bluuebunny/crossref_metadata_2025 huggingface dataset:
A strategy for Cas13 miniaturization based on the structure and AlphaFold
Authors: Zhao Feiyu , Zhang Tao , Sun Xiaodi , Zhang Xiyun , Chen Letong , Wang Hejun , Li Jinze , Fan Peng , Lai Liangxue , Sui Tingting , Li Zhanjun
Published: September 2023

The small size of the Cas nuclease fused with various effector domains enables a broad range of function. Although there are several ways of reducing the size of the Cas nuclease complex, no efficient or generalizable method has been demonstrated to achieve protein miniaturization. In this study, we establish an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturization and generate five compact variants of Cas13 with full RNA binding and cleavage activity comparable the wild-type enzymes based on a combination of IDC strategy and AlphaFold2. In addition, we construct an RNA base editor, mini-Vx, and a single AAV (adeno-associated virus) carrying a mini-RfxCas13d and crRNA expression cassette, which individually shows efficient conversion rate and RNA-knockdown activity. In summary, these findings highlight a feasible strategy for generating downsized CRISPR/Cas13 systems based on structure predicted by AlphaFold2, enabling targeted degradation of RNAs and RNA editing for basic research and therapeutic applications.
CD44 connects autophagy decline and ageing in the vascular endothelium
Authors: Zhang Lu , Yang Peichang , Chen Jingxuan , Chen Zhiqiang , Liu Zhihui , Feng Gaoqing , Sha Fangfang , Li Zirui , Xu Zaoyi , Huang Yating , Shi Xiaotong , Li Xuebiao , Cui Jiatian , Zhang Chenyi , Fan Pei , Cui Liuqing , Shen Yunpeng , Zhou Guangzhou , Jing Hongjuan , Ma Shiwei
Published: September 2023

The decline of endothelial autophagy is closely related to vascular senescence and disease, although the molecular mechanisms connecting these outcomes in vascular endothelial cells (VECs) remain unclear. Here, we identify a crucial role for CD44, a multifunctional adhesion molecule, in controlling autophagy and ageing in VECs. The CD44 intercellular domain (CD44ICD) negatively regulates autophagy by reducing PIK3R4 and PIK3C3 levels and disrupting STAT3-dependent PtdIns3K complexes. CD44 and its homologue clec-31 are increased in ageing vascular endothelium and Caenorhabditis elegans, respectively, suggesting that an age-dependent increase in CD44 induces autophagy decline and ageing phenotypes. Accordingly, CD44 knockdown ameliorates age-associated phenotypes in VECs. The endothelium-specific CD44ICD knock-in mouse is shorter-lived, with VECs exhibiting obvious premature ageing characteristics associated with decreased basal autophagy. Autophagy activation suppresses the premature ageing of human and mouse VECs overexpressing CD44ICD, function conserved in the CD44 homologue clec-31 in C. elegans. Our work describes a mechanism coordinated by CD44 function bridging autophagy decline and ageing.
Laser nanoprinting of 3D nonlinear holograms beyond 25000 pixels-per-inch for inter-wavelength-band information processing
Authors: Chen Pengcheng , Xu Xiaoyi , Wang Tianxin , Zhou Chao , Wei Dunzhao , Ma Jianan , Guo Junjie , Cui Xuejing , Cheng Xiaoyan , Xie Chenzhu , Zhang Shuang , Zhu Shining , Xiao Min , Zhang Yong
Published: September 2023

Nonlinear optics provides a means to bridge between different electromagnetic frequencies, enabling communication between visible, infrared, and terahertz bands through χ(2) and higher-order nonlinear optical processes. However, precisely modulating nonlinear optical waves in 3D space remains a significant challenge, severely limiting the ability to directly manipulate optical information across different wavelength bands. Here, we propose and experimentally demonstrate a three-dimensional (3D) χ(2)-super-pixel hologram with nanometer resolution in lithium niobate crystals, capable of performing advanced processing tasks. In our design, each pixel consists of properly arranged nanodomain structures capable of completely and dynamically manipulating the complex-amplitude of nonlinear waves. Fabricated by femtosecond laser writing, the nonlinear hologram features a pixel diameter of 500 nm and a pixel density of approximately 25000 pixels-per-inch (PPI), reaching far beyond the state of the art. In our experiments, we successfully demonstrate the novel functions of the hologram to process near-infrared (NIR) information at visible wavelengths, including dynamic 3D nonlinear holographic imaging and frequency-up-converted image recognition. Our scheme provides a promising nano-optic platform for high-capacity optical storage and multi-functional information processing across different wavelength ranges.
A comprehensive genomic catalog from global cold seeps
Authors: Han Yingchun , Zhang Chuwen , Zhao Zhuoming , Peng Yongyi , Liao Jing , Jiang Qiuyun , Liu Qing , Shao Zongze , Dong Xiyang
Published: September 2023

Cold seeps harbor abundant and diverse microbes with tremendous potential for biological applications and that have a significant influence on biogeochemical cycles. Although recent metagenomic studies have expanded our understanding of the community and function of seep microorganisms, knowledge of the diversity and genetic repertoire of global seep microbes is lacking. Here, we collected a compilation of 165 metagenomic datasets from 16 cold seep sites across the globe to construct a comprehensive gene and genome catalog. The non-redundant gene catalog comprised 147 million genes, and 36% of them could not be assigned to a function with the currently available databases. A total of 3,164 species-level representative metagenome-assembled genomes (MAGs) were obtained, most of which (94%) belonged to novel species. Of them, 81 ANME species were identified that cover all subclades except ANME-2d, and 23 syntrophic SRB species spanned the Seep-SRB1a, Seep-SRB1g, and Seep-SRB2 clades. The non-redundant gene and MAG catalog is a valuable resource that will aid in deepening our understanding of the functions of cold seep microbiomes.
Postharvest starch and sugars adjustment in potato tubers of wide-ranging dormancy genotypes subjected to various sprout forcing techniques
Authors: Haider Muhammad Wasim , Nafees Muhammad , Iqbal Rashid , Asad Habat Ullah , Azeem Farrukh , Ali Baber , Shaheen Ghazala , Iqbal Javed , Vyas Shweta , Arslan Muhammad , Rahman Muhammad Habib Ur , Elshikh Mohamed S. , Ali M. Ajmal
Published: September 2023

The development of an efficient, safe, and environment-friendly technique to terminate tuber dormancy in potatoes (Solanum tuberosum L.) is of great concern due to the immense scope of multiple cropping all over the globe. The breakage of tuber dormancy has been associated with numerous physiological changes, including a decline in the level of starch and an increase in the levels of sugars during storage of freshly harvested seed potatoes, although their consistency across genotypes and various dormancy-breaking techniques have not yet been fully elucidated. The purpose of the present research is to assess the efficacy of four different dormancy-breaking techniques, such as soaking in 90, 60, or 30 mg L−1 solutions of benzyl amino purine (BAP) and 30, 20, or 10 mg L−1 gibberellic acid (GA3) alone and in the combination of optimized concentrations; cold pre-treatment at 6, 4, or 2 °C; electric shock at 80, 60, 40, or 20 Vs; and irradiation at 3.5, 3, 2.5, 2, 1.5, or 1 kGy on the tuber dormancy period and sprout length of six genotypes. Furthermore, the changes that occurred in tuber weight and endogenous starch, sucrose, fructose, and glucose contents in experimental genotypes following the application of these techniques were also examined. Overall, the most effective technique to terminate tuber dormancy and hasten spout growth was the combined application of BAP and GA3, which reduced the length of dormancy by 9.6 days compared to the untreated control, following 6.7 days of electric current, 4.4 days of cold pre-treatment, and finally irradiation (3.3 days). The 60 mg L−1 solution of BAP greatly reduced the dormancy period in all genotypes but did not affect the sprout length at all. The genotypes showed a weak negative correlation (r =  − 0.4) (P < 0.05) of endogenous starch contents with dormancy breakage and weight loss or a moderate (r =  − 0.5) correlation with sprout length, but a strong positive correlation (r = 0.8) of tuber glucose, fructose, and sucrose contents with dormancy breakage and weight loss. During 3 weeks of storage, sprouting commencement and significant weight loss occurred as tuber dormancy advanced towards breakage due to a reduction in starch and an increase in the sucrose, fructose, and glucose contents of the tubers. These findings could be advantageous for postponing or accelerating seed potato storage as well as investigating related physiological research in the future.
Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K
Authors: Macyszyn Julia , Chyży Piotr , Burmistrz Michał , Lobka Małgorzata , Miszkiewicz Joanna , Wojciechowska Monika , Trylska Joanna
Published: September 2023

Given the widespread demand for novel antibacterial agents, we modified a cell-penetrating peptide (KFF)3K to transform it into an antibacterial peptide. Namely, we inserted a hydrocarbon staple into the (KFF)3K sequence to induce and stabilize its membrane-active secondary structure. The staples were introduced at two positions, (KFF)3K[5–9] and (KFF)3K[2–6], to retain the initial amphipathic character of the unstapled peptide. The stapled analogues are protease resistant contrary to (KFF)3K; 90% of the stapled (KFF)3K[5–9] peptide remained undigested after incubation in chymotrypsin solution. The stapled peptides showed antibacterial activity (with minimal inhibitory concentrations in the range of 2–16 µM) against various Gram-positive and Gram-negative strains, contrary to unmodified (KFF)3K, which had no antibacterial effect against any strain at concentrations up to 32 µM. Also, both stapled peptides adopted an α-helical structure in the buffer and micellar environment, contrary to a mostly undefined structure of the unstapled (KFF)3K in the buffer. We found that the antibacterial activity of (KFF)3K analogues is related to their disruptive effect on cell membranes and we showed that by stapling this cell-penetrating peptide, we can induce its antibacterial character.
Quantifying root colonization by a symbiotic fungus using automated image segmentation and machine learning approaches
Authors: Sciascia Ivan , Crosino Andrea , Genre Andrea
Published: September 2023

Arbuscular mycorrhizas (AM) are one of the most widespread symbiosis on earth. This plant-fungus interaction involves around 72% of plant species, including most crops. AM symbiosis improves plant nutrition and tolerance to biotic and abiotic stresses. The fungus, in turn, receives carbon compounds derived from the plant photosynthetic process, such as sugars and lipids. Most studies investigating AM and their applications in agriculture requires a precise quantification of the intensity of plant colonization. At present, the majority of researchers in the field base AM quantification analyses on manual visual methods, prone to operator errors and limited reproducibility. Here we propose a novel semi-automated approach to quantify AM fungal root colonization based on digital image analysis comparing three methods: (i) manual quantification (ii) image thresholding, (iii) machine learning. We recognize machine learning as a very promising tool for accelerating, simplifying and standardizing critical steps in analysing AM quantification, answering to an urgent need by the scientific community studying this symbiosis.
Effects of rainfall amount and frequencies on soil net nitrogen mineralization in Gahai wet meadow in the Qinghai-Tibetan Plateau
Authors: Xu Guorong , Li Guang , Wu Jiangqi , Ma Weiwei , Wang Haiyan , Yuan Jianyu , Li Xiaodan
Published: September 2023

Global climate change has led to a significant increase in the frequency of extreme rainfall events in the Qinghai-Tibetan Plateau (QTP), thus potentially increasing the annual rainfall amounts and, consequently, affecting the net soil nitrogen (N) mineralization process. However, few studies on the responses of the soil net N mineralization rates to the increases in rainfall amounts and frequencies in alpine wet meadows have been carried out. Therefore, the present study aims to assess the effects of rainfall frequency and amount changes on the N fixation capacity of wet meadow soils by varying the rainfall frequency and amount in the Gahai wet meadow in the northeastern margin of the QTP during the plant-growing season in 2019. The treatment scenarios consisted of ambient rain (CK) and supplementary irrigation at a rate of 25 mm, with different irrigation frequencies, namely weekly (DF1), biweekly (DF2), every three weeks (DF3), and every four weeks (DF4). According to the obtained results, the increased rainfall frequency and amount decreased the soil mineral N stock and increased the aboveground vegetation biomass (AB) amounts and soil water contents in the wet meadows of the QTP. Ammonium (NH4+-N) and nitrate N (NO3–-N) contributed similarly to the mineral N contents. However, the ammonification process played a major role in the soil mineralization process. The effects of increasing rainfall amount and frequency on N mineralization showed seasonal variations. The N mineralization rate showed a single-peaked curve with increasing soil temperature during the rapid vegetation growth phase, reaching the highest value in August. In addition, the N mineralization rates showed significant positive correlations with soil temperatures and NH4+-N contents and a significant negative correlation with AB (P < 0.05). The results of this study demonstrated the key role of low extreme rainfall event frequencies in increasing the net soil N mineralization rates in the vegetation growing season, which is detrimental to soil N accumulation, thereby affecting the effectiveness of soil N contents.
Leveraging the COVID-19 pandemic as a natural experiment to assess changes in antibiotic use and antibiotic-resistant E. coli carriage in semi-rural Ecuador
Authors: Amato Heather K. , Loayza Fernanda , Salinas Liseth , Paredes Diana , García Daniela , Sarzosa Soledad , Saraiva-Garcia Carlos , Johnson Timothy J. , Pickering Amy J. , Riley Lee W. , Trueba Gabriel , Graham Jay P.
Published: September 2023

The coronavirus 2019 (COVID-19) pandemic has had significant impacts on health systems, population dynamics, public health awareness, and antibiotic stewardship, which could affect antibiotic resistant bacteria (ARB) emergence and transmission. In this study, we aimed to compare knowledge, attitudes, and practices (KAP) of antibiotic use and ARB carriage in Ecuadorian communities before versus after the COVID-19 pandemic began. We leveraged data collected for a repeated measures observational study of third-generation cephalosporin-resistant E. coli (3GCR-EC) carriage among children in semi-rural communities in Quito, Ecuador between July 2018 and September 2021. We included 241 households that participated in surveys and child stool sample collection in 2019, before the pandemic, and in 2021, after the pandemic began. We estimated adjusted Prevalence Ratios (aPR) and 95% Confidence Intervals (CI) using logistic and Poisson regression models. Child antibiotic use in the last 3 months declined from 17% pre-pandemic to 5% in 2021 (aPR: 0.30; 95% CI 0.15, 0.61) and 3GCR-EC carriage among children declined from 40 to 23% (aPR: 0.48; 95% CI 0.32, 0.73). Multi-drug resistance declined from 86 to 70% (aPR: 0.32; 95% CI 0.13; 0.79), the average number of antibiotic resistance genes (ARGs) per 3GCR-EC isolate declined from 9.9 to 7.8 (aPR of 0.79; 95% CI 0.65, 0.96), and the diversity of ARGs was lower in 2021. In the context of Ecuador, where COVID-19 prevention and control measures were strictly enforced after its major cities experienced some of the world’s the highest mortality rates from SARS-CoV-2 infections, antibiotic use and ARB carriage declined in semi-rural communities of Quito from 2019 to 2021.
Topographic and climatic controls of peatland distribution on the Tibetan Plateau
Authors: Sun Jingjing , Gallego-Sala Angela , Yu Zicheng
Published: September 2023

The Tibetan Plateau (TP) hosts a variety of mountain peatlands that are sensitive to the amplified warming in this region. However, we still lack a basic understanding of environmental and climatic factors controlling peatland distribution in the region. Here we use a bioclimatic envelope model (PeatStash) and environmental analysis that utilise three peatland datasets—(a) the well-studied Zoige peatland complex, (b) a literature-based dataset of TP peatlands sites, and (c) an existing global peatland map (PEATMAP)—to investigate major drivers of peatland distribution in the TP. The Zoige peatland complex is defined by gentle slopes (< 2°), mean annual temperature at 0–2 °C, and soil moisture index > 1.7, much narrower thresholds than those stemming from PEATMAP. Using these narrower thresholds to predict future changes, we found that the Zoige peatland complex will shrink greatly under full-range future warming scenarios (both SSP1–2.6 and SSP5–8.5). Modelling peatland distribution in the entire TP remains challenging because accurate environmental and climate data at high resolution and a reliable peatland distribution map are still lacking. Improved peatland mapping supported by ground-truthing is necessary to understand drivers of peatland distribution, assess carbon storage and other ecosystem services, and predict the TP’s peatlands fate under climate change.
First identification of an evolving Middle Stone Age ochre culture at Porc-Epic Cave, Ethiopia
Authors: Rosso Daniela Eugenia , Regert Martine , d’Errico Francesco
Published: September 2023

The use of mineral pigments, in particular iron-rich rocks, holds significant importance in understanding the emergence and evolution of human cultures. However, sites that have yielded a number of pieces large enough to precisely identify how the use of this material changed through time are rare. In this study, we examine one of the largest known Middle Stone Age (MSA) ochre collections, from Porc-Epic Cave, Ethiopia, consisting of more than 40 kg of ochre (n = 4213 pieces), 21 ochre processing tools and two ochre-stained artefacts. By combining the analysis of the elemental and mineralogical composition of the archaeological material with that of natural ochre collected in the surroundings of the site, and correlating this information with shifts in ochre modification techniques over time, we unveil how MSA inhabitants of Porc-Epic Cave exploited mineral resources. We show that they could predict the properties of different ochre types accessible in their environment, and gradually adapted their technology to cope with changes in raw material availability. Furthermore, the analysis of ochre residues on a painted pebble, likely used to produce red dots on a surface, identifies an ochre type that was specifically employed for symbolic purposes.
Influence of child and adult faces with face masks on emotion perception and facial mimicry
Authors: Kastendieck Till , Dippel Nele , Asbrand Julia , Hess Ursula
Published: September 2023

Emotional mimicry, the imitation of others’ emotion expressions, is related to increased interpersonal closeness and better interaction quality. Yet, little research has focused on the effect of face masks on emotional mimicry and none on (masked) child faces. To address this gap, we conducted an online experiment (N = 235, German sample, adult perceivers). Masks reduced emotion recognition accuracy for all expressions, except in the case of anger in masked child faces, where perceived anger was even increased. Perceived interpersonal closeness was reduced for masked happy and sad faces. For both child and adult expressers, masks reduced facial mimicry of happy expressions, with no mask effects for sadness and anger expression. A stronger mask effect on facial happiness mimicry of child faces was mediated by the degree of emotion recognition accuracy. Smiles shown by masked children were not recognized well, likely due to the absence of wrinkles around the eyes in child faces. Independent of masks, sadness shown by children was mimicked even more strongly than when shown by adults. These results provide evidence for facial mimicry of child expressions by adult perceivers and show that the effects of face masks on emotion communication may vary when children wear them.
Cross-reactive MHC class I T cell epitopes may dictate heterologous immune responses between respiratory viruses and food allergens
Authors: Balz Kathrin , Kaushik Abhinav , Cemic Franz , Sampath Vanitha , Heger Vanessa , Renz Harald , Nadeau Kari , Skevaki Chrysanthi
Published: September 2023

Respiratory virus infections play a major role in asthma, while there is a close correlation between asthma and food allergy. We hypothesized that T cell-mediated heterologous immunity may induce asthma symptoms among sensitized individuals and used two independent in silico pipelines for the identification of cross-reactive virus- and food allergen- derived T cell epitopes, considering individual peptide sequence similarity, MHC binding affinity and immunogenicity. We assessed the proteomes of human rhinovirus (RV1b), respiratory syncytial virus (RSVA2) and influenza-strains contained in the seasonal quadrivalent influenza vaccine 2019/2020 (QIV 2019/2020), as well as SARS-CoV-2 for human HLA alleles, in addition to more than 200 most common food allergen protein sequences. All resulting allergen-derived peptide candidates were subjected to an elaborate scoring system considering multiple criteria, including clinical relevance. In both bioinformatics approaches, we found that shortlisted peptide pairs that are potentially binding to MHC class II molecules scored up to 10 × lower compared to MHC class I candidate epitopes. For MHC class I food allergen epitopes, several potentially cross-reactive peptides from shrimp, kiwi, apple, soybean and chicken were identified. The shortlisted set of peptide pairs may be implicated in heterologous immune responses and translated to peptide immunization strategies with immunomodulatory properties.
Aspacochioside C from Asparagus cochinchinensis attenuates eumelanin synthesis via inhibition of TRP2 expression
Authors: Yunmam Silvia , Lee Hae Ran , Hong Seong Min , Kim Ji-Young , Kang Tong Ho , Lee Ai Young , Jang Dae Sik , Kim Sun Yeou
Published: September 2023

Aspacochioside C (ACC) is a steroidal saponin isolated from Asparagus cochinchinensis. Steroidal saponins, such as pseudoprotodioscin and dioscin, are known to inhibit melanogenesis, but the role of ACC in melanogenesis remains unknown. Due to the toxic effect of the commonly used skin whitening agents like arbutin, kojic acid and α-lipoic acid alternative plant products are recentlybeen studied for their anti-hypergmentation effect. This study explores the role of ACC in melanogenesis in both in vivo and in vitro models. Here, we for the first time demonstrate that ACC attenuated α-MSH- and UVB-induced eumelanin production by inhibiting tyrosinase-related protein (TRP)-2 protein expression in both murine B16F10 and human melanoma MNT1 cells. However, ACC had no significant effect on pheomelanin concentration. ACC also decreased the pigmentation density in zebrafish embryos, which indicates that ACC targets TRP2 and inhibits eumelanin synthesis. Our results demonstrate that ACC inhibits TRP2, thereby attenuating eumelanin synthesis both in in vitro and in vivo zebrafish model. Therefore, ACC can potentially be used as an anti-melanogenic agent for both aesthetic and pharmaceutical purposes.
A permutation-based approach using a rank-based statistic to identify sex differences in epigenetics
Authors: Sommer Alice J. , Okonkwo Jude , Monteiro Jonathan , Bind Marie-Abèle C.
Published: September 2023

Epigenetic sex differences and their resulting implications for human health have been studied for about a decade. The objective of this paper is to use permutation-based inference and a new ranked-based test statistic to identify sex-based epigenetic differences in the human DNA methylome. In particular, we examine whether we could identify separations between the female and male distributions of DNA methylation across hundred of thousands CpG sites in two independent cohorts, the Swedish Adoption Twin study and the Lamarck study. Based on Fisherian p-values, we set a threshold for methylation differences “worth further scrutiny”. At this threshold, we were able to confirm previously-found CpG sites that stratify with respect to sex. These CpG sites with sex differences in DNA methylation should be further investigated for their possible contribution to various physiological and pathological functions in the human body. We followed-up our statistical analyses with a literature review in order to inform the proposed disease implications for the loci we uncovered.
Numerical correlation between non-visual metrics and brightness metrics—implications for the evaluation of indoor white lighting systems in the photopic range
Authors: Khanh Tran Quoc , Vinh Trinh Quang , Bodrogi Peter
Published: September 2023

From the beginning of the $$21\textrm{st}$$

21
st

century until today, the demand for lighting systems includes not only visual parameters (brightness, contrast perception, color quality), but also non-visual parameters. It is necessary to define the new non-visual parameters for the realization of the new concept of Human Centric Lighting (HCL) or Integrative Lighting. As a contribution to this approach, many international research groups have tried to quantify the non-visual parameters such as Circadian Stimulus by Rea et. al. in USA ($$CS_{2018}$$

C

S
2018

, $$CS_{2021}$$

C

S
2021

), Melanopic Equivalent Daylight ($$D_{65}$$

D
65

) illuminance, mEDI of the CIE S 026/E:2018 or the latest formula by Giménez et al., for the nocturnal melatonin suppression. Therefore, it is necessary to analyze the correlation between these non-visual metrics and brightness metrics such as the equivalent luminance of Fotios et al., or the latest brightness model of TU Darmstadt so that scientists, lighting engineers and lighting system users can correctly apply them in their work. In this context, this paper attempts to investigate and analyze these correlations between the three metric groups based on the database of 884 light sources of different light source technologies and daylight spectra. The obtained results show that the latest Circadian Stimulus model of Rea et. al. $$CS_{2021}$$

C

S
2021

with the improvement of Circadian Light $$CL_{A,2021}$$

C

L

A
,
2021

($$CL_{A\,2.0}$$

C

L

A

2.0

) has solved the disadvantage of $$CS_{2018}$$

C

S
2018

, especially for the interrupted point between warm and cold white (about $$3710\,K$$

3710

K

) or the junction between negative and positive signal of the opponent channel ($$B -(L+M)$$

B
-
(
L
+
M
)

). Moreover, these three metrics of the three research groups contain a high correlation coefficient, so that one metric can be transformed by linear functions to the other two parameters.
Thousands of domestic and public supply wells face failure despite groundwater sustainability reform in California’s Central Valley
Authors: Bostic Darcy , Mendez-Barrientos Linda , Pauloo Rich , Dobbin Kristin , MacClements Victoria
Published: September 2023

Across the world, declining groundwater levels cause wells to run dry, increase water and food insecurity, and often acutely impact groundwater-dependent communities. Despite the ubiquity and severity of these impacts, groundwater research has primarily focused on economic policy instruments for sustainable management or the quantification of groundwater depletion, rather than assessing the impacts of management decisions. In particular, how definitions of groundwater sustainability shape the fate of resource users remains unexplored. Here, we examine one of the world’s largest-scale environmental sustainability reforms, the California Sustainable Groundwater Management Act (SGMA), and estimate the impact of sustainability definitions proposed in groundwater sustainability plans (GSPs) on well failure. We show that locally-proposed sustainability criteria are consistent with business as usual groundwater level decline, and if reached, could impact over 9000 domestic wells and around 1000 public supply wells. These findings highlight the necessity of careful and critical evaluation of locally-developed sustainability definitions and their implementation to prevent detrimental impacts, such as threats to household and municipal water supply.
Features and outcomes of rectal cancer patients treated in a hospital in Bogotá, Colombia: a retrospective cohort study
Authors: Romo Julián Andres , Figueroa Avendaño Carlos Edgar , López Laura A. , Mesa Natalia , González-Muñoz Alejandro , Baquero David , Recamán Andrea , Rabeya Fernando , Villabon Alejandro , Sánchez Isabella Velandia , Flechas Álvaro
Published: September 2023

Rectal cancer is an increasing disease worldwide. The outcomes of its treatment are related to the preoperative characteristics of the patient. The objective of this study was to describe sociodemographic, clinical and surgical characteristics and outcomes of patients operated on for rectal cancer at Hospital Universitario Mayor Méderi (HUM) during the period within 2013–2017.A retrospective descriptive cohort-type study was carried out by consulting the clinical records of patients above the age of 18 years with a clinical/histopathological diagnosis of rectal cancer and an institutional follow-up in those who underwent surgery with laparoscopic anterior resection of the rectum carried out by the coloproctology service of the HUM between 2013 and 2017. For statistical analysis, the SPSS V22 program was used.Data from 133 patients were collected during the study period, most of them male, with more frequent involvement of the lower rectum. Complications occurred in 25% of the patients. Conversion rate to open surgery was 8.6%, in-hospital death was associated with cardiovascular comorbidity, corticosteroid uses and with the presence of complications. Sociodemographic characteristics of the patients were similar to the world population. The institution has a low prevalence of anastomotic dehiscence, global complications are comparable with international statistics.
Angiogenic and inflammatory responses in human induced microglia-like (iMG) cells from patients with Moyamoya disease
Authors: Shirozu Noritoshi , Ohgidani Masahiro , Hata Nobuhiro , Tanaka Shunya , Inamine Shogo , Sagata Noriaki , Kimura Tetsuaki , Inoue Ituro , Arimura Koichi , Nakamizo Akira , Nishimura Ataru , Maehara Naoki , Takagishi Soh , Iwaki Katsuma , Nakao Tomohiro , Masuda Keiji , Sakai Yasunari , Mizoguchi Masahiro , Yoshimoto Koji , Kato Takahiro A.
Published: September 2023

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9, VEGFA, and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.
Clinical outcomes in neovascular age-related macular degeneration: a cohort study of patients with care delay due to the COVID-19 pandemic
Authors: Janetos Timothy M. , Zandi Roya , Younessi David , Johnson Gina , Randolph Amber , Gill Manjot
Published: September 2023

The COVID-19 pandemic has led to both intentional and unintentional care delay among age-related neovascular macular degeneration (nvAMD) patients. Prior studies have demonstrated that patients who discontinue nvAMD treatment for prolonged intervals are at high risk for vision loss, but less is known regarding shorter-term delay, such as during the height of the pandemic. Previous studies have looked at COVID-19 related delay in care and have shown a loss of visual acuity (VA) among these patients, but studies are limited by short follow-up or insufficient comparisons. This was an observational cohort study of nvAMD patients from March 1, 2019, through July 1, 2021, who experienced care delay. VA was modeled using a linear longitudinal mixed-effects model comparing historic data pre-lockdown to data post-lockdown. Covariates included baseline anatomic variables, demographic variables, and time intervals (treatment interval, delay interval). Secondary anatomic and treatment outcomes were modeled using a multilevel binary logistic regression model. 163 eyes among 116 patients were included. Initial longitudinal mixed-effects models found that although overall VA decreased at a yearly rate, when comparing pre-lockdown and post-lockdown time periods, VA slopes were not statistically different. Single-covariate longitudinal models showed that age, sex, and delay interval significantly affected VA slope. The multivariate longitudinal model found that a longer delay interval significantly decreased rate of VA loss. Multilevel binary logistic regression models showed a significant increase in odds of anti-VEGF treatment, presence of subretinal fluid, and macular hemorrhages in the post-lockdown period. Overall, when compared to historic data, rate of VA loss among our cohort did not vary significantly in pre-versus post-lockdown time periods, although treatment and anatomic variables did worsen post-lockdown suggesting that patients may be appropriately delayed but this comes at the risk of increased need for treatment.
Improved mechanical performance of quasi-cubic lattice metamaterials with asymmetric joints
Authors: Solyaev Yury O. , Ustenko Anastasia D. , Babaytsev Arseniy V. , Dobryanskiy Vasiliy N.
Published: September 2023

In this paper, we propose a simple method for the modification of the unit cells in the lattice metamaterials that provides an improvement of their impact strength. The idea is based on the introduction of small mutual offsets of the interconnected struts inside the unit cells. In such way, the joints between the struts become asymmetric and the overall geometry of the unit cells can be defined as the quasi-cubic with the axis of chirality. Considering four types of cubic lattices with BCC, BCT, FCC and octahedron structures, we modified their geometry and investigated the influence of the offsets and the unit cell size on the overall performance in static and dynamic tests. From the experiments we found that the small offsets (less than the strut diameter) can allow to increase the impact strength of 3d-printed polymeric specimens in 1.5–3 times remaining almost the same density and static mechanical properties. Based on the numerical simulations, we show that the explanation of the observed phenomena can be related to the increase of plastic deformations and damage accumulation in the unit-cells with asymmetric joints leading to the transition from the quasi-brittle to the ductile type of fracture in tested specimens.
Biomarker-based validation of a food frequency questionnaire for the assessment of omega-3 fatty acid status in a healthy Iranian population
Authors: Abedimanesh Nasim , Motlagh Behrooz , Hejazi Jalal , Eskandari Mohammad Reza , Asghari-Jafarabadi Mohammad , Mazloomzadeh Saeideh
Published: September 2023

There is no valid instrument to assess n-3 polyunsaturated fatty acids (n-3 PUFAs) intake in Iran. This study aims to develop a food frequency questionnaire (FFQ) that estimates the intake of n-3 PUFA and validate it in a healthy Iranian population based on the n-3 PUFA content of red blood cells (RBCs) and a 3-day food record (FR). A healthy population (n = 221) was recruited between February and July 2021. Participants completed the new FFQ and 3-day FR to evaluate the average intake of n-3 PUFAs. We used gas chromatography to assess the n-3 PUFA content of RBCs. To validate the FFQ based on FR and biomarker as references, the correlation coefficient was calculated. According to the Bland–Altman plots, a good agreement was found between the new FFQ and FR. Moreover, absolute intake values of ALA, EPA, DPA, DHA, and total n-3 PUFAs based on FFQ were positively correlated to their respective RBC membrane levels (coefficients between 0.205 and 0.508, p < 0.005) and FR (coefficients between 0.771 and 0.827, p < 0.001). This new FFQ is a valid instrument that can be applied to estimate the n-3 PUFA status of healthy Iranian adults.
Development and validation of a clinical score for early diagnosis of constipation in critically ill children
Authors: López J. , Sánchez C. , Fernández S. N. , González R. , Solana M. J. , Urbano J. , López-Herce J.
Published: September 2023

Constipation affects almost 50% of critically ill pediatric patients and is related to their morbidity and mortality. However, little attention is paid to it and it is diagnosed late and when there are already complications. The objective of this study is to develop and validate a score to identify critically ill children with high risk of constipation 48 h after admission. A single center two phase-study was carried out; the first one (retrospective observational study) to develop the score and the second one to validate it in another prospective observational study. Children between 15 days of life and 18 years old admitted to the PICU for more than 3 days were included. Demographic and clinical data during the first 48 h after PICU admission were collected. Univariate and multivariate analysis and ROC curves were used to develop and validate the score. Data from 145 patients (62.8% boys) with a mean age of 34.9 ± 7.3 months were used to develop the score. Independent factors identified to develop the score were: weight > 7 kg, admission to PICU after surgery, need of vasoconstrictors, doses of fentanyl ≥ 2 mcg/kg/h, and initiation of enteral nutrition later than 48 h after admission. Two cut-off values were identified to set low constipation risk (< 5.7 points) and high constipation risk (> 6.2 points). This score was validated in 124 patients showing a sensibility of 63.2%, specificity of 95.5% and a positive/negative predictive values (P/NPV) of 100% and 82.1% respectively to identify constipated patients. This is the first score to identify high constipation risk in critically ill children. This score is easy to apply, and internal validation has shown a PPV of 100%.
Testosterone identifies hatchling sex for Mojave desert tortoises (Gopherus agassizii)
Authors: Walden M. A. , Loope Kevin J. , Hunter Elizabeth A. , Divers Stephen J. , Comolli Jessica R. , Esque Todd C. , Shoemaker Kevin T.
Published: September 2023

The threatened Mojave desert tortoise (Gopherus agassizii) exhibits temperature-dependent sex determination, and individuals appear externally sexually monomorphic until sexual maturity. A non-surgical sex identification method that is suitable for a single in situ encounter with hatchlings is essential for minimizing handling of wild animals. We tested (1) whether plasma testosterone quantified by enzyme-linked immunosorbent assay differentiated males from females in 0–3 month old captive hatchlings, and (2) whether an injection of follicle-stimulating hormone (FSH) differentially elevates testosterone in male hatchlings to aid in identifying sex. We validated sex by ceolioscopic (laparoscopic) surgery. We then fit the testosterone concentrations to lognormal distributions and identified the concentration below which individuals are more likely female, and above which individuals are more likely male. Using a parametric bootstrapping procedure, we estimated a 0.01–0.04% misidentification rate for naïve testosterone samples, and a 1.26–1.39% misidentification rate for challenged (post-FSH injection) testosterone samples. Quantification of plasma testosterone concentration from small volume (0.1 mL) blood samples appears to be a viable, highly accurate method to identify sex of 0–3 month old hatchlings and could be a valuable tool for conservation measures and investigation of trends and variation in sex ratios for in situ wild nests.
Numerical simulation analysis of carbon defects in the buffer on vertical leakage and breakdown of GaN on silicon epitaxial layers
Authors: Cao Weicheng , Song Chunyan , Liao Hui , Yang Ningxuan , Wang Rui , Tang Guanghui , Ji Hongyu
Published: September 2023

Carbon doping in GaN-on-Silicon (Si) epitaxial layers is an essential way to reduce leakage current and improve breakdown voltage. However, complicated occupy forms caused by carbon lead to hard analysis leakage/breakdown mechanisms of GaN-on-Si epitaxial layers. In this paper, we demonstrate the space charge distribution and intensity in GaN-on-Si epitaxial layers from 0 to 448 V by simulation. Depending on further monitoring of the trapped charge density of CN and CGa in carbon-doped GaN at 0.1 μm, 0.2 μm, 1.8 μm and 1.9 μm from unintentionally doped GaN/carbon-doped GaN interface, we discuss the relationship between space charge and plateau, breakdown at CN concentrations from 6 × 1016 cm−3 to 6 × 1018 cm−3. The results show that CN in different positions of carbon-doped GaN exhibits significantly different capture and release behaviors. By utilizing the capture and release behavior differences of CN at different positions in carbon-doped GaN, the blocking effect of space charge at unintentionally doped GaN/carbon-doped GaN interface on electron conduction was demonstrated. The study would help to understand the behavior of CN and CGa in GaN-on-Si epitaxial layers and more accurate control of CN and CGa concentration at different positions in carbon-doped GaN to improve GaN-on-Si device performance.
Effect of loading rate and source of energy on the drying parameters of the basil during drying
Authors: Khater El-Sayed G. , Bahnasawy Adel H. , Abbas Wael , Morsy Osama M.
Published: September 2023

The basil leaves were dried different sources of energy at different loading rates. Using hybrid solar drying compared to the conventional source of energy such as fossil and propane. Drying parameters were studied. Also, product quality was assessed under study treatments. The results indicated that the higher accumulated weight loss of basil leaves (75.56%) were obtained at 25 kg m−2 loading rate and solar drying system. The highest rate of the decrease in moisture content of basil leaves was happened at the 45 kg m−2 loading rates. Meanwhile, the lowest rate of the decrease in moisture content of basil leaves was found at 15 kg m−2 loading rates. The highest drying rate of basil leaves (219.54 gwater kg−1 h−1) was obtained at the loading rate of 15 kg m−2. The highest values of total chlorophyll and color of basil leaves 745.9 and 36.35 were found for solar dryer. The lowest values of total chlorophyll and color of basil leaves 703.5 and 31.66 were found for diesel dryer. The drying efficiency ranged from 33.98 to 40.33% for all batch loads. The highest essential oil yield obtained for solar dryer, the lowest essential oil yield occurred for diesel dryer. The highest value of volatile compounds with found for solar dryer. The total costs for basil drying were 19.73, 26.70 and 23.93 LE h−1 for solar, diesel and propane dryers, respectively. Also, the total costs of basil drying were 8.77, 13.15 and 12.27 LE kg−1 dried for solar, diesel and propane dryers, respectively.
Real-world analysis of survival benefit of surgery and adjuvant therapy in elderly patients with colorectal cancer
Authors: Zhang Lei , Li Qixin , Hu Chenhao , Zhang Zhe , She Junjun , Shi Feiyu
Published: September 2023

Treatment guidelines for colorectal cancer (CRC) in elderly patients remain unclear. This study aimed to investigate whether elderly patients (≥ 70 years) with CRC benefit from surgery and adjuvant therapy. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into a surgery group and a no-surgery group. After being matched by propensity score matching at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan‒Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were utilized to confirm independent prognostic factors for OS and CSS. In age-stratified analysis (70–74; 75–79; 80–84; ≥ 85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Adjuvant therapy was an independent prognostic factor for OS and CSS in elderly patients with CRC (all P < 0.001). Further analysis showed that elderly colon cancer patients with stage III and stage IV disease gained a survival benefit from adjuvant chemotherapy. Adjuvant chemoradiotherapy can significantly improve OS and CSS in elderly rectal cancer patients with stage II, III, and IV disease. In conclusion, among CRC patients aged ≥ 70 years reported in the SEER database, treatment with surgical resection is significantly associated with improved OS and CSS. Moreover, adjuvant therapy led to a significant prognostic advantage for elderly advanced CRC patients who underwent surgery.
Evaluating of neonatal early onset sepsis through lactate and base excess monitoring
Authors: Yilmaz Aslan , Kaya Nesrin , Gonen Ilker , Uygur Abdulkerim , Perk Yildiz , Vural Mehmet
Published: September 2023

Early-onset sepsis (EOS) is one of the leading causes of neonatal death and morbidity worldwide and timely initiation of antibiotic therapy is, therefore, of paramount importance. This study aimed to evaluate the predictive effect of lactate and base excess (BE) values in the cord arterial blood gas and the 6th hour of life venous blood gas analysis on clinical sepsis in newborns. This is a cohort case–control study. In this study, 104 cases were divided into clinical and suspected sepsis groups according to the evaluation at the 24th hour after delivery. Lactate and BE values were evaluated in the cord arterial blood gas analysis (ABGA) and at the postnatal 6th-hour venous blood gas. The cord ABGA and postnatal 6th-hour results were compared in the clinical and suspected sepsis groups. Clinical sepsis was found to be associated with a lactate value above 2 mMol/L at postnatal 6th-hour venous blood gas (p = 0.041). This association was the highest when the clinical sepsis group's postnatal 6th-hour lactate cut-off value was determined as 3.38 mMol/L (sensitivity 57.9% and specificity 68.5%) (p = 0.032). However, no association was found between clinical sepsis diagnosis and venous BE's value in cord ABGA at the postnatal 6th hour. We found that a venous lactate value above 3.38 mMol/L at the postnatal 6th hour was the cut-off value that could indicate early-onset clinical sepsis. However, none of the biomarkers used in diagnosing EOS can accurately show all cases.