bluuebunny/crossref_metadata_2025_split huggingface dataset:
PAMless SpRY recognizes a non-PAM region for efficient targeting
Authors: Xue Chaoyou , Yang Chen , Zhou Zhiwei , Sun Xuanlong , Ju Haiyan , Yue Xinmin , Rao Shuquan 
Published: July 2023

Abstract
Protospacer-adjacent motif (PAM) recognition licenses Cas nucleases for genome engineering applications, thereby restricting gene targets to regions containing PAMs. To overcome the PAM constraint, studies have applied protein engineering and successfully acquired PAM-relaxed SpCas9 variants, such as SpG (NGN PAMs) and SpRY (NRN>NYN PAMs). Given the evolved role of PAMs in facilitating target searching kinetics, it remains unclear how SpG and SpRY are able to quickly find their targets for cleavage after PAM relaxation. Here we combined experiments, simulations and theoretical analyses to investigate how SpG and SpRY search for their targets. Our results show that SpG and SpRY are spacer-dependent PAM-relaxed variants. To compensate for the relaxed PAM recognition, SpG and SpRY have been engineered to recognize position 1 or 1 to 3 of the target sequence through R61 and R1322, respectively. Moreover, our results demonstrate a significant decrease in target search kinetics for SpCas9 PAMless variants when PAM recognition is absent, with a slowdown of 3-4 orders of magnitude compared to wild-type SpCas9. This highlights the importance of considering Cas9 target searching kinetics in the successful engineering of PAMless SpCas9 variants. Overall, our results provide valuable insights for further PAMless Cas9 protein engineering efforts.
Nutritional counselling and risk factors for obesity: an observational study in toddlers.
Authors: Limauro Raffaele , Cioffi Luigi , Bianco Vincenzo , Caruso Vincenzo , Casani Antonella , Gaizo Donatella Del , Esposito Aldo , Farris Evelina , Gallo Patrizia , Giuliano Maria , Iannone Agnese , Izzo Annamaria , Vecchia Maria Teresa La , Raineri Luca , Sabetti Patrizia , Sassi Roberto , Servodidio Carmela , Sorice Nunziatina , Cioffi Valentina , Antignani Angelo , Valerio Giuliana 
Published: July 2023

Abstract

Background
Nutrition exerts a fundamental role in the prevention of pediatric obesity (OB). The effect of a strict nutritional counselling on the prevalence of overweight (OW) or OB according to the association with potential risk factors has never been explored in toddlers.
Methods
The eligible population was represented by 676 toddlers aged 24–36 months, assigned to 18 primary care pediatricians specifically trained on nutritional issues in the Campania region. Six-hundred-twenty-nine children (333 boys, 296 girls), mean age 27.8 ± 4.2 months were effectively included in this observational study. Specifically, children received nutritional advice with particular emphasis to proteins and sugar composition supported by leaflets and reinforced at each visit. Weight, height and body mass index were assessed at the last control visit, at the age of 24–36 months. The following individual and family risk factors were considered: gestational age, birth weight, eutocic/caesarean delivery, milk feeding history, household smoking or antibiotics exposure, parents’ weight, height and educational level.
Results
Twenty-two% children were classified as OW and 6% as OB. High birth weight, parental OW/OB, and caesarean delivery were significant risk factors for OW/OB. In adjusted models, cesarean versus vaginal delivery was independently associated with a more than 70% risk of OW/OB, while paternal OW/OB vs normal-weight was associated with a nearly twofold increase of OW/OB in toddlers.
Conclusions
The high prevalence of OW/OB in toddlers underlines that a strict nutritional counseling should be implemented in a primary care setting. Toddlers with high parental BMI or born by cesarean delivery represent a category at particular risk for OW/OB, and may require a more intensive surveillance.
The Impact of the Agency Model on E-book Prices: Evidence from the UK
Authors: Gail Maximilian Maurice , Klotz Phil-Adrian 
Published: July 2023

Abstract
This paper empirically analyzes the effect of the widely used agency model on retail prices of e-books sold in the United Kingdom. Using an unique cross-sectional dataset of e-book prices for a large number of book titles across all major publishing houses, we exploit cross-genre and cross-publisher variation to identify the effect of the agency model on e-book prices. Since the genre information is ambiguous and even missing for some titles in our original dataset, we also apply a Latent Dirichlet Allocation (LDA) approach to determine detailed book genres based on the book's descriptions. Using a matching procedure, we find that retail prices for e-books sold under the agency model are approximately 18% cheaper than book titles sold under the wholesale model. Our results are robust to different regression specifications and double machine learning techniques.
JEL: D12, D22, L42, L81, L82, Z11
Rab11a in the Spinal Cord: An Essential Contributor to Complete Freund's Adjuvant-Induced Inflammatory Pain in Mice
Authors: Gu Jun-Xiang , Wang Jian , Ma Fu-Juan , Liu Miao-Miao , Chen Si-Hai , Wei Yi , Xiao Yi-Fan , Lv Pei-Yuan , Liu Xin , Qu Jian-Qiang , Yan Xian-Xia , Chen Tao 
Published: July 2023

Abstract
Inflammatory pain is a commonly observed clinical symptom in a range of acute and chronic diseases. However, the mechanism of inflammatory pain is far from clear yet. Rab11a, a small molecule guanosine triphosphate enzyme, is reported to regulate orofacial inflammatory pain in our previous works. However, the mechanism of Rab11a’s involvement in the regulation of inflammatory pain remains obscure. Here, we aim to elucidate the potential mechanisms through which Rab11a contributes to the development of inflammatory pain in the spinal level. It’s shown that neurons, rather than glial cells, were the primary cell type expressing Rab11a in the spinal dorsal horn (SDH). After intra-plantar injection of CFA, both the number of Fos/Rab11a-immunopositive neurons and the expression of Rab11a were increased. Administration of Rab11a-shRNA into the SDH resulted in significantly analgesic effect in mice with CFA injection. Application of Rab11a-shRNA also reduced the NMDA receptor-mediated excitatory post-synaptic current (EPSC) and the spike number of neurons in lamina II of the SDH in mice with CFA injection, without affecting the presynaptic glutamate release and the postsynaptic AMPA receptor-mediated EPSC. Our results thus suggest that the enhanced expression of neuronal Rab11a may be important for the process of inflammatory pain in mice with CFA injection, which is likely mediated by Rab11a’s potentiation of the competence of post-synaptic NMDAR and spiking of SDH neurons.
Gradient Porous Structures of Mycelium: A Quantitative Structure-Mechanical Property Analysis
Authors: Olivero Eric , Gawronska Elzbieta , Manimuda Praveena , Jivani Devyani , Chaggan Faemia Zullfikar , Corey Zachary , Almeida Thaicia Stona , Kaplan-Bie Jessica , McIntyre Gavin , Wodo Olga , Nalam Prathima C. 
Published: July 2023

Abstract
Gradient porous structures (GPS) are characterized by structural variations along a specific direction, leading to enhanced mechanical and functional properties compared to homogeneous structures. This study explores the potential of mycelium, the root part of a fungus, as a biomaterial for generating GPS. During the intentional growth of mycelium, the filamentous network undergoes structural changes as the hyphae grow away from the feed substrate. Through microstructural analysis of sections obtained from the mycelium tissue, systematic variations in fiber characteristics (such as fiber radii distribution, crosslink density, network density, segment length) and pore characteristics (including pore size, number, porosity) are observed. Furthermore, the mesoscale mechanical moduli of the mycelium networks exhibit a gradual variation in local elastic modulus, with a significant change of approximately 50% across a 1.2-inch-thick mycelium tissue. The structure-property analysis reveals a direct correlation between the local mechanical moduli and the network crosslink density of the mycelium. This study presents the potential of controlling growth conditions to generate mycelium-based GPS with desired functional properties. This approach, which is both sustainable and economically viable, expands the applications of mycelium-based GPS to include filtration membranes, bio-scaffolds, tissue regeneration platforms, and more.
Field and management factors can reduce potato early blight severity - An observational study on farms combined with field trials in southern Sweden
Authors: Stridh Linnea Johanna , Malm Gabriella , Lankinen Åsa , Liljeroth Erland 
Published: July 2023

Abstract
Background and aims
The necrotrophic fungal pathogen Alternaria solani is causing early blight and thereby yield reduction in the potato production. The pathogen is today mainly controlled by fungicide applications. The severity of early blight can vary largely among farms and fields. The aim of this study was to improve the understanding of what field and management parameters that are most important for early blight infection to create more farm specific fungicide treatment recommendations.
Methods
Over three seasons, 2019–2021, more than 50 field plots were observed at farms in southern Sweden. In each field a 24 m x 24 m plot was left untreated against early blight. However, late blight fungicides were applied. The disease rate was scored in the untreated plot and information about various soil/plant parameters and farmer’s management was collected from each field. In addition to the observational study, field trials were performed in 2021 and 2022, evaluating the effect of potassium fertilizer levels on severeness of infection.
Results
We found that the soil composition was of significant importance for the rate of infection, in particular the sand, clay, and potassium content. Low levels of leaf potassium increased the severity of early blight infection and this observation was confirmed in field trials where different levels of potassium fertilizer were applied.
Conclusion
With knowledge about field and management factors that influence disease field specific recommendations can be developed supporting an integrated pest management strategy for early blight to reduce and optimize the fungicide usage.
Classifying Workers for Mitigating Adversarial Attacks in Crowdsourcing
Authors: First Ayswarya R Kurup , Second G P Sajeev 
Published: July 2023

Abstract
Crowdsourcing is adopted as a fast and cost-effective system for human computation and acquiring data for training models in machine learning. Although crowdsourcing has broad applicability, it still has the following challenges. Normally, workers have access to crowdsourcing platforms with simple authentication mechanisms. As a result, malicious workers may get into the system and submit unreliable answers rendering the platform fraudulent. Moreover, when workers perform tasks, their lack of expertise and the difficulty of tasks affects the accuracy. Truth inference benefits the data quality and worker reliability. A truth inference algorithm estimates workers' trustworthiness and correctness of the answers from their responses. Besides, it helps in filtering out low-quality answers. However, due to adversarial attacks by malicious workers, ground truth inference algorithms perform poorly. This research considers how to defend against adversarial attacks on crowdsourcing platforms and improve the truth inference process. The proposed method estimates the trust and reliability scores of the workers and classifies them as normal and malicious workers. Based on this classification , tasks are assigned to the workers. Moreover, these predicted scores are used for inferring the correct answers, thereby improving the ground truth inference. Experiments consistently show that the proposed truth inference method is tolerant to adversarial attacks with competent accuracy.
Cord Blood TSH and Free T4 Correlation with Maternal and Neonatal Factors and Heel-Stick TSH For the Early Detection of Congenital Hypothyroidism: A Cross-sectional Study in Iran
Authors: Sadeghi Nahideh , Mousavi Safa , Mirmohammadkhani Majid , Rahmanian Mojgan 
Published: July 2023

Abstract
Background- Congenital hypothyroidism (CH) is the most frequent cause of mental retardation in children. Despite the success of the screening programs in detecting CH cases, high recalling rate and false positive results impose a burden to the health system worldwide. Although cord blood thyroid stimulating hormone (CBTSH) is an accepted screening tool for CH, data about it are sparse in Iran. Therefore, we aimed to evaluate the umbilical cord blood TSH and Free T4 and its relationship with maternal and neonatal factors, as well as heel-stick TSH.
Methods- This study included 120 mother-newborn pairs in Amir-Al-Momenin Hospital, Semnan, Iran from October 2021 to May 2022. The mean values of Free T4 and CBTSH were measured with respect to various maternal and neonatal factors. The heel-stick TSH on day 2-3 after birth were determined in all participants.
Results- The mean CBTSH concentration was significantly higher in preterm newborns and male sex than term newborns and females (P=0.039 and P<0.001, respectively). Newborns born via cesarean section had lower CBTSH levels than those born by vaginal deliveries (P=0.040). The CBTSH was also positively correlated with heel-stick TSH (P<0.001). The mean umbilical cord blood Free T4 was significantly higher in multigravida newborns than primigravida cases (P=0.023). There was no statistically significant relation between umbilical cord blood Free T4 and TSH and maternal age, preeclampsia, gestational diabetes, twin or singleton delivery, 1- and 5- minutes Apgar scores, birthweight, and cord gases (P>0.05). The optimal cut-off point of CBTSH for discrimination of suspicious cases to hypothyroidism was 14.75 mIU/L.
Conclusions- Method of delivery, gestational age, and male sex were influential variables on the umbilical cord TSH that must be considered when interpreting the results of the CBTSH. This study augments findings that CBTSH may be considered a predictive factor in CH screening programs.
Cough and sputum in long COVID are associated with severe acute COVID-19: a Japanese nation-wide cohort study
Authors: Watase Mayuko , Miyata Jun , Terai Hideki , Sunata Keeya , Matsuyama Emiko , Asakura Takanori , Namkoong Ho , Masaki Katsunori , Yagi Kazuma , Ohgino Keiko , Chubachi Shotaro , Kawada Ichiro , Mochimaru Takao , Satomi Ryosuke , Oyamada Yoshitaka , Kobayashi Keigo , Hirano Toshiyuki , Inoue Takashi , Lee Ho , Sugihara Kai , Omori Nao , Sayama Koichi , Mashimo Shuko , Makino Yasushi , Kaido Tatsuya , Ishii Makoto , Fukunaga Koichi 
Published: July 2023

Abstract
Background: Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID.
Methods: Hospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps.
Results: At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan–Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months.
Conclusions: In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach for COVID-19 is highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.
CMLCNet: Medical image segmentation network based on convolution capsule encoder and multi-scale local co-occurrence
Authors: Qin Chendong , Wang Yongxiong , Zhang Jiapeng 
Published: July 2023

Abstract

Medical images have low contrast and blurred boundaries between different tissues or between tissues and lesions. Because labeling medical images is laborious and requires expert knowledge, the labeled data are expensive or simply unavailable. UNet has achieved great success in the field of medical image segmentation. However, the pooling layer in downsampling tends to discard important information such as location information. It is difficult to learn global and long-range semantic interactive information well due to the locality of convolution operation. The usual solution is increasing the number of datasets or enhancing the training data though augmentation methods. However, to obtain a large number of medical datasets is tough, and the augmentation methods may increase the training burden. In this work, we propose a 2D medical image segmentation network with a convolutional capsule encoder and a multiscale local co-occurrence module. To extract more local detail and contextual information, the capsule encoder is introduced to learn the information about the target location and the relationship between the part and the whole. Multi-scale features can be fused by a new attention mechanism, which can then selectively emphasize salient features useful for a specific task by capturing global information and suppress background noise. The proposed attention mechanism is used to preserve the information that is discarded by pooling layers of the network. In addition, a multi-scale local co-occurrence algorithm is proposed, where the context and dependencies between different regions in an image can be better learned. Experimental results on the dataset of Liver and ISIC show that our network is superior to the UNet and other previous medical image segmentation networks under the same experimental conditions.
Stellar Rotation and Evolution in Young Clusters
Authors: Bateson Richard Douglas 
Published: July 2023

Abstract

Understanding stellar rotation and the role of magnetic braking remains a major outstandingproblem in astrophysics. In this paper, stellar rotation of the young open cluster Blanco 1 is investigated and compared with other clusters with ages ranging from ∼35 Myr to ∼950 Myr and star masses in the range 0.2 < M⊙ < 1.4. It is proposed that rotation rates of stars in young open clusters are determined by the early angular momentum acquired during formation and not by magnetic braking effects, which operate on longer time scales. On the convective C Sequence, for lighter stars, the early angular velocity is related directly to the moment of inertia. However, for the interface or I Sequence, differential rotation exists and observed rotation rates are essentially the rotation rates of the outer convection zone. It is estimated that the convection zone can rotate at over 10× the rate of the inner radiative zone for heavier stars. This differential rotation process can drive saturated interface dynamos that lead to large rotational mass dependences which can be described by a simple energy transfer model. Comparing with clusters of different ages magnetic braking outlines the evolution of older clusters from young clusters. For old clusters such as Praesepe the majority of stars have experienced spin down, that can be described by a simple model based on an additional momentum loss proportional to the angular momentum of the early cluster, which for the I Sequence is consistent with the well known Skumanich relation.
Prioritizing Barriers to Resilience in Blood Supply Chains: An Integrated Multi-Criteria Decision-Making Approach
Authors: Sibevei Ali , Roozkhosh Pardis 
Published: July 2023

Abstract

Supply chains face numerous disruptions in today's dynamic world, and achieving resilience is vital for healthcare systems, especially in the blood supply chain (BSC). However, there are several barriers hindering resilience, and identifying and prioritizing them is essential for developing effective strategies to improve resilience. This study proposes an integrated multi-criteria decision-making (MCDM) approach that combines the Best Worst Method (BWM), Delphi, and Preference Ranking Organization Method for Enrichment Evaluation (PROMETHEE) to recognize and prioritize SC resilience barriers in the BSC of Tehran, the largest BSC in Iran. The proposed approach provides real-time results for future improvements, and sensitivity analysis investigates the effects of criteria weights on decision-making. Additionally, the proposed method is compared with two existing methods, namely BWM- VlseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR) and BWM-Weighted Aggregated Sum Product Assessment (WASPAS). The results demonstrated that the most critical barriers are a lack of financial resources and the presence of managerial weaknesses at various levels. By highlighting these barriers, the study provides valuable insights for decision-makers to develop effective strategies and allocate resources to address the identified obstacles and improve the resilience of the blood supply chain.