bluuebunny/crossref_metadata_2025 huggingface dataset:
New Aspects of Fibrillary and Immunotactoid Glomerulonephritis
Authors: Salvadori Maurizio , Tsalouchos Aris
Published: December 2022

Renal diseases involving glomerular deposits of fibrillary material are an important diagnostic challenge for an ultrastructural pathologist. Several renal diseases are characterised by the presence of fibrillary material in the glomeruli. Two disorders of this type, termed ‘fibrillary glomerulonephritis’ (characterised by fibrils measuring approximately 20 nm in diameter) and ‘immunotactoid glomerulonephritis’ (characterised by larger, microtubular deposits), have been described. The possible relatedness of these two disorders and their potential association with other systemic illnesses are the subjects of current debate. Other multisystemic diseases, including amyloidosis and various forms of cryoglobulinaemia, can also present with fibrillary or microtubular deposits in the kidney.

The distinction between fibrillary glomerulonephritis, immunotactoid glomerulonephritis, and other processes that have similar ultrastructural features are discussed in this review. Recently, both in fibrillary glomerulonephritis and in immunotactoid glomerulonephritis, the presence of a DnaJ homolog subfamily member 9 has been detected. This antigen is not present in amyloidosis and could be involved in the pathogenesis of these diseases. This review will discuss the role and the relevance of this antigen.
Kepatuhan Penggunaan Masker dalam Upaya Pencegahan Penularan Covid-19 di Kota Samarinda
Authors: Apriyani Apriyani , Kusumawati Rindha Mareta , Wulandari Kartina
Published: December 2022

Cases in Indonesia are still showing an increase in the number of positive cases exposed to COVID-19, so the government has implemented various efforts to reduce the number of positive cases in Indonesia. One of them is the policy of using masks. The use of mask is part of a comprehensive series of prevention and control measures that can limit the spread of certain viral respiratory tract diseases, including COVID-19. Masks can be used to protect healthy people (used to protect themselves when in contact with infected people) or to control the source (used by an infected person to prevent further transmission). One of the methods to increase compliance with wearing masks is to increase patient understanding of the importance of preventing transmission of the corona virus by obediently wearing masks. The results showed that respondents with low knowledge in the use of mask were 51.7% with a total of 120 respondents and those with good knowledge were 48.3% with a total of 112 respondents. Respondents with poor compliance in using masks were 39.7% with a total of 92 respondents and those with good compliance in using masks were 60.3% with a total of 140 respondents. The results of the chi-square test showed that there was no relationship between public knowledge and compliance with the use of mask in Samarinda City with a p-value of 0.146 (p-value>0.05).
Asupan Makan Sehari, Status Gizi, dan Produktivitas Kerja Guru SMK Pelita Ciampea Bogor
Authors: Hayatunnufus Fadilatunnisa , Melani Vitria , Ronitawati Putri , Swamilaksita Prita Dhiyani
Published: December 2022

Teachers are one of the key factors determining the quality of education. Teacher’s work productivity might be influenced by their daily food intake and nutritional status. The objective of this study is to determine the relationship between daily food intake and nutritional status to the work productivity of teachers. This research used a cross-sectional approach that was carried out at SMK Pelita Ciampea Bogor. The research samples were 75 teachers selected by simple random sampling method. Characteristic data was obtained through interviews and filling out questionnaires. The instruments used to measure nutritional status were digital scales and microtoise. The daily food intake data were obtained from the interview results using the 1x24 hour food recall form. Work productivity data was obtained by filling out a questionnaire containing 25 closed questions. The data were analyzed using the chi-square test. The results showed that teacher's food intake was lower than their recommended dietary allowance. Most of the teachers were obese but had very good work productivity. Bivariate analysis showed that there was no significant relationship between nutritional intake and work productivity (p>0,05). In daily food intake, only fat intake had a significant relationship to work productivity (p=0,004). It could be concluded that fat intake had a significant relation to work productivity.
Sayısal Koruma Koalisyonu Hızlı Değerlendirme Modeli: Elektronik Belgelerin Güvenilirliği Açısından Bir İnceleme
Authors: SAĞLIK Özhan
Published: December 2022

Kurumlarda oluşan ve arşivlik değere sahip olan belgelerin uzun dönemli korunması gerekir. Bunun için sayısal koruma tekniklerinden yararlanıldığı bilinmektedir. Bu teknikler, aynı zamanda belgelerin güvenilirliğinin korunmasına yardımcı olmaktadır. Kurumların sayısal koruma faaliyetlerini uygularken hangi durumda olduklarını ve gelecekte nereye varmak istediklerini değerlendirebilmek için mevcut yeteneklerin analiz edilmesi gündeme gelmekte ve bir analiz aracına ihtiyaç duyulmaktadır. Bu ihtiyacı karşılamak amacıyla pek çok model hazırlanmıştır. Bunlardan biri de Digital Preservation Coalition (DPC - Sayısal Koruma Koalisyonu) tarafından geliştirilen Hızlı Değerlendirme Modeli’dir (HDM - Rapid Assessment Model). Model, kurumların mevcut sayısal koruma yeteneklerini değerlendirirken geleceğe ilişkin de bir plan sunmaktadır. Bundan dolayı HDM’nin belgelerin uzun dönemli korunmasını hedefleyen güvenilirlikle ilişkilendirilebileceği düşünülmüştür. Bu çalışmada HDM’de belirtilen sayısal koruma yetenekleri, elektronik belgelerin (e-belge) güvenilirliği açısından incelenmektedir. Bu inceleme sonucunda hem sayısal koruma kapasitelerini değerlendirmek isteyen kurumlara bir metodolojinin zeminini oluşturmak hem de sayısal korumayla ilgili yetenekleri güvenilirlikle örtüştürmek istenmiştir. Nitel araştırma deseninden faydalanılan bu çalışmada doküman analizinden yararlanılmıştır. Hem saha gözlemleri hem de yapılan araştırmalar, kurumlarda sayısal koruma yetenekleri ve güvenilirlik konusunda yeterli farkındalığın bulunmadığını göstermektedir. Durum böyle olunca çalışmanın sorusu HDM’de belirtilen yetenekler güvenilirlikle nasıl ilişkilendirilebilir şeklindedir. Çalışma sonucunda HDM’de yer alan sayısal koruma yeteneklerinin belgelerin güvenilirlik analizinde kullanılabileceği gözlenmiştir. Ancak, HDM’nin geliştirilmesi gereken yönleri de fark edilmiştir. Bunlardan biri kararlaştırılan hedeflere erişmek için somut kriterlerin belirlenmesidir. Bu kriterlerin güvenilirlik analizlerinde kullanılabileceği kanaati oluşmuştur. Yapılacak yeni çalışmalarla bu gibi kanaatlerin hipoteze dönüştürülmesi, hem kurumların sayısal koruma kapasitelerini güçlendirmelerine yardımcı olacak hem de güvenilirlik analizlerinin zenginleşmesine katkıda bulunacaktır. İşbu çalışma ile kurumlarda arşivlik değere sahip olan belgeleri daha iyi korumak noktasında bir farkındalık oluşturması beklenmektedir.
O RELATÓRIO SÍNTESE DE AVALIAÇÃO DE TRABALHOS DE UMA FEIRA DE MATEMÁTICA: REVELAÇÕES A PARTIR DA ESCRITA
Authors: Scheller Morgana , Zabel Marília , Tenfen Rita de Cássia , Borba Girardi Nilva
Published: December 2022

A avaliação dos trabalhos expostos na Feira de Matemática é discutida no interior de cada um dos grupos de avaliação no dia da exposição e culmina no relatório síntese de avaliação (RT). Este estudo quali-quantitativo considera esses relatórios, centrado no questionamento: Que indícios são revelados nos RT acerca da escrita registrada pela coordenação de grupo de avaliação (CGA)? Para tanto, procedeu com um estudo documental, analisando 72 RT elaborados por 17 diferentes grupos de avaliação de uma edição de Feira Regional de Matemática. Os resultados indicam uma escrita que traz aspectos diferentes daqueles que são pretendidos nos dois enunciados que compõe o RT, com apresentação de elementos de síntese e de sugestão mesclados e/ou em item inapropriado. Evidenciou-se, registros mais atentos e mais próximos dos propósitos difundidos na Feira para os trabalhos que recebem indicação para etapa catarinense em detrimento daqueles indicados como menção honrosa. Ainda, a escrita apresenta fragilidades em termos de elaboração de síntese. Diante disso, sugere-se que se promova espaço para discussão acerca do que consiste ou comporia “uma síntese de avaliação considerando os aspectos observados”, para que haja avanços em relação ao que vem sendo difundido a partir de experiências isoladas. A partir disso, sugere-se a alteração das orientações expressas no RT que é utilizado atualmente. Concluiu-se que se tem ainda obstáculos e desafios na tarefa da CGA, o que indica necessidade de promover espaço dialógico para tratar do assunto e de formação permanente dos envolvidos.
Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients
Authors: Han Jiyu , Zhao Zitong , Wang Yanhong , Yu Tao , Wan Daqian
Published: December 2022

The most common primary malignant bone sarcoma is Osteogenic sarcoma (OS) which has a bimodal age distribution. Unfortunately, the treatment of OS was less effective for elderly patients than for younger ones. The study aimed to explore a new microRNA (miRNA) which can bind to combining engineered exosomes for treatment of older OS patients. Based on GSE65071 and miRNet 2.0, two up-regulated miRNAs (miR-328, miR-107) and seven down-regulated miRNAs (miR-133b, miR-206, miR-1-3p, miR-133a, miR-449a, miR-181daysay, miR-134) were selected. Next, we used FunRich software to predict the up-stream transcription factors (TFs) of differentially expressed miRNAs (DE-miRNAs). By comparing target genes predicted from DE-miRNAs with differentially expressed genes, we identified 12 down-regulated and 310 up-regulated mRNAs. For KEGG analysis, the most enriched KEGG pathway was Cell cycle, Spliceosome, and Protein digestion and absorption. By using protein-protein interactions network, topological analysis algorithm and GEPIA database, miR-449a /CCNB1 axis was identified. Experiments in vitro were conducted to confirm the results too. MiRNA-449a is down-regulated in osteosarcoma and suppresses cell proliferation by targeting CCNB1. Our findings not only reveal a novel mechanism of miR-449a /CCNB1 in OS but also had laid the groundwork for further investigation and analysis in the field of exosome engineering.
Metabolomic profiling of triple negative breast cancer cells suggests that valproic acid can enhance the anticancer effect of cisplatin
Authors: Granit Avital , Mishra Kumudesh , Barasch Dinorah , Peretz-Yablonsky Tamar , Eyal Sara , Kakhlon Or
Published: December 2022

Cisplatin is an effective chemotherapeutic agent for treating triple negative breast cancer (TNBC). Nevertheless, cisplatin-resistance might develop during the course of treatment, allegedly by metabolic reprograming, which might influence epigenetic regulation. We hypothesized that the histone deacetylase inhibitor (HDACi) valproic acid (VPA) can counter the cisplatin-induced metabolic changes leading to its resistance. We performed targeted metabolomic and real time PCR analyses on MDA-MB-231 TNBC cells treated with cisplatin, VPA or their combination. 22 (88%) out of the 25 metabolites most significantly modified by the treatments, were acylcarnitines (AC) and three (12%) were phosphatidylcholines (PCs). The most discernible effects were up-modulation of AC by cisplatin and, contrarily, their down-modulation by VPA, which was partial in the VPA-cisplatin combination. Furthermore, the VPA-cisplatin combination increased PCs, sphingomyelins (SM) and hexose levels, as compared to the other treatments. These changes predicted modulation of different metabolic pathways, notably fatty acid degradation, by VPA. Lastly, we also show that the VPA-cisplatin combination increased mRNA levels of the fatty acid oxidation (FAO) promoting enzymes acyl-CoA synthetase long chain family member 1 (ACSL1) and decreased mRNA levels of fatty acid synthase (FASN), which is the rate limiting enzyme of long-chain fatty acid synthesis. In conclusion, VPA supplementation altered lipid metabolism, especially fatty acid oxidation and lipid synthesis, in cisplatin-treated MDA-MB-231 TNBC cells. This metabolic reprogramming might reduce cisplatin resistance. This finding may lead to the discovery of new therapeutic targets, which might reduce side effects and counter drug tolerance in TNBC patients.
Is histogram manipulation always beneficial when trying to improve model performance across devices? Experiments using a Meibomian gland segmentation model
Authors: Deng Xianyu , Tian Lei , Zhang Yinghuai , Li Ao , Cai Shangyu , Zhou Yongjin , Jie Ying
Published: December 2022

Meibomian gland dysfunction (MGD) is caused by abnormalities of the meibomian glands (MG) and is one of the causes of evaporative dry eye (DED). Precise MG segmentation is crucial for MGD-related DED diagnosis because the morphological parameters of MG are of importance. Deep learning has achieved state-of-the-art performance in medical image segmentation tasks, especially when training and test data come from the same distribution. But in practice, MG images can be acquired from different devices or hospitals. When testing image data from different distributions, deep learning models that have been trained on a specific distribution are prone to poor performance. Histogram specification (HS) has been reported as an effective method for contrast enhancement and improving model performance on images of different modalities. Additionally, contrast limited adaptive histogram equalization (CLAHE) will be used as a preprocessing method to enhance the contrast of MG images. In this study, we developed and evaluated the automatic segmentation method of the eyelid area and the MG area based on CNN and automatically calculated MG loss rate. This method is evaluated in the internal and external testing sets from two meibography devices. In addition, to assess whether HS and CLAHE improve segmentation results, we trained the network model using images from one device (internal testing set) and tested on images from another device (external testing set). High DSC (0.84 for MG region, 0.92 for eyelid region) for the internal test set was obtained, while for the external testing set, lower DSC (0.69–0.71 for MG region, 0.89–0.91 for eyelid region) was obtained. Also, HS and CLAHE were reported to have no statistical improvement in the segmentation results of MG in this experiment.
Causal relationship between gut microbes and cardiovascular protein expression
Authors: Zhang Wenchuan , Zhang Shuwan , Zhao Feng , Du Jinda , Wang Zhe
Published: December 2022

Evidence supports associations between gut microbiota and cardiovascular protein levels in plasma. However, it is unclear whether these associations reflect a causal relationship. To reveal the causal relationship between gut microbiota and cardiovascular protein levels in plasma, we estimated their causal effects using two-sample Mendelian randomization (MR) analysis. Sensitivity analysis was also performed to assess the robustness of our results. Genome-wide association study (GWAS) of microbiomes in the MiBioGen study included 211 bacterial taxa (18,473 individuals), and GWAS of 90 cardiovascular proteins included 30,931 individuals. There were 196 bacterial taxa from five levels available for analysis. The following 14 causal relationships were identified: phylum Euryarchaeota and carbohydrate antigen 125 (β = 0.289), order Bacillales and CSF-1 (β = -0.211), genus Dorea and HSP-27 (β = 0.465), phylum Actinobacteria and IL-8 (β = 0.274), order Enterobacteriales and KIM-1 (β = -0.499), class Actinobacteria, genus Bifidobacterium, phylum Actinobacteria and LEP (β = -0.219, β = -0.201, and β = -0.221), genus Methanobrevibacter and NT-proBNP (β = 0.371), family Peptostreptococcaceae and SRC (β = 0.191), order Verrucomicrobiales, phylum Verrucomicrobia and TNF-R2 (β = 0.251 and β = 0.233), family Veillonellaceae and t-PA (β = 0.271), and class Erysipelotrichia and VEGF-D (β = 0.390). Sensitivity analysis showed no evidence of pleiotropy or heterogeneity. The results of the reverse MR analysis showed no reverse causality for any of the 13 gut microbes and 11 cardiovascular proteins. Mendelian randomization estimates provide strong evidence for a causal effect of gut microbiota-mediated alterations on cardiovascular protein expression.
Global city densities: Re-examining urban scaling theory
Authors: Burger Joseph R. , Okie Jordan G. , Hatton Ian A. , Weinberger Vanessa P. , Shrestha Munik , Liedtke Kyra J. , Be Tam , Cruz Austin R. , Feng Xiao , Hinojo-Hinojo César , Kibria Abu S. M. G. , Ernst Kacey C. , Enquist Brian J.
Published: December 2022

Understanding scaling relations of social and environmental attributes of urban systems is necessary for effectively managing cities. Urban scaling theory (UST) has assumed that population density scales positively with city size. We present a new global analysis using a publicly available database of 933 cities from 38 countries. Our results showed that (18/38) 47% of countries analyzed supported increasing density scaling (pop ~ area) with exponents ~⅚ as UST predicts. In contrast, 17 of 38 countries (~45%) exhibited density scalings statistically indistinguishable from constant population densities across cities of varying sizes. These results were generally consistent in years spanning four decades from 1975 to 2015. Importantly, density varies by an order of magnitude between regions and countries and decreases in more developed economies. Our results (i) point to how economic and regional differences may affect the scaling of density with city size and (ii) show how understanding country- and region-specific strategies could inform effective management of urban systems for biodiversity, public health, conservation and resiliency from local to global scales.

200 word statement of contribution: Urban Scaling Theory (UST) is a general scaling framework that makes quantitative predictions for how many urban attributes spanning physical, biological and social dimensions scale with city size; thus, UST has great implications in guiding future city developments. A major assumption of UST is that larger cities become denser. We evaluated this assumption using a publicly available global dataset of 933 cities in 38 countries. Our scaling analysis of population size and area of cities revealed that while many countries analyzed showed increasing densities with city size, about 45% of countries showed constant densities across cities. These results question a key assumption of UST. Our results suggest policies and management strategies for biodiversity conservation, public health and sustainability of urban systems may need to be tailored to national and regional scaling relations to be effective.
Can prebiotic systems survive in the wild? An interference chemistry approach
Authors: Walton Craig R. , Rimmer Paul , Shorttle Oliver
Published: December 2022

It is challenging to evaluate the relevance of any given chemical system or geological environment to the origin of life. At the same time, life is the product of prebiotic chemistry that took place in some environment. We may attempt to quantify the probability landscape of organic systems and their host environments on prebiotic worlds as a preliminary step to solving the origin of life. Mapping out the environments and chemical systems of prebiotic habitable worlds requires an integration of at least two fields: prebiotic chemistry, which can discover relevant systems of reactions; and geosciences, which can identify likely planetary environments in which prebiotic systems can develop. However, parallel exploration of prebiotic environmental conditions and chemical systems is inefficient given the immense parameter space available. Here, we propose to emphasize the combined experimental study of prebiotic systems and their proposed host environments, which we term interference chemistry. Environmental variables may interfere either constructively, neutrally, or destructively with specific pathways of organic chemical synthesis, as tracked by e.g., yields or rates of reactions. In turn, prebiotic chemical systems may modify the wider environment, e.g., bulk solution chemistry. Interference chemistry therefore offers an efficient way to construct, describe, and discover prebiotic environmental scenarios, which should in turn assist us assess plausibility for origin of life scenarios.
Executive function in early childhood: Harnessing the potential of nature-based practices to elevate and equalize outcomes
Authors: Ernst Julie , Sobel David , Neil Ahna
Published: December 2022

This study examined the effect of nature-based practices on preschoolers’ executive function (EF). The Minnesota Executive Function Scale was administered to 147 children within one school district at the beginning and end of the preschool year. Results suggest incorporating nature-based practices into preschool was effective, as children in preschool classrooms where nature-based practices were used had significantly higher levels of EF at the end of the school year than children in programs where nature-based practices were more minimally used. Preschools that used a blended approach (some incorporation of nature-based practices) were significantly more effective than preschools that had lesser incorporation of nature-based practices. Results also point to the effectiveness of a blended approach for supporting EF in lower SES children. This study contributes to the literature regarding effective practices for supporting EF development and adds to the growing body of research surrounding the impact of nature play on child development and school readiness.
Molecular targets in acromegaly
Authors: Labadzhyan Artak , Melmed Shlomo
Published: December 2022

Molecular therapeutic targets in growth hormone (GH)-secreting adenomas range from well-characterized surface receptors that recognize approved drugs, to surface and intracellular markers that are potential candidates for new drug development. Currently available medical therapies for patients with acromegaly bind to somatostatin receptors, GH receptor, or dopamine receptors, and lead to attainment of disease control in most patients. The degree of control is variable: however, correlates with both disease aggressiveness and tumor factors that predict treatment response including somatostatin receptor subtype expression, granulation pattern, kinases and their receptors, and other markers of proliferation. A better understanding of the mechanisms underlying these molecular markers and their relationship to outcomes holds promise for expanding treatment options as well as a more personalized approach to treating patients with acromegaly.
Voltaiq data format—A standard data format for collection of battery data to enable big data comparisons and analyses across the battery lifecycle
Authors: Lininger Christianna N. , Thai Tony , Juran Taylor R. , Leland Eli S. , Sholklapper Tal Z.
Published: December 2022

Batteries have enabled modernization of society through portability of electricity. Batteries are also a crucial component to enabling clean technologies of the future such as grid storage and electrified transportation. Because of their ubiquity in modern society, global organizations develop and commercialize batteries for their electrified products. Across the field of battery development, in both commercial and academic settings, there is broad utility in standardization of data formats amongst disparate data sources, labs, equipment, organizations, industries, and lifecycle phases. Due to the way the nascent industry developed, there is a lack of standardization for how performance data is recorded, which is now hindering the industry’s ability to learn from data and accelerate growth. Herein, we describe the different types of data, formats, conventions, and standardization for each phase in the battery lifecycle. Next, we provide a standard data format and conventions for the community to either utilize in their data collection practices or map their existing data into: the Voltaiq Data Format (VDF). This standard data format provides the flexibility needed to capture the variability in data formats and conventions along the battery lifecycle. The utility of this standard format aids in collaboration within and across organizations, accelerating innovation across the industry, and paves the way for the battery community to start utilizing the power of machine learning and data science.
Leak test for solid oxide fuel cells and solid oxide electrolysis cells
Authors: Chou Yeong-Shyung , Hardy John , Marina Olga A.
Published: December 2022

A simple, fast, and economical alcohol penetration method for assessing the solid oxide cell to metal window frame seal in a typical planar design is presented. An alcohol such as ethanol or isopropanol is placed into the cavity of a cell sealed to the window frame. Within 3–5 min, one can determine if the glass seal is hermetic by visual observation along the seal edges on the side of the sealed frame. Cross bubbling and open circuit voltage methods for determining whether the seal failed or cracked at high temperature after final stack firing are also discussed.
Modelling crop production, river low flow, and sediment load trade-offs under agroforestry land-use scenarios in Nyangores catchment, Kenya
Authors: Kamamia Ann W. , Strauch Michael , Mwangi Hosea M. , Feger Karl-Heinz , Sang Joseph , Julich Stefan
Published: December 2022

The largest impact of land-use change on catchment hydrology can be linked to deforestation. This change, driven by exponential population growth, intensified food and industrial production, has resulted in alterations in river flow regimes such as high peaks, reduced base flows, and silt deposition. To reverse this trend more extensive management practices are becoming increasingly important, but can also lead to severe losses in agricultural production. Land-use optimization tools can help catchment managers to explore numerous land-use configurations for the evaluation of trade-offs amongst various uses. In this study, the Soil and water assessment tool (SWAT) model was coupled with a genetic algorithm to identify land-use/management configurations with minimal trade-offs between environmental objectives (reduced sediment load, increased stream low flow) and the crop yields of maize and soybean in Nyangores catchment (Kenya). During the land-use optimization, areas under conventional agriculture could either remain as they are or change to agroforestry or conservation agriculture (CA), where the latter was represented by introducing contour farming and vegetative filter strips. From the sets of the resulting Pareto-optimal solutions we selected mid-range solutions, representing a fair compromise among all objectives, for further analysis. We found that a combined measure implementation strategy (agroforestry on certain sites and conservation agriculture on other sites within the catchment) proved to be superior over single measure implementation strategies. On the catchment scale, a 3.6% change to forests combined with a 35% change to CA resulted in highly reduced sediment loads (−78%), increased low flow (+14%) and only slightly decreased crop yields (<4%). There was a tendency of the genetic algorithm to implement more extensive management practices in the upper part of the catchment while leaving conventional agriculture in the lower part. Our study shows that a spatially targeted implementation strategy for different conservation management practices can remarkably improve environmental sustainability with only marginal trade-offs in crop production at the catchment-level. Incentive policies such as payments for ecosystem services (PES), considering upstream and downstream stakeholders, could offer a practical way to effect these changes.
Pathological complete response after neoadjuvant immunotherapy combined with chemotherapy in pediatric rectal carcinoma: A case report
Authors: Cao Xiaomeng , Luo Jianwei , Zhao Baoyin , Fu Hongjiang , Kang Wendi
Published: December 2022

Background

Pediatric colorectal carcinoma (PCRC) is a rare non-embryonal tumor with an incidence of 0.1% to 1% of adults. Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) have shown significant efficacy in defective mismatch repair/Microsatellite instability-high (dMMR/MSI-H) metastatic CRC (mCRC). Although several studies have reported neoadjuvant immunotherapy (NIT) in MSI-H/dMMR non-mCRC patients, not all patients achieved pathological complete remission (pCR). There are differences between PCRC and adult colorectal carcinoma (CRC), and the role of NIT in PCRC remains to be further defined.

Case presentation

We report the case of a 12-year-old child who was admitted to the hospital with abdominal pain and vomiting for more than 3 months. The child’s diagnosis was difficult and complex. He was initially diagnosed with intestinal obstruction, eventually diagnosed with a rare PCRC and identified as locally advanced colorectal cancer (LACRC) with genetic sequencing results showing MSI-H. After a thorough evaluation by clinicians, he received 4 cycles of Camrelizumab (anti-PD-1 antibody) + CapeOx (capecitabine and oxaliplatin) NIT combination chemotherapy. Repeat imaging and all tumor markers were unremarkable, and R0 resection was achieved. Postoperative pathology showed a tumor regression grade (TRG) of 0 grade determined as pCR. Postoperative review has not shown any recurrence or metastasis to date and the prognosis is good.

Conclusion

PCRC should improve the diagnostic efficiency to prevent misdiagnosis and miss the best time for treatment. NIT and or chemotherapy can be a reasonable and effective treatment option for dMMR/MSI-H locally advanced PCRC. Our report provides some support and evidence for neoadjuvant immunotherapy for locally advanced PCRC, while highlighting the importance of preoperative detection of microsatellite status for locally advanced PCRC.
A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis
Authors: Tricarico Paola Maura , Gratton Rossella , Santos-Silva Carlos André dos , Moura Ronald Rodrigues de , Ura Blendi , Sommella Eduardo , Campiglia Pietro , Del Vecchio Cecilia , Moltrasio Chiara , Berti Irene , D’Adamo Adamo Pio , Elsherbini Ahmed M. A. , Staudenmaier Lena , Chersi Karin , Boniotto Michele , Krismer Bernhard , Schittek Birgit , Crovella Sergio
Published: December 2022

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin’s physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach.
Fisherwomen’s Indigenous and local knowledge - the hidden gems for the management of marine and freshwater resources in Fiji
Authors: Kitolelei Salanieta , Breckwoldt Annette , Kitolelei Jokim , Makhoul Natalie
Published: December 2022

Fisherwomen in Fiji play a vital role in the daily sustenance of their families and they use their Indigenous and local knowledge to harvest resources. Marine and freshwater resources harvested by fisherwomen contribute to the primary protein intake of their families, particularly for those who have limited or no access to other animal products or plant proteins. Over a span of three decades, Fiji experienced an influx in the documentation of women’s contribution and need for fisherwomen's recognition in the fisheries sector; in areas of cultural and/or socio-economic, resource management and decision-making processes. This study examines the Indigenous and local knowledge which fisherwomen utilize to identify their targeted marine and freshwater resources and gauge the population health of their resources. Furthermore, fisherwomen’s perceptions on the conservation status of their resources is used to provide the basis for improved management of culturally, economically and ecologically valuable species. The results of this study compiles Indigenous taxonomic classifications and associated species knowledge which fisherwomen from 11 communities use to help them in identifying and capturing resources. Moreover, the fishing methods, ecological knowledge and perceptions on environmental changes over thirty years provides temporal background on the fisherwomen’s knowledge. The results address knowledge gap between fisherwomen's Indigenous and local knowledge and science by marrying the well-developed knowledge systems. Finally, this study provides recommendations on how the Indigenous and local knowledge of women can contribute to practical and efficient resource management for localized challenges in Fiji.
Mitigating shrinkage in ultra-high performance concrete using MgO expansion agents with different activity levels
Authors: Zhang Zhanqiang , Li Shunkai , Chen Ping , Liu Xiaoyan , Wang Jingyang
Published: December 2022

To mitigate the shrinkage properties of ultra-high performance concrete (UHPC), MgO expansion agents (MEAs) with different activity levels (R-MEA, M-MEA, and S-MEA) were prepared and incorporated into UHPC. The effect of MEA activity on the mechanical properties and volumetric stability of UHPC were evaluated by using hydration heat tests, XRD-Rietveld quantitative analysis, MIP, X-CT and SEM. The results showed that MEA addition reduces the mechanical properties of UHPC, especially at high activity levels. However, it is beneficial for compensating early shrinkage. By combining MIP and X-CT analyses, it was found that MEA effectively increases the porosity of UHPC, with R-MEA (with the strongest activity) increasing it most. The w/b ratio had a greater effect on MEA hydration than the activity level. At lower w/b ratios, R-MEA reduced autogenous shrinkage even less effectively than M-MEA. Considering both the mechanical properties and shrinkage-reducing effect, it is recommended to prepare shrinkage-reducing UHPC with a w/b ratio of 0.18 and moderately reactive M-MEA.
Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
Authors: Pavan Kumar Nathella , Venkataraman Aishwarya , Varadarjan Poovazhagi , Nancy Arul , Rajamanickam Anuradha , Selladurai Elilarasi , Sankaralingam Thangavelu , Thiruvengadam Kannan , Selvam Ramya , Thimmaiah Akshith , Natarajan Suresh , Ramaswamy Ganesh , Putlibai Sulochana , Sadasivam Kalaimaran , Sundaram Balasubramanian , Hissar Syed , Ranganathan Uma Devi , Nutman Thomas B. , Babu Subash
Published: December 2022

Introduction

Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases.

Methods

To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations).

Results

Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84–100% and specificity 80–100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels.

Discussion

Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation.
A study of the risk factors for phlebitis in patients stratified using the acute physiology and chronic health evaluation II score and admitted to the intensive care unit: A post hoc analysis of the AMOR-VENUS study
Authors: Kishihara Yuki , Yasuda Hideto , Moriya Takashi , Kashiura Masahiro , Koike Midori , Kotani Yuki , Kondo Natsuki , Sekine Kosuke , Shime Nobuaki , Morikane Keita , Abe Takayuki
Published: December 2022

Introduction

Peripheral intravascular catheters (PIVCs) are inserted in most patients admitted to the intensive care unit (ICU). Previous research has discussed various risk factors for phlebitis, which is one of the complications of PIVCs. However, previous studies have not investigated the risk factors based on the patient’s severity of illness, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Different treatments can be used based on the relationship of risk factors to the illness severity to avoid phlebitis. Therefore, in this study, we investigate whether the risk factors for phlebitis vary depending on the APACHE II score.

Materials and methods

This study was a post hoc analysis of the AMOR-VENUS study involving 23 ICUs in Japan. We included patients with age ≥ 18 years and consecutive admissions to the ICU with PIVCs inserted during ICU admission. The primary outcome was phlebitis, and the objective was the identification of the risk factors evaluated by hazard ratio (HR) and 95% confidence interval (CI). The cut-off value of the APACHE II score was set as ≤15 (group 1), 16–25 (group 2), and ≥26 (group 3). Multivariable marginal Cox regression analysis was performed for each group using the presumed risk factors.

Results

A total of 1,251 patients and 3,267 PIVCs were analyzed. Multivariable marginal Cox regression analysis reveals that there were statistically significant differences among the following variables evaluated HR (95%CI): (i) in group 1, standardized drug administration measures (HR, 0.4 [0.17–0.9]; p = 0.03) and nicardipine administration (HR, 2.25 [1.35–3.75]; p < 0.01); (ii) in group 2, insertion in the upper arm using the forearm as a reference (HR, 0.41 [0.2–0.83]; p = 0.01), specified polyurethane catheter using polyurethane as a reference (HR, 0.56 [0.34–0.92]; p = 0.02), nicardipine (HR, 1.9 [1.16–3.12]; p = 0.01), and noradrenaline administration (HR, 3.0 [1.52–5.88]; p < 0.01); (iii) in group 3, noradrenaline administration (HR, 3.39 [1.14–10.1]; p = 0.03).

Conclusion

We found that phlebitis risk factors varied according to illness severity. By considering these different risk factors, different treatments may be provided to avoid phlebitis based on the patient’s severity of illness.
Fiber manipulation and post-assembly nanobody conjugation for adenoviral vector retargeting through SpyTag-SpyCatcher protein ligation
Authors: Kadkhodazadeh Maryam , Mohajel Nasir , Behdani Mahdi , Baesi Kazem , Khodaei Behzad , Azadmanesh Kayhan , Arashkia Arash
Published: December 2022

For adenoviruses (Ads) to be optimally effective in cancer theranostics, they need to be retargeted toward target cells and lose their natural tropism. Typically, this is accomplished by either engineering fiber proteins and/or employing bispecific adapters, capable of bonding Ad fibers and tumor antigen receptors. This study aimed to present a simple and versatile method for generating Ad-based bionanoparticles specific to target cells, using the SpyTag-SpyCatcher system. The SpyTag peptide was inserted into the HI loop of fiber-knob protein, which could act as a covalent anchoring site for a targeting moiety fused to a truncated SpyCatcher (SpyCatcherΔ) pair. After confirming the presence and functionality of SpyTag on the Ad type-5 (Ad5) fiber knob, an adapter molecule, comprising of SpyCatcherΔ fused to an anti-vascular endothelial growth factor receptor 2 (VEGFR2) nanobody, was recombinantly expressed in Escherichia coli and purified before conjugation to fiber-modified Ad5 (fmAd5). After evaluating fmAd5 detargeting from its primary coxsackie and adenovirus receptor (CAR), the nanobody-decorated fmAd5 could be efficiently retargeted to VEGFR2-expressing 293/KDR and human umbilical vein endothelial (HUVEC) cell lines. In conclusion, a plug-and-play platform was described in this study for detargeting and retargeting Ad5 through the SpyTag-SpyCatcher system, which could be potentially applied to generate tailored bionanoparticles for a broad range of specific targets; therefore, it can be introduced as a promising approach in cancer nanotheranostics.
Heterogeneous nuclear ribonucleoprotein hnRNPA2/B1 regulates the abundance of the copper-transporter ATP7A in an isoform-dependent manner
Authors: McCann Courtney J. , Hasan Nesrin M. , Padilla-Benavides Teresita , Roy Shubhrajit , Lutsenko Svetlana
Published: December 2022

Copper (Cu) is an essential micronutrient with a critical role in mammalian growth and development. Imbalance of Cu causes severe diseases in humans; therefore, cellular Cu levels are tightly regulated. Major Cu-transport proteins and their cellular behavior have been characterized in detail, whereas their regulation at the mRNA level and associated factors are not well-understood. We show that the heterogeneous nuclear ribonucleoprotein hnRNPA2/B1 regulates Cu homeostasis by modulating the abundance of Cu(I)-transporter ATP7A. Downregulation of hnRNPA2/B1 in HeLa cells increases the ATP7A mRNA and protein levels and significantly decreases cellular Cu; this regulation involves the 3′ UTR of ATP7A transcript. Downregulation of B1 and B1b isoforms of hnRNPA2/B1 is sufficient to elevate ATP7A, whereas overexpression of either hnRNPA2 or hnRNPB1 isoforms decreases the ATP7A mRNA levels. Concurrent decrease in hnRNPA2/B1, increase in ATP7A, and a decrease in Cu levels was observed in neuroblastoma SH-SY5Y cells during retinoic acid-induced differentiation; this effect was reversed by overexpression of B1/B1b isoforms. We conclude that hnRNPA2/B1 is a new isoform-specific negative regulator of ATP7A abundance.
Comparison of ischemic stroke diagnosis models based on machine learning
Authors: Yang Wan-Xia , Wang Fang-Fang , Pan Yun-Yan , Xie Jian-Qin , Lu Ming-Hua , You Chong-Ge
Published: December 2022

Background

The incidence, prevalence, and mortality of ischemic stroke (IS) continue to rise, resulting in a serious global disease burden. The prediction models have a great value in the early prediction and diagnosis of IS.

Methods

The R software was used to screen the differentially expressed genes (DEGs) of IS and control samples in the datasets GSE16561, GSE58294, and GSE37587 and analyze DEGs for enrichment analysis. The feature genes of IS were obtained by several machine learning algorithms, including the least absolute shrinkage and selector operation (LASSO) logistic regression, the support vector machine-recursive feature elimination (SVM-RFE), and the Random Forest (RF). The IS diagnostic models were constructed based on transcriptomics by machine learning and artificial neural network (ANN).

Results

A total of 69 DEGs, mainly involved in immune and inflammatory responses, were identified. The pathways enriched in the IS group were complement and coagulation cascades, lysosome, PPAR signaling pathway, regulation of autophagy, and toll-like receptor signaling pathway. The feature genes selected by LASSO, SVM-RFE, and RF were 17, 10, and 12, respectively. The area under the curve (AUC) of the LASSO model in the training dataset, GSE22255, and GSE195442 was 0.969, 0.890, and 1.000. The AUC of the SVM-RFE model was 0.957, 0.805, and 1.000, respectively. The AUC of the RF model was 0.947, 0.935, and 1.000, respectively. The models have good sensitivity, specificity, and accuracy. The AUC of the LASSO+ANN, SVM-RFE+ANN, and RF+ANN models was 1.000, 0.995, and 0.997, respectively, in the training dataset. However, the AUC of LASSO+ANN, SVM-RFE+ANN, and RF+ANN models was 0.688, 0.605, and 0.619, respectively, in the GSE22255 dataset. The AUC of the LASSO+ANN and RF+ANN models was 0.740 and 0.630, respectively, in the GSE195442 dataset. In the training dataset, the sensitivity, specificity, and accuracy of the LASSO+ANN model were 1.000, 1.000, and 1.000, respectively; of the SVM-RFE+ANN model were 0.946, 0.982, and 0.964, respectively; and of the RF+ANN model were 0.964, 1.000, and 0.982, respectively. In the test datasets, the sensitivity was very satisfactory; however, the specificity and accuracy were not good.

Conclusion

The LASSO, SVM-RFE, and RF models have good prediction abilities. However, the ANN model is efficient at classifying positive samples and is unsuitable at classifying negative samples.
Safety and effectiveness of double microcatheter technique in the treatment of ruptured aneurysms of anterior cerebral circulation
Authors: Zhao Xintong , Zhang Zihuan , Liu Jiaqiang , Qin Feiyun , Hu Liying , Li Zhenbao
Published: December 2022

Objective

To evaluate the safety and effectiveness of the double microcatheter technique in the treatment of ruptured aneurysms of the anterior cerebral circulation.

Methods

Between 2012 and 2019, 113 patients with ruptured aneurysms of the anterior cerebral circulation were treated using the double microcatheter technique. Clinical records, angiographic results, and procedure-related complications were reviewed. Clinical and angiographic follow-up was performed.

Results

Complete occlusion, neck remnant, and partial occlusion were, respectively, recorded in 56.6, 38.9, and 4.4% of the total cases. For all patients, the incidence of intraoperative complications was 5.3% (6/113), and the overall rate of morbidity was 10.6% (12/113). Before discharge, three patients (2.7%) died. There was no procedure-related mortality. At discharge, favorable outcomes were observed in 79.6% (90/113) of the patients. High Hunt-Hess grades and receiving a craniotomy or external ventricular drainage were risk factors for clinical outcomes at discharge. Clinical follow-up was performed in 91 patients at a mean interval of 14.07 ± 11.68 months. At follow-up, favorable outcomes were observed in 92.3% (84/91) of the patients. Angiographic follow-up was performed in 66 patients at an average of 11.53 ± 11.13 months. The recurrence rate was 37.9%. Of these patients, 13 (19.7%) received retreatment.

Conclusion

The double microcatheter technique can be performed in ruptured aneurysms with high technical success and low morbidity/mortality. However, recurrence remains a problem, and patients should be followed up regularly.