bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward individualized medicine in stroke—The TiMeS project: Protocol of longitudinal, multi-modal, multi-domain study in stroke
Authors: Fleury Lisa , Koch Philipp J. , Wessel Maximilian J. , Bonvin Christophe , San Millan Diego , Constantin Christophe , Vuadens Philippe , Adolphsen Jan , Cadic Melchior Andéol , Brügger Julia , Beanato Elena , Ceroni Martino , Menoud Pauline , De Leon Rodriguez Diego , Zufferey Valérie , Meyer Nathalie H. , Egger Philip , Harquel Sylvain , Popa Traian , Raffin Estelle , Girard Gabriel , Thiran Jean-Philippe , Vaney Claude , Alvarez Vincent , Turlan Jean-Luc , Mühl Andreas , Léger Bertrand , Morishita Takuya , Micera Silvestro , Blanke Olaf , Van De Ville Dimitri , Hummel Friedhelm C.
Published: September 2022

Despite recent improvements, complete motor recovery occurs in <15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of brain network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification toward individually tailored treatment concepts using neuro-technologies, thus paving the way toward personalized precision medicine approaches in stroke rehabilitation.
Continuing early mTICI 2b recanalization may improve functional outcome but is associated with a higher risk of intracranial hemorrhage
Authors: Steffen Paul , Van Horn Noel , McDonough Rosalie , Deb-Chatterji Milani , Alegiani Anna Christina , Thomalla Götz , Fiehler Jens , Flottmann Fabian
Published: September 2022

Background

Successful reperfusion (mTICI 2c/3) and low number of passes are key determinants for good clinical outcome in acute large vessel occlusion. While final mTICI 2c/3 reperfusion is superior to partial reperfusion (mTICI 2b) it remains unclear if this is also true for the subgroup of patients with early mTICI 2b (achieved in ≤2 retrieval attempts) reperfusion who are secondarily improved to mTICI 2c/3. This study was designed to examine if early mTICI2b should be continued or stopped during mechanical thrombectomy (MT).

Methods

Nine hundred and thirteen ischemic stroke patients who received MT were retrospectively analyzed. Angiography runs following each recanalization attempt were scored for mTICI. The patients with early mTICI 2b reperfusions were dichotomized in “TICI2b-stopped” (MT withdrawal after mTICI 2b was achieved with first or second retrieval) and “TICI2b-continued” (MT was continued after mTICI 2b was achieved with first or second retrieval). Functional outcome was obtained after 90 days using the modified Rankin scale (mRS90).

Results

Of 362 Patients with a M1-occlusion, 100 patients fulfilled the inclusion criteria with an early mTICI 2b. 78/100 patients were included in the “TICI2b-stopped” group and 22/100 patients were in the “TICI2b-continued” group. Of these 22 patients, none had a final mTICI score lower than 2b and 11 patients had a final mTICI score of 2c/3. Regarding good functional outcome at mRS90, “TICI2b-continued” showed by trend a slight advantage of 40.1 vs. 35.6% in “TICI2b-stopped” but in multivariate logistic regression analysis adjusted for confounders, no significant difference was found between the two groups (OR 0.75, 95% CI 0.19–2.87, p = 0.67). Symptomatic intracranial hemorrhage was significantly higher in “TICI2b-continued” compared to “TICI2b-stopped” (31.8 vs. 10.3%, p = 0.031).

Conclusion

Successfully improving an early mTICI 2b to mTICI 2c/3 reperfusion is possible in a substantial number of patients and might improve functional outcome. However, an increase in symptomatic intracranial hemorrhage (SICH) due to further retrieval attempts may diminish the potential functional benefit to continue early mTICI 2b. To support this finding, further investigation with more power is needed to account for the low number of events regarding SICH.
Dose-response relationship between the variables of unilateral optogenetic stimulation and transcallosal evoked responses in rat motor cortex
Authors: Skoven Christian Stald , Tomasevic Leo , Kvitsiani Duda , Pakkenberg Bente , Dyrby Tim Bjørn , Siebner Hartwig Roman
Published: September 2022

Efficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control. We employed optogenetic stimulation to establish a framework for probing transcallosal M1–M1 interactions in rats. We performed optogenetic stimulation of excitatory neurons in right M1 of male Sprague-Dawley rats. We recorded the transcallosal evoked potential in contralateral left M1 via chronically implanted electrodes. Recordings were performed under anesthesia combination of dexmedetomidine and a low concentration of isoflurane. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1. Optogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. A combination of stimulation intensities of 5–10 mW with stimulus durations of 1–10 ms were generally sufficient to elicit a robust transcallosal response in most animal, with our optic fiber setup. Optogenetically stimulated excitatory neurons in M1 can reliably evoke a transcallosal response in anesthetized rats. Characterizing the relationship between “stimulation dose” and “response magnitude” (i.e., the gain function) of transcallosal M1-to-M1 excitatory connections can be used to optimize the variables of optogenetic stimulation and ensure stimulation efficacy.
Analysis of the different growth years accumulation of flavonoids in Dendrobium moniliforme (L.) Sw. by the integration of metabolomic and transcriptomic approaches
Authors: Yuan Yingdan , Zuo Jiajia , Zhang Hanyue , Zu Mengting , Liu Sian
Published: September 2022

Dendrobium moniliforme (L.) Sw. is a valuable herbal crop, and flavonoids are primarily distributed as active ingredients in the stem, but the composition and synthesis mechanisms of flavonoids in different growth years are not clear. The accumulation of flavonoids in D. moniliforme from four different years was investigated, using a combined metabolomics and transcriptomics approach in this study. The phenylpropanoid and flavonoid biosynthetic pathways were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). The widely targeted metabolomics technique revealed a total of 173 kinds of flavonoid metabolites. The metabolomics data confirmed the trend of total flavonoids (TF) content in stems of D. moniliforme, with chalcone, naringenin, eriodictyol, dihydroquercetin, and other flavonoids considerably up-accumulating in the third year. Twenty DEGs were detected that regulate flavonoid synthesis and the expression of these genes in different growth years was verified using real-time quantitative PCR (qRT-PCR). Furthermore, a comprehensive regulatory network was built for flavonoid biosynthesis and it was discovered that there is one FLS gene, one CCR gene and two MYB transcription factors (TFs) with a high connection with flavonoid biosynthesis by weighted gene co-expression network analysis (WGCNA). In this study, the correlation between genes involved in flavonoid biosynthesis and metabolites was revealed, and a new regulatory mechanism related to flavonoid biosynthesis in D. moniliforme was proposed. These results provide an important reference for the farmers involved in the cultivation of D. moniliforme.
Association between visceral adiposity index and kidney stones in American adults: A cross-sectional analysis of NHANES 2007–2018
Authors: Wang Jiahao , Yang Zhenzhen , Bai Yunjin , Yin Shan , Cui Jianwei , Xiao Yunfei , Wang Jia
Published: September 2022

Objective

To explore the association between Visceral Adiposity Index (VAI) and kidney stones in an American adult population.

Materials and methods

National Health and Nutrition Examination Survey (NHANES) datasets from 2007 to 2018 were used. Participants aged ≥20 years who reported kidney stone history and VAI were included. Weighted proportions, multivariable analysis, generalized additive model (GAM), and spline smoothing were used to evaluate the associations between VAI and kidney stones by adjusting gender, age, race, education, marital status, poverty income ratio, smoking, alcohol, high blood pressure, diabetes, congestive heart failure, cancer, vigorous activity, moderate activity, HEI2015 total score, and energy.

Results

Totally 13,871 American adults were included. All the participants were divided by the VAI into four groups according to the quartile: Q1 (11.96–42.89), Q2 (42.90–74.45), Q3 (74.45–131.43), and Q4 (131.45–611.34). The mean ± standard deviation of the VAI in the four groups were Q1 (29.07 ± 8.22), Q2 (57.53 ± 8.81), Q3 (99.52 ± 16.25), and Q4 (225.92 ± 95.83). In the fully adjusted multivariable model, VAI was positively correlated with urolithiasis [odds ratio (OR) = 1.001; 95% confidence interval (CI) 1.000–1.001]. Compared with the first quartile of VAI, the population in the fourth quartile of VAI had a higher prevalence of kidney stones (OR = 1.329; 95% CI 1.104–1.600). Subgroup analysis detected no significant interaction effect after adjusting for covariates.

Conclusion

The value of VAI is positively correlated with the prevalence of kidney stones, which suggest VAI can be used to assess the potential risk of the prevalence of kidney stones.
Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study
Authors: Nie Caiyun , Lv Huifang , Chen Beibei , Xu Weifeng , Wang Jianzheng , Liu Yingjun , Wang Saiqi , Zhao Jing , He Yunduan , Chen Xiaobing
Published: September 2022

Objectives

The antitumor activity of nivolumab plus regorafenib in colorectal cancer from a phase Ib REGONIVO study is encouraging. The present study was conducted to evaluate the efficacy and safety of regorafenib or fruquintinib plus sintilimab as third-line or above therapy in patients with microsatellite stable (MSS) metastatic colorectal cancer.

Methods

Patients with MSS metastatic colorectal cancer who have failed from prior treatment and received regorafenib or fruquintinib plus sintilimab as third-line or above therapy from January 2019 to December 2020 were prospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

Results

42 patients received regorafenib plus sintilimab(RS), and the other 30 patients received fruquintinib plus sintilimab(FS). In the general population, the ORR and DCR were 13.9% and 70.8%, and the median PFS and OS was 4.2(95% CI=2.9-5.5) and 10.5 (95% CI=8.6-12.4) months, respectively. There were no statistically significant differences between RS and FS group in PFS (3.5(2.2-4.8) vs. 5.5(3.5-7.5) months, P=0.434) and OS (11.0(7.0-15.0) vs. 10.5(3.8-17.2) months, P=0.486). Subgroup analysis suggested that patients without liver metastasis responded well to this combination regimen (ORR: 21.4% vs. 9.1%) and obtained better OS (26(8.8-43.2) vs. 10.0(7.4-12.6) months, P=0.016). The incidence of Grade 3-4 adverse events (AEs) was 15.3% and the toxicities were generally tolerable and manageable.

Conclusions

Regorafenib or fruquintinib plus sintilimab as third-line or above therapy provide a feasible treatment regimen for MSS metastatic colorectal cancer with tolerated toxicity. Patients without liver metastasis may be the preferred population for this combination regimen.
Case Report: A novel intergenic MIR4299/MIR8070-RET fusion with RET amplification and clinical response to pralsetinib in a lung adenocarcinoma patient
Authors: Wang Sha-Sha , Wang Fang , Zeng Zhen , Gao Fang , Liu Huan-Huan , Wang Hui-Na , Hu Yi , Qin Hai-Feng
Published: September 2022

The identification of receptor-tyrosine kinase gene (RET) fusions in lung cancer has become crucial owing to actionable events that predict responsiveness to tyrosine kinase inhibitors (TKIs). However, RET fusions with distinct partner genes respond differently to TKIs. In this case, a 60-year-old man was diagnosed with advanced lung adenocarcinoma. A novel RET-MIR4299/MIR8070 fusion and RET amplification were identified using next-generation sequencing (NGS). The patient was then administered with pralsetinib. After 3 weeks of therapy, the patient had a partial response. At the time of reporting, the patient was on continuous pralsetinib. These findings broaden the range of RET fusion types and provide the basis for the hypothesis that RET intergenic fusion and amplification respond to pralsetinib treatment in lung adenocarcinoma.
In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO
Authors: Moglioni Martina , Kraan Aafke Christine , Baroni Guido , Battistoni Giuseppe , Belcari Nicola , Berti Andrea , Carra Pietro , Cerello Piergiorgio , Ciocca Mario , De Gregorio Angelica , De Simoni Micol , Del Sarto Damiano , Donetti Marco , Dong Yunsheng , Embriaco Alessia , Fantacci Maria Evelina , Ferrero Veronica , Fiorina Elisa , Fischetti Marta , Franciosini Gaia , Giraudo Giuseppe , Laruina Francesco , Maestri Davide , Magi Marco , Magro Giuseppe , Malekzadeh Etesam , Marafini Michela , Mattei Ilaria , Mazzoni Enrico , Mereu Paolo , Mirandola Alfredo , Morrocchi Matteo , Muraro Silvia , Orlandi Ester , Patera Vincenzo , Pennazio Francesco , Pullia Marco , Retico Alessandra , Rivetti Angelo , Da Rocha Rolo Manuel Dionisio , Rosso Valeria , Sarti Alessio , Schiavi Angelo , Sciubba Adalberto , Sportelli Giancarlo , Tampellini Sara , Toppi Marco , Traini Giacomo , Trigilio Antonio , Valle Serena Marta , Valvo Francesca , Vischioni Barbara , Vitolo Viviana , Wheadon Richard , Bisogni Maria Giuseppina
Published: September 2022

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam’s Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.
The prognostic value of baseline and early variations of peripheral blood inflammatory ratios and their cellular components in patients with metastatic renal cell carcinoma treated with nivolumab: The Δ-Meet-URO analysis
Authors: Rebuzzi Sara Elena , Signori Alessio , Stellato Marco , Santini Daniele , Maruzzo Marco , De Giorgi Ugo , Pedrazzoli Paolo , Galli Luca , Zucali Paolo Andrea , Fantinel Emanuela , Carella Claudia , Procopio Giuseppe , Milella Michele , Boccardo Francesco , Fratino Lucia , Sabbatini Roberto , Ricotta Riccardo , Panni Stefano , Massari Francesco , Sorarù Mariella , Santoni Matteo , Cortellini Alessio , Prati Veronica , Soto Parra Hector Josè , Atzori Francesco , Di Napoli Marilena , Caffo Orazio , Messina Marco , Morelli Franco , Prati Giuseppe , Nolè Franco , Vignani Francesca , Cavo Alessia , Roviello Giandomenico , Llaja Obispo Miguel Angel , Porta Camillo , Buti Sebastiano , Fornarini Giuseppe , Banna Giuseppe Luigi
Published: September 2022

Background

Treatment choice for metastatic renal cell carcinoma (mRCC) patients is still based on baseline clinical and laboratory factors.

Methods

By a pre-specified analysis of the Meet-URO 15 multicentric retrospective study enrolling 571 pretreated mRCC patients receiving nivolumab, baseline and early dynamic variations (Δ) of neutrophil, lymphocyte, and platelet absolute cell counts (ACC) and their inflammatory ratios (IR) were evaluated alongside their association with the best disease response and overall (OS) and progression-free survival (PFS). Multivariable analyses on OS and PFS between baseline and Δ ACC and IR values were investigated with receiving operating curves-based cut-offs.

Results

The analysis included 422 mRCC patients. Neutrophil-to-lymphocyte ratio (NLR) increased over time due to consistent neutrophil increase (p < 0.001). Higher baseline platelets (p = 0.044) and lower lymphocytes (p = 0.018), increasing neutrophil Δ (p for time-group interaction <0.001), higher baseline IR values (NLR: p = 0.012, SII: p = 0.003, PLR: p = 0.003), increasing NLR and systemic immune-inflammatory index (SII) (i.e., NLR x platelets) Δ (p for interaction time-group = 0.0053 and 0.0435, respectively) were associated with disease progression. OS and PFS were significantly shorter in patients with baseline lower lymphocytes (p < 0.001 for both) and higher platelets (p = 0.004 and p < 0.001, respectively) alongside early neutrophils Δ (p = 0.046 and p = 0.033, respectively). Early neutrophils and NLR Δ were independent prognostic factors for both OS (p = 0.014 and p = 0.011, respectively) and PFS (p = 0.023 and p = 0.001, respectively), alongside baseline NLR (p < 0.001 for both) and other known prognostic variables.

Conclusions

Early neutrophils and NLR Δ may represent new dynamic prognostic factors with clinical utility for on-treatment decisions.
Clinical and pathological findings in neurolymphomatosis: Preliminary association with gene expression profiles in sural nerves
Authors: Cerri Federica , Gentile Francesco , Clarelli Ferdinando , Santoro Silvia , Falzone Yuri Matteo , Dina Giorgia , Romano Alessandro , Domi Teuta , Pozzi Laura , Fazio Raffaella , Podini Paola , Sorosina Melissa , Carrera Paola , Esposito Federica , Riva Nilo , Briani Chiara , Cavallaro Tiziana , Filippi Massimo , Quattrini Angelo
Published: September 2022

Although inflammation appears to play a role in neurolymphomatosis (NL), the mechanisms leading to degeneration in the peripheral nervous system are poorly understood. The purpose of this exploratory study was to identify molecular pathways underlying NL pathogenesis, combining clinical and neuropathological investigation with gene expression (GE) studies. We characterized the clinical and pathological features of eight patients with NL. We further analysed GE changes in sural nerve biopsies obtained from a subgroup of NL patients (n=3) and thirteen patients with inflammatory neuropathies as neuropathic controls. Based on the neuropathic symptoms and signs, NL patients were classified into three forms of neuropathy: chronic symmetrical sensorimotor polyneuropathy (SMPN, n=3), multiple mononeuropathy (MN, n=4) and acute motor-sensory axonal neuropathy (AMSAN, n=1). Predominantly diffuse malignant cells infiltration of epineurium was present in chronic SMPN, whereas endoneurial perivascular cells invasion was observed in MN. In contrast, diffuse endoneurium malignant cells localization occurred in AMSAN. We identified alterations in the expression of 1266 genes, with 115 up-regulated and 1151 down-regulated genes, which were mainly associated with ribosomal proteins (RP) and olfactory receptors (OR) signaling pathways, respectively. Among the top up-regulated genes were actin alpha 1 skeletal muscle (ACTA1) and desmin (DES). Similarly, in NL nerves ACTA1, DES and several RPs were highly expressed, associated with endothelial cells and pericytes abnormalities. Peripheral nerve involvement may be due to conversion towards a more aggressive phenotype, potentially explaining the poor prognosis. The candidate genes reported in this study may be a source of clinical biomarkers for NL.
Treatment and outcome of metastatic parathyroid carcinoma: A systematic review and pooled analysis of published cases
Authors: Alberti Andrea , Smussi Davide , Zamparini Manuel , Turla Antonella , Laini Lara , Marchiselli Chiara , Grisanti Salvatore , Bossi Paolo , Berruti Alfredo
Published: September 2022

Background

Parathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have been published on treatments and outcomes of PC patients with loco-regional disease, little is known about the prognosis, treatment strategies, and prognostic factors of patients with distant metastasis.

Materials and methods

We performed a systematic review and a pooled analysis of histopathologically confirmed PC cases published in literature using the following keywords: “metastasis–metastatic–secondary nodes” AND “parathyroid carcinoma”. Original case reports and case series reporting metastatic parathyroid carcinoma were included. Data from 58 articles were extracted in a piloted form by five reviewers on a shared database.

Results

Seventy-nine patients with metastatic PC were identified between 1898 and 2018. Ten (13%) patients had synchronous metastases, while metachronous metastases occurred in 43 (54%) patients. The remaining 26 patients developed metastatic disease concomitantly to local recurrence. Primary hyperparathyroidism guided the diagnosis of metastatic recurrence in 58 (73%) patients. Surgery was the main primary approach adopted, as it was performed in 43 (54%) patients. Twenty (25%) patients underwent systemic antineoplastic therapy, consisting of chemotherapy, immunotherapy, tyrosine kinase inhibitors, and hexestrol therapy. Bone resorption inhibitors had a limited efficacy in the long-term control of hypercalcemia. After a median follow-up of 37.5 months, 43 (55%) patients died, 22 (51%) due to the consequences of uncontrolled PHPT. The median overall survival was 36 months (range: 1–252). Surgery was associated with a better OS (HR 0.48, 95% CI 0.26–0.88), whereas bone metastases represented a negative prognostic factor (HR 2.7, 95% CI 1.4–5.2).

Conclusion

Metastatic PC has a relatively poor prognosis. The main goals of treatment are to counteract tumor growth and control hypercalcemia. Surgery of metastases is the best approach to achieve rapid control of PHPT and longer survival. Target therapies and immunotherapy deserve to be extensively tested in metastatic PC and strategies to better control hypercalcemia should be implemented.
Impact of integrated care coordination on pediatric asthma hospital presentations
Authors: Homaira Nusrat , Dickins Emma , Hodgson Stephanie , Chan Mei , Wales Sandra , Gray Melinda , Donnelly Sarah , Burns Christine , Owens Louisa , Plaister Michael , Flynn Anthony , Andresen Jennifer , Keane Kimberley , Wheeler Karen , Gould Bronwyn , Shaw Nadine , Jaffe Adam , Breen Christie , Altman Lisa , Woolfenden Susan
Published: September 2022

Introduction

Frequent asthma attacks in children result in unscheduled hospital presentations. Patient centered care coordination can reduce asthma hospital presentations. In 2016, The Sydney Children's Hospitals Network launched the Asthma Follow up Integrated Care Initiative with the aim to reduce pediatric asthma emergency department (ED) presentations by 50% through developing and testing an integrated model of care led by care coordinators (CCs).

Methods

The integrated model of care was developed by a multidisciplinary team at Sydney Children's Hospital Randwick (SCH,R) and implemented in two phases: Phase I and Phase II. Children aged 2–16 years who presented ≥4 times to the ED of the SCH,R in the preceding 12 months were enrolled in Phase I and those who had ≥4 ED presentations and ≥1 hospital admissions with asthma attack were enrolled in Phase II. Phase I included a suite of interventions delivered by CCs including encouraging parents/carers to schedule follow-up visits with GP post-discharge, ensuring parents/carers are provided with standard asthma resource pack, offering referrals to asthma education sessions, sending a letter to the child's GP advising of the child's recent hospital presentation and coordinating asthma education webinar for GPs. In addition, in Phase II CCs sent text messages to parents/carers reminding them to follow-up with the child's GP. We compared the change in ED visits and hospital admissions at baseline (6 months pre-enrolment) and at 6-and 12-months post-enrolment in the program.

Results

During December 2016-January 2021, 160 children (99 in Phase I and 61 in Phase II) were enrolled. Compared to baseline at 6- and 12-months post-enrolment, the proportion of children requiring ≥1 asthma ED presentations reduced by 43 and 61% in Phase I and 41 and 66% in Phase II. Similarly, the proportion of children requiring ≥1 asthma hospital admissions at 6- and 12-months post-enrolment reduced by 40 and 47% in Phase I and 62 and 69% in Phase II.

Conclusion

Our results support that care coordinator led integrated model of asthma care which enables integration of acute and primary care services and provides families with asthma resources and education can reduce asthma hospital presentations in children.
Antimicrobial activity of natural products against MDR bacteria: A scientometric visualization analysis
Authors: Zhou Yan-Xi , Cao Xiao-Yu , Peng Cheng
Published: September 2022

Objective: A growing number of studies have demonstrated the antimicrobial activity of natural products against multidrug-resistant bacteria. This study aimed to apply scientometric method to explore the current status and future trends in this field.

Methods: All relevant original articles and reviews for the period 1997–2021 were retrieved from the Web of Science Core Collection database. VOSviewer, a scientometric software, and an online bibliometric analysis platform were used to conduct visualization study.

Results: A total of 1,267 papers were included, including 1,005 original articles and 262 reviews. The United States and India made the largest contribution in this field. The University of Dschang from Cameroon produced the most publications. Coutinho HDM, Kuete V, and Gibbons S were key researchers, as they published a great many articles and were co-cited in numerous publications. Frontiers in Microbiology and Antimicrobial Agents and Chemotherapy were the most influential journals with the highest number of publications and co-citations, respectively. “Medicinal plants”, “methicillin-resistant Staphylococcus aureus”, “biofilm”, “minimum inhibitory concentration”, and “efflux pumps” were the most frequently used keywords, so these terms are presumed to be the current hot topics. All the included keywords could be roughly divided into four major themes, of which the theme of “natural product development approach” had attracted much attention in recent years. Furthermore, “Pseudomonas aeruginosa”, “nanoparticles”, “green synthesis”, “antimicrobial peptides”, “antibiofilm”, “biosynthetic gene clusters”, and “molecular dynamics simulation” had the latest average appearance year, indicating that these topics may become the research hot spots in the coming years.

Conclusion: This study performed a scientometric analysis of the antibacterial activity of natural products against multidrug-resistant bacteria from a holistic perspective. It is hoped to provide novel and useful data for scientific research, and help researchers to explore this field more intuitively and effectively.
Different coherent states for lightly supported coupled pendula
Authors: Dudkowski Dawid , Jaros Patrycja , Kapitaniak Tomasz
Published: September 2022

In this paper we discuss and explain the phenomenon of synchronization in lightly supported mechanical systems. The investigations are focused on the models of self–excited pendula hanged on the horizontally oscillating beam, which is lightly connected with the external support. Our results are based on the Centre-of-Mass (CoM) Theorem, which can be applied to the considered systems and allows to analytically confirm the observed behaviours. We present typical dynamical solutions, including periodic and quasiperiodic oscillations, within which the oscillators synchronize. The possible synchronous configurations are analyzed and examined, depending on the number of the pendula creating the system, their parameters and the initial conditions. We discuss bifurcations between different types of solutions, determining the regions and the conditions supporting the synchronization. Our investigations exhibit, that with the increase of the size of the network, the number of co–existing attractors also increases, leading to possible multistability and new types of behaviours (e.g., the traveling phase one). The results obtained numerically match with the analytical ones obtained from the CoM Theorem, which explains the existence of particular types of dynamical configurations. The study presented in this paper involves classical lightly supported pendula systems and due to their basic character, one can expect to observe similar behaviours in other types of mechanical models.
New insights into proteinuria/albuminuria
Authors: Comper Wayne D. , Vuchkova Julijana , McCarthy Kevin J.
Published: September 2022

The fractional clearance of proteins as measured in healthy human subjects increases 10,000–100,000- fold when studied in nephrotic patients. This remarkable increase cannot be accounted for by extracellular biophysical mechanisms centered at the glomerular filtration barrier. Rather, it is the nephron and its combination of filtration and cellular uptake that can provide a plausible explanation of these fractional clearance changes. The nephron has two regions that critically determine the level proteinuria/albuminuria. Glomerular filtration of plasma proteins is primarily a size selective event that is basically unchanged in acquired and genetic kidney disease. The glomerular concepts of ‘charge selectivity’ and of ‘large pores’, previously used to explain proteinuria, are now recognized to be flawed and non-existent. Filtered proteins then encounter downstream two protein receptors of the Park and Maack type associated with the proximal tubular cell. The high capacity receptor is thought to retrieve the majority of filtered proteins and return them to the blood supply. Inhibition/saturation of this pathway in kidney disease may create the nephrotic condition and hypoproteinemia/hypoalbuminemia. Inhibitors of this pathway (possibly podocyte derived) are still to be identified. A relatively small proportion of the filtered protein is directed towards a high affinity, low capacity receptor that guides the protein to undergo lysosomal degradation. Proteinuria in normoproteinemic states is derived by inhibition of this pathway, such as in diabetes. The combination of glomerular sieving, and the degradation and retrieval pathways can quantitatively account for the changes in fractional clearance of proteins in the nephrotic condition. Finally, the general retrieval of filtered protein by the proximal tubular cell focuses on the teleological importance of this cell as this retrieval represents the third pillar of retrieval that this cell participates in (it also retrieves water and salt).
LncRNAs regulate ferroptosis to affect diabetes and its complications
Authors: Chen Qianqian , Ji Hao , Lin Yue , Chen Zheyan , Liu Yinai , Jin Libo , Peng Renyi
Published: September 2022

Worldwide, the rapid increase in the incidence of diabetes and its complications poses a serious threat to human health. Ferroptosis, which is a new nonapoptotic form of cell death, has been proven to be closely related to the occurrence and development of diabetes and its complications. In recent years, lncRNAs have been confirmed to be involved in the occurrence and development of diabetes and play an important role in regulating ferroptosis. An increasing number of studies have shown that lncRNAs can affect the occurrence and development of diabetes and its complications by regulating ferroptosis. Therefore, lncRNAs have great potential as therapeutic targets for regulating ferroptosis-mediated diabetes and its complications. This paper reviewed the potential impact and regulatory mechanism of ferroptosis on diabetes and its complications, focusing on the effects of lncRNAs on the occurrence and development of ferroptosis-mediated diabetes and its complications and the regulation of ferroptosis-inducing reactive oxygen species, the key ferroptosis regulator Nrf2 and the NF-κB signaling pathway to provide new therapeutic strategies for the development of lncRNA-regulated ferroptosis-targeted drugs to treat diabetes.
Phenotypic variability and genetic diversity analysis of cultivated potatoes in China
Authors: Hu Jun , Mei Meng , Jin Fang , Xu Jianfei , Duan Shaoguang , Bian Chunsong , Li Guangcun , Wang Xiyao , Jin Liping
Published: September 2022

Phenotypic evaluation and molecular biotechnology are both important in the identification and utilization of crop germplasm resources. In this study, the phenotypic variation and genetic diversity of 149 main potato cultivars in China were investigated with 12 phenotypic traits and 24 SSR markers. The coefficient of variation of 12 phenotypic traits ranged from 12.11% to 156.93%. The results of SSR markers exhibited a relatively high level of genetic variation (Na =5.458 ± 1.499, Ne =3.300 ± 1.087, I =1.397 ± 0.298, Ho =0.797 ± 0.178, He = 0.660 ± 0.117, and PIC=0.702 ± 0.087). Population structure and phylogenetic tree analysis divided the varieties into three subgroups. The results indicated that ninety percent of the molecular variance was attributed to within-group differences, and the remaining 10% was attributed to variation among groups. Consistent with previous report, alleles of the STI032 marker were significantly associated with tuber starch content and growth period traits in the population. The results of this study could facilitate the utilization of potato germplasm resources, molecular genetic breeding and improvement.
Biogenic silver nanoparticles improve bioactive compounds in medicinal plant Juniperus procera in vitro
Authors: Salih Abdalrhaman M. , Al-Qurainy Fahad , Khan Salim , Nadeem Mohammad , Tarroum Mohamed , Shaikhaldein Hassan O.
Published: September 2022

Bioactive compounds of medicinal plants present as natural ingredients provide health benefits beyond the basic nutritional value of these products. However, the availability of bioactive compounds in the current natural sources is limited. Hence, the induction of bioactive compound production from medicinal plants through nanoparticles (NPs) might play a vital role in industrially important medicinal compounds. Therefore, this study aimed to synthesize silver nanoparticles (AgNPs) biologically and to investigate their effect on phytochemical compound production from the callus of Juniperus procera. AgNPs were synthesized biologically using aqueous leaf extract of Phoenix dactylifera, which acted as a reducing and capping agent, and silver nitrate solution. The formation of AgNPs has been confirmed through different analytical techniques such as UV-Visible spectroscopy (UV), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and scanning electron microscope (SEM). The impact of different concentrations (0.0, 5, 20, and 50 mg/L) of AgNPs on enzymatic and non-enzymatic antioxidants of the callus of J. procera was investigated. The obtained results showed a significant effect of AgNPs on biomass accumulation and non-enzymatic antioxidants (phenol, tannin, and flavonoid content). Additionally, total protein content and superoxide dismutase (SOD) activity were increased in response to AgNPs. Furthermore, bioactive compounds like gallic acid, tannic acid, coumarin, hesperidin, rutin, quercetin, and ferruginol were chromatographically separated and quantified using high-performance liquid chromatography (HPLC) with reference standards. These compounds were increased significantly in response to AgNPs treatments. We concluded that AgNPs could be a promising elicitor for improving the production of phytochemical compounds in medicinal plants. This work can serve asa good model for improving the production of bioactive compounds from medicinal plants in vitro. This molecular investigation should be done to understand better the metabolic mechanism leading to bioactive compound production scaling.
Complementary effects of phosphorus supply and planting density on maize growth and phosphorus use efficiency
Authors: Gong Haiqing , Xiang Yue , Wako Bilisuma Kabeto , Jiao Xiaoqiang
Published: September 2022

Phosphorus (P) supply and planting density regulate plant growth by altering root morphological traits and soil P dynamics. However, the compensatory effects of P supply and planting density on maize (Zea mays L.) growth and P use efficiency remain unknown. In this study, we conducted pot experiments of approximately 60 days to determine the effect of P supply, i.e., no P (CK), single superphosphate (SSP), and monoammonium phosphate (MAP), and different planting densities (low: two plants per pot; and high: four plants per pot) on maize growth. A similar shoot biomass accumulation was observed at high planting density under CK treatment (91.5 g plot–1) and low planting density under SSP treatment (94.3 g plot–1), with similar trends in P uptake, root morphological traits, and arbuscular mycorrhizal colonization. There was no significant difference in shoot biomass between high planting density under SSP (107.3 g plot–1) and low planting density under MAP (105.2 g plot–1); the corresponding P uptake, root growth, and P fraction in the soil showed the same trend. These results suggest that improved P supply could compensate for the limitations of low planting density by regulating the interaction between root morphological traits and soil P dynamics. Furthermore, under the same P supply, the limitations of low planting density could be compensated for by substituting MAP for SSP. Our results indicate that maize growth and P use efficiency could be improved by harnessing the compensatory effects of P supply and planting density to alter root plasticity and soil P dynamics.
Assessing the effect of roads on mountain plant diversity beyond species richness
Authors: Li Honglin , Luo Peng , Yang Hao , Luo Chuan , Xie Wenwen , Jia Honghong , Cheng Yue , Huang Yu
Published: September 2022

A comprehensive understanding of the effects of mountain roads on plant diversity is critical to finding the most effective solutions for managing this particular driver. Little is known, however, about the simultaneous effects that road have on the multiple facets of biodiversity, although roads are considered to be one of the major disturbances in the Qionglai mountain range. In this study, we analyzed the impact of roads on the multiple facets of plant diversity (taxonomic, functional and phylogenetic diversity) in the study area using Hill numbers by comparing plant diversity between roadside and interior plots at the landscape scale, then, we used linear mixed models to analyze the effect of mountain roads on the multiple facets of plant diversity along an elevational gradient. The results showed that the roadside plots lacked 29.45% of the total number of species with particular functional traits (such as a relatively high specific leaf area (SLA), a relatively low leaf dry matter content (LDMC) and relatively old clades) and exclusively contained 14.62% of the total number of species. Compared with the interior community, the taxonomic, functional and phylogenetic diversity of roadside community decreased by no more than 26.78%, 24.90% and 16.62%, respectively. Taxonomic and functional diversity of dominant and common species showed greater changes to road disturbances, while rare species showed the greatest change in phylogenetic diversity. Taxonomic homogenization of roadside communities was accompanied by functional and phylogenetic homogenization. Additionally, the impact of roads on these three facets of plant diversity showed the characteristics of peak clipping along the elevation gradient. Our findings highlight the negative impact of roads on the taxonomic, functional and phylogenetic diversity of the Qionglai mountain range, as roads promote communities that are more similar in taxonomic, functional, and phylogenetic composition, and to a greater extent contributed to compositional evenness. These effects tend to be functionally and phylogenetically non-random, and species in some clades or with some functional traits are at higher risk of loss. Our results are important for the conservation and management of nature reserves, especially for local governments aiming to create new infrastructure to connect natural mountainous areas.
De novo transcriptome analysis of high-salinity stress-induced antioxidant activity and plant phytohormone alterations in Sesuvium portulacastrum
Authors: Chen YiQing , Zhou Yan , Cai Yuyi , Feng Yongpei , Zhong Cairong , Fang ZanShan , Zhang Ying
Published: September 2022

Sesuvium portulacastrum has a strong salt tolerance and can grow in saline and alkaline coastal and inland habitats. This study investigated the physiological and molecular responses of S. portulacastrum to high salinity by analyzing the changes in plant phytohormones and antioxidant activity, including their differentially expressed genes (DEGs) under similar high-salinity conditions. High salinity significantly affected proline (Pro) and hydrogen peroxide (H2O2) in S. portulacastrum seedlings, increasing Pro and H2O2 contents by 290.56 and 83.36%, respectively, compared to the control. Antioxidant activities, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), significantly increased by 83.05, 205.14, and 751.87%, respectively, under high salinity. Meanwhile, abscisic acid (ABA) and gibberellic acid (GA3) contents showed the reverse trend of high salt treatment. De novo transcriptome analysis showed that 36,676 unigenes were matched, and 3,622 salt stress-induced DEGs were identified as being associated with the metabolic and biological regulation processes of antioxidant activity and plant phytohormones. POD and SOD were upregulated under high-salinity conditions. In addition, the transcription levels of genes involved in auxin (SAURs and GH3), ethylene (ERF1, ERF3, ERF114, and ABR1), ABA (PP2C), and GA3 (PIF3) transport or signaling were altered. This study identified key metabolic and biological processes and putative genes involved in the high salt tolerance of S. portulacastrum and it is of great significance for identifying new salt-tolerant genes to promote ecological restoration of the coastal strand.
Salsola soda as selenium biofortification crop under high saline and boron growing conditions
Authors: Bañuelos Gary S. , Centofanti Tiziana , Zambrano Maria C. , Vang Kaomine , Lone Todd A.
Published: September 2022

In California, there is a shortage of good quality water available for irrigated agriculture due to severe drought. Consequently, saline groundwaters and drainage waters containing natural-occurring selenium (Se) and boron (B) salts are being considered as alternative sources of water for irrigation on salt and B tolerant crops like the edible halophyte-agretti (Salsola soda L.). In this multi-year field study, we evaluated agretti grown as a Se-biofortification crop in typical saline/B-laden soils (10 dS m−1 and 12 mg B/L) and irrigated with saline (3–8 dS m−1) and low-saline water (<1 d/S m) containing B (3–6 mg B/L) and Se (0.02–0.25 mg Se/L) at different evaporation transpiration (Eto) rates (100, 75, and 50 %, respectively). During the four-year study, fresh biomass yields ranged from 1 to 3 kg/m2 and were generally highest with irrigation at 100 % Eto with either saline or low-saline water. Tissue Se concentrations ranged from 2 to 3.2 mg Se / kg DW and 0.4–0.5 mg Se/kg DW with saline and low-saline irrigation, respectively. Selenium speciation in plant tissue showed the following: selenomethionine (SeMet) > selenate (SeO4) > methylselenocysteine (MeSeCys), irrespective of any treatment (i.e., year of planting, saline or low saline irrigation, rate of water application, direct seeding or transplanted). Agretti did not exhibit any toxicity symptoms as indicated by changes in total phenolic concentrations. Total phenolics ranged from 180 to 257 GAE/L and showed no significant differences among all treatments, although they were generally higher at the lowest water treatment (50% Eto). In regard to toxic ion accumulation, agretti tolerated excessive sodium (Na) and boron (B) and tissue concentrations ranging from 5.5 to 8.8% Na and 60 to 235 mg B/kg DW, respectively. Results from this multi-year study have identified a unique Se-biofortification strategy for producing Se-enriched agretti using saline, B- and Se-laden soil and irrigating with saline and low-saline water, respectively. Successful production of this crop may promote Se- biofortification strategies in poor quality regions where natural- occurring Se is present in soils and in waters used for irrigation.