bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Chitosan-Based Hydrogel Obtained from Insects in Pine Planting
Authors: Zhatkanbayev Yerlan , Zhatkanbayeva Zhanna , Iskakova Zhanar , Kolpek Ainagul , Serikov Almas , Moldagulova Nazira , Danlybayeva Gaziza , Sarsenova Ainur , Anuarbekova Sandugash
Published: March 2023

Agrogels, a hydrogel applied in the soil that collects water during irrigation or rainfall and distributes moisture to plant roots during drought, are a solution to water shortage concerns. Extending the release of low molecular weight chemicals has the potential to minimise mineral fertiliser losses as well as water and soil pollution. Thus, the aim of the research is to obtain chitosan from insect chitin, to synthesize a hydrogel based on chitosan with included mineral and organic fertilisers, and to report on experiments with agrogels in the field. In this study, chitosan was obtained from the adult beetles Zophobas morio. IR spectroscopy was used to examine chitosan. The existence of absorption lines typical of primary amines was demonstrated. In one step, a technique for the manufacture of chitosan-based hydrogels containing embedded mineral fertilisers was established. Hydrogel has a swelling coefficient of 60 g/g. Agrogels were evaluated while planting spruce seedlings on “Semei Ormany” LLP experimental locations. The survival rate of seedlings was found to be 40% higher in the experimental group than in the control group.
A Combined Method Based on the FIPV N Monoclonal Antibody Immunofluorescence Assay and RT-nPCR Method for the Rapid Diagnosis of FIP-Suspected Ascites
Authors: Xu Liang , Ye Shaotang , Ding Yulin , Xiao Yuqing , Yao Congwen , Wang Zhen , Cai Siqi , Ou Jiajun , Mao Jianwei , Hu Xuerui , Cheng Song , Wang Jingyu , Lu Gang , Li Shoujun
Published: March 2023

Feline infectious peritonitis (FIP), which is caused by feline infectious peritonitis virus (FIPV), is a fatal and immunologically mediated infectious disease among cats. At present, due to the atypical clinical symptoms and clinicopathological changes, the clinical diagnosis of FIP is still difficult. The gold standard method for the differential diagnosis of FIP is immunohistochemistry (IHC) which is time-consuming and requires specialized personnel and equipment. Therefore, a rapid and accurate clinical diagnostic method for FIPV infection is still urgently needed. In this study, based on the etiological investigation of FIPV in parts of southern China, we attempted to explore a new rapid and highly sensitive method for clinical diagnosis. The results of the etiological investigation showed that the N gene of the FIPV BS8 strain had the highest homology with other strains. Based on this, a specific FIPV BS8 N protein monoclonal antibody was successfully prepared by expression of the recombinant proteins, immunization of mice, fusion and selection of hybridoma cell lines, and screening and purification of monoclonal antibodies. Furthermore, we carried out a time-saving combination method including indirect immunofluorescence assay (IFA) and nested reverse transcription polymerase chain reaction (RT-nPCR) to examine FIP-suspected clinical samples. These results were 100% consistent with IHC. The results revealed that the combined method could be a rapid and accurate application in the diagnosis of suspected FIPV infection within 24 hours. In conclusion, the combination of IFA and RT-nPCR was shown to be a fast and reliable method for clinical FIPV diagnosis. This study will provide insight into the exploitation of FIPV N antibodies for the clinical diagnosis of FIP-suspected ascites samples.
Sedimentary Facies Evaluation of Tight Oil Reservoirs of Yanchang Formation in the Ordos Basin
Authors: Peng Yu , Zhang Huaijie , Zheng Xiaoli , Wang Yi , Li Jiye , Zhu Yinhui , Doolen Quine
Published: March 2023

Tight sandstone gas has become one of the important unconventional resources. It is of great significance to study the pore throat structure of tight sandstone for the development of tight sandstone gas reservoirs. On the basis of previous research results, this paper studies the tight reservoir characteristics of Yanchang Formation by combining geological data with geophysical logging. The reservoir characteristics are described and studied in detail by ordinary thin section, casting thin section, graphic granularity, and scanning electron microscope experiment. The experimental results show that the reservoir sandstone types of long 6 segments are mainly lithic feldspathic sandstone and feldspathic lithic sandstone, with high component maturity and structural maturity. The components of cement mainly include authigenic clay minerals illite, chlorite, and carbonate minerals. The reservoir space is mainly composed of feldspar-dissolved pores and residual intergranular pores. Compaction and cementation are the decisive factors of pore reduction. At present, the average porosity of the reservoir is 8.33% and the average permeability is 0.12 × 10−3 μm2, which belong to an ultralow porosity and ultralow permeability reservoir. On the basis of studying the origin, superimposition, and distribution of sand bodies and taking into account the sedimentary characteristics, origin, and trigger mechanism of gravity flow, a multisource sedimentary model is established in the study area, which is dominated by sandy debris flow, accompanied by turbidity current and local development of sandy slump. The thick massive sandstone with the most exploration significance in the study area is formed by the superimposition of multistage sandy clastic flow sediments along the gully in the direction of delta to lake. Summarizing the characteristics of reservoir development and evaluating and predicting it can provide geological basis for the next exploration and development of deep-water tight reservoirs in the study area.
Supplementary Figure S7 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Supplementary Figures 7A, 7B and 7C Cetuximab enhances anti-tumor cytokines: Cytokine concentrations in the sample supernatants were determined by enzyme-linked immunosorbent assay (ELISA) using a Luminex assay (R&Dsystems, a bio-techne brand, Minneapolis, MN) according to the manufacturer's protocol. Cetuximab alone decreased pro-tumorigenic IL-6 levels and increased IP-10 suggesting an anti-tumor response (Supplementary Figure 7A and 7B); however, these cytokines were not significantly changed between responders (those with CR, PR, SD) and non-responders. The full panel of tested cytokines, shown in Supplementary Figure 7C.Abbreviations: CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; NK: Natural Killer; IL: interleukin; IP: Interferon gamma inducible protein-10 (IP-10).
Data from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

AbstractPurpose:
Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development of targeted cancer therapies. Although many of these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One of the main approaches for preventing this refractory condition relies on the implementation of combination therapies. This includes dual-specificity reagents that affect both of their targets with a high level of selectivity. Unfortunately, selection of target combinations for these treatments is often confounded by limitations in our understanding of tumor biology. Here, we describe and validate a multipronged unbiased strategy for predicting optimal co-targets for bispecific therapeutics.
Experimental Design:
Our strategy integrates ex vivo genome-wide loss-of-function screening, BioID interactome profiling, and gene expression analysis of patient data to identify the best fit co-targets. Final validation of selected target combinations is done in tumorsphere cultures and xenograft models.
Results:
Integration of our experimental approaches unambiguously pointed toward EGFR and EPHA2 tyrosine kinase receptors as molecules of choice for co-targeting in multiple tumor types. Following this lead, we generated a human bispecific anti-EGFR/EPHA2 antibody that, as predicted, very effectively suppresses tumor growth compared with its prototype anti-EGFR therapeutic antibody, cetuximab.
Conclusions:
Our work not only presents a new bispecific antibody with a high potential for being developed into clinically relevant biologics, but more importantly, successfully validates a novel unbiased strategy for selecting biologically optimal target combinations. This is of a significant translational relevance, as such multifaceted unbiased approaches are likely to augment the development of effective combination therapies for cancer treatment.
Co-Clinical Study of [fam-] Trastuzumab Deruxtecan (DS8201a) in Patient-Derived Xenograft Models of Uterine Carcinosarcoma and Its Association with Clinical Efficacy
Authors: Yagishita Shigehiro , Nishikawa Tadaaki , Yoshida Hiroshi , Shintani Daisuke , Sato Sho , Miwa Maiko , Suzuki Mikiko , Yasuda Masanori , Ogitani Yusuke , Jikoh Takahiro , Yonemori Kan , Hasegawa Kosei , Hamada Akinobu
Published: March 2023

Purpose:

Uterine carcinosarcoma (UCS), a subtype of endometrial carcinoma, is a rare and aggressive cancer with a poor prognosis. High clinical efficacy of trastuzumab deruxtecan (T-DXd) in HER2-expressing UCS was recently reported in a phase II trial (STATICE trial). We performed a co-clinical study of T-DXd using patient-derived xenograft (PDX) models of participants in the STATICE trial.

Experimental Design:

Tumor specimens were resected during primary surgery or biopsied at recurrence from patients with UCS and transplanted into immunodeficient mice. Seven UCS-PDXs from six patients were established and HER2, estrogen receptor (ER), and p53 expression in PDX and the original tumor was assessed. Drug efficacy tests were performed using six of the seven PDXs. Of the six UCS-PDXs tested, two were derived from patients enrolled in the STATICE trial.

Results:

The histopathological characteristics of the six PDXs were well-conserved from the original tumors. HER2 expression was 1+ in all PDXs, and ER and p53 expression was almost similar to that in the original tumors. Remarkable tumor shrinkage after T-DXd administration was observed in four of the six PDXs (67%), comparable with the response rate (70%) of HER2 1+ patients in the STATICE trial. Two patients enrolled in the STATICE trial showed partial response as the best response, and the clinical effect was well-replicated with marked tumor shrinkage.

Conclusions:

We successfully performed a co-clinical study of T-DXd in HER2-expressing UCS, along with the STATICE trial. Our PDX models can predict clinical efficacy and serve as an effective preclinical evaluation platform.
BLEACH&STAIN 15-marker Multiplexed Imaging in 3,098 Human Carcinomas Reveals Six Major PD-L1–driven Immune Phenotypes with Distinct Spatial Orchestration
Authors: Bady Elena , Möller Katharina , Mandelkow Tim , Raedler Jonas B. , Yang Cheng , Ebner Julia , Lurati Magalie C.J. , Simon Ronald , Vettorazzi Eik , Büscheck Franziska , Luebke Andreas M. , Dum David , Menz Anne , Sauter Guido , Höflmayer Doris , Weidemann Sören , Fraune Christoph , Uhlig Ria , Bernreuther Christian , Jacobsen Frank , Clauditz Till S. , Wilczak Waldemar , Burandt Eike , Steurer Stefan , Minner Sarah , Lennartz Maximilian , Blessin Niclas C.
Published: March 2023

Multiplex fluorescence IHC (mfIHC) approaches were yet either limited to six markers or limited to a small tissue size that hampers translational studies on large tissue microarray cohorts. Here we have developed a BLEACH&STAIN mfIHC method that enabled the simultaneous analysis of 15 biomarkers (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, and CD31) in 3,098 tumor samples from 44 different carcinoma entities within one week. To facilitate automated immune checkpoint quantification on tumor and immune cells and study its spatial interplay an artificial intelligence–based framework incorporating 17 different deep-learning systems was established. Unsupervised clustering showed that the three PD-L1 phenotypes (PD-L1+ tumor and immune cells, PD-L1+ immune cells, PD-L1−) were either inflamed or noninflamed. In inflamed PD-L1+patients, spatial analysis revealed that an elevated level of intratumoral M2 macrophages as well as CD11c+ dendritic cell (DC) infiltration (P < 0.001 each) was associated with a high CD3+ CD4± CD8± FOXP3± T-cell exclusion and a high PD-1 expression on T cells (P < 0.001 each). In breast cancer, the PD-L1 fluorescence intensity on tumor cells showed a significantly higher predictive performance for overall survival (OS; AUC, 0.72, P < 0.001) compared with the commonly used percentage of PD-L1+ tumor cells (AUC, 0.54). In conclusion, our deep-learning–based BLEACH&STAIN framework facilitates rapid and comprehensive assessment of more than 60 spatially orchestrated immune cell subpopulations and its prognostic relevance.

Implications:

The development of an easy-to-use high-throughput 15+1 multiplex fluorescence approach facilitates the in-depth understanding of the immune tumor microenvironment (TME) and enables to study the prognostic relevance of more than 130 immune cell subpopulations.
Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways
Authors: Spain Lavinia , Coulton Alexander , Lobon Irene , Rowan Andrew , Schnidrig Desiree , Shepherd Scott T.C. , Shum Benjamin , Byrne Fiona , Goicoechea Maria , Piperni Elisa , Au Lewis , Edmonds Kim , Carlyle Eleanor , Hunter Nikki , Renn Alexandra , Messiou Christina , Hughes Peta , Nobbs Jaime , Foijer Floris , van den Bos Hilda , Wardenaar Rene , Spierings Diana C.J. , Spencer Charlotte , Schmitt Andreas M. , Tippu Zayd , Lingard Karla , Grostate Lauren , Peat Kema , Kelly Kayleigh , Sarker Sarah , Vaughan Sarah , Mangwende Mary , Terry Lauren , Kelly Denise , Biano Jennifer , Murra Aida , Korteweg Justine , Lewis Charlotte , O'Flaherty Molly , Cattin Anne-Laure , Emmerich Max , Gerard Camille L. , Pallikonda Husayn Ahmed , Lynch Joanna , Mason Robert , Rogiers Aljosja , Xu Hang , Huebner Ariana , McGranahan Nicholas , Al Bakir Maise , Murai Jun , Naceur-Lombardelli Cristina , Borg Elaine , Mitchison Miriam , Moore David A. , Falzon Mary , Proctor Ian , Stamp Gordon W.H. , Nye Emma L. , Young Kate , Furness Andrew J.S. , Pickering Lisa , Stewart Ruby , Mahadeva Ula , Green Anna , Larkin James , Litchfield Kevin , Swanton Charles , Jamal-Hanjani Mariam ,   for the PEACE Consortium, Turajlic Samra
Published: March 2023

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.

Significance:

Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.

See related commentary by Shain, p. 1294.

This article is highlighted in the In This Issue feature, p. 1275
Mehrsprachigkeit in Rio Grande do Sul: Zur Negation im Brasilianischen Hunsrückisch
Authors: Rinke Esther , Flores Cristina
Published: March 2023

Im vorliegenden Artikel wird anhand eines spontansprachlichen Korpus bilingualer Sprecher ein sprachliches Phänomen im brasilianischen Hunsrückischen genauer betrachtet: die Negation. Die Negation ist insofern linguistisch interessant, als sie in den beiden involvierten Kontaktvarietäten (deutsche Minderheitensprache, brasilianisches Portugiesisch (BP)) unterschiedlich ausgeprägt ist. Von Interesse ist insbesondere die Stellung des Negationswortes in Hinblick auf das finite Verb und das direkte Objekt sowie die Frage, ob zwei Negationselemente in einem Satz vorkommen können, ohne dass die negative Interpretation des Satzes sich in eine Affirmation wandelt (Negative Concord). Ziel der Analyse ist es, mögliche Sprachkontaktphänomene und sprachkontaktbedingten Wandel zu identifizieren. Es wird geschlussfolgert, dass die Negation im Hunsrückischen sehr stabil ist und deutschen Wortstellungsmustern folgt. Diese grammatische Stabilität beruht auf dem regelmäßigen Gebrauch des Dialekts. Dennoch finden sich wie im BP Phänomene von Negative Concord, das im Standarddeutschen nicht in gleicher Weise möglich ist. Im Gegensatz zum brasilianischen Portugiesischen handelt es sich allerdings nicht um ein kategorisches, sondern um ein variables Phänomen, das in ähnlicher Weise in anderen deutschen Dialekten existiert bzw. existierte.
Do gerúndio e gerundivo latinos ao gerúndio português: Consensos revisados e descobertas incidentais
Authors: Queriquelli Luiz Henrique Milani
Published: March 2023

Esta pesquisa busca revisar, à luz de larga base empírica e estudos recentes, o consenso de que o gerúndio português deriva do gerúndio ablativo latino, considerando a hipótese de que o gerundivo latino (idêntico em termos morfológicos) possa ter tido participação na deriva da forma portuguesa. Para tanto, são analisados dados de dois corpora, um de latim, outro de português arcaico, a fim de verificar a extensão e o emprego das formas com a desinência -nd- nessas línguas. Os resultados em geral confirmam o entendimento consensual, embora apresentem algumas descobertas incidentais, como a vasta ocorrência, em latim, de um fenômeno que convertia o gerúndio em gerundivo, a variedade de usos do gerúndio português não coincidentes com os usos do gerúndio latino, além de empregos isolados de formas pseudo-gerundivas em português arcaico.
Sleep Irregularity Is Associated With Hypertension: Findings From Over 2 Million Nights With a Large Global Population Sample
Authors: Scott Hannah , Lechat Bastien , Guyett Alisha , Reynolds Amy C. , Lovato Nicole , Naik Ganesh , Appleton Sarah , Adams Robert , Escourrou Pierre , Catcheside Peter , Eckert Danny J.
Published: March 2023

Background:

Irregularities in sleep duration and sleep timing have emerged as potential risk factors for hypertension. This study examined associations between irregularity in sleep duration and timing with hypertension in a large, global sample over multiple months.

Methods:

Data from 12 287 adults, who used an under-mattress device to monitor sleep duration and timing and also provided blood pressure recordings on ≥5 separate occasions, were analyzed. Sleep duration irregularity was assessed as the SD in total sleep time across the ≈9-month recording period. Sleep timing irregularity was assessed as SDs in sleep onset time, sleep midpoint, and sleep offset time. Logistic regressions were conducted to investigate associations between sleep irregularity and hypertension, defined as median systolic blood pressure ≥140 mm Hg or median diastolic blood pressure ≥90 mm Hg.

Results:

Participants were middle-aged (mean±SD, 50±12 years), mostly men (88%) and overweight (body mass index, 28±6 kg/m
−2
). Sleep duration irregularity was consistently associated with an ≈9% to 17% increase in hypertension independently of the total sleep time. A ≈34-minute increase in sleep onset time irregularity was associated with a 32% increase in hypertension (1.32 [1.20–1.45]). A 32-minute increase in sleep midpoint irregularity was associated with an 18% increase in hypertension (1.18 [1.09–1.29]), while a 43-minute increase in sleep offset time irregularity was associated with an 8.9% increase in hypertension (1.09 [1.001–1.18]).

Conclusions:

These findings support that sleep irregularity, both in duration and timing, is a risk marker for poor cardiovascular health. Further mechanistic investigations of temporal relationships between day-to-day fluctuations in sleep duration and timing, next-day blood pressure, and other cardiovascular outcomes are warranted.
Intrarenal Renin-Angiotensin System Activation Alters Relationship Between Systolic Blood Pressure and Progression of Chronic Kidney Disease
Authors: Park Cheol Ho , Kim Hyung Woo , Park Jung Tak , Chang Tae Ik , Yoo Tae-Hyun , Lee Joongyub , Sung Suah , Jung Ji Yong , Hyun Young Youl , Oh Kook-Hwan , Kang Shin-Wook , Han Seung Hyeok ,   on the behalf of the KNOW-CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease) Investigators
Published: March 2023

Background:

Elevated blood pressure and intrarenal renin-angiotensin system activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between blood pressure and intrarenal renin-angiotensin system activity on the risk of CKD progression is unknown.

Methods:

We analyzed 2076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic blood pressure (SBP). The urinary angiotensinogen-to-creatinine ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy.

Results:

During 10 550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and urinary angiotensinogen-to-creatinine ratio on the risk of the primary outcome (
P
value for interaction=0.019). In patients with urinary angiotensinogen-to-creatinine <3.65 μg/gCr, the hazard ratios (95% CIs) for SBP 120 to 129, 130 to 139, and ≥140 mmHg were 1.46 (1.07–1.99), 1.71 (1.25–2.35), and 2.40 (1.73–3.32), respectively, compared with SBP <120 mmHg. However, these associations were not observed in patients with urinary angiotensinogen-to-creatinine ≥3.65 μg/gCr.

Conclusions:

In this prospective CKD cohort, higher SBP was associated with CKD progression when urinary angiotensinogen levels were low, while this association was not seen when urinary angiotensinogen levels were high. This finding suggests that intrarenal renin-angiotensin system activity may modify the relationship between SBP and adverse kidney outcome.
Prognostic Value of Machine‐Learning‐Based PRAISE Score for Ischemic and Bleeding Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Shi Boqun , Wang Hao‐Yu , Liu Jinpeng , Cai Zhongxing , Song Chenxi , Yin Dong , Wang Hongjian , Dong Qiuting , Song Weihua , Dou Ke‐Fei
Published: March 2023

Background

The PRAISE (Prediction of Adverse Events Following an Acute Coronary Syndrome) score is a machine‐learning‐based model for predicting 1‐year all‐cause death, myocardial infarction, and Bleeding Academic Research Consortium (BARC) type 3/5 bleeding. Its utility in an unselected Asian population undergoing percutaneous coronary intervention for acute coronary syndrome remains unknown. We aimed to validate the PRAISE score in a real‐world Asian population.

Methods and Results

A total of 6412 consecutive patients undergoing percutaneous coronary intervention for acute coronary syndrome were prospectively included. The PRAISE scores were compared with established scoring systems (GRACE [Global Registry of Acute Coronary Events] 2.0, PRECISE‐DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy), and PARIS [Patterns of Non‐Adherence to Anti‐Platelet Regimen in Stented Patients]) to evaluate their discrimination, calibration, and reclassification. The risk of all‐cause mortality (hazard ratio [HR], 12.24 [95% CI, 5.32–28.15]) and recurrent acute myocardial infarction (HR, 3.92 [95% CI, 1.76–8.73]) was greater in the high‐risk group than in the low‐risk group. The C‐statistics for death, myocardial infarction, and major bleeding were 0.75 (0.67–0.83), 0.61 (0.52–0.69), and 0.62 (0.46–0.77), respectively. The observed to expected ratio of death, myocardial infarction, and major bleeding was 0.427, 0.260, and 0.106, respectively. Based on the decision curve analysis, the PRAISE score displayed a slightly greater net benefit for the 1‐year risk of death (5%–10%) than the GRACE score did.

Conclusions

The PRAISE score showed limited potential for risk prediction in our validation cohort with acute coronary syndrome. As a result, new prediction models or model refitting are required with improved discrimination and accuracy in risk prediction.
Circ_0022920
Maintains the Contractile Phenotype of Human Aortic Vascular Smooth Muscle Cells Via Sponging
microRNA‐650
and Promoting Transforming Growth Factor Beta Receptor 1 Expression in Angiotensin II‐Induced Models for Aortic Dissection
Authors: Huang Mao‐Xun , Piao Hu‐Lin , Wang Yong , Zhu Zhi‐Cheng , Xu Ri‐Hao , Wang Tian‐Ce , Li Dan , Liu Ke‐Xiang
Published: March 2023

Background

Abnormal regulation of vascular smooth muscle cells is regarded as the iconic pathological change of aortic dissection (AD). Herein, we aim to identify
circ_0022920
as a crucial regulator in AD.

Methods and Results

Microarray analysis of circular RNAs, messenger RNAs, and micro RNAs in patients with AD was performed, and we identified that
circ_0022920
was significantly downregulated in these patients. The Pearson correlation analysis uncovered the negative correlation between
miR‐650
and
circ_0022920
or TGFβR1 (transforming growth factor beta receptor 1). Angiotensin II was used to treat human aortic vascular smooth muscle cells (HASMCs) and mice as models for AD. Hematoxylin and eosin and Masson's trichrome staining were used to analyze AD histopathology. Cell proliferation was analyzed with Cell Counting Kit‐8 assay and EdU incorporation. Cell migration was assessed with transwell and wound healing assays. Enhanced
circ_0022920
expression dramatically inhibited HASMC proliferation and migration and maintained contractile marker expression induced by angiotensin II, whereas
miR‐650
exerted opposite effects.
MiR‐650
was a target of
circ_0022920
.
MiR‐650
targeted IRF1 (interferon regulatory factor 1) and thus negatively regulated TGFβR1 expression to promote HASMC proliferation and migration and inhibit contractile marker expression.
Circ_0022920
suppressed the progression of AD in vivo.

Conclusions

Circ_0022920
modulates the contractile phenotype of HASMCs via regulating the
miR‐650
‐IRF1‐TGFβR1 axis in angiotensin II‐induced models for AD, which provides potential therapeutic targets for AD.
Pentose Pathway Activation Is Superior to Increased Glycolysis for Therapeutic Angiogenesis in Peripheral Arterial Disease
Authors: Zaied Abdelrahman A. , Ushio‐Fukai Masuko , Fukai Tohru , Kovacs‐Kasa Anita , Alhusban Suhib , Sudhahar Varadarajan , Ganta Vijay C. , Annex Brian H.
Published: March 2023

Background

In endothelial cells (ECs), glycolysis, regulated by PFKFB3 (6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase, isoform‐3), is the major metabolic pathway for ATP generation. In preclinical peripheral artery disease models, VEGF
165
a (vascular endothelial growth factor
165
a) and microRNA‐93 both promote angiogenesis.

Methods and Results

Mice following hind‐limb ischemia (HLI) and ECs with, and without, hypoxia and serum starvation were examined with, and without, microRNA‐93 and VEGF
165
a. Post‐HLI perfusion recovery was monitored. EC metabolism was studied using seahorse assay, and the expression and activity of major metabolism genes were assessed. Reactive oxygen species levels and EC permeability were evaluated. C57Bl/6J mice generated a robust angiogenic response to HLI, with ECs from ischemic versus nonischemic muscle demonstrating no increase in glycolysis. Balb/CJ mice generated a poor angiogenic response post‐HLI; ischemic versus nonischemic ECs demonstrated significant increase in glycolysis. MicroRNA‐93‐treated Balb/CJ mice post‐HLI showed better perfusion recovery, with ischemic versus nonischemic ECs showing no increase in glycolysis. VEGF
165
a‐treated Balb/CJ mice post‐HLI showed no improvement in perfusion recovery with ischemic versus nonischemic ECs showing significant increase in glycolysis. ECs under hypoxia and serum starvation upregulated PFKFB3. In ECs under hypoxia and serum starvation, VEGF
165
a versus control significantly upregulated PFKFB3 and glycolysis, whereas miR‐93 versus control demonstrated no increase in PFKFB3 or glycolysis. MicroRNA‐93 versus VEGF
165
a upregulated glucose‐6‐phosphate dehydrogenase expression and activity, activating the pentose phosphate pathway. MicroRNA‐93 versus control increased reduced nicotinamide adenine dinucleotide phosphate and virtually eliminated the increase in reactive oxygen species. In ECs under hypoxia and serum starvation, VEGF
165
a significantly increased and miR‐93 decreased EC permeability.

Conclusions

In peripheral artery disease, activation of the pentose phosphate pathway to promote angiogenesis may offer potential therapeutic advantages.
American Heart Association's Children's Strategically Focused Research Network Experience
Authors: Sable Craig , Li Jennifer S. , Tristani‐Firouzi Martin , Fagerlin Angela , Silver Robert M. , Yandel Mark , Yost H. Joseph , Beaton Andrea , Dale James , Engel Mark Emmanuel , Watkins David , Spurney Christopher , Skinner Asheley C. , Armstrong Sarah C. , Shah Svati H. , Allen Norrina , Davis Matthew , Hou Lifang , Van Horn Linda , Labarthe Darwin , Lloyd‐Jones Donald , Marino Bradley
Published: March 2023

The American Heart Association's Strategically Focused Children's Research Network started in July 2017 with 4 unique programs at Children's National Hospital in Washington, DC; Duke University in Durham, North Carolina; University of Utah in Salt Lake City, Utah; and Lurie Children's Hospital/Northwestern University in Chicago, Illinois. The overarching goal of the Children's National center was to develop evidence‐based strategies to strengthen the health system response to rheumatic heart disease through synergistic basic, clinical, and population science research. The overall goals of the Duke center were to determine risk factors for obesity and response to treatment including those that might work on a larger scale in communities across the country. The integrating theme of the Utah center focused on leveraging big data‐science approaches to improve the quality of care and outcomes for children with congenital heart defects, within the context of the patient and their family. The overarching hypothesis of the Northwestern center is that the early course of change in cardiovascular health, from birth onward, reflects factors that result in either subsequent development of cardiovascular risk or preservation of lifetime favorable cardiovascular health. All 4 centers exceeded the original goals of research productivity, fellow training, and collaboration. This article describes details of these accomplishments and highlights challenges, especially around the COVID‐19 pandemic.
A Personal Perspective on Evolutionary Computation: A 35-Year
Journey
Authors: Michalewicz Zbigniew
Published: March 2023

This paper presents a personal account of the author's 35 years “adventure” with Evolutionary Computation—from the first encounter in 1988 and many years of academic research through to working full-time in business—successfully implementing evolutionary algorithms for some of the world's largest corporations. The paper concludes with some observations and insights.
Of Peacekeepers and Pandemics
Authors: Leib Julia
Published: March 2023

Little is known about the role social media can play in support of peacekeeping missions, especially in times of crisis. Looking at the use of Facebook by the UN Mission in South Sudan (UNMISS) before and during the Covid-19 pandemic, this article reconstructs social media practices of a peacekeeping mission in a global crisis. To assess how UNMISS used Facebook, it first connects research on discursive legitimation efforts by international organizations with work on strategic communication. Second, it provides a content analysis on Facebook posts published by UNMISS between 2018 and 2022 to determine how the mission engaged with its audience, how it framed its engagement, what topics were being addressed, and how the Covid-19 pandemic changed these communication patterns. Results show a conscious “propaganda for peace” strategy of the peacekeeping mission as UNMISS framed itself as a positive force for the peace process, using tailored communication strategies that rarely engaged in two-way communication, even in times of crisis.
Notes on the diatom collection of the Natural History Museum, London (BM) VII: An account of some original specimens of Pyrgodiscus (Bacillariophyta) with notes on Stephanogonia (Bacillariophyta)
Authors: WILLIAMS DAVID M. , SIMS PAT A.
Published: March 2023

Specimens of the diatom genus Pyrgodiscus held at the BM have been examined and two species are recognised and accepted: Pyrgodiscus armatus and Pyrgodiscus simplex. Both are extinct fossil species but known only from light microscope data. The sole defining character recognised (so far) is two series of spines: (1) one series of spines surrounding the base of the valve, (2) the other series surrounding the central pillar. The status of the genus, however, is unclear as they may be resting spores. The classification of Pyrgodiscus is uncertain. Although a relationship with Stephanogonia was suggested some time ago, the only option at this time is to leave Pyrgodiscus as incertae sedis and to encourage investigation and characterisation of higher taxa.
Research on Mechanism of miR-488-5p Carried with Magnetic Carbon Nanotubes in Restraining Lymphatic Metastasis in Cervical Cancer Through Induction of mTOR/P70S6K Signaling Pathway
Authors: Wang Donghua , Liu Xiaoli , Gong Shixiong , Jia Yijuan , Wang Ping
Published: March 2023

This study intends to discuss mechanism of miR-488-5p carried with magnetic carbon nanotubes (MAGCNTs) in restraining lymphatic metastasis in cervical cancer through induction of mTOR/P70S6K signaling pathway. Fifty female rats were randomly divided into five sets, which included control
set, miR-488-5p set, empty carrier set, set of miR-488-5p carrier and inhibitor set. The MAGCNTs were prepared and characterized. Condition and quantity of lymphatic metastasis in cervical cancer, miR-488-5p expression and protein expression of factors related with mTOR/P70S6K signaling transduction
pathway were observed. Quantity of lymphatic metastasis in the control set was highest, while quantity of lymphatic metastasis in the set of miR-488-5p and carrier were lowest. Expressions of miR-488-5p in of the miR-488-5p and carrier sets were highest and lowest in the control set, and mTOR/P70S6K
expression was reversed. miR-488-5p was carried with multi-walled carbon nanotubes (MWCNTs) and entered into cells more rapidly. There was over expression of miR-488-5p and activity of mTOR/P70S6K signaling pathway was restrained. The information conduction was slowed down, and therefore,
the lymphatic metastasis in the cervical cancer was restrained.
Intervertebral Disk Regeneration in a Rat Model via a Nanocomposite Collagen Hydrogel Loaded with Galanthus Extract: An In Vitro and In Vivo Study
Authors: Mu Jiang , Liu Zhize , Chen Shuang , Niu Haoming , Zhang Guiqi , Lian Xiaodong
Published: March 2023

In the current study, Galanthus extract was loaded into electrospun gelatin scaffolds using an electrospun method and then crushed. The resulting nanofibers were loaded into a collagen hydrogel to develop a filler material to treat nucleus pulposus injuries in the intervertebral
disks. The nanocomposite hydrogel was studied regarding its biocompatibility, antiinflammatory activity, and swelling behavior. In Vivo study was performed in a rat model of intervertebral disk injury. Histopathological studies showed that the animals treated with the nanocomposite
hydrogel restored its nucleus pulposus to a significantly higher extent than other experimental groups.
Fuzheng Kangai Decoction Restrains the Progression and Angiogenesis of Hepatocellular Carcinoma
Authors: Zeng Hui , Wei Xiaoyan , Wang Chunlei
Published: March 2023

Fuzheng Kangai decoction (FZKA) has been preliminarily proved to be effective in hepatocellular carcinoma (HCC). This study plans to investigate the clear role of FZKA on HCC progression. After establishing a HCC tumor-bearing mice model and treated with FZKA, the volumes and weights
of HCC tumor were monitored, and tumor pathology was analyzed by HE staining. The expression of the molecules related to angiogenesis, apoptosis and angiogenesis in tumor tissues were detected by immunohistochemistry, Western blot and qRT-PCR assays. In addition, HCC cells were administrated
with increasing concentrations of FZKA. Then the cell proliferation, migration and invasion ability were tested. In HCC tumor bearing mice, it was found that FZKA significantly decreased the tumor volumes, weights, aggravated tumor pathological damage, reduced VEGF, CD34, Bcl-2 expression,
but promoted the expression of Bax, cleaved caspase 3, Cyt-C in tumor tissues. Moreover, in vitro experiments demonstrated that FZKA co-incubation suppressed the proliferation, migration and invasion ability of HCC cells. This study demonstrated that FZKA has the potential to inhibit
HCC progression by promoting apoptosis and inhibiting angiogenesis.
Reactive Oxygen Species-Enhanced Low-Dose Chemo-Photodynamic Therapy for Gastric Cancer
Authors: Wang Jing , Li Wenbo , Liu Xiaofeng , Xin Jing
Published: March 2023

A photosensitizer can react with oxygen or a substrate based on energy or electron transfer processes in order to generate free radicals, singlet oxygen (SOG), or other reactive oxygen species (ROS). SOG can damage cellular components and eventually cause cell death. However, SOG generation
requires sufficient oxygen. Therefore, the effect of photodynamic therapy (PDT) via SOG may be decreased in oxygen-deficient tumor tissues, including gastric cancer. Here, we synthesized a nanosized cationic liposome integrated with a photosensitizer and low-dose chemotherapeutic drug related
to ROS to improve the ROS-mediated PDT effect and lower the risk of drug resistance and side effects induced by chemotherapy. The cationic liposome was used as a drug carrier to increase the efficiency of drug delivery, prolong drug circulation time, and achieve the simultaneous delivery of
the photosensitizer and chemotherapeutic drug. The low-dose chemotherapeutic agent related to ROS was adopted for increasing the permeability of the mitochondrial membrane and inducing the entry of high levels of the photosensitizer into the cell so as to generate toxic ROS. Generally, the
ROS-mediated enhanced effect could quickly induce long-lasting apoptosis. This integrated nanosized cationic liposome system is a potential agent for gastric cancer therapy and is based on enhanced ROS-mediated synergistic therapy.
Detection of Land-Use Change and Rapid Recovery of Vegetation after Deforestation in the Congo Basin
Authors: Adams Coralie E. , Garcia-Carreras Luis
Published: March 2023

The Congo Basin is severely understudied compared to other tropical regions; this is partly due to the lack of meteorological stations and the ubiquitous cloudiness hampering the use of remote sensing products. Clustering of small-scale agricultural deforestation events within the basin may result in deforestation on scales that are atmospherically important. This study uses 500-m MODIS data and the Global Forest Change dataset (GFC) to detect deforestation at a monthly and subkilometer scale and to quantify how deforestation impacts vegetation proxies (VPs) within the basin, the time scales over which these changes persist, and how they are affected by the deforestation driver. Missing MODIS data meant that a new method, based on two-date image differencing, was developed to detect deforestation on a monthly scale. Evaluation against the yearly GFC data shows that the highest detection rate was 79% for clearing sizes larger than 500 m2. Recovery to predeforestation levels occurred faster than expected; analysis of postdeforestation evolution of the VPs found 66% of locations recovered within a year. Separation by land-cover type also showed unexpected regrowth, as over 50% of rural complex and plantation land recovered within a year. The fallow period in the study region was typically short; by the sixth year after the initial deforestation event, ∼88% of the locations underwent a further considerable drop. These results show the importance of fine spatial and temporal information to assess Congo Basin deforestation and highlight the large differences in the impacts of land-use change compared to other rain forests.
Assessment of IMERG v06 Satellite Precipitation Products in the Canadian Great Lakes Region
Authors: Zhao Bo , Hudak David , Rodriguez Peter , Mekis Eva , Brunet Dominique , Eckert Ellen , Melo Stella
Published: March 2023

The Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (GPM; IMERG) is a high-resolution gridded precipitation dataset widely used around the world. This study assessed the performance of the half-hourly IMERG v06 Early and Final Runs over a 5-yr period versus 19 high-quality surface stations in the Great Lakes region of North America. This assessment not only looked at precipitation occurrence and amount, but also studied the IMERG Quality Index (QI) and errors related to passive microwave (PMW) sources. Analysis of bias in accumulated precipitation amount and precipitation occurrence statistics suggests that IMERG presents various uncertainties with respect to time scale, meteorological season, PMW source, QI, and land surface type. Results indicate that 1) the cold season’s (November–April) larger relative bias can be mitigated via backward morphing; 2) IMERG 6-h precipitation amount scored best in the warmest season (JJA) with a consistent overestimation of the frequency bias index − 1 (FBI-1); 3) the performance of five PMW sources is affected by the season to different degrees; 4) in terms of some metrics, skills do not always enhance with increasing QI; 5) local lake effects lead to higher correlation and equitable threat score (ETS) for the stations closest to the lakes. Results of this study will be beneficial to both developers and users of IMERG precipitation products.

Significance Statement

The purpose of the study was to assess the performance of the gridded precipitation product from the Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG) version 6 over the Great Lakes region of North America. The assessment performs a statistical comparison of precipitation amounts from IMERG versus surface stations as a function of time scale, season, precipitation event threshold, and input source among satellites. Interpretation of the results identifies shortcomings in the IMERG algorithms, particularly in extreme precipitation events and over ice-covered surfaces. The results also describe spatial variability in the IMERG data quality due to the complex geography of the study area and offer a clear threshold in the Quality Index (QI) flag for optimal application of the precipitation products.
An Evaluation of Non-Gaussian Data Assimilation Methods in Moist Convective Regimes
Authors: McCurry Joshua , Poterjoy Jonathan , Knopfmeier Kent , Wicker Louis
Published: March 2023

Obtaining a faithful probabilistic depiction of moist convection is complicated by unknown errors in subgrid-scale physical parameterization schemes, invalid assumptions made by data assimilation (DA) techniques, and high system dimensionality. As an initial step toward untangling sources of uncertainty in convective weather regimes, we evaluate a novel Bayesian data assimilation methodology based on particle filtering within a WRF ensemble analysis and forecasting system. Unlike most geophysical DA methods, the particle filter (PF) represents prior and posterior error distributions nonparametrically rather than assuming a Gaussian distribution and can accept any type of likelihood function. This approach is known to reduce bias introduced by Gaussian approximations in low-dimensional and idealized contexts. The form of PF used in this research adopts a dimension-reduction strategy, making it affordable for typical weather applications. The present study examines posterior ensemble members and forecasts for select severe weather events between 2019 and 2020, comparing results from the PF with those from an ensemble Kalman filter (EnKF). We find that assimilating with a PF produces posterior quantities for microphysical variables that are more consistent with model climatology than comparable quantities from an EnKF, which we attribute to a reduction in DA bias. These differences are significant enough to impact the dynamic evolution of convective systems via cold pool strength and propagation, with impacts to forecast verification scores depending on the particular microphysics scheme. Our findings have broad implications for future approaches to the selection of physical parameterization schemes and parameter estimation within preexisting data assimilation frameworks.

Significance Statement

The accurate prediction of severe storms using numerical weather models depends on effective parameterization schemes for small-scale processes and the assimilation of incomplete observational data in a manner that faithfully represents the probabilistic state of the atmosphere. Current generation methods for data assimilation typically assume a standard form for the error distributions of relevant quantities, which can introduce bias that not only hinders numerical prediction, but that can also confound the characterization of errors from the model itself. The current study performs data assimilation using a novel method that does not make such assumptions and explores characteristics of resulting model fields and forecasts that might make such a method useful for improving model parameterization schemes.