bluuebunny/crossref_metadata_2025 huggingface dataset:
A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID‐19
Authors: Field Benjamin C. T. , Ruan Yue , Várnai Kinga A. , Davies Jim , Ryder Robert E. J. , Gandhi Rajiv , Harris Sophie , Nagi Dinesh , Patel Dipesh , Kempegowda Punith , Wild Sarah H. , Wilmot Emma G. , Khunti Kamlesh , Rea Rustam , Narendran Parth ,   the ABCD COVID‐19 Audit Group
Published: April 2023

Aims

To investigate characteristics of people hospitalized with coronavirus‐disease‐2019 (COVID‐19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.

Materials and methods

Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID‐19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age‐adjusted odds ratios were calculated using logistic regression.

Results

In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID‐19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non‐White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non‐users [21.4% vs. 52.2%; age‐adjusted odds ratio 0.13 (95% CI 0.03‐0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non‐users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.

Conclusions

Hospitalization with COVID‐19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes‐associated DKA.
Structural changes after ankle joint distraction in haemophilic arthropathy: an explorative study investigating biochemical markers and 3D joint space width
Authors: van Bergen Eline D. P. , Mastbergen Simon C. , Lafeber Floris P. J. G. , Bay‐Jensen Anne‐Christine , Madsen Sofie F. , Port Helena , Foppen Wouter , Schutgens Roger E. G. , Jansen Mylène P. , van Vulpen Lize F. D.
Published: April 2023

Introduction

Ankle joint distraction (AJD) is a promising treatment for patients with severe haemophilic ankle arthropathy (HAA). However, some patients showed no clinical improvement after AJD and these differences may be related to structural differences.

Aim

Primarily to quantify the structural changes after AJD in patients with HAA by the use of 3D joint space width (JSW) measurements and biochemical markers and secondarily to correlate these findings with clinical pain/function.

Methods

Patients with haemophilia A/B who underwent AJD were included for this study. Bone contours on MRI (performed before and 12 and 36 months after AJD) were drawn manually and percentage change in JSW was calculated. Blood/urine (before and 6, 12, 24 and 36 months after AJD) was collected for biomarker measurement (COMP, CS846, C10C, CALC2, PRO‐C2, CTX‐II) and combined indexes of markers were calculated. Mixed effects models were used for analyses on group level. Structural changes were compared with clinical parameters.

Results

Eight patients were evaluated. On group level, percentage changes in JSW showed a slight decrease after 12 months followed by a non‐statistically significant increase in JSW after 36 months compared to baseline. Biochemical marker collagen/cartilage formation also showed an initial decrease, followed by a trend towards net formation 12, 24 and 36 months after AJD. On individual patient level, no clear correlations between structural changes and clinical parameters were observed.

Conclusion

Cartilage restoration activity on group level in patients with HAA after AJD was in concordance with clinical improvements. Correlating structural modifications with clinical parameters in the individual patient remains difficult.
A review on the potential health benefits of sweet potato: insights into its preclinical and clinical studies
Authors: Elgabry Rehab Mohammed , Sedeek Mohamed S. , Meselhy Khaled M , Fawzy Ghada Ahmed
Published: April 2023

Sweet potato (Ipomoea batatas (L.) Lam) has become a research focus in recent decades because of its nutritional and functional properties. Its leaves, stems and roots are a valuable source of bioactive carbohydrates, lipids, proteins, carotenoids, anthocyanins, phenolic acids and flavonoids. These bioactive metabolites possess many biological activities, such as antioxidant, antidiabetic, anticancer, hepatoprotective, antimicrobial, antiulcer and immunostimulant activities. Moreover, previous investigations proved that bioactivity varies qualitatively and quantitatively among sweet potato cultivars. So, the purpose of this review was to summarise the preclinical and clinical studies that have been conducted on different varieties of sweet potatoes, aiming to find the gap between them. This may consequently help in recommending additional clinical investigations on sweet potatoes maximising their potential as a functional food.
Paediatric obesity: Documentation, screening, and pharmacotherapy in a national cohort
Authors: Hidirsah Arek , Chai Yan , Flores Ryan , Vidmar Alaina P. , Borzutzky Claudia , Espinoza Juan
Published: April 2023

Background

Multiple organizations have published guidelines for the screening and treatment of obesity and related comorbidities in youth, including the use of anti‐obesity medications (AOM). This study aimed to determine which paediatric patients: (1) receive a diagnostic code for obesity; (2) are most likely to be screened for hyperlipidaemia, non‐alcoholic fatty liver disease, and type 2 diabetes mellitus; and (3) are most likely to be prescribed AOM.

Methods

A cohort of 35 898 patients 9 years 4 months to 17 years 6 months of age with a BMI > 30 or greater than the 95th% on three separate outpatient encounters was generated using the TriNetX database. Logistic regression models were used to estimate the associations between demographics in the study population and the likelihood of diagnosis of obesity, screening for comorbidities, and prescription of AOMs.

Results

Asian, Black, and Hispanic youths had increased odds of having a diagnosis of obesity and being screened for all three comorbidities. Documentation of obesity was associated with increased odds of screening for all comorbidities. Female sex, documentation of obesity, and higher BMIs were associated with increased odds of being prescribed AOMs. Black and Native American races decreased the likelihood of being prescribed AOM.

Conclusions

Management of obesity in terms of documentation of disease, screening for comorbidities, and initiation of AOM continues to fall short of the guidelines put forth by multiple organizations. Race/ethnicity, sex, and BMI correlate with differences in care provided to obese paediatric patients. Further research is needed to identify the barriers to and causes of these disparities.
Machine learning‐based accelerated design of fluorphlogopite glass ceramic chemistries with targeted hardness
Authors: Garg Prachi , Broderick Scott , Mazumder Baishakhi
Published: April 2023

In this work, we develop and employ an accelerated design strategy using a machine learning algorithm to overcome the challenges for designing a new machinable glass ceramic. The trained machine learning model predicts the specific hardness value for numerous possibilities of processing conditions such as growth temperature and time. We report that the optimized growth parameters of 1200°C and 5 h achieve the highest machinability of 0.4 in the glass ceramic. Furthermore, we predicted the eight most promising candidates containing specific ratios of silicon, magnesium, aluminum, lithium, boron, potassium, barium, and oxygen. Combining machine learning with experimental data enables a systemic and rapid design of a ceramic material while capturing the underlying physics represented in the experimental data.
Effects of limited bedding and nesting on postpartum mood state in rats
Authors: Gifford Janace J. , Pluchino Jenna R. , Della Valle Rebecca , Van Weele Brooke , Brezoczky Emma , Caulfield Jasmine I. , Cavigelli Sonia A. , Schwarz Jaclyn M.
Published: April 2023

This study examined the effect of limited bedding and nesting (LBN) stress on postpartum anhedonia, maternal behaviors, anxiety‐like behaviors, and neuroendocrine and neuroimmune function as a potential model of postpartum depression. Dams underwent sucrose preference tests prior to breeding, during gestation and again postpartum, to examine the potential onset of anhedonia. On embryonic day 19, dams were placed into either a LBN or control housing condition. Contrary to our predictions, LBN stress had no effect on postpartum sucrose preference. We also found no effect of LBN condition on fecal estradiol or corticosterone levels, both of which increased at birth and decreased postpartum. Regardless of housing conditions, approximately 40% of new mothers exhibited a decrease in sucrose preference, while others show no change, suggesting an individual susceptibility to postpartum anhedonia. In a separate cohort of LBN and control dams, we measured pup retrieval, hoarding behavior, elevated plus maze (EPM), and marble burying. LBN dams exhibited increased anxiety, associated with decreased time spent in the open arms of the EPM. We also measured a significant increase in IL‐6 expression in the dorsal hippocampus and medial prefrontal cortex of postpartum dams compared to nonpregnant dams. These findings suggest that while LBN stress has effects on anxiety and maternal care, it does not induce postpartum anhedonia. Rather, there are inherent differences in susceptibility to anhedonia in individual dams, and future studies should be conducted to better understand individual vulnerability and resilience to postpartum anhedonia.
A Novel Approach to Investigate the Impact of Mindset and Physiology on the Choice to Invest Effort During an Arithmetic Task
Authors: Nieuwenhuis Smiddy , Janssen Tieme W. P. , van der Mee Denise J. , Rahman Farah A. , Meeter Martijn , van Atteveldt Nienke M.
Published: April 2023

Growth mindset, the belief that personal attributes such as intelligence are malleable, has previously been related to more effort investment. Here, we investigated how undergraduates' mindset (N = 114) relates to the choice to invest effort during an arithmetic task, indexed by whether they make low vs. high effort‐related choices. Social cognitive theory suggests that past performance experiences (mastery vs. failure) and physiological state are important sources for competence self‐evaluations. Therefore, in addition to mindset, we also investigated how effort‐related choices are influenced more dynamically, by failures and physiological responses during the task. Growth mindset and physiological effort mobilization did not predict effort‐related choices but making mistakes did predict lower effort choices in the subsequent round. This study further supports the importance of mastery experiences for effort investment and provides a novel approach for integrating different levels of influence on effort‐related choices during an educationally‐relevant task.
A simulation‐based generalized framework to model vulnerability of interdependent critical infrastructure systems under incomplete information
Authors: Ganguly Prasangsha , Mukherjee Sayanti
Published: April 2023

This paper proposes a novel simulation‐based hybrid approach coupled with time‐dependent Bayesian network analysis to model multi‐infrastructure vulnerability over time under physical, spatial, and informational uncertainties while considering cascading failures within and across infrastructure networks. Unlike existing studies that unrealistically assume that infrastructure managers have full knowledge of all the infrastructure systems, the proposed approach considers a realistic scenario where complete information about the infrastructure network topology or the supply–demand flow characteristics is not available while estimating multi‐infrastructure vulnerability. A novel heuristic algorithm is proposed to construct a dynamic fault tree to abstract the network topology of any infrastructure. In addition, to account for the unavailability of exact supply–demand flow characteristics, the proposed approach constructs the interdependence links across infrastructure network systems using different simulated parameters considering the physical, logical, and geographical dependencies. Finally, using parameters for geographical proximity, infrastructure managers' risk perception, and the relative importance of one infrastructure on another, the multi‐infrastructure vulnerability over time is estimated. Results from the numerical experiment show that for an opportunistic risk perception, the interdependencies attribute to redundancies, and with an increase in redundancy, the vulnerability decreases. On the other hand, from a conservative risk perspective, the interdependencies attribute to deficiencies/liabilities, and the vulnerability increases with an increase in the number of such interdependencies.
Epidemiology of disorders of gut‐brain interaction in Belgium and differences between two language groups: Results from the Rome foundation global epidemiology study
Authors: Broeders Bert , Devolder Elise , Jones Michael , Simrén Magnus , Bangdiwala Shrikant I. , Sperber Ami D. , Palsson Olafur S. , Tack Jan
Published: April 2023

Background

The Rome Foundation carried out a worldwide epidemiology study on DGBI according to the Rome IV criteria in 33 countries, including Belgium. DGBI prevalence varied between continents and countries, but prevalence differences within language groups in a single country have not yet been described.

Methods

We analyzed the prevalence rates of 18 DGBI and their psychosocial impact in Belgium in the French and Dutch language groups.

Key Results

DGBI prevalence was similar in the French‐speaking and Dutch‐speaking population. Having one or more DGBI was negatively associated with psychosocial well‐being. The scores for depression were lower in the Dutch‐speaking participants with one or more DGBI compared to the French‐speaking participants. Interestingly, we also found significantly lower scores in the general Dutch‐speaking versus the French‐speaking population for depression and non‐gastrointesinal somatic symptoms, and higher global physical health and mental health quality‐of‐life component scores. In the Dutch‐speaking group, medication use for gastric acid was lower, but use of prescribed analgesics was more common. Nevertheless, the use of non‐prescribed pain medication was higher in the French‐speaking group. Anxiety and sleep medication use was also higher in the latter group.

Conclusions & Interferences

The results of this first in‐depth analysis of Rome IV DGBI in Belgium show a higher prevalence for some DGBI in the French‐speaking cohort, and a larger associated disease burden. These differences between language/culture groups in the same country support the psychosocial pathophysiological model of DGBI.
Effect of environmental and spatial factors on the phylogenetic and functional diversity of the Mediterranean tree communities of Europe
Authors: Albassatneh M. C. , Dubuisson J.‐Y. , Escudero M. , Fady B. , Ponger L. , Muller S.
Published: April 2023

The tree flora of the Mediterranean Basin contains an outstanding taxonomic richness and a high proportion of endemic taxa. Contrary to other regions of the Mediterranean biome, a comprehensive phylogenetic analysis of the relationship between phylogenetic diversity, trait diversity and environmental factors in a spatial ecological context is lacking.

We inferred the first calibrated phylogeny of 203 native tree species occurring in the European Mediterranean Basin based on 12 DNA regions. Using a set of four functional traits, we computed phylogenetic diversity for all 10,042 grid cells of 10 × 10 km spatial resolution to completely cover Mediterranean Europe. Then, we tested the spatial influence of environmental factors on tree diversity.

Our results suggest that the nature of the relationship between traits and phylogeny varies among the different studied traits and according to the evolutionary distance considered. Phylogenetic diversity and functional diversity of European Mediterranean trees correlated strongly with species richness. High values of these diversity indices were located in the north of the study area, at high altitude, and minimum temperature of the coldest month. In contrast, the two phylogenetic indices that were not correlated with species richness (Mean Phylogenetic Distance, Phylogenetic Species Variability) were located in the south of the study area and were positively correlated with high altitude, soil organic carbon stock and sand soil texture.

Our study provides support for the use of phylogenies in conservation biology to assess ecosystem functioning, and provides insights for the implementation of sustainable forest ecosystem management.
The novel HLA‐A*29:172 allele identified in a patient indicated for hematopoietic stem cell transplantation
Authors: Mrazek Frantisek , Pubalova Sarka , Novak Zbynek , Mojtkova Nikola , Vrana Milena
Published: April 2023

HLA‐A*29:172 allele differs from HLA‐A*29:01:01:01 by one missense single C/G nucleotide exchange in codon 77.
Identification of the novel HLA‐C*04:495 allele by sequencing‐based typing
Authors: Alkhaibari Abdulrhman , Alqasem Afnan , Alblaihed Asma , Alajlan Abdulaziz , Hajeer Ali H.
Published: April 2023

The HLA‐C*04:495 allele differs from HLA‐C*04:01:01:31 by two nucleotide changes in the 5′UTR and exon 5.
Characterization of the novel HLA‐C*03:552 allele by sequencing‐based typing
Authors: Elsermans Vincent , Visentin Jonathan , Top Isabelle , Pajot Thibault , Labalette Myriam
Published: April 2023

HLA‐C*03:552 differs from HLA‐C*03:04:01:01 by one nucleotide substitution in codon 72 in exon 2.
The novel HLA‐C allele, HLA‐C*07:02:141 was identified in a Chinese individual
Authors: Zhao Shuoxian , Li Ying , Wang Fang , Zhang Wei , Zhu Faming
Published: April 2023

HLA‐C*07:02:141 shows one nucleotide substitution at position 4 when compared to HLA‐C*07:02:01:01.
Application of droplet digital PCR combined with TaqMan real‐time PCR in Dombrock blood group genotyping in Northwest China
Authors: Li Zhuolin , Wang Yufeng , Sun Mao , Chen Tangdong , Wu Yuanming , Chen Kun
Published: April 2023

Background and Objectives

The Dombrock blood group system is based on the DO gene. DO*A and DO*B antigens are the result of a single‐nucleotide polymorphism (SNP) on this gene. The introduction of Do antigens through blood transfusion or other invasive factors like infection may result in the production of Do antibodies, which may cause serious haemolytic transfusion reactions. In this study, TaqMan real‐time PCR and droplet digital PCR were used to detect rare DO*A allele, guide the search for rare DO*A allele donors, and calculate DO alleles frequencies in mixed populations in Northwest China.

Materials and Methods

In this study, the highly sensitive and accurate TaqMan real‐time polymerase chain reaction (PCR) method was used to detect and screen DO genotype SNPs in combination with droplet digital PCR. We also searched for rare DO*A allele donors and calculated the frequencies of DO alleles in mixed populations.

Results

A total of 1202 donor DNA samples were collected from Northwest China, of which 202 were used to detect DO allele SNPs using TaqMan real‐time PCR. The rare DO*A allele was detected in the other 1000 blood donors by droplet digital PCR, and gene frequencies were inferred from dual channel droplet digital PCR data. Among 1202 donors from Northwest China, the allele frequencies of DO*A and DO*B were 0.1128 and 0.8872, respectively.

Conclusion

The sequencing results confirmed that this new way of detecting DO alleles by droplet digital PCR with specific probes can detect rare DO*A allele to predict the presence of the rare antigen Doa and infer DO allele frequencies. This method is highly sensitive and specific.
Microcirculation surrounding end‐stage human chronic skin wounds is associated with endoglin/CD146/ALK‐1 expression, endothelial cell proliferation and an absence of p16Ink4a
Authors: Wang Jiarong , Tinney Dylan , Grynyshyn Michael , Pickering J. Geoffrey , Power Adam , Dubois Luc , Hamilton Douglas W.
Published: April 2023

Angiogenesis is an essential part of normal skin healing, re‐establishing blood flow in developing granulation tissue. Non‐healing skin wounds are associated with impaired angiogenesis and although the role of re‐establishing macroscopic blood flow to limbs to prevent wound chronicity is well investigated, less is known about vascular alterations at the microcirculatory level. We hypothesised that significant phenotypic changes would be evident in blood vessels surrounding chronic skin wounds. Wound edge tissue, proximal to wound (2 cm from wound edge) and non‐involved skin (>10 cm from wound edge) was harvested under informed consent from 20 patients undergoing elective amputation due to critical limb ischemia. To assess blood vessel structure and viability, tissue was prepared for histological analysis and labelled with antibodies specific for PECAM‐1 (CD31), CD146, endoglin, ALK‐1, ALK‐5, and p16Ink4a as a marker of cellular senescence. Density of microvasculature was significantly increased in wound edge dermis, which was concomitant with increased labelling for endoglin and CD146. The number of CD31 positive vessel density was unchanged in wound edge tissue relative to non‐involved tissue. Co‐labelling of endoglin with the transforming growth factor receptor ALK‐1, and to a lesser extent ALK‐5, demonstrated activation of endothelial cells which correlated with PCNA labelling indicative of proliferation. Analysis of p16Ink4a staining showed a complete lack of immunoreactivity in the vasculature and dermis, although staining was evident in sub‐populations of keratinocytes. We conclude that the endoglin‐ALK‐1‐endothelial proliferation axis is active in the vasculature at the edge of chronic skin wounds and is not associated with p16Ink4a mediated senescence. This information could be further used to guide treatment of chronic skin wounds and optimise debridement protocols.
Challenges in Geometry Assurance of Megacasting in the Automotive Industry
Authors: Wärmefjord Kristina , Hansen Josefin , Söderberg Rikard
Published: April 2023

Megacasting is a new concept in the automotive industry. A large number of sheet metal parts will be replaced with one large aluminum casting, i.e., a megacasting. This helps to reduce weight, opens up for larger design flexibility, allows for a more circular production, and takes away a large number of assembly steps in the production process. However, there are also challenges related to the use of megacastings. This position paper outlines challenges associated with the geometrical quality of the final product. It covers robust design and tolerancing in early product development phases as well as inspection preparation during pre-production and digital twin setup during full production to ensure the geometrical quality of a product containing a megacasting. Simulations of both part-level and assembly-level deviation and variation are discussed. The paper outlines a geometry assurance process for products containing megacastings in the automotive industry, and what research challenges that are the most important ones to address in this area. It is concluded that computer-aided tolerancing tools must be able to predict the dimensional effects from joining methods such as flow-drill fasteners or self-pierced riveting, to use casting simulation as input, and to handle combinations of solid and surface meshes. Furthermore, there might be a need for adjustments to the joining process based on digital twins to achieve proper quality at a reasonable price. Experiences in using megacastings in the body-in-white are lacking and a fast learning curve is required.
Global beta-diversity of angiosperm trees is shaped by Quaternary climate change
Authors: Xu Wu-Bing , Guo Wen-Yong , Serra-Diaz Josep M. , Schrodt Franziska , Eiserhardt Wolf L. , Enquist Brian J. , Maitner Brian S. , Merow Cory , Violle Cyrille , Anand Madhur , Belluau Michaël , Bruun Hans Henrik , Byun Chaeho , Catford Jane A. , Cerabolini Bruno E. L. , Chacón-Madrigal Eduardo , Ciccarelli Daniela , Cornelissen J. Hans C. , Dang-Le Anh Tuan , de Frutos Angel , Dias Arildo S. , Giroldo Aelton B. , Gutiérrez Alvaro G. , Hattingh Wesley , He Tianhua , Hietz Peter , Hough-Snee Nate , Jansen Steven , Kattge Jens , Komac Benjamin , Kraft Nathan J. B. , Kramer Koen , Lavorel Sandra , Lusk Christopher H. , Martin Adam R. , Ma Ke-Ping , Mencuccini Maurizio , Michaletz Sean T. , Minden Vanessa , Mori Akira S. , Niinemets Ülo , Onoda Yusuke , Onstein Renske E. , Peñuelas Josep , Pillar Valério D. , Pisek Jan , Pound Matthew J. , Robroek Bjorn J. M. , Schamp Brandon , Slot Martijn , Sun Miao , Sosinski Ênio E. , Soudzilovskaia Nadejda A. , Thiffault Nelson , van Bodegom Peter M. , van der Plas Fons , Zheng Jingming , Svenning Jens-Christian , Ordonez Alejandro
Published: April 2023

As Earth’s climate has varied strongly through geological time, studying the impacts of past climate change on biodiversity helps to understand the risks from future climate change. However, it remains unclear how paleoclimate shapes spatial variation in biodiversity. Here, we assessed the influence of Quaternary climate change on spatial dissimilarity in taxonomic, phylogenetic, and functional composition among neighboring 200-kilometer cells (beta-diversity) for angiosperm trees worldwide. We found that larger glacial-interglacial temperature change was strongly associated with lower spatial turnover (species replacements) and higher nestedness (richness changes) components of beta-diversity across all three biodiversity facets. Moreover, phylogenetic and functional turnover was lower and nestedness higher than random expectations based on taxonomic beta-diversity in regions that experienced large temperature change, reflecting phylogenetically and functionally selective processes in species replacement, extinction, and colonization during glacial-interglacial oscillations. Our results suggest that future human-driven climate change could cause local homogenization and reduction in taxonomic, phylogenetic, and functional diversity of angiosperm trees worldwide.
Therapeutic gene silencing of
CKAP5
leads to lethality in genetically unstable cancer cells
Authors: Chatterjee Sushmita , Naidu Gonna Somu , Hazan-Halevy Inbal , Grobe Hanna , Ezra Assaf , Sharma Preeti , Goldsmith Meir , Ramishetti Srinivas , Sprinzak David , Zaidel-Bar Ronen , Peer Dan
Published: April 2023

The potential of microtubule-associated protein targets for cancer therapeutics remains largely unexplored due to the lack of target-specific agents. Here, we explored the therapeutic potential of targeting cytoskeleton-associated protein 5 (CKAP5), an important microtubule-associated protein, with
CKAP5
-targeting siRNAs encapsulated in lipid nanoparticles (LNPs). Our screening of 20 solid cancer cell lines demonstrated selective vulnerability of genetically unstable cancer cell lines in response to
CKAP5
silencing. We identified a highly responsive chemo-resistant ovarian cancer cell line, in which
CKAP5
silencing led to significant loss in EB1 dynamics during mitosis. Last, we demonstrated the therapeutic potential in an in vivo ovarian cancer model, showing 80% survival rate of si
CKAP5
LNPs-treated animals. Together, our results highlight the importance of CKAP5 as a therapeutic target for genetically unstable ovarian cancer and warrants further investigation into its mechanistic aspects.
Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold
Authors: Liu Shun , Chen Hua , Yin Yan , Lu Defen , Gao Guoming , Li Jie , Bai Xiao-Chen , Zhang Xuewu
Published: April 2023

The FAM46 (also known as TENT5) proteins are noncanonical poly(A) polymerases (PAPs) implicated in regulating RNA stability. The regulatory mechanisms of FAM46 are poorly understood. Here, we report that the nuclear protein BCCIPα, but not the alternatively spliced isoform BCCIPβ, binds FAM46 and inhibits their PAP activity. Unexpectedly, our structures of the FAM46A/BCCIPα and FAM46C/BCCIPα complexes show that, despite sharing most of the sequence and differing only at the C-terminal portion, BCCIPα adopts a unique structure completely different from BCCIPβ. The distinct C-terminal segment of BCCIPα supports the adoption of the unique fold but does not directly interact with FAM46. The β sheets in BCCIPα and FAM46 pack side by side to form an extended β sheet. A helix-loop-helix segment in BCCIPα inserts into the active site cleft of FAM46, thereby inhibiting the PAP activity. Our results together show that the unique fold of BCCIPα underlies its interaction with and functional regulation of FAM46.
Disordered topological graphs enhancing nonlinear phenomena
Authors: Jia Zhetao , Seclì Matteo , Avdoshkin Alexander , Redjem Walid , Dresselhaus Elizabeth , Moore Joel , Kanté Boubacar
Published: April 2023

Complex networks play a fundamental role in understanding phenomena from the collective behavior of spins, neural networks, and power grids to the spread of diseases. Topological phenomena in such networks have recently been exploited to preserve the response of systems in the presence of disorder. We propose and demonstrate topological structurally disordered systems with a modal structure that enhances nonlinear phenomena in the topological channels by inhibiting the ultrafast leakage of energy from edge modes to bulk modes. We present the construction of the graph and show that its dynamics enhances the topologically protected photon pair generation rate by an order of magnitude. Disordered nonlinear topological graphs will enable advanced quantum interconnects, efficient nonlinear sources, and light-based information processing for artificial intelligence.
Design of medical tympanostomy conduits with selective fluid transport properties
Authors: Patel Haritosh , Pavlichenko Ida , Grinthal Alison , Zhang Cathy T. , Alvarenga Jack , Kreder Michael J. , Weaver James C. , Ji Qin , Ling Christopher W. F. , Choy Joseph , Li Zihan , Black Nicole L. , Bispo Paulo J. M. , Lewis Jennifer A. , Kozin Elliott D. , Aizenberg Joanna , Remenschneider Aaron K.
Published: April 2023

Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary–length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.
ADAR1 Biology Can Hinder Effective Antiviral RNA Interference
Authors: Uhl Skyler , Jang Chanyong , Frere Justin J. , Jordan Tristan X. , Simon Anne E. , tenOever Benjamin R.
Published: April 2023

All life at the cellular level has the capacity to induce an antiviral response. Here, we examine the result of imposing the antiviral response of one branch of life onto another and find evidence for conflict.
Mechanisms Underpinning Morphogenesis of a Symbiotic Organ Specialized for Hosting an Indispensable Microbial Symbiont in Stinkbugs
Authors: Oishi Sayumi , Harumoto Toshiyuki , Okamoto-Furuta Keiko , Moriyama Minoru , Fukatsu Takema
Published: April 2023

Diverse organisms are associated with microbial mutualists, in which specialized host organs often develop for retaining the microbial partners. In light of the origin of evolutionary novelties, it is important to understand what mechanisms underpin the elaborate morphogenesis of such symbiotic organs, which must have been shaped through interactions with the microbial symbionts.
A Potential Draft Sequence Analysis of Enterobacter asburiae Strain B6_18 of an Endophytic Bacterium
Authors: Babalola Olubukola Oluranti , Agunbiade Victor Funso , Fadiji Ayomide Emmanuel
Published: April 2023

The work presented here describes the genomic analysis of the maize plant-isolated endophytic strain
Enterobacter asburiae
B6_18 from Northwest Province, South Africa, for potential maize plant growth-promoting traits.
Proximity-Dependent Biotinylation and Identification of Flagellar Proteins in Trypanosoma cruzi
Authors: Won Madalyn M. , Baublis Aaron , Burleigh Barbara A.
Published: April 2023

Trypanosoma cruzi
is a protozoan parasite that causes Chagas disease, which causes substantial morbidity and mortality in South and Central America. Throughout its life cycle,
T. cruzi
interacts with insect and mammalian hosts via its single flagellum, establishing intimate contact with host membranes.
Amino Acid Starvation-Induced Glutamine Accumulation Enhances Pneumococcal Survival
Authors: Zhang Chengwang , Liu Yanhong , An Haoran , Wang Xueying , Xu Lina , Deng Haiteng , Wu Songquan , Zhang Jing-Ren , Liu Xiaohui
Published: April 2023

Bacteria are known to cope with amino acid starvation by halting growth and prolonging survival via the stringent response signaling system. Previous investigations have allowed us to understand how the stringent response regulates many aspects of macromolecule synthesis and catabolism, but how amino acid starvation promotes bacterial survival at the metabolic level remains largely unclear.
Electroacupuncture as a complement to usual care for patients with non-acute low back pain after back surgery: a pilot randomised controlled trial
Authors: Heo In , Hwang Man-Suk , Hwang Eui-Hyoung , Cho Jae-Heung , Ha In-Hyuk , Shin Kyung-Min , Lee Jun-Hwan , Kim Nam-Kwen , Son Dong-Wuk , Shin Byung-Cheul
Published: April 2023

Objectives

The aim of this pilot study was to estimate the sample size for a large pragmatic study of the comparative effectiveness of electroacupuncture (EA) for low back pain (LBP) after back surgery.

Design

A randomised, active-controlled, assessor-blinded trial.

Participants

Patients with recurrent or persistent LBP, defined as a Visual Analogue Scale (VAS) score of ≥50 mm, with or without leg pain after back surgery.

Interventions

Patients were randomised to an EA plus usual care (UC) group or to a UC alone group at a 1:1 ratio. Patients assigned to each group received UC, including drug therapy, physical therapy and back pain education, twice a week for 4 weeks; those assigned to the EA plus UC group additionally received EA.

Outcome measures

The primary outcome was severity of LBP as measured by VAS. Secondary outcomes included back pain-related disability, assessed using the Oswestry Disability Index (ODI) and quality of life, assessed using the EuroQol Five Dimensions (EQ-5D) questionnaire. Statistical analysis was performed using paired and independent t-tests. A p value of <0.05 was considered statistically significant.

Results

Thirty-nine patients were allocated to receive EA plus UC (n=18) or UC alone (n=21). There was no statistically significant difference in VAS or EQ-5D scores between the two groups, but there was a significant decrease in ODI scores (p=0.0081). Using G*Power, it was calculated that 40 participants per group would be needed for a future trial according to VAS scores. Considering for a 25% dropout rate, 108 participants (54 per group) would be needed.

Conclusions

A future trial addressing the risk of bias and including the estimated sample size would allow for better clinical assessment of the benefits of EA plus UC in treatment of patients with non-acute pain after back surgery.

Trial registration number

NCT01966250.
How does exercise dose affect patients with long-term osteoarthritis of the knee? A study protocol of a randomised controlled trial in Sweden and Norway: the SWENOR Study
Authors: Torstensen Tom Arild , Grooten Wilhelmus J A , Østerås Håvard , Heijne Annette , Harms-Ringdahl Karin , Äng Björn Olov
Published: April 2023

Introduction

Osteoarthritis (OA) of the knee is characterised by knee pain, disability and degenerative changes, and places a burden on societies all over the world. Exercise therapy is an often-used modality, but there is little evidence of what type of exercise dose is the most effective, indicating a need for controlled studies of the effect of different dosages. Thus, the aim of the study described in this protocol is to evaluate the effects of high-dose versus low-dose medical exercise therapy (MET) in patients with knee OA.

Methods and analysis

This is a multicentre prospective randomised two-arm trial with blinded assessment and data analysis. We are planning to include 200 patients aged 45–85 years with symptomatic (pain and decreased functioning) and X-ray verified diagnosis of knee OA. Those eligible for participation will be randomly allocated to either high-dose (n=100) or low-dose (n=100) MET. All patients receive three supervised treatments each week for 12 weeks, giving a total of 36 MET sessions. The high-dose group exercises for 70–90 min compared with 20–30 min for the low-dose group. The high-dose group exercises for a longer time, and receives a greater number of exercises with more repetitions and sets. Background and outcome variables are recorded at inclusion, and outcome measures are collected after every sixth treatment, at the end of treatment, and at 6-month and 12-month follow-ups. Primary outcome is self-rated knee functioning and pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The primary end point is at the end of treatment after 3 months, and secondary end points are at 6 months and 12 months after the end of treatment.

Ethics and dissemination

This project has been approved by the Regional Research Ethics Committees in Stockholm, Sweden, and in Norway. Our results will be submitted to peer-reviewed journals and presented at national and international conferences.

Trial registration number

NCT02024126
IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians
Authors: Vasan Senthil K , Roy Ambuj , Samuel Viji Thomson , Antonisamy Belavendra , Bhargava Santosh K , Alex Anoop George , Singh Bhaskar , Osmond Clive , Geethanjali Finney S , Karpe Fredrik , Sachdev Harshpal , Agrawal Kanhaiya , Ramakrishnan Lakshmy , Tandon Nikhil , Thomas Nihal , Premkumar Prasanna S , Asaithambi Prrathepa , Princy Sneha F X , Sinha Sikha , Paul Thomas Vizhalil , Prabhakaran Dorairaj , Fall Caroline H D
Published: April 2023

Introduction

South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians.

Methods and analysis

We propose to study approximately 3000 men and women aged 43–50 years from two birth cohorts established in 1969–1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes.

Ethics and dissemination

The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals.

Trialregistrationnumber

NCT13432279.
Protocol of a Multicenter International Randomized Controlled Manikin Study on Different Protocols of Cardiopulmonary Resuscitation for laypeople (MANI-CPR)
Authors: Baldi Enrico , Contri Enrico , Burkart Roman , Borrelli Paola , Ferraro Ottavia Eleonora , Tonani Michela , Cutuli Amedeo , Bertaia Daniele , Iozzo Pasquale , Tinguely Caroline , Lopez Daniel , Boldarin Susi , Deiuri Claudio , Dénéréaz Sandrine , Dénéréaz Yves , Terrapon Michael , Tami Christian , Cereda Cinzia , Somaschini Alberto , Cornara Stefano , Cortegiani Andrea
Published: April 2023

Introduction

Out-of-hospital cardiac arrest is one of the leading causes of death in industrialised countries. Survival depends on prompt identification of cardiac arrest and on the quality and timing of cardiopulmonary resuscitation (CPR) and defibrillation. For laypeople, there has been a growing interest on hands-only CPR, meaning continuous chest compression without interruption to perform ventilations. It has been demonstrated that intentional interruptions in hands-only CPR can increase its quality. The aim of this randomised trial is to compare three CPR protocols performed with different intentional interruptions with hands-only CPR.

Methods and analysis

This is a prospective randomised trial performed in eight training centres. Laypeople who passed a basic life support course will be randomised to one of the four CPR protocols in an 8 min simulated cardiac arrest scenario on a manikin: (1) 30 compressions and 2 s pause; (2) 50 compressions and 5 s pause; (3) 100 compressions and 10 s pause; (4) hands-only. The calculated sample size is 552 people. The primary outcome is the percentage of chest compression performed with correct depth evaluated by a computerised feedback system (Laerdal QCPR).

Ethics and dissemination

. Due to the nature of the study, we obtained a waiver from the Ethics Committee (IRCCS Policlinico San Matteo, Pavia, Italy). All participants will sign an informed consent form before randomisation. The results of this study will be published in peer-reviewed journal. The data collected will also be made available in a public data repository.

Trial registration number

NCT02632500.
Efficacy of practising Tai Chi for older people with mild dementia: protocol for a randomised controlled study
Authors: Lyu Jihui , Li Wenjie , Rong Xiangjiang , Wei Lian , Huang Nayan , Champ Mei , Xiong Qian , Chen Xueli , Li Mo , Li Fangling
Published: April 2023

Introduction

Many studies suggest that Tai Chi exercise is a safe and appropriate mind-body exercise for older people and effectively slows down age-related cognitive decline. A set of bespoke Tai Chi exercise named ‘Cognition Protecting Tai Chi’ (CPT) has been created for older people with cognitive impairments by the research team of geriatricians, neurologists, rehabilitation specialists, experts of sports medicine and experienced practitioners of traditional Chinese medicine. This trial is designed to evaluate its effects on cognitive function, behaviour/moods, risk of falls and activities of daily living of the participants with mild dementia.

Methods and analysis

A randomised controlled study will be conducted. Eighty participants with mild dementia will be recruited and randomly allocated to an intervention group and a control group. The intervention group will practice the CPT exercise three times a week for 20 min each time under the guidance of professional therapists. The control group will continue receiving their routine treatments. The duration of this study will be 10 months. All participants will be assessed with a battery of neuropsychological and functional evaluations, which include Mini Mental State Examination, Montreal Cognitive Assessment, the WHO-University of California Los Angeles-Auditory Verbal Learning test (WHO-UCLA-AVLT), Trail Making Test (TMT), Geriatric Depression Scale, Neuropsychological Inventory and Barthel Index, at the baseline, 5 and 10 months during the study period. Fall incident will also be recorded. The primary outcome will be the WHO-UCLA-AVLT delayed recall score. The secondary outcome will be the TMT score.

Ethics and dissemination

This study has been approved by the ethical review committee of the Beijing Geriatric Hospital (protocol number: 2015–021). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the findings of the study to peer-reviewed journals or academic conferences to be published.

Trial registration number

NCT16009872; Pre-results.