bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of simulated water mass transformation on the Antarctic shelf to tides, topography and model resolution
Authors: Boeira Dias Fabio , Rintoul Stephen R. , Richter Ole , Galton-Fenzi Benjamin Keith , Zika Jan D. , Pellichero Violaine , Uotila Petteri
Published: April 2023

Water mass transformation (WMT) around the Antarctic margin controls Antarctica Bottom Water formation and the abyssal limb of the global meridional overturning circulation, besides mediating ocean-ice shelf exchange, ice sheet stability and its contribution to sea level rise. However, the mechanisms controlling the rate of WMT in the Antarctic shelf are poorly understood due to the lack of observations and the inability of climate models to simulate those mechanisms, in particular beneath the floating ice shelves. We used a circum-Antarctic ocean-ice shelf model to assess the contribution of surface fluxes, mixing, and ocean-ice shelf interaction to the WMT on the continental shelf. The salt budget dominates the WMT rates, with only a secondary contribution from the heat budget. Basal melt of ice shelves drives buoyancy gain at lighter density classes (27.2<σθ< 27.6 kg m-3), while salt input associated with sea-ice growth in coastal polynyas drives buoyancy loss at heavier densities (σθ> 27.6). We found a large sensitivity of the WMT rates to model horizontal resolution, tides and topography within the Filchner-Ronne, East and West Antarctica ice shelf cavities. In the Filchner-Ronne Ice Shelf, an anticyclonic circulation in front of the Ronne Depression regulates the rates of basal melting/refreezing and WMT and is substantially affected by tides and model resolution. Model resolution is also found to affect the Antarctic Slope Current in both East and West Antarctica, impacting the on-shelf heat delivery, basal melt and WMT. Moreover, the representation of the ice shelf draft associated with model resolution impacts the freezing temperature and thus basal melt and WMT rates in the East Antarctica. These results highlight the importance of resolving small-scale features of the flow and topography, and to include the effects of tidal forcing, to adequately represent water mass transformations on the shelf that directly influence the abyssal global overturning circulation.
The endogenous thrombin potential in patients with left ventricular assist device or heart transplant
Authors: Schlagenhauf Axel , Haidl Harald , Trummer Georg , Berchtold-Herz Michael , Pooth Jan-Steffen , Strini Tanja , Geisen Ulrich , Beyersdorf Friedhelm , Zieger Barbara
Published: April 2023

Background

The Heartmate 3 (HM 3) is a left ventricular assist device featuring less shear stress, milder acquired von Willebrand syndrome, and fewer bleeding incidences than its predecessor the Heartmate II (HM II). The novel surface coating of the HM 3 suggests less contact activation of plasmatic coagulation. We hypothesized that patients with HM 3 exhibit fewer aberrations in their thrombin potential than patients with HM II. We compared these results with the thrombin potential of patients with heart transplantation (HTX).

Methods

Thrombin generation in plasma samples of patients with HM II (n = 16), HM 3 (n = 20), and HTX (n = 13) was analyzed 3 days after implantation/transplantation and after long-term support (3–24 months) with HM II (n = 16) or HM 3 (n = 12) using calibrated automated thrombography. Heparin in postoperative samples was antagonized with polybrene.

Results

Three days postoperatively HM II patients exhibited a lower endogenous thrombin potential (ETP) than HM 3 and HTX patients (HM II: 947 ± 291 nM*min; HM 3: 1231 ± 176 nM*min; HTX: 1376 ± 162 nM*min, p < 0.001) and a lower velocity index of thrombin generation (HM II: 18.74 ± 10.90 nM/min; HM 3: 32.41 ± 9.51 nM/min; HTX: 37.65 ± 9.41 nM/min, p < 0.01). Subtle differences in the thrombin generation profiles remained in HM II and HM 3 patients under long-term support (Velocity Index: HM II: 38.70 ± 28.46 nM/min; HM 3: 73.32 ± 32.83 nM/min, p < 0.05). Prothrombin fragments 1 + 2 were higher in HM II than in HM 3 patients (HM II: 377.7 ± 208.4 pM; HM 3: 202.1 ± 87.7 pM, p < 0.05) and correlated inversely with the ETP (r = −0.584, p < 0.05).

Conclusion

We observed a more aberrant thrombin generation in HM II than in HM 3 despite comparable anticoagulation and routine parameters. A trend toward lower values was still observable in HM 3 compared to HTX patients. Calibrated automated thrombography may be a good tool to monitor the coagulation state of these patients and guide anticoagulation in the future.
Long-term survival benefits of intrathecal autologous bone marrow-derived mesenchymal stem cells (Neuronata-R®: lenzumestrocel) treatment in ALS: Propensity-score-matched control, surveillance study
Authors: Nam Jae-Yong , Chun Sehwan , Lee Tae Yong , Seo Yunjeong , Kim Kwijoo , Park Jinseok , Sung Wonjae , Oh Ki-Wook , Lee Sanggon , Park Jin-Sung , Oh Juyeon , Chung Kyung Cheon , An Hyonggin , Chu Hyeon Sik , Son Bugyeong , Kim Seung Hyun
Published: April 2023

Objective

Neuronata-R® (lenzumestrocel) is an autologous bone marrow-derived mesenchymal stem cell (BM-MSC) product, which was conditionally approved by the Korean Ministry of Food and Drug Safety (KMFDS, Republic of Korea) in 2013 for the treatment of amyotrophic lateral sclerosis (ALS). In the present study, we aimed to investigate the long-term survival benefits of treatment with intrathecal lenzumestrocel.

Methods

A total of 157 participants who received lenzumestrocel and whose symptom duration was less than 2 years were included in the analysis (BM-MSC group). The survival data of placebo participants from the Pooled-Resource Open-Access ALS Clinical Trials (PROACT) database were used as the external control, and propensity score matching (PSM) was used to reduce confounding biases in baseline characteristics. Adverse events were recorded during the entire follow-up period after the first treatment.

Results

Survival probability was significantly higher in the BM-MSC group compared to the external control group from the PROACT database (log-rank, p < 0.001). Multivariate Cox proportional hazard analysis showed a significantly lower hazard ratio for death in the BM-MSC group and indicated that multiple injections were more effective. Additionally, there were no serious adverse drug reactions found during the safety assessment, lasting a year after the first administration.

Conclusion

The results of the present study showed that lenzumestrocel treatment had a long-term survival benefit in real-world ALS patients.
Perception of length and orientation in dry immersion
Authors: Lyakhovetskii Vsevolod , Chetverikov Andrey , Zelenskaya Inna , Tomilovskaya Elena , Karpinskaia Valeriia
Published: April 2023

Introduction

How does gravity (or lack thereof) affect sensory-motor processing? We analyze sensorimotor estimation dynamics for line segments with varying direction (orientation) in a 7-day dry immersion (DI), a ground-based model of gravitational unloading.

Methods

The measurements were carried out before the start of the DI, on the first, third, fifth and seventh days of the DI, and after its completion. At the memorization stage, the volunteers led the leading hand along the visible segment on a touchscreen display, and at the reproduction stage they repeated this movement on an empty screen. A control group followed the same procedure without DI.

Results

Both in the DI and control groups, when memorizing, the overall error in estimating the lengths and directions of the segments was small and did not have pronounced dynamics; when reproducing, an oblique effect (higher variability of responses to oblique orientations compared to cardinal ones) was obtained. We then separated biases (systematic error) and uncertainty (random error) in subjects’ responses. At the same time, two opposite trends were more pronounced in the DI group during the DI. On the one hand the cardinal bias (a repulsion of orientation estimates away from cardinal axes) and, to a small extent, the variability of direction estimates decreased. On the other hand, the overestimation bias in length estimates increased.

Discussion

Such error pattern strongly supports the hypotheses of the vector encoding, in which the direction and length of the planned movement are encoded independently of each other when the DI disrupts primarily the movement length encoding.
Cognitive functions and patterns of brain activity in patients after simultaneous coronary and carotid artery revascularization
Authors: Tarasova Irina , Trubnikova Olga , Kupriyanova Darya S. , Maleva Olga , Syrova Irina , Kukhareva Irina , Sosnina Anastasia , Tarasov Roman , Barbarash Olga
Published: April 2023

Background

On-pump coronary artery bypass grafting (CABG) is associated with a high risk of neurological complications in patients with severe carotid stenosis. Moreover, early postoperative cognitive dysfunction (POCD) incidence remains high in patients undergoing simultaneous coronary and carotid surgery. Recent studies have shown that even moderate carotid stenosis (≥50%) is associated with postoperative cognitive decline after CABG. Data on brain health in the postoperative period of simultaneous coronary and carotid surgery are limited.

Objectives

This study aimed to analyze early postoperative changes in the cognitive function and patterns of brain electrical activity in patients after simultaneous coronary and carotid artery revascularization.

Materials and methods

Between January 2017 and December 2020, consecutive patients were assigned to on-pump CABG with or without carotid endarterectomy (CEA) according to clinical indications. An extended neuropsychological and electroencephalographic (EEG) assessment was performed before surgery and at 7–10 days after CABG or CABG + CEA.

Results

A total of 100 patients were included [median age 59 (55; 65), 95% men, MMSE 27 (26; 28)], and among these, 46 underwent CEA. POCD was diagnosed in 29 (63.0%) patients with CABG + CEA and in 32 (59.0%) patients with isolated CABG. All patients presented with a postoperative theta power increase. However, patients with CABG + right-sided CEA demonstrated the most pronounced theta power increase compared to patients with isolated CABG.

Conclusion

The findings of our study show that patients with CABG + CEA and isolated CABG have comparable POCD incidence; however, patients with CABG + right-sided CEA presented with lower brain activity.
The effect of small incision lenticule extraction on contrast sensitivity
Authors: Yue Pinqing , Wang Zeng , Wu Di , Zhang Hua , Zhang Pan
Published: April 2023

The improvements due to small incision lenticule extraction (SMILE) in vision, e.g., in spherical equivalent (SE) and visual acuity (VA), has been widely recognized. However, the contrast sensitivity (CS) change after SMILE was not certain. Here, we investigated the effect of SMILE on CS before, 1 day after and 7 days after surgery and then clarified the corresponding mechanism by using a perceptual template model (PTM). In addition, the relationship among SE, VA, and CS was discussed. The quick contrast sensitivity function (qCSF) was applied to measure CS with high precision and accuracy. We found that (1) CS was significantly improved 1 day after SMILE and was also increased 7 days after the surgery, (2) CS improvements were dependent on spatial frequency and external noise, (3) the increase in CS was due to the decreased internal additive noise and an enhanced perceptual template, and (4) Greater SE improvements predicted better VA improvements 1 day after SMILE, and a positive correlation between SE improvements and AULCSF improvements 7 days after SMILE was observed. These findings help us better understand the effect of SMILE and provide effective indicators for future visual research.
The cerebrospinal fluid immune cell landscape in animal models of multiple sclerosis
Authors: Wu Gregory F.
Published: April 2023

The fluid compartment surrounding the central nervous system (CNS) is a unique source of immune cells capable of reflecting the pathophysiology of neurologic diseases. While human clinical and experimental studies often employ cerebrospinal fluid (CSF) analysis, assessment of CSF in animal models of disease are wholly uncommon, particularly in examining the cellular component. Barriers to routine assessment of CSF in animal models of multiple sclerosis (MS) include limited sample volume, blood contamination, and lack of feasible longitudinal approaches. The few studies characterizing CSF immune cells in animal models of MS are largely outdated, but recent work employing transcriptomics have been used to explore new concepts in CNS inflammation and MS. Absence of extensive CSF data from rodent and other systems has curbed the overall impact of experimental models of MS. Future approaches, including examination of CSF myeloid subsets, single cell transcriptomics incorporating antigen receptor sequencing, and use of diverse animal models, may serve to overcome current limitations and provide critical insights into the pathogenesis of, and therapeutic developments for, MS.
Denervated mouse CA1 pyramidal neurons express homeostatic synaptic plasticity following entorhinal cortex lesion
Authors: Lenz Maximilian , Eichler Amelie , Kruse Pia , Stöhr Phyllis , Kleidonas Dimitrios , Galanis Christos , Lu Han , Vlachos Andreas
Published: April 2023

Structural, functional, and molecular reorganization of denervated neural networks is often observed in neurological conditions. The loss of input is accompanied by homeostatic synaptic adaptations, which can affect the reorganization process. A major challenge of denervation-induced homeostatic plasticity operating in complex neural networks is the specialization of neuronal inputs. It remains unclear whether neurons respond similarly to the loss of distinct inputs. Here, we used in vitro entorhinal cortex lesion (ECL) and Schaffer collateral lesion (SCL) in mouse organotypic entorhino-hippocampal tissue cultures to study denervation-induced plasticity of CA1 pyramidal neurons. We observed microglia accumulation, presynaptic bouton degeneration, and a reduction in dendritic spine numbers in the denervated layers 3 days after SCL and ECL. Transcriptome analysis of the CA1 region revealed complex changes in differential gene expression following SCL and ECL compared to non-lesioned controls with a specific enrichment of differentially expressed synapse-related genes observed after ECL. Consistent with this finding, denervation-induced homeostatic plasticity of excitatory synapses was observed 3 days after ECL but not after SCL. Chemogenetic silencing of the EC but not CA3 confirmed the pathway-specific induction of homeostatic synaptic plasticity in CA1. Additionally, increased RNA oxidation was observed after SCL and ECL. These results reveal important commonalities and differences between distinct pathway lesions and demonstrate a pathway-specific induction of denervation-induced homeostatic synaptic plasticity.
Nutritional risk and a high NRS2002 score are closely related to disease progression and poor prognosis in patients with COVID-19
Authors: Zhou Yuanyuan , Chen Yi , Zhang Xinyi , Zhao Bennan , Gao Fengjiao , Yuan Xiaoyan , Zhu Yanfeng , Liu Dafeng
Published: April 2023

Background

Organism can lead to excessive nutrient consumption in the infected state and increase nutritional risk, which is detrimental to the control of the infection and can further aggravate the disease.

Objectives

To investigate the impact of nutritional risk and the NRS2002 score on disease progression and prognosis in patients with COVID-19.

Methods

This was a retrospective cohort study including 1,228 COVID-19 patients, who were divided into a with-nutritional risk group (patients with NRS2002 score ≥ 3) and a without-nutritional risk group (patients with NRS2002 score < 3) according to the NRS2002 score at admission. The differences in clinical and outcome data between the two groups were compared, and the relationship between the NRS2002 score and the disease progression and prognosis of COVID-19 patients was assessed.

Results

Of 1,228 COVID-19 patients, including 44 critical illness patients and 1,184 non-critical illness patients, the rate of harboring nutritional risk was 7.90%. Compared with those in the without-nutritional risk group, patients in the with-nutritional risk group had a significantly longer coronavirus negative conversion time, significantly lower serum albumin (ALB), total serum protein (TP) and hemoglobin (HGB) at admission, discharge or 2 weeks, a significantly greater proportion with 3 or more comorbidities, and a significantly higher rate of critical illness and mortality (all p < 0.001). Multiple regression analysis showed that nutritional risk, NRS2002 score and ALB at admission were risk factors for disease severity. In addition, nutritional risk, NRS2002 score and TP at admission were risk factors for prognosis. The NRS2002 score showed the best utility for predicting critical illness and death in COVID-19 patients.

Conclusion

Nutritional risk and a high NRS2002 score are closely related to disease progression and poor prognosis in COVID-19 patients. For patients with NRS2002 score > 0.5, early intervention of malnutrition is needed to reduce the occurrence of critical disease. Additionally, for patients with NRS2002 score > 5.5, continuous nutritional support therapy is needs to reduce mortality and improve prognosis.

Clinical Trial registration: [https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2000034563], identifier [Chinese Clinical Trial Register ChiCTR2000034563].
Human intravital microscopy in the study of sarcomas: an early trial of feasibility
Authors: Gabriel Emmanuel M. , Sukniam Kulkaew , Popp Kyle , Bagaria Sanjay P.
Published: April 2023

Sarcomas comprise a vast and heterogenous group of rare tumors. Because of their diversity, it is challenging to study sarcomas as a whole with regard to their biological and molecular characteristics. This diverse set of tumors may also possess differences related to their tumor-associated vasculature, which in turn may impact the ability to deliver systemic therapies (e.g., chemotherapy, targeted therapies, and immunotherapy). Consequently, response to systemic treatment may also be variable as these depend on the ability of the therapy to reach the tumor target via the tumor-associated vasculature. There is a paucity of data regarding sarcoma-related tumor vessels, likely in part to the rarity and heterogeneity of this cancer as well as the previously limited ability to image tumor-associated vessels in real time. Our group has previously utilized confocal fluorescent imaging technology to observe and characterize tumor-associated vessels in real time during surgical resection of tumors, including cutaneous melanoma and carcinomatosis implants derived from gastrointestinal, gynecological, or primary peritoneal (e.g., mesothelioma) tumors. Our prior studies have demonstrated the feasibility of real-time, human intravital microscopy in the study of these tumor types, leading to early but important new data regarding tumor vessel characteristics and their potential implications on drug delivery and efficacy. In this brief report, we present our latest descriptive findings in a cohort of patients with sarcoma who underwent surgical resection and real-time, intravital microscopy of their tumors. Overall, intravital imaging was feasible during the surgical resection of large sarcomas.

Clinical trial registrations

ClinicalTrials.gov, identifier NCT03517852; ClinicalTrials.gov, identifier NCT03823144.
A scoping review of natural language processing of radiology reports in breast cancer
Authors: Saha Ashirbani , Burns Levi , Kulkarni Ameya Madhav
Published: April 2023

Various natural language processing (NLP) algorithms have been applied in the literature to analyze radiology reports pertaining to the diagnosis and subsequent care of cancer patients. Applications of this technology include cohort selection for clinical trials, population of large-scale data registries, and quality improvement in radiology workflows including mammography screening. This scoping review is the first to examine such applications in the specific context of breast cancer. Out of 210 identified articles initially, 44 met our inclusion criteria for this review. Extracted data elements included both clinical and technical details of studies that developed or evaluated NLP algorithms applied to free-text radiology reports of breast cancer. Our review illustrates an emphasis on applications in diagnostic and screening processes over treatment or therapeutic applications and describes growth in deep learning and transfer learning approaches in recent years, although rule-based approaches continue to be useful. Furthermore, we observe increased efforts in code and software sharing but not with data sharing.
Family care reduces the incidence of neonatal sepsis: A systematic review and meta-analysis
Authors: Ganji Niloofar , Alganabi Mashriq , Yamoto Masaya , Chusilp Sinobol , Pierro Agostino , Li Bo
Published: April 2023

Purpose

Family-involved care in the neonatal intensive care unit (NICU) helps to alleviate neonatal anxiety and promotes breastmilk intake, body growth and neurological development, but its effect on reducing the incidence of neonatal sepsis is not known. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate whether neonates receiving family care have a lower incidence of neonatal sepsis compared to neonates receiving standard NICU care.

Methods

MEDLINE, Embase, Web of Science, and CENTRAL were searched for RCTs that compared preterm neonates receiving family care vs. standard NICU care. From 126 articles that were identified and screened, 34 full-text articles were assessed for eligibility, and 5 RCTs were included. The primary outcome was the development of sepsis. The RevMan 5.4 software was used to conduct the Meta-analysis.

Results

The metanalysis, based on 5 RCTs demonstrated that neonates receiving family-involved care had significantly lower incidence of sepsis (12.0% vs. 16.3%), increased body weight, and reduced length of hospital stay compared to those receiving standard NICU care.

Conclusion

This study suggests that family-involved care in NICU can (i) reduce the incidence of neonatal sepsis, (ii) improve growth, and (iii) reduce the length of hospital stay. This study highlights the need for evaluating whether family-involved care improves other neonatal outcomes.
Treatment of visual axis opacification and secondary membranes with Nd:YAG laser after pediatric cataract surgery under intranasal sedation
Authors: Chang Pingjun , Li Siyan , Wang Dandan , Chen Chaoqiao , Fu Yana , Hu Man , Qian Shuyi , Zhao Yun-e
Published: April 2023

Purpose

To describe neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser treatment of visual axis opacification and secondary membranes in pediatric patients with cataracts under intranasal dexmedetomidine sedation.

Methods

Twenty eyes of 17 patients with secondary membrane formation after cataract extraction were enrolled in this study. Intranasal dexmedetomidine sedation (3 ug/kg) was administered, and Nd:YAG laser (Ellex Super Q, Adelaide, Australia) procedures were performed with children in the sitting position with their chin supported on a laser delivery slit lamp. Preoperative and postoperative visual acuities were documented, and medical records were reviewed.

Results

The age of the patients ranged from 5 to 83 months (31.82 ± 27.73). Nineteen (95.0%) eyes had congenital cataracts and one (5.0%) had a traumatic cataract. Nd:YAG laser treatment of VAO with ten (50.0%) eyes, pupillary membranes with three (15.0%) eyes, pupillary cortical proliferation with six (30.0%) eyes, and anterior capsule contraction with one (5.0%) eye. Five (25.0%) eyes demonstrated visual acuity improvement, whereas six (30.0%) eyes remained unchanged after laser treatment. The recurrence rate was 30.0% and four eyes underwent a second Nd:YAG membranectomy. No side effects or tolerances due to sedative drugs were observed.

Conclusion

Nd:YAG laser membranectomy under intranasal dexmedetomidine sedation was safely performed in children as young as 5 months old in a sitting position. This approach facilitates patient convenience, doctor proficiency, and cost reductions. Patients with recurrence can be treated by repeating the procedure.
Prenatal diagnosis of micrognathia: a systematic review
Authors: Cang Zhengqiang , Cui Jiangbo , Pei Jiaomiao , Wang Zheng , Du Yichen , Mu Siqi , Dou Wenjie , Fan Xing , Zhang Xi , Li Yang
Published: April 2023

Purpose

This systematic review aimed to analyze the characteristics of different diagnostic techniques for micrognathia, summarize the consistent diagnostic criteria of each technique, and provide a simple and convenient prenatal diagnosis strategy for micrognathia.

Methods

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the search was undertaken in three international databases (PubMed, Scopus, and Web of Science). The three reviewers assessed all papers and extracted the following variables: author's name and year of publication, country, study design, number of participants, gestational age, equipment for prenatal examination, biometric parameters related to micrognathia, main results.

Results

A total of 25 articles included in the analysis. Nineteen articles described cross-sectional studies (76 percent), 4 (16 percent) were case-control studies, and 2 (8 percent) were cohort studies. Fifteen studies (60 percent) had a prospective design, 9 (36 percent) had a retrospective design, and one (4 percent) had both prospective and retrospective design. Thirty-two percent of the studies (n = 8) were performed in USA, and the remaining studies were performed in China (n = 4), Israel (n = 3), Netherlands (n = 3), UK (n = 1), France (n = 1), Italy (n = 1), Belgium(n = 1), Germany (n = 1), Spain (n = 1), and Austria (n = 1). The prenatal diagnosis of micrognathia can be performed as early as possible in the first trimester, while the second and third trimester of pregnancy were the main prenatal diagnosis period. The articles that were included in the qualitative synthesis describe 30 biometric parameters related to the mandible.

Conclusion

Of the 30 biometric parameters related to the mandible, 15 can obtain the simple and convenient diagnostic criteria or warning value for micrognathia. Based on these diagnostic criteria or warning value, clinicians can quickly make a preliminary judgment on facial deformities, to carry out cytologic examination to further clarify the diagnosis of micrognathia.
Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictive markers in hepatoblastoma
Authors: Xie Tan , Hou Dongliang , Wang Jiaxiang , Zhao Song
Published: April 2023

Background

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been presented to be a prognostic indicator in several cancers. We were supposed to evaluate the prognostic role of such inflammatory markers in hepatoblastoma (HB).

Methods

Total of 101 children, diagnosed with hepatoblastoma between January 2010 and January 2018, were enrolled before treatment in the study. The clinicopathological parameters, and outcomes were collected through laboratory analyses and patient follow-up. The association between NLR, PLR, and clinicopathological characters were analyzed with Wilcoxon test, Chi-Squared test, Kaplan-Meier, Log-rank and Cox regression analyses.

Results

NLR and PLR were significantly elevated in HB patients (P < 0.001), and related to age (P < 0.001), risk stratification system (P < 0.001), and pretreatment extent of disease (P < 0.0001). NLR was significantly related to alpha-fetoprotein (P = 0.034) and lactate dehydrogenase (P = 0.026). The 3-year overall survival (OS) and event-free survival (EFS) were poor in the high-NLR group (OS: 44.3% vs. 90.3%, P < 0.0001, EFS: 38.6% vs. 80.6%, P = 0.0001). The 3-year OS and EFS were poor in the high-PLR group (OS: 49.1% vs. 68.8%, P = 0.016, EFS: 39.6% vs. 64.6%, P = 0.0117). The multivariate analysis suggested that NLR (HR: 11.359, 95% CI: 1.218–105.947; P = 0.033) and risk stratification (HR: 44.905, 95% CI: 2.458–820.36; P = 0.01), were independent predictors of OS.

Conclusion

Our research showed that elevated NLR and PLR were the poor prognostic factors in HB patients before treatment. The NLR was an independent prognostic factor for OS.
MiRNA-Drug Resistance Association Prediction Through the Attentive Multimodal Graph Convolutional Network
Authors: Niu Yanqing , Song Congzhi , Gong Yuchong , Zhang Wen
Published: April 2023

MiRNAs can regulate genes encoding specific proteins which are related to the efficacy of drugs, and predicting miRNA-drug resistance associations is of great importance. In this work, we propose an attentive multimodal graph convolution network method (AMMGC) to predict miRNA-drug resistance associations. AMMGC learns the latent representations of drugs and miRNAs from four graph convolution sub-networks with distinctive combinations of features. Then, an attention neural network is employed to obtain attentive representations of drugs and miRNAs, and miRNA-drug resistance associations are predicted by the inner product of learned attentive representations. The computational experiments show that AMMGC outperforms other state-of-the-art methods and baseline methods, achieving the AUPR score of 0.2399 and the AUC score of 0.9467. The analysis demonstrates that leveraging multiple features of drugs and miRNAs can make a contribution to the miRNA-drug resistance association prediction. The usefulness of AMMGC is further validated by case studies.
Therapeutics of Charcot neuroarthropathy and pharmacological mechanisms: A bone metabolism perspective
Authors: Liu Liang , Wang Qiong , Zhang Yan , Liang Jingqi , Liu Peilong , Zhao Hongmou
Published: April 2023

Charcot neuroarthropathy (CN) is a chronic, destructive, and painless damage of the skeletal system that affects the life quality of patients. CN, with an unclear mechanism, is characterized with invasive destruction of bones and a serious abnormality of bone metabolism. Unfortunately, development of an effective prevention and treatment strategy for CN is still a great challenge. Of note, recent studies providing an insight into the molecular mechanisms of bone metabolism and homeostasis have propelled development of novel CN therapeutic strategies. Therefore, this review aims to shed light on the pathogenesis, diagnosis, and treatment of CN. In particular, we highlight the eminent role of the osteoprotegerin (OPG)-receptor activator of nuclear factor-κB (RANK)-RANK ligand (RANKL) system in the development of CN. Furthermore, we summarize and discuss the diagnostic biomarkers of CN as well as the potential pharmacological mechanisms of current treatment regimens from the perspective of bone metabolism. We believe that this review will enhance the current state of knowledge on the diagnosis, prevention, and therapeutic efficacy of CN.
I13 overrides resistance mediated by the T315I mutation in chronic myeloid leukemia by direct BCR-ABL inhibition
Authors: Gao Congying , Zhang Lei , Xu Yun , Ma Xiangyu , Chen Peilei , Chen Zhe-Sheng , Wei Liuya
Published: April 2023

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by a BCR-ABL fusion gene. Imatinib has significantly improved the treatment of CML as a first-generation tyrosine kinase inhibitor (TKIs). The T315I mutant form of BCR-ABL is the most common mutation that confers resistance to imatinib or the second-generation TKIs, resulting in poor clinical prognosis. In this work, we assessed the effect of a potent histone deacetylase (HDAC) inhibitor, I13, on the differentiation blockade in CML cells harboring T315I-mutated and wild-type BCR-ABL by MTT assay, flow cytometery, cell colony formation assay, mRNA Sequencing, Quantitative real-time PCR and Western blotting analysis. We found that I13 possessed highly potent activity against T315I-mutated BCR-ABL mutant-expressing cells and wild-type BCR-ABL-expressing cells. I13 induced cell differentiation and significantly suppressed the proliferation of these CML cells via the cell cycle G0/G1-phase accumulation. Moreover, it was revealed that I13 triggered the differentiation of BaF3-T315I cells, which was attributed to the block of the chronic myeloid leukemia signaling pathway via the depletion of BCR-ABL that was mediated by the inhibition of HDAC activity presented by the acetylation of histones H3 and H4. Taken together, I13 efficiently depleted BCR-ABL in CML cells expressing the BCR-ABL-T315I mutation, which blocked its function, serving as a scaffold protein that modulated the chronic myeloid leukemia signaling pathway mediating cell differentiation. The present findings demonstrate that I13 is a BCR-ABL modulator for the development of CML therapy that can override resistance caused by T315I-mutated BCR-ABL.
Clarifying Nonstatic-Quantum-Wave Behavior Through Extending Its Analysis to the p-Quadrature Space: Interrelation Between the q- and p-Space Wave-Nonstaticities
Authors: Choi Jeong Ryeol
Published: April 2023

If electromagnetic parameters of a medium vary in time, quantum light waves traveling in it become nonstatic. A recent report shows that such nonstatic waves can also appear even when the environment is static where the parameters of the medium do not vary. In this work, the properties of nonstatic waves in a static environment are investigated from their p-space analysis, focusing on the interrelation between the q- and p-space nonstatic waves. The probability densities in p-space (as well as in q-space) for both the nostatic Fock and Gaussian states evolve in a periodic manner, i.e., they constitute belly and node in turn successively as time goes by. If we neglect the displacement of waves, the q- and p-space wave phases are opposite each other. Since the intensity of the wave in each space is relatively large whenever the wave forms a belly, such a phase difference indicates that periodical intensity exchange between the q- and p-component waves takes place through their nonstatic evolutions. This is the novel reciprocal optical phenomenon arisen on account of the wave nonstaticity.
Can Lightning Network’s Autopilot Function Use BA Model as the Underlying Network?
Authors: Wang Zhen , Zhang Rui , Sun Yipeng , Ding Hong , Lv Qiuyun
Published: April 2023

By extending micropayment channel technology and building a transaction network, the Lightning Network solves inefficient bitcoin transactions. Currently, more than 1,000 Bitcoins have been deposited in the Lightning Network. In designing the Lightning Network routing protocol, simulating its transactions, and evaluating the network robustness, researchers have almost always used the Barabasi Albert Model as a substrate network. In particular, as the network grows in size, it becomes particularly important to automatically establish links for the network of joined nodes—the autopilot function—and it becomes a crucial question whether the Barabasi Albert Model as the underlying network for the autopilot function conforms to the real topology of the Lightning Network. In this paper, we construct the temporal network of Lightning Network and compare the topological properties of Lightning Network with those of Barabasi Albert Model of the same scale in detail. Lightning Network has a large gap with Barabasi Albert Model in terms of assortativity and network diameter. We found that nodes tend to connect to nodes with greater Closeness Centrality in terms of node preference connectivity. Our findings suggest that using the Barabasi Albert Model as the underlying network for the autopilot function is not a reasonable choice.
Electron dynamics and metastable species generation in atmospheric pressure non-equilibrium plasmas controlled by dual LF–RF frequency discharges
Authors: Yu Yilin , Zhang Zhonglin , Nie Qiuyue , Zeng Jiacheng , Zhao Zhibo , Wang Xiaogang
Published: April 2023

In this work, we report an approach to control electron dynamics and metastable species generation and enhance the density of atmospheric pressure non-equilibrium plasmas by using dual-frequency excitation sources. The atmospheric dielectric barrier discharge (DBD) of an α-mode radio frequency (RF = 5 MHz) discharge controlled by a low-frequency (LF = 50 kHz) bias is studied based on a one-dimensional (1D) fluid model. Results show that the variation in amplitude ratio of RF and LF modulates the electron dynamic process, resulting in different spatial distributions of electron and metastable particle densities. Moreover, it is further shown that the electron density is substantially increased when the LF component voltage amplitude is larger than 300 V for the initial setting. The discharge process is characterized by fast Fourier transform of the spatio-temporal evolution of the electron power absorption and discharge current. As the LF is applied, three-wave interactions induced by LF and RF coupling are clearly observed, where the sum and beat frequencies between LF and RF are increased, which results in a substantial increase in the electron density. On the other hand, the high RF harmonics, especially for the fundamental and the third harmonic components, are suppressed when increasing the LF component. This work demonstrates that dual-frequency excitation is efficacious to modulate the electron dynamic behaviors and metastable species generation of atmospheric pressure plasma, which can provide a possible approach of optimizing plasma parameters.
Superconducting radio frequency photoinjectors for CW-XFEL
Authors: Xiang R. , Arnold A. , Lewellen J. W.
Published: April 2023

A dependable and consistent electron source is a crucial requirement for the achievement of high-power free electron lasers (FELs). Over the past two decades, it has been demonstrated that photoinjectors based on SRF technology (SRF guns) are suitable for continuous wave (CW) beam generation. SRF guns possess both the high accelerating field gradients of normal conducting RF photoinjectors and the low power dissipation thanks to mature SRF cavity technology, and therefore have the potential to provide the high-brightness, high-current beams required for CW-XFELs. After the demonstration of the first SRF gun in Dresden-Rossendorf, several SRF gun programs based on different approaches have achieved promising progress and even succeeded in routine operation. SRF guns are expected to play an important role in XFEL facilities in the near future. In this paper, we give an overview of design concepts, important parameters and development status of the worldwide SRF gun projects.
Impact of the central refractive index dip of fibers on high-power applications
Authors: An Yi , Chen Xiao , Ren Yankun , Wu Hanshuo , Huang Liangjin , Pan Zhiyong , Jiang Zongfu , Zhou Pu
Published: April 2023

Central refractive index dip is a common phenomenon in the fibers fabricated by the modified chemical vapor deposition (MCVD) technology, which is the main fabrication technique for high-power laser fibers. In this paper, we present a numerical analysis of the dip effect on high-power-related parameters for the first time, to the best of our knowledge. Three aspects including mode field parameter, beam quality, and bending performance are studied under different dip parameters and bending radii. It is found that the dip is possible to increase the effective mode area and the bending loss, which offers a flexible way to suppress the non-linear effects and filter the higher-order modes by optimizing the dip parameters. Besides, different from the mode area and bending loss, beam quality exhibits an interesting trend when the dip radius increases. The results could facilitate a comprehensive understanding of the dip fiber properties, which also offer guidance to evaluate and design the fiber with central refractive index dip for high-power applications.
Protein Targeting Into the Thylakoid Membrane Through Different Pathways
Authors: Zhu Dan , Xiong Haibo , Wu Jianghao , Zheng Canhui , Lu Dandan , Zhang Lixin , Xu Xiumei
Published: April 2023

In higher plants, chloroplasts are essential semi-autonomous organelles with complex compartments. As part of these sub-organellar compartments, the sheet-like thylakoid membranes contain abundant light-absorbing chlorophylls bound to the light-harvesting proteins and to some of the reaction center proteins. About half of the thylakoid membrane proteins are encoded by nuclear genes and synthesized in the cytosol as precursors before being imported into the chloroplast. After translocation across the chloroplast envelope by the Toc/Tic system, these proteins are subsequently inserted into or translocated across the thylakoid membranes through distinct pathways. The other half of thylakoid proteins are encoded by the chloroplast genome, synthesized in the stroma and integrated into the thylakoid through a cotranslational process. Much progress has been made in identification and functional characterization of new factors involved in protein targeting into the thylakoids, and new insights into this process have been gained. In this review, we introduce the distinct transport systems mediating the translocation of substrate proteins from chloroplast stroma to the thylakoid membrane, and present the recent advances in the identification of novel components mediating these pathways. Finally, we raise some unanswered questions involved in the targeting of chloroplast proteins into the thylakoid membrane, along with perspectives for future research.
Impact of chronic potassium binder treatment on the clinical outcomes in patients with hyperkalemia: Results of a nationwide hospital-based cohort study
Authors: Kanda Eiichiro , Morita Naru , Yajima Toshitaka
Published: April 2023

Introduction: Hyperkalemia (HK) is a common disorder in patients with heart failure or chronic kidney disease, and potassium binders (PBs) are recommended to control serum potassium (S-K) levels. Although HK is often a chronic condition, short-term and intermittent PBs treatment has been largely applied to control S-K levels, and little is known about the impact of long-term and chronic PBs treatment on clinical outcomes.

Method: This retrospective cohort study was conducted using a Japanese claims database (April 2008–September 2018). HK was defined as at least two S-K ≥5.1 mmol/L within a 12-month(M) interval. The index date was defined as the initial PB prescription date, and the S-K values were examined at 3M, 6M, and 12M after the index. The medication possession ratio (MPR) was used to evaluate the length of the prescribed period of PB, as prescription refill was not allowed in Japan. Clinical outcomes were analyzed by comparing MPR <80% to MPR ≥80% using Cox proportional hazards regression.

Results: We found 4,321 patients with HK and were on initial PB treatments, and 993 and 3,328 patients were categorized in the MPR <80% and MPR ≥80% groups, respectively. The mean prescription days ±SD in the MPR <80% and MPR ≥80% groups were 114.7 ± 9.1 and 1151.2 ± 22.5, respectively. S-K value with adjustment by covariates in MPR <80% and MPR ≥80% groups were 5.62 (95% CI: 5.57–5.68) and 5.72 (95% CI: 5.68–5.76) at index followed by 4.65 (95% CI: 4.58–4.71) and 4.57 (95% CI: 4.51–4.62) at 3M, respectively. The hazard ratios of incidence rates in hospitalization was 1.41 (p < 0.001), introduction of renal replacement therapy was 1.25 (p < 0.003), recurrent HK was 1.67 (p < 0.001), and decreased eGFR was 1.41 (p < 0.001), respectively.

Conclusion: These results indicate a higher risk of adverse outcomes when PBs were not prescribed chronically, whereas S-K levels were similarly controlled. Chronic control with continued PBs rather than temporary treatment may be associated with the reduction of adverse clinical outcomes in patients with HK.
Metabolomic evaluation of PGPR defence priming in wheat (Triticum aestivum L.) cultivars infected with Puccinia striiformis f. sp. tritici (stripe rust)
Authors: Mashabela Manamele D. , Tugizimana Fidele , Steenkamp Paul A. , Piater Lizelle A. , Dubery Ian A. , Terefe Tarekegn , Mhlongo Msizi I.
Published: April 2023

Plant-microbe interactions are a phenomenal display of symbiotic/parasitic relationships between living organisms. Plant growth-promoting rhizobacteria (PGPR) are some of the most widely investigated plant-beneficial microbes due to their capabilities in stimulating plant growth and development and conferring protection to plants against biotic and abiotic stresses. As such, PGPR-mediated plant priming/induced systemic resistance (ISR) has become a hot topic among researchers, particularly with prospects of applications in sustainable agriculture. The current study applies untargeted ultra-high performance liquid chromatography-high-definition mass spectrometry (UHPLC-HDMS) to investigate PGPR-based metabolic reconfigurations in the metabolome of primed wheat plants against Puccinia striiformis f. sp. tricti (Pst). A seed bio-priming approach was adopted, where seeds were coated with two PGPR strains namely Bacillus subtilis and Paenibacillus alvei (T22) and grown under controlled conditions in a glasshouse. The plants were infected with Pst one-week post-germination, followed by weekly harvesting of leaf material. Subsequent metabolite extraction was carried out for analysis on a UHPLC-HDMS system for data acquisition. The data was chemometrically processed to reveal the underlying trends and data structures as well as potential signatory biomarkers for priming against Pst. Results showed notable metabolic reprogramming in primary and secondary metabolism, where the amino acid and organic acid content of primed-control, primed-challenged and non-primed-challenged plants were differentially reprogrammed. Similar trends were observed from the secondary metabolism, in which primed plants (particularly primed-challenged) showed an up-regulation of phenolic compounds (flavonoids, hydroxycinnamic acids-HCAs- and HCA amides) compared to the non-primed plants. The metabolomics-based semi-quantitative and qualitative assessment of the plant metabolomes revealed a time-dependent metabolic reprogramming in primed-challenged and primed-unchallenged plants, indicating the metabolic adaptations of the plants to stripe rust infection over time.
Effects of different altitudes on the structure and properties of potato starch
Authors: Hu Tingyuan , Yang Hongkun , Zhang Kaiqin , Hafsa Cheema Nazir , Fang Xiaoting , Ma Haiyan , Liao Jiangxiu , Zheng Shunlin
Published: April 2023

The main element influencing the quality of potato starch is the environment. To investigate the effects of different altitude cultivation locations on the molecular structure and physicochemical properties of starch, two potato varieties, Jiusen No.1 B1 and Qingshu No.9 B2, were planted in three different altitude zones: A1 at low altitude (Chongzhou 450 m), A2 at middle altitude (Xichang 2800 m), and A3 at high altitude (Litang 3650 m). The results showed that the average volume, number, surface area diameter, average branched polymerization degree, crystallinity, and gelatinization temperature of two potato granules in high altitude areas were significantly lower than those in middle and low altitude areas were, and the gelatinization performance of potato starch was affected according to the correlation of starch structure characteristics. Potato starch with more short-branched chains and less long branched chains resulted in a lower gelatinization temperature in high altitude areas. The results showed that Jiusen No. 1 and Qingshu No. 9 were mainly affected by accumulated radiation and accumulated rainfall in Litang, a high altitude area, and by effective accumulated temperature in Xichang, a middle altitude area. This study quantified the influence of meteorological factors on the main starch quality of potato tubers. The results can be used as a theoretical basis for the scientific planting of high-quality potatoes.