bluuebunny/crossref_metadata_2025 huggingface dataset:
An Investigation of the Dynamic Response of Continuous Fibre Reinforced Composite Laminates - Failure Morphology
Authors: Li R.K.Y. , Choy C.L. , Duan Zhuping , Zhang Mingqiu
Published: March 2023

By using the split Hopkinson pressure bar technique, impact tests were carried out on fully clamped three-point bending, laminated beam specimens made from continuous glass fibre and carbon fibre reinforced polyphenylene sulphide of three different lay-up sequences. This paper focuses on scanning electron microscope investigations of the impact failure morphology, with the aim of providing a phenomenological background for a new model which can describe the dynamic response behaviour during transverse impact, as well as understanding comprehensively the dominant failure patterns at high strain rate. The results show that the fracture morphology possesses distinct features for each type of laminate, and is a function of both the material characteristics and lay-up sequence. Fibre to matrix adhesion exerts a strong influence on the microcracking mechanism.
Evaluation of Phytochemical Contents, Antimicrobial, and antioxidant Potential of Haloxylon Griffithii Collected From Northern Region of Balochistan, Pakistan
Authors: Asif Rizwan , Ali Muhammad , Mazhar Modasrah , Mustafa Madiha , Yasmin Riffat
Published: March 2023

Background

The therapeutic potential of Haloxylon griffithii found in northern region of Balochistan, so far has been neglected.

Purpose

The current study was aimed to assess the phytochemicals and pharmacological potential of fractions isolated from H griffithii.

Research Design

During phytochemicals analysis of H griffithii using GC/MS showed various bioactive compounds like alkaloids, flavonoids, terpenoids, tannins, saponins, and carboxylic acids. In vitro antioxidant activity of H griffithii was determined by 2, 2’- diphenyl-1-picrylhydrazyl (DPPH) assay. Disc diffusion method was used to evaluate the antimicrobial activity.

Results

The quantitative analysis of ethyl acetate showed highest total flavonoid contents (1.19 ± .05) while ethanol with lowest value (.52 ± .01). The total phenolic contents in ethyle acetate was 1.50 ± .42, whereas ethanol showed lowest value (.77 ± .02). Ethanol exhibited excellent (88.68 ± 3.0) free radical scavenging potential measured by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay. For antimicrobial activity, different bacterial and fungal strains like B subtilis, S aureus, E coli, S typhi, C albicans, and A. niger were selected . The essential oil showed maximum % inhibition diameter (9 mm) against B. Subtillus and (5 mm) against C albicans, respectively . The ethyl acetate presented % inhibition diameter (9 mm) against S aureus and (6 mm) against A niger. Anti-urease activity also showed positive response.

Conclusions

The presence of high (%) bioactive compounds with great therapeutic potential suggest that H griffithii can be used as natural alternative of synthetic drugs without side effects.
Quantitative evaluation of metamictisation of columbite-(Mn) from rare-element pegmatites using Raman spectroscopy
Authors: Hao Yuanyuan , Feng Yonggang , Liang Ting , Brzozowski Matthew , Ju Minghui , Zhou Ruili , Wang Yan
Published: March 2023

Raman spectroscopic analysis was performed on columbite-(Mn) samples from a variety of previously studied rare-element pegmatites in Xinjiang, China, including the Jing'erquan No. 1 spodumene-subtype, Dakalasu No. 1 beryl–columbite-subtype and Kalu'an spodumene-subtype pegmatites, to quantify the relationship between the degree of metamictisation of columbite and Raman spectra. For all of the analysed columbites-(Mn), the position (p) and the full width at half maximum (FWHM) of the strongest band, A1g vibration mode related to the Nb/Ta–O bond, in the Raman spectra have a negative correlation. Combined with previously determined U–Pb isotopic data and major–minor-element data for the columbites-(Mn), the degree of metamictisation was quantified using the alpha-decay dose (D) and displacement per atom (dpa), both of which were corrected for effects caused by annealing. The results demonstrate that the columbite-(Mn) from Jing'erquan and Kalu'an are very crystalline, whereas those from Dakalasu are transitional between crystalline and amorphous stages. The main factor influencing the key parameters, i.e. band position and FWHM, of the strongest Raman band of columbite-(Mn) is metamictisation caused by radiation damage, whereas composition and crystal orientation have limited influence. A set of equations are established to quantify the degree of metamictisation of columbite using the band position and the full width at half maximum: FWHM = 8.309 × ln(aD) + 30.11 (R2 = 0.9861); p = –5.187 × ln(aD) + 867.09 (R2 = 0.966); FWHM = 8.1453 × ln(adpa) + 48.425 (R2 = 0.9822); and p = –5.078 × ln(adpa) + 855.67 (R2 = 0.9594).
Grpel2 maintains cardiomyocyte survival in diabetic cardiomyopathy through DLST-mediated mitochondrial dysfunction: a proof-of-concept study
Authors: Yang Rongjin , Zhang Xiaomeng , Zhang Yunyun , Wang Yingfan , Li Man , Meng Yuancui , Wang Jianbang , Wen Xue , Yu Jun , Chang Pan
Published: March 2023

Background

Diabetic cardiomyopathy (DCM) has been considered as a major threat to health in individuals with diabetes. GrpE-like 2 (Grpel2), a nucleotide exchange factor, has been shown to regulate mitochondrial import process to maintain mitochondrial homeostasis. However, the effect and mechanism of Grpel2 in DCM remain unknown.

Methods

The streptozotocin (STZ)-induced DCM mice model and high glucose (HG)-treated cardiomyocytes were established. Overexpression of cardiac-specific Grpel2 was performed by intramyocardial injection of adeno-associated virus serotype 9 (AAV9). Bioinformatics analysis, co-immunoprecipitation (co-IP), transcriptomics profiling and functional experiments were used to explore molecular mechanism of Grpel2 in DCM.

Results

Here, we found that Grpel2 was decreased in DCM induced by STZ. Overexpression of cardiac-specific Grpel2 alleviated cardiac dysfunction and structural remodeling in DCM. In both diabetic hearts and HG-treated cardiomyocytes, Grpel2 overexpression attenuated apoptosis and mitochondrial dysfunction, including decreased mitochondrial ROS production, increased mitochondrial respiratory capacities and increased mitochondrial membrane potential. Mechanistically, Grpel2 interacted with dihydrolipoyl succinyltransferase (DLST), which positively mediated the import process of DLST into mitochondria under HG conditions. Furthermore, the protective effects of Grpel2 overexpression on mitochondrial function and cell survival were blocked by siRNA knockdown of DLST. Moreover, Nr2f6 bond to the Grpel2 promoter region and positively regulated its transcription.

Conclusion

Our study provides for the first time evidence that Grpel2 overexpression exerts a protective effect against mitochondrial dysfunction and apoptosis in DCM by maintaining the import of DLST into mitochondria. These findings suggest that targeting Grpel2 might be a promising therapeutic strategy for the treatment of patients with DCM.
Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications
Authors: Gonzalez-Ortiz Fernando , Kac Przemysław R. , Brum Wagner S. , Zetterberg Henrik , Blennow Kaj , Karikari Thomas K.
Published: March 2023

As the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, and healthcare systems. Although AD can be identified and diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence and clinical symptoms, challenges regarding practicality and accessibility hinder their widespread availability and implementation. Consequently, many people with suspected cognitive impairment due to AD do not receive a biomarker-supported diagnosis. Blood biomarkers have the capacity to help expand access to AD diagnostics worldwide. One such promising biomarker is plasma phosphorylated tau (p-tau), which has demonstrated specificity to AD versus non-AD neurodegenerative diseases, and will be extremely important to inform on clinical diagnosis and eligibility for therapies that have recently been approved. This review provides an update on the diagnostic and prognostic performances of plasma p-tau181, p-tau217 and p-tau231, and their associations with in vivo and autopsy-verified diagnosis and pathological hallmarks. Additionally, we discuss potential applications and unanswered questions of plasma p-tau for therapeutic trials, given their recent addition to the biomarker toolbox for participant screening, recruitment and during-trial monitoring. Outstanding questions include assay standardization, threshold generation and biomarker verification in diverse cohorts reflective of the wider community attending memory clinics and included in clinical trials.
Multiorgan failure and death from a mixed Dettol and Clorox poisoning: a case report
Authors: Alao David Olukolade , Moin Kinza , Abraham Snaha
Published: March 2023

Background

Dettol and sodium hypochlorite have wide use as household disinfectants and cleaners. Intentional and nonintentional ingestion are widespread, mainly causing mild symptoms that require no specific treatment. However, severe complications can occur when large volumes are ingested. Both products affect the same organ systems in the body, which can result in fatalities when ingested together.

Case presentation

We present the case of a 26-year-old Asian man who died from multiorgan failure after deliberately ingesting a presumed large volume of Dettol and sodium hypochlorite. The case illustrates the severe complications that can occur with mixed ingestion of these commonly used household products.

Conclusion

Clinicians must be aware of the increased risk of death caused by the combined ingestion of chloroxylenol and sodium hypochlorite.
Physicochemical, antioxidant and microbial properties of sweetened yoghurt produced from partial substitution of sugar with soursop puree
Authors: Sanusi Mayowa Saheed , Sunmonu Musliu Olushola , Alaka Abdulquadri , Raji Akeem Olayemi , Abdulazeez Ahmed , Joshua Victoria Auhoiza , Adeyemi Ikimot Adejoke
Published: March 2023

This study was targeted towards evaluating the outcome of partially substituting sugar with soursop puree at different proportions, varying pasteurization temperatures, storage durations and with the application of sodium benzoate and potassium sorbate as chemical preservatives on physiochemical, antioxidant and microbial qualities of yoghurt. There was a strong correlation (R2 = 0.7, Adjusted R2 = 0.65) between the syneresis and the water-holding capacity of the yoghurt as the substitution increased. At 50% soursop puree substitution in the yoghurt production, DPPH radical scavenging activity, total phenolic content, vitamin C, carbohydrate, protein, and ash contents increased to 34.40%, 1.25 mg GAE/L, 58.50 mg/100 g, 29.26, 4.02 and 0.69%, respectively. Storage duration does not have a significant influence on the proximate composition of the yoghurt samples. However, the vitamin C content of the yoghurt decreased when the pasteurization temperature was more than 80 °C. The growth of lactic acid bacteria ranged between 2.9 × 105 and 2.16 × 106 CFU/ml. The use of sodium benzoate inhibited yeast growth more than potassium sorbate while soursop substitution inhibited the growth of mould from 1.0 × 106 CFU/ml to 3.05 × 105 CFU/ml than the preservatives. Coliform was absent in all the yoghurt samples with or without preservatives. This information would be valuable in yoghurt development and quality control.

Graphical Abstract
349 ZYX is a Novel Candidate Gene in Moyamoya Pathogenesis
Authors: Barak Tanyeri , Yalcin Kanat , Miyagishima Danielle F. , Gunel Murat
Published: March 2023

INTRODUCTION:

Moyamoya disease (MMD) is characterized by progressive bilateral stenosis in the proximal branches of the internal carotid arteries with compensatory angiogenesis. It is common in Japanese population; accounting for one fifth of pediatric stroke cases associated with arteriopathies. Although the etiology remains largely unknown, genetic factors have been implicated in the pathophysiology of MMD.

METHODS:

We performed gene-based mutational burden analysis using WES results of 23 MMD patients and a control cohort of 8380 Japanese individuals obtained from jMorp (8.3 kjpn). We performed a case-control analysis by comparing the enrichment of rare (Japanese minor allele frequency <2.5e-4) and deleterious variants including loss of function (LoF) variants (stop gain, start loss, frameshift, splice acceptor and splice donor) and missense variants annotated as “deleterious” in MetaSVM (D-Mis).

RESULTS:

We identified ZYX gene, encoding a focal adhesion molecule Zyxin, top significantly enriched gene in MMD cohort (two tailed Fisher's P = 1.52E-5; OR 77.55 [95% CI 13.91–291.69]), with three individuals were found to carry a heterozygous LoF and two missense mutations in ZYX gene. ZYX expression was found above 96th percentile for an ‘arterial-enrichment ratio’ calculated using GtEX portal, suggesting its critical role in vascular cell types.

CONCLUSIONS:

In this study, we identified ZYX as a novel candidate gene in Moyamoya pathogenesis. Zyxin is a known focal adhesion molecule involved in mechanosensation in the vasculature, while its implication in MMD has not been previously reported.
867 Postoperative Metformin is Associated With Improved Survival of Glioblastoma Patients
Authors: Mohammad Amro , Jatana Sukhdeep , Al-Saadi Tariq , Shenouda George , Diaz Roberto
Published: March 2023

INTRODUCTION:

Metformin may improve clinical outcomes for glioblastoma (GBM) patients as metformin showed in vitro tumor suppressor functions, such as reducing the proliferation of GBM tumor-initiating cells by reversing Akt kinase activation.

METHODS:

A single-centre retrospective study of 288 patients who underwent biopsy or surgery for GBM between 2014-2018 was conducted. Postoperative metformin treatment includes patients who received metformin as part of an adjuvant therapy with temozolomide and/or hyper-fractionated radiotherapy. Kaplan-Meier curves and log-rank p test were used for univariate analysis. Cox-proportional hazards model was used to generate adjusted hazard ratios with 95% CI for multivariate analysis.

RESULTS:

Metformin use impacted OS of patients with MGMT-methylated (MGMTm+) tumors (n = 71 no metformin (Met-), n = 35 metformin use (Met +); median OS = 442 vs. 662 days; p = 0.13) but not in patients with unmethylated MGMT tumors (n = 104 Met-, n = 44 Met+; median OS = 279 vs 295 days; p = 0.674). Postoperative metformin treatment of MGMTm+ tumor patients improved OS when compared to no or only preoperative metformin treatment (n = 66 no or preoperative metformin use, n = 40 postoperative metformin use; median OS = 443 vs 595; p = 0.012). Further, postoperative metformin treatment of nondiabetic patients with MGMTm+ tumors improved OS (n = 70 Met-, n = 18 postoperative Met+; median OS = 422 vs 582; p = 0.017). A multivariable model considering age, Karnofsky Performance Status (KPS), and extent of resection (EOR), demonstrated that postoperative metformin improves OS of MGMTm+ patients (aHR 0.500, 0.287-0.872, p = 0.015). Comparing postoperative with no or preoperative use of metformin produced a similar effect on OS (aHR 0.411, 0.177-0.954, p = 0.038). Postoperative treatment of nondiabetic patients with MGMTm+ tumors demonstrated improved OS (aHR 0.367, 0.156-0.864, p = 0.022).

CONCLUSIONS:

Postoperative metformin treatment of patients with MGMTm+ tumors is associated with improved OS, irrespective of age, diabetic status, KPS, or EOR.
Automated staging of zebrafish embryos using machine learning
Authors: Jones Rebecca A. , Renshaw Matthew J. , Barry David J. , Smith James C.
Published: March 2023

The zebrafish (Danio rerio), is an important biomedical model organism used in many disciplines, including development, disease modeling and toxicology, to better understand vertebrate biology. The phenomenon of developmental delay in zebrafish embryos has been widely reported as part of a mutant or treatment-induced phenotype, and accurate characterization of such delays is imperative. Despite this, the only way at present to identify and quantify these delays is through manual observation, which is both time-consuming and subjective. Machine learning approaches in biology are rapidly becoming part of the toolkit used by researchers to address complex questions. In this work, we introduce a machine learning-based classifier that has been trained to detect temporal developmental differences across groups of zebrafish embryos. Our classifier is capable of rapidly analyzing thousands of images, allowing comparisons of developmental temporal rates to be assessed across and between experimental groups of embryos. Finally, as our classifier uses images obtained from a standard live-imaging widefield microscope and camera set-up, we envisage it will be readily accessible to the zebrafish community, and prove to be a valuable resource.
EXPLORING LEADERSHIP LEARNING THROUGH SHORT-TERM STUDY ABROAD EXPERIENCES
Authors: Beatty Cameron C. , Manning-Ouellette Amber
Published: March 2023

Pre COVID-19 there were a growing number of opportunities for study abroad across higher education in the United States, (Rosch & Haber-Curran, 2013; Martinez, 2012). This paper aims to examine phenomena surrounding outcomes of student abroad experiences while centering students’ leadership learning. Centering leadership learning as a framework, findings indicate participants in the study grew in the of areas of leadership efficacy and capacity through the short-term study abroad.
Data-Driven Surgical Tray Optimization to Improve Operating Room Efficiency
Authors: Deshpande Vinayak , Mundru Nishanth , Rath Sandeep , Knowles Martyn , Rowe David , Wood Benjamin C.
Published: March 2023

Improving Operating Room Efficiency

After each surgery in a hospital, every reusable instrument that has entered the operating room must be sterilized before it can be used again. Hospitals spend several million dollars a year on this sterilization process, instrument tray assembly, and instrument repurchase costs. However, 70%–80% of instruments that enter the operating room are not used at a large majority of hospitals resulting in wastage of millions of dollars. For a medium-sized hospital, approximately $4–$7 million are spent on the sterilization process. Across more than 5,000 hospitals in the United States, several billion dollars per year are wasted on unnecessary sterilization. Researchers at UNC Kenan-Flagler Business School, with partners from healthcare technology firm Operative Flow Technologies, have developed an algorithm that uses detailed data of instruments used to create optimized instrument tray configuration. The algorithm creates trays informed by historical usage of instruments to reduce unused instruments in trays significantly. This algorithm scales for hundreds of trays, thousands of instruments, and thousands of surgeries and can be applied to major healthcare systems. At one implementation, the number of unused instruments was reduced by 54%. Their solution has subsequently been implemented at multiple healthcare systems leading to several million dollars of cost savings for the hospitals.
Recognizing giant cell arteritis in dental practice
Authors: Shenoy Riddhi , French Kathryn , Eke Tom , Mukhtyar Chetan
Published: March 2023

Giant cell arteritis (GCA) is a rare condition that causes inflammation of blood vessels. Early diagnosis and treatment is essential to prevent ischaemic complications, including blindness, tongue necrosis and stroke. GCA can present with orofacial symptoms, such as toothache and pain/difficulty in chewing, which may cause individuals with GCA to first present to the dentist. This has important patient safety and medicolegal implications. Dental practitioners should be alert to the possibility of GCA and should direct suspected cases to their general medical practitioner or a hospital specialist. Increased awareness of GCA should minimize the risk of blindness and stroke.

CPD/Clinical Relevance: Early recognition and treatment of GCA is key to prevent complications, such as blindness, tongue necrosis and stroke.
Pica: recognizing the presentation in primary dental care
Authors: Atkinson James , Kavanagh Grace , McCracken Giles
Published: March 2023

Pica is an eating disorder characterized by compulsive eating of non-food items. It can present to dentists through patient medical histories, and also through causing atypical patterns of non-carious tooth surface loss. In highlighting two cases of pica presenting in general practice, we aim to raise awareness of this condition and its dental implications.

CPD/Clinical Relevance: This article advises on how pica may present to a general dentist and gives advice on management.
Progress is not linear
Authors: Allingham Sue
Published: March 2023

Sue Allingham explains the risks of local and national expectations in early years education being set by people in positions of authority with little to no understanding of child development. This leads to the perpetuation of myths and affects children's learning, at times also directly contradicting the Statutory Framework.
Trajectory play
Authors: Grimmer Tamsin
Published: March 2023

Trajectory play is one of the earliest forms of schematic play that we can observe in babies. In this month's article, Tamsin Grimmer explores the benefits of trajectory play and shares practical advice on supporting it in your setting.

Trajectory – children are fascinated with movement including moving themselves or moving objects (e.g. throwing, kicking, running). Repeated behaviours include dropping items or food from cots, high-chairs etc. Playing with running water from the tap, building and knocking down towers, climbing and jumping off furniture, throwing, bouncing or kicking balls.
Supporting service children: Celebrating the Month of the Military Child
Authors: Barton Debra
Published: March 2023

In this three-part series, Debra Barton, early years specialist lead for the Ministry of Defence (MOD) Armed Forces Families and Safeguarding (AFFS) team, explains who service children are, and how practitioners and providers from the early childhood and early education sector can support them and their families. This first article will look at how early childhood education and childcare providers can celebrate the Month of the Military child in April.
Sociodemographic and environmental factors associated with dengue, Zika, and chikungunya among adolescents from two Brazilian capitals
Authors: Dalvi Ana Paula Razal , Gibson Gerusa , Ramos Alberto Novaes , Bloch Katia V. , Sousa Geziel dos Santos de , Silva Thiago Luiz Nogueira da , Braga José Ueleres , Castro Marcia C. , Werneck Guilherme Loureiro
Published: March 2023

Among the emerging and reemerging arboviral diseases, Zika, dengue and chikungunya deserve special attention due to their wide geographical distribution and clinical severity. The three arboviruses are transmitted by the same vector and can present similar clinical syndromes, bringing challenges to their identification and register. Demographic characteristics and individual and contextual social factors have been associated with the three arboviral diseases. However, little is known about such associations among adolescents, whose relationships with the social environment are different from those of adult populations, implying potentially different places, types, and degrees of exposure to the vector, particularly in the school context. This study aims to identify sociodemographic and environmental risk factors for the occurrence of Zika, dengue, and chikungunya in a cohort of adolescents from the Study of Cardiovascular Risks in Adolescents—ERICA—in the cities of Rio de Janeiro/RJ and Fortaleza/CE, from January 2015 to March 2019. Cases were defined as adolescents with laboratory or clinical-epidemiological diagnosis of Zika, dengue, or chikungunya, notified and registered in the Information System for Notifiable Diseases (SINAN). The cases were identified by linkage between the databases of the ERICA cohort and of SINAN. Multilevel Cox regression was employed to estimate hazard ratios (HR) as measures of association and respective 95% confidence intervals (95%CI). In comparison with adolescents living in lower socioeconomic conditions, the risk of becoming ill due to any of the three studied arboviral diseases was lower among those living in better socioeconomic conditions (HR = 0.43; 95%CI: 0.19–0.99; p = 0.047) and in the adolescents who attended school in the afternoon period (HR = 0.17; 95%CI: 0.06–0.47; p<0.001). When compared to areas whose Building Infestation Index (BII) for Aedes aegypti was considered satisfactory, a BII in the school region classified as “alert” and “risk” was associated with a higher risk of arboviral diseases (HR = 1.62, 95%CI: 0.98–2.70; p = 0.062; HR = 3.72, 95%CI: 1.27–10.9; p = 0.017, respectively). These findings indicate that living in less favored socioeconomic conditions, attending school in the morning, and having a high BII for Ae. aegypti in school’s region can contribute to an increased risk of infection by Zika, dengue, or chikungunya in adolescents. The identification of residential or school areas based on those variables can contribute to the implementation of control measures in population groups and priority locations.
Improved and optimized drug repurposing for the SARS-CoV-2 pandemic
Authors: Cohen Sarel , Hershcovitch Moshik , Taraz Martin , Kißig Otto , Issac Davis , Wood Andrew , Waddington Daniel , Chin Peter , Friedrich Tobias
Published: March 2023

The active global SARS-CoV-2 pandemic caused more than 426 million cases and 5.8 million deaths worldwide. The development of completely new drugs for such a novel disease is a challenging, time intensive process. Despite researchers around the world working on this task, no effective treatments have been developed yet. This emphasizes the importance of drug repurposing, where treatments are found among existing drugs that are meant for different diseases. A common approach to this is based on knowledge graphs, that condense relationships between entities like drugs, diseases and genes. Graph neural networks (GNNs) can then be used for the task at hand by predicting links in such knowledge graphs. Expanding on state-of-the-art GNN research, Doshi et al. recently developed the Dr-COVID model. We further extend their work using additional output interpretation strategies. The best aggregation strategy derives a top-100 ranking of 8,070 candidate drugs, 32 of which are currently being tested in COVID-19-related clinical trials. Moreover, we present an alternative application for the model, the generation of additional candidates based on a given pre-selection of drug candidates using collaborative filtering. In addition, we improved the implementation of the Dr-COVID model by significantly shortening the inference and pre-processing time by exploiting data-parallelism. As drug repurposing is a task that requires high computation and memory resources, we further accelerate the post-processing phase using a new emerging hardware—we propose a new approach to leverage the use of high-capacity Non-Volatile Memory for aggregate drug ranking.
Paleohistology of Caraguatypotherium munozi (Mammalia, Notoungulata, Mesotheriidae) from the early late Miocene of northern Chile: A preliminary ontogenetic approach
Authors: Campos-Medina Jorge , Montoya-Sanhueza Germán , Moreno Karen , Bostelmann Torrealba Enrique , García Marcelo
Published: March 2023

The Miocene Caragua fossil fauna in northern Chile contains a considerable number (7) of articulated partial skeletons tentatively assigned to Caraguatypotherium munozi (Notoungulata, Mesotheriidae), which presents up to 40% body size difference. Since either inter- and intra- specific wide size range has been observed in the Mesotheriidae family in general, we wanted explore the ontogenic stage signature of the sample, by carrying out the first comprehensive paleohistological description of the appendicular system in Notoungulata. Results show that: 1) they can be classified as subadults and adults, based on the presence of bone tissues typical of ceased somatic growth; 2) there is a notorious inter-skeletal variation on bone growth rates (skeletal modularity), particularly, the humerus showed a slower diameter growth and less remodelling than the femur, resulting as a better element for ontogenetic analyses; 3) marked cyclical growth is observed, characterised by fast early ontogenic continuous growth, and subsequent fast/slow stratified bone tissue layering. In general, such growth pattern suggests that C. munozi had a similar ontogenetic growth process as other modern mammals, that it should also be influenced by other sex-related, ecological and environmental factors. Likely related to the presence of rapid climatic variations, due to orogenic uplift and concomitant re-organization of the drainage processes along the western tectonic front of the Central Andes at that time.
A small dynamic leaf-level model predicting photosynthesis in greenhouse tomatoes
Authors: Joubert Dominique , Zhang Ningyi , Berman Sarah.R. , Kaiser Elias , Molenaar Jaap , Stigter J.D.
Published: March 2023

The conversion of supplemental greenhouse light energy into biomass is not always optimal. Recent trends in global energy prices and discussions on climate change highlight the need to reduce our energy footprint associated with the use of supplemental light in greenhouse crop production. This can be achieved by implementing “smart” lighting regimens which in turn rely on a good understanding of how fluctuating light influences photosynthetic physiology. Here, a simple fit-for-purpose dynamic model is presented. It accurately predicts net leaf photosynthesis under natural fluctuating light. It comprises two ordinary differential equations predicting: 1) the total stomatal conductance to CO2diffusion and 2) the CO2concentration inside a leaf. It contains elements of the Farquhar-von Caemmerer-Berry model and the successful incorporation of this model suggests that for tomato (Solanum lycopersicum L.), it is sufficient to assume that Rubisco remains activated despite rapid fluctuations in irradiance. Furthermore, predictions of the net photosynthetic rate under both 400ppm and enriched 800ppm ambient CO2concentrations indicate a strong correlation between the dynamic rate of photosynthesis and the rate of electron transport. Finally, we are able to indicate whether dynamic photosynthesis is Rubisco or electron transport rate limited.
Understanding urban concentration of complex manufacturing activities in China
Authors: Li Linzhuo , Zhao Nannan
Published: March 2023

The increasing prominence of urban scaling laws highlights the importance of a systematic understanding of the variational scaling rates for different economic activities. In this article, we utilize several datasets to provide the first systematic investigation of the urban scaling of manufacturing industries in China. Most existing literature assumes that the divergence in urban scaling can be explained by returns to agglomeration, with a few exceptions instead highlighting the role of knowledge complexity or a mixture of both. Our main purpose in this paper is to explain the inter-sector variation of urban scaling rates. In doing this, we provide a clearer approach to demonstrating the relations between urban scaling, returns to agglomeration, and knowledge complexity. Our findings are twofold. First, after uncovering the scaling rates (denoted asurban concentration) and returns to agglomeration (denoted asurban productivity) for each sub-manufacturing sector, we prove that, rather than being a positive predictor, returns to agglomeration is slightly negatively associated with urban scaling rates. This finding reveals that urban concentration of manufacturing may not simply be a natural consequence driven by the maximization of performance. We also show that this result of the manufacturing system contrasts with what would be found in other pure knowledge systems such as patents. Secondly, we measure the complexity for each sector and demonstrate that the variation of urban concentration can be largely explained by their complexity, consistent with the knowledge complexity perspective. Specifically, complex manufacturing sectors are found to concentrate more in large cities than less complex sectors in China. This result provides support for the view that the growth of complex activities hinges more on diversity than on efficiency. The findings above can greatly reduce the current level of ambiguity associated with urban scaling, returns to agglomeration and complexity, and have important policy implications for urban planners, highlighting the significance of a more balanced and diversified configuration of urban productive activities for the growth of innovation economy.
Development of an ectopic huLiver model for Plasmodium liver stage infection
Authors: Samayoa-Reyes Gabriela , Flaherty Siobhan M. , Wickham Kristina S. , Viera-Morilla Sara , Strauch Pamela M. , Roth Alison , Padrón Laura , Jackson Conner M. , Meireles Patricia , Calvo David , Roobsoong Wanlapa , Kangwanrangsan Niwat , Sattabongkot Jetsumon , Reichard Gregory , Lafuente-Monasterio Maria José , Rochford Rosemary
Published: March 2023

Early Plasmodium falciparum and P. vivax infection requires parasite replication within host hepatocytes, referred to as liver stage (LS). However, limited understanding of infection dynamics in human LS exists due to species-specificity challenges. Reported here is a reproducible, easy-to-manipulate, and moderate-cost in vivo model to study human Plasmodium LS in mice; the ectopic huLiver model. Ectopic huLiver tumors were generated through subcutaneous injection of the HC-04 cell line and shown to be infectible by both freshly dissected sporozoites and through the bite of infected mosquitoes. Evidence for complete LS development was supported by the transition to blood-stage infection in mice engrafted with human erythrocytes. Additionally, this model was successfully evaluated for its utility in testing antimalarial therapeutics, as supported by primaquine acting as a causal prophylactic against P. falciparum. Presented here is a new platform for the study of human Plasmodium infection with the potential to aid in drug discovery.
Neonatal administration of synthetic estrogen, diethylstilbestrol to mice up-regulates inflammatory Cxclchemokines located in the 5qE1 region in the vaginal epithelium
Authors: Kitamura Ayaka , Jiayue Chen , Suwa Tomoya , Kato Yasuhiko , Wada Tadashi , Watanabe Hajime
Published: March 2023

A synthetic estrogen, diethylstilbestrol (DES), is known to cause adult vaginal carcinoma by neonatal administration of DES to mice. However, the carcinogenic process remains unclear. By Cap Analysis of Gene Expression method, we found that neonatal DES exposure up-regulated inflammatory Cxcl chemokines 2, 3, 5, and 7 located in the 5qE1 region in the vaginal epithelium of mice 70 days after birth. When we examined the gene expressions of these genes much earlier stages, we found that neonatal DES exposure increased these Cxcl chemokine genes expression even after 17 days after birth. It implies the DES-mediated persistent activation of inflammatory genes. Intriguingly, we also detected DES-induced non-coding RNAs from a region approximately 100 kb far from the Cxcl5 gene. The non-coding RNA up-regulation by DES exposure was confirmed on the 17-day vagina and continued throughout life, which may responsible for the activation of Cxcl chemokines located in the same region, 5qE1. This study shows that neonatal administration of DES to mice causes long-lasting up-regulation of inflammatory Cxcl chemokines in the vaginal epithelium. DES-mediated inflammation may be associated with the carcinogenic process.
Stocks and cryptocurrencies: Antifragile or robust? A novel antifragility measure of the stock and cryptocurrency markets
Authors: Alatorre Darío , Gershenson Carlos , Mateos José L.
Published: March 2023

In contrast with robust systems that resist noise or fragile systems that break with noise, antifragility is defined as a property of complex systems that benefit from noise or disorder. Here we define and test a simple measure of antifragility for complex dynamical systems. In this work we use our antifragility measure to analyze real data from return prices in the stock and cryptocurrency markets. Our definition of antifragility is the product of the return price and a perturbation. We explore different types of perturbations that typically arise from within the system. Our results suggest that for both the stock market and the cryptocurrency market, the tendency among the ‘top performers’ is to be robust rather than antifragile. It would be important to explore other possible definitions of antifragility to understand its role in financial markets and in complex dynamical systems in general.
Population structure and adaptive differentiation in the sea cucumber Apostichopus californicus and implications for spatial resource management
Authors: Lowell Natalie , Suhrbier Andy , Tarpey Carolyn , May Samuel , Carson Henry , Hauser Lorenz
Published: March 2023

A growing body of evidence suggests that spatial population structure can develop in marine species despite large population sizes and high gene flow. Characterizing population structure is important for the effective management of exploited species, as it can be used to identify appropriate scales of management in fishery and aquaculture contexts. The California sea cucumber, Apostichopus californicus, is one such exploited species whose management could benefit from further characterization of population structure. Using restriction site-associated DNA (RAD) sequencing, we developed 2075 single nucleotide polymorphisms (SNPs) to quantify genetic structure over a broad section of the species’ range along the North American west coast and within the Salish Sea, a region supporting the Washington State A. californicus fishery and developing aquaculture production of the species. We found evidence for population structure (global fixation index (FST) = 0.0068) with limited dispersal driving two patterns of differentiation: isolation-by-distance and a latitudinal gradient of differentiation. Notably, we found detectable population differences among collection sites within the Salish Sea (pairwise FST = 0.001–0.006). Using FST outlier detection and gene-environment association, we identified 10.2% of total SNPs as putatively adaptive. Environmental variables (e.g., temperature, salinity) from the sea surface were more correlated with genetic variation than those same variables measured near the benthos, suggesting that selection on pelagic larvae may drive adaptive differentiation to a greater degree than selection on adults. Our results were consistent with previous estimates of and patterns in population structure for this species in other extents of the range. Additionally, we found that patterns of neutral and adaptive differentiation co-varied, suggesting that adaptive barriers may limit dispersal. Our study provides guidance to decision-makers regarding the designation of management units for A. californicus and adds to the growing body of literature identifying genetic population differentiation in marine species despite large, nominally connected populations.
Tinnea gombea (Lamiaceae), a new species from the Sudanian savanna region, Nigeria based on integrative evidence
Authors: Zhigila Daniel A. , Aigbokhan Emmanuel I. , Muasya A. Muthama
Published: March 2023

Tinnea gombea, endemic to the Sudan savanna grasslands in northern Nigeria, is described and illustrated. We used integrative evidence from morphological characters, ecology and molecular phylogenetic data. The new species is morphologically and ecologically similar to T. barteri and T. aethiopica, but can be readily delimited from these taxa by unique characters including a subshrub growth habit, leaves alternate to subopposite, blades lanceolate, apically acuminate, inflorescences raceme, bearing solitary flowers in upper leaf and bract axils, lilac to purplish dusky flowers and the inflated fruits dehiscent. The distribution and habitat of T. gombea are also distinctive, being restricted to the Sudan savanna, while the two most similar species are widespread in tropical Africa. Additionally, molecular phylogenetic assessments using nrITS and chloroplast trnL-F, matK and rbcL support the placement of T. gombea as a distinct species. Tinnea gombea is here assessed as Critically Endangered due to its small population size and restriction to a small area lacking conservation prioritization.
Accurate bundle matching and generation via multitask learning with partially shared parameters
Authors: Jeon Hyunsik , Jang Jun-Gi , Kim Taehun , Kang U.
Published: March 2023

How can we recommend existing bundles to users accurately? How can we generate new tailored bundles for users? Recommending a bundle, or a group of various items, has attracted widespread attention in e-commerce owing to the increased satisfaction of both users and providers. Bundle matching and bundle generation are two representative tasks in bundle recommendation. The bundle matching task is to correctly match existing bundles to users while the bundle generation is to generate new bundles that users would prefer. Although many recent works have developed bundle recommendation models, they fail to achieve high accuracy since they do not handle heterogeneous data effectively and do not learn a method for customized bundle generation. In this paper, we propose BundleMage, an accurate approach for bundle matching and generation. BundleMage effectively mixes user preferences of items and bundles using an adaptive gate technique to achieve high accuracy for the bundle matching. BundleMage also generates a personalized bundle by learning a generation module that exploits a user preference and the characteristic of a given incomplete bundle to be completed. BundleMage further improves its performance using multi-task learning with partially shared parameters. Through extensive experiments, we show that BundleMage achieves up to 6.6% higher nDCG in bundle matching and 6.3× higher nDCG in bundle generation than the best competitors. We also provide qualitative analysis that BundleMage effectively generates bundles considering both the tastes of users and the characteristics of target bundles.
Reliability of the retrospective Clinical Interview Schedule Revised (rCIS-R) to assess relapse in depression in primary care patients
Authors: Duffy Larisa , Marston Louise , Lewis Gemma , Lewis Glyn
Published: March 2023

Objectives

We are not aware of a simple and short structured measure that retrospectively assesses time to relapse for depression. We developed the retrospective Clinical Interview Schedule Revised (rCIS-R) to assess depression relapse in the previous 12 weeks, for use in a clinical trial of maintenance antidepressant treatment. We assessed test-retest reliability and construct validity in relation to a Global Rating Question (GRQ) about worsening mood, participants stopping their study medication and Patient Health Questionnaire (PHQ‐9) scores.

Methods

In our study 444 participants provided data for rCIS-R, GRQ and PHQ-9 and 396 participants completed rCIS-R on two occasions about 30 minutes apart. The reliability study was nested within a randomised controlled trial (ANTLER).

Results

We found substantial test-retest agreement for the rCIS-R definition of relapse (kappa 0.84 (95%CI 0.71 to 0.97)), for individual sections and timing of relapse (Intraclass Correlation Coefficient 0.94 (95%CI 0.92 to 0.95)). Comparison of relapse with GRQ, stopping study medication and PHQ-9 supported the construct validity of the rCIS-R.

Conclusions

The rCIS-R provides a reliable way of assessing relapse of depression over the previous 12 weeks. Its brevity, self-report format, simplicity of scoring and absence of training requirement makes it attractive to use in randomised controlled trials.
Perceptions of pandemic resume gaps: Survey experimental evidence from the United States
Authors: Bateson Regina
Published: March 2023

As a result of the COVID-19 pandemic, millions of people found themselves out of work in 2020 and 2021. Going forward, will their pandemic resume gaps be stigmatized or forgiven? In a recent survey experiment in the United States, I find that US adults have negative perceptions of individuals who were unemployed during the novel coronavirus pandemic. When asked to select among fictional applicants for a job opening in the hospitality industry, respondents prefer those who were employed continuously throughout the pandemic. Respondents are about 20% less likely to choose applicants with pandemic resume gaps, regardless of whether they were laid off, stopped working to supervise virtual school, or yo-yoed in and out of employment. Respondents also describe applicants with pandemic resume gaps in more negative terms, perceiving them as less hardworking, less dedicated, less professional, and less qualified than otherwise identical applicants who remained employed. Public opinion toward individuals with breaks in employment during the pandemic matters because it may affect public policy, and because stigma harms job seekers in multiple ways. Furthermore, the results of the experiment are consistent among survey respondents with hiring and managerial experience. While we should always be cautious about generalizing from survey experiments, these findings suggest that people who were out of work during the COVID-19 pandemic may face disadvantages when they return to the labor market.
Diuretic treatment before and after transcatheter aortic valve implantation: A Danish nationwide study
Authors: Begun Xenia , Butt Jawad Haider , Kristensen Søren Lund , Weeke Peter Ejvin , De Backer Ole , Schou Morten , Køber Lars , Loldrup Fosbøl Emil
Published: March 2023

Objectives

We examined loop diuretic treatment before and 1-year after transcatheter aortic valve implantation (TAVI), as a proxy for changes in symptom severity and secondly assessed how changes in loop diuretics related to mortality risk.

Background

Randomized clinical trials suggest that approximately one third of patients undergoing TAVI do not achieve symptom relief, but “all-comer” data are lacking.

Methods

Using Danish nationwide registries, we identified all citizens, who underwent TAVI from 2008 to 2019 and were alive at 1-year post-discharge. Loop diuretic treatment pre-TAVI and at 1-year post-TAVI were assessed and grouped as receiving 1) no-loop diuretics; 2) low: 1–40 mg of furosemide (or equivalent bumetanide) daily; 3) intermediate: 41–120 mg of furosemide daily; or 4) high: >120 mg furosemide daily.

Results

Among the 4431 patients undergoing TAVI, 2173 (49%) patients were not treated with loop diuretics at the time of TAVI, 918 (21%) had low-loop diuretics, 881 (20%) had intermediate-loop diuretics, and 459 (10%) had high-loop diuretics. At 1-year post-TAVI, 893 (20%) patients had increased, 1010 (23%) had reduced, and 2528 (57%) had unchanged loop diuretic treatment. The cumulative 5-year risk of death in patients surviving one year, was 61% (95% CI: 56.4% to 65.3%) in patients with increased and 47% (95% CI: 44.9% to 49.9%) in patients with reduced/unchanged loop diuretic treatment, respectively. In multivariable Cox proportional hazard analysis, increased loop diuretic treatment was associated with a higher risk of death compared with reduced/unchanged loop diuretic treatment (Hazard ratio: 1.4; 95% CI: 1.22 to 1.52).

Conclusions

Among patients undergoing TAVI, surviving one year, one fifth of patients had increased loop diuretic treatment, and a little over one fifth had reduced loop diuretic treatment 1-year post-procedure. In patients with increased diuretic treatment, the risk of death was higher compared to those with reduced/unchanged loop diuretic treatment.