic.

Case Report: This paper describes a 67-year-old female patient with hypopituitarism who presented as NCSE. She had surgical resection of pituitary tumor half a year before the seizures and did not get regular hormone replacement therapy. She presented general convulsive status epilepsy as the initial symptom and got sedation and antiepileptic drug in the emergency room. The seizure was terminated but the patient fell in coma in the following days. The patient had magnetic resonance imaging (MRI) and other inspects, and EEG showed epileptic discharges. Combining these clinical symptoms and examinations, we made the diagnosis of NCSE. Finally, she regained consciousness after the treatment with diazepam.

Conclusion: This case report and literature review investigated the possible mechanism of hypopituitarism presenting with NCSE.
Association of Serum Uric Acid Levels in Meige’s Syndrome
Authors: Guan Haochen , Geng Zhi , Yuan Weijie , Chang Bowen
Published: October 2021

Uric acid (URIC) is a natural antioxidant, and it has been shown that low levels of URIC could be a risk factor for the development of Parkinson’s disease. Our aim was to investigate whether URIC also plays a role in Meige’s syndrome (MS). We conducted a cohort study to compare serum URIC levels between patients with MS and healthy controls. In addition, we analyzed the impact of URIC on the risk of MS and symptom severity. Compared with normal subjects, URIC content was remarkably decreased in MS patients. In addition, URIC was regarded as a protective factor for MS, as verified by multivariate logistic regression models. We also found non-linear relationships between the levels of serum URIC and the incidence rate of MS and the Burke-Fahn-Marsden dystonia rating scale score. Our study is the first to show a connection between serum URIC levels and MS. Low serum URIC levels indicate an increased risk of MS incidence and more severe clinical symptoms. Our findings provide new insights into the prevention and treatment of MS.
Hypoalbuminaemia as a Prognostic Biomarker of First-Line Treatment Resistance in Metastatic Non-small Cell Lung Cancer
Authors: Stares Mark , Swan Amanda , Cumming Kirsten , Ding Tze-En , Leach James , Stratton Cory , Thomson Findlay , Barrie Colin , MacLennan Kirsty , Campbell Sorcha , Evans Tamasin , Tufail Aisha , Harrow Stephen , MacKean Melanie , Phillips Iain
Published: October 2021

Introduction: Despite significant advances in systemic anticancer therapy (SACT) for non-small cell lung cancer (NSCLC), many patients still fail to respond to treatment or develop treatment resistance. Albumin, a biomarker of systemic inflammation and malnutrition, predicts survival in many cancers. We evaluated the prognostic significance of albumin in patients receiving first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC.

Methods: All patients treated with first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC at a regional Scottish cancer centre were identified. Serum albumin at pre-treatment, after 12-weeks of treatment, and at the time of progressive disease were recorded. The relationship between albumin (≥ 35g/L v <35g/L) and overall survival (OS) was examined.

Results: Data were available for 389 patients of both targeted therapy cohort (n = 159) and immunotherapy-based therapy cohort (n = 230). Pre-treatment albumin was predictive of OS in each cohort at HR1.82 (95%CI 1.23–2.7) (p =0.003) and HR2.55 (95%CI 1.78–3.65) (p < 0.001), respectively. Pre-treatment albumin <35 g/L was associated with a significantly higher relative risk of death within 12 weeks in each cohort at RR9.58 (95%CI 2.20–41.72, p = 0.003) and RR3.60 (95%CI 1.74–6.57, p < 0.001), respectively. The 12-week albumin was predictive of OS in each cohort at HR1.88 (95%CI 1.86–4.46) (p < 0.001) and HR2.67 (95%CI 1.74–4.08) (p < 0.001), respectively. 46 out of 133 (35%) evaluable patients treated with targeted therapy and 43 out of 169 (25%) treated with immunotherapy-based therapy crossed over albumin prognostic groups between pre-treatment and 12-week. The prognostic value of 12-week albumin was independent of pre-treatment albumin status. A majority of patients had albumin <35g/L at the time of progressive disease when it was also predictive of survival following progressive disease at HR2.48 (95%CI 1.61–3.82) (p < 0.001) and HR2.87 (95%CI 1.91–4.31) (p < 0.001) respectively).

Conclusions: Albumin is a reliable prognostic factor in patients with metastatic NSCLC, predicting survival independent of the class of drug treatment at various time points during the patient journey. Tracking albumin concentrations during systemic therapy may indicate disease activity or treatment response over time.
MRI-Derived Subcutaneous and Visceral Adipose Tissue Reference Values for Children Aged 6 to Under 18 Years
Authors: Marunowski Kacper , Świętoń Dominik , Bzyl Włodzimierz , Grzywińska Małgorzata , Kaszubowski Mariusz , Bandosz Piotr , Khrichenko Dmitry , Piskunowicz Maciej
Published: October 2021

The assessment of body composition in pediatric population is essential for proper nutritional support during hospitalization. However, currently available methods have limitations. This study aims to propose a novel approach for nutrition status assessment and introduce magnetic resonance imaging (MRI)-derived subcutaneous and visceral fat normative reference values. A total of 262 healthy subjects aged from 6 to 18 years underwent MRI examinations and anthropometric measurements. MRI images at the second lumbar vertebrae were used by two radiologists to perform the semi-automatic tissue segmentation. Based on obtained adipose tissue surface areas and body mass index (BMI) scores sex-specific standard percentile curves (3rd, 10th, 25th, 50th, 75th, 90th, 97th) and z-scores were constructed using LMS method. Additionally, 85th and 95th centiles of subcutaneous and visceral adipose tissue were proposed as equivalents of overweight and obesity. Bland-Altman plots revealed an excellent intra-observer reproducibility and inter-observer agreement. In conclusion, our findings demonstrate highly reproducible method and suggest that MRI-derived reference values can be implemented in clinical practice.
Predictive Value of Preoperative Positive Urine Cytology for Development of Bladder Cancer After Nephroureterectomy in Patients With Upper Urinary Tract Urothelial Carcinoma: A Prognostic Nomogram Based on a Retrospective Multicenter Cohort Study and Systematic Meta-Analysis
Authors: Fan Bo , Huang Yuanbin , Wen Shuang , Teng Qiliang , Yang Xinrui , Sun Man , Chen Tingyu , Huang Yan , Wang Yumei , Liu Zhiyu
Published: October 2021

Background

Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare.

Methods

We first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior.

Results

Firstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan–Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63).

Conclusions

Preoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.
Axillary Lymph Node Dissection Rates and Prognosis From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer
Authors: Gwark Sungchan , Noh Woo Chul , Ahn Sei Hyun , Lee Eun Sook , Jung Yongsik , Kim Lee Su , Han Wonshik , Nam Seok Jin , Gong Gyungyub , Kim Seon-Ok , Kim Hee Jeong
Published: October 2021

In this study, we aimed to evaluate axillary lymph node dissection (ALND) rates and prognosis in neoadjuvant chemotherapy (NCT) compare with neoadjuvant endocrine therapy (NET) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), lymph node (LN)-positive, premenopausal breast cancer patients (NCT01622361). The multicenter, phase 3, randomized clinical trial enrolled 187 women from July 5, 2012, to May 30, 2017. The patients were randomly assigned (1:1) to either 24 weeks of NCT including adriamycin plus cyclophosphamide followed by intravenous docetaxel, or NET involving goserelin acetate and daily tamoxifen. ALND was performed based on the surgeon’s decision. The primary endpoint was ALND rate and surgical outcome after preoperative treatment. The secondary endpoint was long-term survival. Among the 187 randomized patients, pre- and post- neoadjuvant systemic therapy (NST) assessments were available for 170 patients. After NST, 49.4% of NCT patients and 55.4% of NET patients underwent mastectomy after treatment completion. The rate of ALND was significantly lower in the NCT group than in the NET group (55.2% vs. 69.9%, P=.046). Following surgery, the NET group showed a significantly higher mean number of removed LNs (14.96 vs. 11.74, P=.003) and positive LNs (4.84 vs. 2.92, P=.000) than the NCT group. The axillary pathologic complete response (pCR) rate was significantly higher in the NCT group (13.8% vs. 4.8%, P=.045) than in the NET group. During a median follow-up of 67.3 months, 19 patients in the NCT group and 12 patients in the NET group reported recurrence. The 5-year ARFS (97.5%vs. 100%, P=.077), DFS (77.2% vs. 84.8%, P=.166), and OS (97.5% vs. 94.7%, P=.304) rates did not differ significantly between the groups. In conclusion, although survival did not differ significantly, more NCT patients might able to avoid ALND, with fewer LNs removed with lower LN positivity.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT01622361, identifier NCT01622361.
Comparing Hypofractionated With Conventional Fractionated Radiotherapy After Breast-Conserving Surgery for Early Breast Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Gu Lihu , Dai Wei , Fu Rongrong , Lu Hongfeng , Shen Jingyi , Shi Yetan , Zhang Mengting , Jiang Ke , Wu Feng
Published: October 2021

Background

The purpose of this meta-analysis was to compare the safety and efficacy between hypofractionated and conventional fractionation radiotherapy in patients with early-stage breast cancer after breast-conserving surgery.

Methods

We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) published before February 2021. At the same time, the hazard ratio (HR), risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate local recurrence (LR), relapse-free survival (RFS), overall survival (OS), adverse events, and cosmetic outcomes.

Results

A total of 14 articles were included in this meta-analysis. Four thousand eight hundred and sixty-nine patients were randomly assigned to the control group to receive conventional radiotherapy (CFRT); 6,072 patients were randomly assigned to the experimental group and treated with hypofractionated radiotherapy (HFRT). The results showed that there was no statistical difference between HFRT and CFRT in LR (HR = 0.99, 95%CI = 0.97–1.02, p = 0.476), RFS (HR = 0.99, 95%CI = 0.97–1.02, p = 0.485), OS (HR = 1.00, 95%CI = 0.97–1.03, p = 0.879), and cosmetic outcomes (RR = 1.03, 95%CI = 0.95–1.12, p = 0.53). In addition, HFRT showed fewer severe adverse reactions such as acute skin toxicity, induration, breast atrophy, and pain.

Conclusion

Our results suggest that there is no statistical difference between HFRT and CFRT in terms of LR, RFS, OS, and cosmetic outcomes. HFRT reduces the risk of developing toxicity reactions compared to CFRT. HFRT may be a better option for patients with early breast cancer after breast-conserving surgery.
Wheezing Characteristics and Predicting Reactivity to Inhaled β2-Agonist in Children for Home Medical Care
Authors: Habukawa Chizu , Ohgami Naoto , Arai Takahiro , Makata Haruyuki , Nishikido Tomoki , Tomikawa Morimitsu , Murakami Katsumi
Published: October 2021

Background: Given that wheezing is treated with inhaled β2-agonists, their effect should be reviewed before the condition becomes severe; however, few methods can currently predict reactivity to inhaled β2-agonists. We investigated whether preinhalation wheezing characteristics identified by lung sound analysis can predict reactivity to inhaled β2-agonists.

Methods: In 202 children aged 10–153 months, wheezing was identified by auscultation. Lung sounds were recorded for 30 s in the chest region on the chest wall during tidal breathing. We analyzed the wheezing before and after β2-agonist inhalation. Wheezing was displayed as horizontal bars of intensity defined as a wheeze power band, and the wheezing characteristics (number, frequency, and maximum intensity frequency) were evaluated by lung sound analysis. The participants were divided into two groups: non-disappears (wheezing did not disappear after inhalation) and disappears (wheezing disappeared after inhalation). Wheezing characteristics before β2-agonist inhalation were compared between the two groups.

The characteristics of wheezing were not affected by body size. The number of wheeze power bands of the non-responder group was significantly higher than those of the responder group (P < 0.001). The number of wheeze power bands was a predictor of reactivity to inhaled β2-agonists, with a cutoff of 11.1. The 95% confidence intervals of sensitivity, specificity, and positive and negative predictive values were 88.8, 42, 44, and 81.1% (P < 0.001), respectively.

Conclusions: The number of preinhalation wheeze power bands shown by lung sound analysis was a useful indicator before treatment. This indicator could be a beneficial index for managing wheezing in young children.
Case Report: Off-Label Use of Omalizumab in a 6-Year-Old Boy With ASD Ameliorated Severe Allergic Rhinitis and Subsequently Improved Behavioral Symptoms
Authors: Kong Xue-Jun , Clairmont Cullen , Wang Bryan
Published: October 2021

Children with ASD have elevated risk for developing allergic symptoms. The severity of allergic symptoms can exacerbate behavioral problems in children with ASD. Omalizumab, an anti-IgE antibody, has previously shown efficacy in treating allergic rhinitis and behavioral problems in a 12-year-old child with ASD. The present case report provides robust characterization of behavioral improvement in a 6-year-old child with ASD, allergic rhinitis, and autoimmune disorder. A 6-year-old boy with ASD and Hashimoto's disease presented to the clinic with severe allergic rhinitis, irritability, and language delay. After other treatments failed to improve symptoms, our patient was treated with omalizumab at 300 mg/month via subcutaneous injection for a total of 6 months. Marked improvement in allergic symptoms were observed at 2 months into treatment and were maintained through the treatment period. At the conclusion of the treatment period, results from multiple behavioral questionnaires, including the SRS-2, ABC, RBS-R, and PSQI, demonstrated substantial improvement in ASD-related behavioral symptoms. In this case, omalizumab markedly improved ASD-related and sleep behavior in a 6-year-old with ASD, allergic rhinitis, and autoimmune disorder. Future studies with larger patient populations are warranted to investigate the efficacy of omalizumab in patients with ASD and allergy symptoms.
Effects of TPMT, NUDT15, and ITPA Genetic Variants on 6-Mercaptopurine Toxicity for Pediatric Patients With Acute Lymphoblastic Leukemia in Yunnan of China
Authors: Mao Xiaoyan , Yin Runxiu , Sun Gaoyuan , Zhou Yan , Yang Chunhui , Fang Chunlian , Wu Yuhong , Cui Tingting , Liu Li , Gan Jiaxin , Tian Xin
Published: October 2021

Background: 6-Mercaptopurine (6-MP) is the cornerstone of current antileukemia regimen and contributes greatly to improve the survival of pediatric acute lymphoblastic leukemia (ALL) patients. However, 6-MP dose-related toxicities limit its application. TPMT, NUDT15, and ITPA are pharmacogenetic markers predicting 6-MP-related toxicities, but their genetic polymorphisms differ from those of ethnic populations. In Yunnan province, a multiethnic region of China, we had no genetic data to predict 6-MP toxicities. In this study, we evaluated the most common variants involved in 6-MP metabolism—TPMT*3C (rs1142345), NUDT15 c.415C>T (rs116855232), and ITPA c.94C>A (rs1127354) variants—in our cohort of pediatric ALL patients.

Methods: A total of 149 pediatric ALL patients in the Affiliated Children's Hospital of Kunming Medical University (Yunnan Children's Medical Center) from 2017 to 2019 were enrolled in this retrospective study. We assessed the TPMT*3C (rs1142345), NUDT15 c.415C>T (rs116855232), and ITPA c.94C>A (rs1127354) frequencies and evaluated association between genotypes and 6-MP toxicities, 6-MP dose, and event-free survival (EFS) in these ALL patients.

Results: The allele frequencies of TPMT*3C (rs1142345), NUDT15 c.415C>T (rs116855232), and ITPA c.94C>A (rs1127354) were 1.34%, 14.43%, and 18.79%, respectively. Only NUDT15 c.415C>T (rs116855232) was strongly associated with 6-MP toxicity and 6-MP tolerable dose. NUDT15 c.415C>T was related to leukopenia, p = 0.008, OR = 2.743 (95% CI: 1.305–5.768). The T allele was significantly correlated with 6-MP tolerable dose, dose of NUDT15 c.415C>T wild genotype CC 39.80 ± 1.32 mg/m2, heterozygotes CT 35.20 ± 2.29 mg/m2, and homozygotes TT 18.95 ± 3.95 mg/m2. 6-MP tolerable dose between CC and TT had a significant difference, p = 0.009. Between CC and CT, and CT and TT, they had no significant difference. EFS showed no significant difference among NUDT15 c.415C>T genotypes.

Conclusion:NUDT15 c.415C>T (rs116855232) was an optimal predictor for 6-MP toxicity and tolerable dose in pediatric ALL patients from Yunnan province, a multiethnic region in China, and would play an important role in precise therapy for ALL.
Sacral Curvature in Addition to Sacral Ratio to Assess Sacral Development and the Association With the Type of Anorectal Malformations
Authors: Chen Zhen , Zheng Lingling , Zhang Minzhong , Zhang Jie , Kong Ruixue , Chen Yunpei , Liang Zijian , Levitt Marc A. , Wei Chin-Hung , Wang Yong
Published: October 2021

Introduction: Sacral ratio (SR) is currently the only measurement to quantitatively evaluate sacral development in patients with anorectal malformations (ARM). This study proposes sacral curvature (SC) as a new indicator to qualitatively assess the sacrum and hypothesizes that sacral development, both quantitatively and qualitatively, can be an indicator to predict the type of ARM. The study aims to investigate the difference of SR and SC between ARM types and the association with the type of ARM.

Methods and Materials: This study was retrospectively conducted between August 2008 and April 2019. Male patients with ARMs were enrolled and divided into three groups based on the types of ARM: (1) rectoperineal fistulae, (2) rectourethral-bulbar fistulae, and (3) rectourethral-prostatic or rectobladder-neck fistulae. SC was measured in the sagittal views of an MRI or a lateral radiograph of the sacrum.

Results: Included in the study were 316 male patients with ARMs. SRs were 0.73 ± 0.12, 0.65 ± 0.12, and 0.57 ± 0.12 in perineal, bulbar, and prostatic/bladderneck fistula, respectively (p < 0.01). The SCs in perineal fistulae and bulbar fistulae were significantly higher than that in prostatic/bladderneck fistulae (0.25 ± 0.04, 0.22 ± 0.14, and 0.14 ± 0.18, p < 0.01). When SR ≥ 0.779, there was an 89.9% of possibility that the child has a perineal fistula. When SR ≤ 0.490 and SC ≤ 0, the possibilities of the child having prostatic/bladderneck fistulae were 91.6 and 89.5%, respectively. SC < 0 was also noted in 27 (27.8%), 19 (10.5%), and no (0%) patients of prostatic/bladderneck, bulbar, and perineal fistulae (p < 0.01), respectively. Sacral defect was noted in 63% of patients with SC ≤ 0, compared to none with SC > 0 (p < 0.01).

Conclusions: The higher the rectal level is in an ARM, the lower are the objective measurements of the sacrum. SC ≤ 0 is associated with sacral defects and implies a high likelihood of prostatic/bladderneck fistulae.