bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical Analysis of Double‐Level Oblique Lumbar Fusion with Different Types of Fixation: A Finite Element‐Based Study
Authors: Fan Kaibin , Zhang Di , Xue Rui , Chen Wei , Hou Zhiyong , Zhang Yingze , Meng Xianzhong
Published: April 2023

Objective

One well‐liked less invasive procedure is oblique lumbar interbody fusion (OLIF). The biomechanical characteristics of double‐level oblique lumbar interbody fusion in conjunction with various internal fixations are poorly understood. The purpose of this study was to clarify the biomechanical characteristics of double‐level oblique lumbar interbody fusion for osteoporosis spines using various internal fixation techniques.

Methods

Based on CT scans of healthy male volunteers, a complete finite element model of osteoporosis in L1–S1 was established. After validation, L3–L5 was selected as the surgical segment to construct four surgical models: (a) two stand‐alone cages (SA); (b) two cages with unilateral pedicle screws (UPS); (c) two cages with bilateral pedicle screws (BPS); and (d) two cages with bilateral cortical bone trajectory screws (CBT). Segmental range of motion (ROM), cage stress, and internal fixation stress were studied in all surgical models and compared with the intact osteoporosis model.

Results

The SA model had a minimal reduction in all motions. The CBT model had the most noticeable reduction in flexion and extension activities, while the reduction in the BPS model was slightly less than that in the CBT model but larger than that in the UPS model. The BPS model had the greatest limitation in left–right bending and rotation, which was greater than the UPS and CBT models. CBT had the smallest limitation in left–right rotation. The cage stress of the SA model was the highest. The cage stress in the BPS model was the lowest. Compared with the UPS model, the cage stress in the CBT model was larger in terms of flexion and LB and LR but slightly smaller in terms of RB and RR. In the extension, the cage stress in the CBT model is significantly smaller than in the UPS model. The CBT internal fixation was subjected to the highest stress of all motions. The BPS group had the lowest internal fixation stress in all motions.

Conclusions

Supplemental internal fixation can improve segmental stability and lessen cage stress in double‐level OLIF surgery. In limiting segmental mobility and lowering the stress of cage and internal fixation, BPS outperformed UPS and CBT.
Analgesic effects of intrathecal morphine and bupivacaine during robotic‐assisted surgery: A prospective randomized controlled study
Authors: Engström Anders J. E. , Ivarsson Carina A. , Aldergård Åsa , Henningsson Ragnar N.
Published: April 2023

Background

Limited data exist concerning the management of postoperative pain after robotic‐assisted surgery. The present study was performed to investigate the efficacy of intrathecal morphine and bupivacaine to treat postoperative pain in adult women undergoing robot‐assisted laparoscopic hysterectomy.

Methods

The primary outcomes of this study were opioid consumption and pain scores during and after robotic surgery. 96 patients were prospectively enrolled and randomized to a nonspinal group (n = 48) and a spinal group (n = 48). The intrathecal regimen consisted of 100 μg morphine and 15 mg of bupivacaine. The numeric rating scale scores (NRS) were assessed every 15 min in the postoperative care unit (PACU) and pain was treated with iv fentanyl or morphine when NRS was above 5 and orally oxycodone when NRS was 3–5. Cumulative iv opioid‐consumption and NRS scores were compared.

Results

Intrathecal morphine and bupivacaine resulted in a significantly lower cumulative total iv opioid (morphine equivalents) consumption (9.4 ± 3.9 vs. 22.8 ± 6.1 mg equivalents). Highest recorded NRS scores in the PACU were also significantly lower in the spinal group (2.0 ± 2.6 vs. 5.3 ± 3.2).

Conclusion

Intrathecal morphine and bupivacaine to treat postoperative pain after robotic‐assisted laparoscopic hysterectomy decrease total opioid consumption and NRS pain scores. This might be of great importance to diminish the rate of other serious disadvantages related to opioids.
Metaethics as conceptual engineering
Authors: Skarsaune Knut Olav
Published: April 2023

On the traditional approach to metaethics, theories are expected to be faithful to ordinary normative discourse—or at worst (if we think the ordinary discourse is metaphysically unsound) to deviate from it as little as possible. This paper develops an alternative, “conceptual engineering” approach to metaethical enquiry, which is not in this way restricted by our present discourse. On this approach, we will seek to understand the psychology, semantics, metaphysics and epistemology, not just of our present concepts, but also of other possible normative concepts. The ultimate point of the enquiry is to choose between the available alternatives: to decide what kinds of normative concepts to use, going forward. The paper aims to make this suggestion precise, in a way that (a) answers worries about circularity, (b) answers worries about “changing the subject”, (c) retains metaethics as a truth‐seeking enquiry, and (d) leads to an independently plausible methodology.
Switching to profitable outside options under supplier encroachment
Authors: Liang Liang , Chen Jingxian , Yao Dong‐qing
Published: April 2023

In practice, manufacturers may encroach on retail markets through a variety of methods, one being through the use of an online channel direct to the consumers, called encroachment. Current research typically assumes that downstream retailers retain procurement from the encroaching supplier. In reality, however, retailers may have the option of switching suppliers after encroachment. By considering a supply chain consisting of one manufacturer and one retailer with outside options, this paper analyzes the effects of the option of switching suppliers on the supply chain players' strategic interactions under the threat of supplier encroachment. We consider that the manufacturer makes encroachment decision preceding the retailer's switch decision. We capture various outcomes of the encroachment and switch decisions by using a classic encroachment model with quantity decisions (Cournot model). Specifically, we identify two effects of the outside option on the strategic encroachment decision. The first, the deterrence effect, means that the manufacturer's encroachment is deterred by the threat of switching supplies altogether; while the second, the permissive effect, indicates that the retailer intends to switch to the alternative source after the encroachment. Interestingly, we show that the encroachment could improve the total profit of the incumbent manufacturer and the retailer even when the retailer's switch has occurred. In this case, however, the manufacturer profits while the retailer is hurt by the encroachment and the switch. Finally, we also investigate several extended cases to demonstrate the robustness of our findings.
Compliance in crisis: Concern, trust and distrustful complacency in the COVID‐19 pandemic
Authors: Lalot Fanny , Abrams Dominic , Jessop Curtis , Curtice John
Published: April 2023

Two studies tested a distrustful complacency hypothesis, according to which either concern or political trust would be enough to sustain law‐abiding attitudes and compliance with health‐protective policies during the COVID‐19 pandemic; but the absence of both concern and trust would result in markedly lower support and compliance. Study 1 supported this hypothesis with NatCen nationally representative sample of Great Britain (N = 2413; weighted regression analyses), focussing on law‐abiding attitudes. Study 2 (preregistered) replicated these findings with a representative sample (N = 1523) investigating support for COVID‐19 policies and compliant behaviour. Participants who were less concerned about the consequences of the pandemic (for themselves and for others) and simultaneously less trustful of the government expressed weaker law‐abiding attitudes and reported less compliance with COVID‐19 restrictions. These findings have implications for policy and public health strategies in time of crisis.
Expanding access to STEM pathways: Professional learning for high school counselors
Authors: Ross Lydia , Dalal Medha , Carberry Adam
Published: April 2023

This study is situated within a large‐scale national high school level engineering education initiative that aims to “demystify” engineering for high school students, teachers, and counselors through an all‐inclusive high school level engineering course. Counselors participated in a series of PD activities centered on the following components: (1) design and development of a new engineering course open to all high school students, (2) teacher and counselor PD, and (3) a learning community of teachers, counselors, engineering educators, and practicing engineers. We utilized an exploratory qualitative research design to understand counselors’ perceptions and experiences. Through their own hands‐on experiences, counselors had concrete examples to share with students about engineering as a field to consider for postsecondary education and careers. Further, through a broadened understanding of the skills needed to excel in engineering, counselors expressed that they would work with all students to recommend them towards engineering, rather than just the “math and science” students. Through this study, we identified an important gap in the engineering pipeline: high school guidance counselors. In order to broaden participation in engineering, we must first expand the knowledge of those people working closely with high school students on postsecondary plans.
Autologous i‐PRF promotes healing of radiation‐induced skin injury
Authors: Tian Kai , Ye Jingcheng , Zhong Yuanyuan , Jia Zou , Xu Wushuang , Gao Suyue , Cao Shikun , Li Ke , Wu Lijun
Published: April 2023

Skin, as an exposed tissue, often suffers damage after exposure to radiotherapy and accidental events, which may lead to the formation of chronic refractory wounds. However, effective treatment options are usually limited for severe radiation‐induced skin injury (RSI). Platelet‐rich plasma (PRP) has been identified to promote wound healing, but whether a new generation of blood‐derived biomaterial, injectable platelet‐rich fibrin (i‐PRF), is effective in repairing RSI remains unclear. In this study, blood was drawn from humans and Sprague–Dawley rats to prepare PRP and i‐PRF, and the regenerative functions of PRP and i‐PRF were investigated by exposing the dorsal skin of SD rats to local radiation (45 Gy) and exposing HDF‐α cells and human umbilical vein endothelial cells (HUVECs) cells to X‐rays (10 Gy). The healing effect of i‐PRF on RSI was analysed by tube formation assay, cell migration and apoptosis assays, ROS assay, wound healing assay, histological characterisation and immunostaining. The results showed that exposure to high doses of radiation reduced cell viability, increased ROS levels and induced cell apoptosis, thereby causing dorsal trauma of rats. However, both PRP and i‐PRF could resisted RSI, and they were capable of reducing inflammation and promoting angiogenesis and vascular regeneration. i‐PRF has a higher concentration of platelets and platelet‐derived growth factors, which has a more convenient preparation method and better repair effect and possesses a good application prospect for the repair of RSI.
Preclinical assessment of novel longer‐duration wear negative pressure wound therapy dressing in a porcine model
Authors: Allen Diwi , Robinson Timothy , Schmidt Marisa , Kieswetter Kristine
Published: April 2023

While reticulated open cell foam (ROCF) is a well‐established dressing for negative pressure wound therapy (NPWT), there is the known potential for granulation tissue ingrowth if left in place for longer than 72 h. This may cause wound bed disruption, bleeding, and pain upon dressing removal. In addition, any retained foam fragments may elicit an adverse tissue reaction. A novel, easy to use dressing designed to utilise the advantages of ROCF while addressing its challenges has recently been created. This 7 day study investigated the utility of a novel NPWT dressing under longer‐duration wear circumstances while assessing the prevalence of tissue ingrowth and ease of dressing removal in full‐thickness excisional wounds utilising a porcine model. Histopathology and morphometry evaluations indicated thicker granulation tissue with, depending on the parameters assessed, either comparable or better tissue quality for wounds treated with the novel dressing. Greater re‐epithelialization levels were also evident compared with ROCF. Three‐dimensional imaging analysis indicated faster wound fill with a corresponding decrease in wound area with the novel dressing. Furthermore, tissue ingrowth was limited to only ROCF‐treated wounds, which was not unexpected in this longer‐duration wear study. The force required to remove the novel dressing was considerably lower compared with ROCF, correlating to the tissue ingrowth results. Results of this study illustrate that the novel dressing provided more favourable wound healing results compared with traditional ROCF. In addition, reduction in the risk of tissue ingrowth and low dressing peel force may allow it to be used as a longer‐wear dressing.
SPRING-BACK ANALYSIS OF THE VEE BENDING PROCESS FOR HIGH-STRENGTH STAINLESS STEEL
Authors: Rahdiana Nana , - Sukarman , - Khoirudin , Abdulah Amri , Shieddieque Apang Djafar
Published: April 2023

This study discussed the evaluation of bending process using high-strength SUS 304 (HS-SUS-304) material of high degree tolerances, and its application in a safe, strongbox, and strongroom protection system. This bending process is one of the several material-forming techniques widely used in the manufacturing industry. Moreover, incorrectly selected parameters such as the V-die punch radius, the angle of V-die bending, and the angle of machine parameters often leads to material failure and wrong final dimensions. The V-bending process was chosen for evaluation because it exhibits significant spring-back effect and has a wide range of industrial applications. The experimental method utilized HS-SUS 304 with a thickness of 3.0 mm that meets the ASTM A-240 requirement, and the input parameters used for V-die angle as well as tip punch radius were chosen in order to achieve the 90o ± 0.5o, and 50o ± 0.5o degrees of the workpieces. The V-die angle of 89o was selected with a tip punch radius of 1.0 mm and 1.2 mm. Furthermore, the spring-back effect was analyzed and evaluated to meet the standard angle requirement, and the results showed that the settings on the bending machine need to be adjusted to achieve angles within tolerances of degrees. It was observed that when the process bend angles on the machine was set at 93.75o and 52.83o with 1.0 mm V-dies tip punch radius, the spring-back factor results produce an average of 0.9609, 0.9618, and 0.9600. Meanwhile, this average increased to 0.9634, 0.9641, and 0.9655, by using 1.2 mm.
FATIGUE BEHAVIOUR OF TEMPERED AND ISOTHERMAL HEAT TREATED AISI 5160 LEAF SPRING STEEL
Authors: Sultan Jamal Nayief , Karash Emad Toma , Najim Majid Kalel
Published: April 2023

The oil quench and temper technique have a lot of benefits for heavy duty spring manufacture since it may expose the best balance of toughness and ductility, as well as increase fatigue life. The current study looked at the fatigue behavior of tempered AISI 5160 leaf spring steel samples at tempering temperatures of 400, 450, 500, 550, and 600 °C, as well as isothermally heat- treated steel samples at 830 °C. All leaf spring steel samples that had undergone thermal tempering and isothermal heat treatment were then tested up to fracture utilizing rotational fatigue test equipment under the effect of various stress levels. All steel samples subjected to tempering heat treatments of 400°C to 600°C showed a decrease in hardness ratings. The Rockwell hardness ratings of the steel samples that treated to isothermal heat treatment increased significantly. Experimental fatigue testing revealed that the values of fatigue resistance for steel samples tempered at (400 and 450) °C temperatures dropped by a small amount. The fatigue resistance values for steel specimens tempered at 500 °C to 600 °C temperatures decreased more than the values for steel samples tempered at 500 to 600 °C temperatures. A fatigue resistance of steel samples that were treated to isothermal heat treatments, on the other hand, increased. Steel samples that were isothermally heat-treated at 830 °C and then chilled in a salt brine solution, on the other hand, showed an increase in fatigue resistance
KEYWORD SPOTTING SYSTEM WITH NANO 33 BLE SENSE USING EMBEDDED MACHINE LEARNING APPROACH
Authors: Abbas Nurul Atikah , Ahmad Mohd Ridzuan
Published: April 2023

Due to the obvious advancement of artificial intelligence, keyword spotting has become a fast-growing technology that was first launched a few years ago by hidden Markov models. Keyword spotting is the technique of finding terms that have been pre-programmed into a machine learning model. However, because the keyword spotting system model will be installed on a small and resource-constrained device, it must be minimal in size. It is difficult to maintain accuracy and performance when minimizing the model size. We suggested in this paper to develop a TinyML model that responds to voice commands by detecting words that are utilized in a cascade architecture to start or control a program. The keyword detection machine learning model was built, trained, and tested using the edge impulse development platform. The technique follows the model-building workflow, which includes data collection, preprocessing, training, testing, and deployment. 'On,' 'Off,' noise, and unknown databases were obtained from the Google speech command database V1 and applied for training and testing. The MFCC was used to extract features and CNN was used to generate the model, which was then optimized and deployed on the microcontroller. The model's evaluation represents an accuracy of 84.51% based on the datasets. Finally, the KWS was successfully implemented and assessed on Arduino Nano 33 BLE Sense for two studies in terms of accuracy at three different times and by six different persons.
ANALYSIS OF GRAVITY ON ALTITUDE CHANGES IN GRAVITY MICRO DATA USING POLYNOMIAL EQUATION APPROACH (CASE STUDIES OF MERAPI AND KELUD VOLCANOES)
Authors: Setiawan Ari , Huda Immanatul , Lewerissa Richard
Published: April 2023

Analysis of gravity changes to altitude changes from gravity measurements at Merapi Volcano and Kelud Volcano was carried out to determine the characteristics of the two mountains based on the gravity method. Merapi Volcano and Kelud Volcano are two very active mountains in Indonesia and have different physiography, especially at the top of Kelud there is a crater filled with water. Repeated gravity surveys will be useful for studying deformation in volcanoes and providing information about changes in subsurface mass. The gravity data on Merapi Volcano is secondary data from BPPTKG (Research and Development Center for Geological Disaster Technology), and data on Kelud Volcano is obtained from the 2019 data collection survey. Volcanic monitoring using the gravity method is carried out by observing changes in gravity with changes in altitude  to study deformation in the volcano and providing information about changes in subsurface mass using a polynomial equation approach of  to  . The findings indicate that there was little variation in the gravity anomaly within Merapi Volcano between 2018 and 2019. The highest coefficient of determination, at 96%, was observed in the gravity anomaly data from inside the Kelud Volcano in 2019, after applying Bouguer corrections in the form of spherical effects. Additionally, the coefficients of the second and third order polynomials of the Merapi Volcano data had opposite signs to those of Kelud Volcano, suggesting that the internal source of the gravity anomaly within Merapi Volcano is distinct from that within Kelud Volcano.
ACTIVE EXTRAPOLATION OF DIMSIMS IN NORDSIECK REPRESENTATION
Authors: Kadhim Ali Jameel , Gorgey Annie , Razali Noorhelyna
Published: April 2023

Diagonally implicit multistage integration methods (DIMSIMs) are widely utilized in finding the solution to any problems in the subject of ordinary differential equations. These methods are selected from the general linear methods, which is considerable potential for efficient implementations. The extrapolation is derived from the stability of the explicit Runge-Kutta methods. In this paper, the combination of DIMSIMs with Richardson extrapolation of different orders shows that numerical solutions give higher accuracy when the extrapolation is applied with the base method.
The asymptotics of the holomorphic analytic torsion forms
Authors: Puchol Martin
Published: April 2023

The purpose of this paper is to give an asymptotic formula for the holomorphic analytic torsion forms of a fibration associated with a sequence of direct images of increasing powers of a line bundle on a bigger manifold. To handle the growing dimension of the direct images, we use the theory of Toeplitz operators. This is the family versions of the results of Bimsut and Vasserot on the asymptotics of the holomorphic torsion, as well an extension for more general bundles.
Separable Tendon-Driven Robotic Manipulator With a Long, Flexible, Passive Proximal Section
Authors: DeBuys Christian , Ghesu Florin C. , Jayender Jagadeesan , Langari Reza , Kim Young-Ho
Published: April 2023

This work tackles practical issues that arise when using a tendon-driven robotic manipulator (TDRM) with a long, flexible, passive proximal section in medical applications. Tendon-driven devices are preferred in medicine for their improved outcomes via minimally invasive procedures, but TDRMs come with unique challenges such as sterilization and reuse, simultaneous control of tendons, hysteresis in the tendon-sheath mechanism, and unmodeled effects of the proximal section shape. A separable TDRM that overcomes difficulties in actuation and sterilization is introduced, in which the body containing the electronics is reusable and the remainder is disposable. An open-loop redundant controller that resolves the redundancy in the kinematics is developed. Simple linear hysteresis compensation and re-tension compensation based on the physical properties of the device are proposed. The controller and compensation methods are evaluated on a testbed for a straight proximal section, a curved proximal section at various static angles, and a proximal section, which dynamically changes angles, and overall, distal tip error was reduced.
Numerical Investigation of Cross-Flow Water Cooling Towers
Authors: Can Omer F. , Alabbas Muhammed
Published: April 2023

In this study, thermal performance of the forced cross-flow water cooling tower is numerically investigated by using the commercial computational fluid dynamics software ansys-cfx. The temperature variation between inlet and outlet of the water, namely, process water temperature, is the main extracted result of simulations. Additionally, the cooling range (CR) that is the difference between inlet water temperature and outlet water temperature is the second representative result of the analysis. The effect of air velocity (Va), water droplet diameter (dw), and water temperature at the inlet of tower (Tw) are the variables that are considered to be the effective design parameters on the process temperature of the water. The process water temperature decreases, but the cooling range increases when the air velocity increases. When the inlet water temperature increases, the process water temperature and the cooling range also increase. On the other hand, the process water temperature decreases with the decreasing diameter of water droplets.
Performance Prediction Model Development for Solar Box Cooker Using Computational and Machine Learning Techniques
Authors: Anilkumar B. C. , Maniyeri Ranjith , Anish S.
Published: April 2023

The development of prediction models for solar thermal systems has been a research interest for many years. The present study focuses on developing a prediction model for solar box cookers (SBCs) through computational and machine learning (ML) approaches. The prime objective is to forecast cooking load temperatures of SBC through ML techniques such as random forest (RF), k-nearest neighbor (k-NN), linear regression (LR), and decision tree (DT). ML is a commonly used form of artificial intelligence, and it continues to be popular and attractive as it finds new applications every day. A numerical model based on thermal balance is used to generate the dataset for the ML algorithm considering different locations across the world. Experiments on the SBC in Indian weather conditions are conducted from January through March 2022 to validate the numerical model. The temperatures for different components obtained through numerical modeling agree with experimental values with less than 7% maximum error. Although all the developed models can predict the temperature of cooking load, the RF model outperformed the other models. The root-mean-square error (RMSE), determination coefficient (R2), mean absolute error (MAE), and mean square error (MSE) for the RF model are 2.14 (°C), 0.992, 1.45 (°C), and 4.58 (°C), respectively. The regression coefficients indicate that the RF model can accurately predict the thermal parameters of SBCs with great precision. This study will inspire researchers to explore the possibilities of ML prediction models for solar thermal conversion applications.
Energy Saving Optimization of Chilled Water System Based on Improved Fruit Fly Optimization Algorithm
Authors: Feng Zengxi , Wang Wenjing , He Xin , Li Gangting , Zhang Lutong , Xiang Weipeng
Published: April 2023

As the main energy consumption part of the central air-conditioning system, the energy saving of the chilled water system is particularly important. In this paper, an improved fruit fly optimization algorithm (IFOA) is used to optimize the operating parameters of the chilled water system to reduce the energy consumption of the chilled water system. In IFOA, the 3-D position coordinate is introduced to expand the search space of the algorithm, the variable-step strategy balances the global search ability and local search ability of the algorithm and helps a single fruit fly jump out of the local optimization through chaos mapping. In order to verify the optimization effect of IFOA on the chilled water system, the energy consumption model of the chilled water system is established. With the lowest total energy consumption of the system as the goal, the operating parameters such as the chilled water supply temperature and the speed ratio of the chilled water pump are optimized. The simulation results show that the energy-saving optimization method of a central air-conditioning chilled water system based on IFOA can make the average energy-saving rate of the system reach 7.9%. Compared with other optimization algorithms, the method has a better energy-saving effect and is more stable.
Passion for Work and Job Satisfaction in Sports Coaches: The Mediating Role of Flow Experiences
Authors: Peixoto Evandro Morais , Palma Bartira Pereira , Romano Amanda Rizzieri , Vieira Tatiana Cristina Henrique , Galatti Larissa Rafaela
Published: April 2023

Sports coaching is a volatile and stressful career that may impact professionals’ well-being. Thus, variables that can promote coaches’ job satisfaction need to be investigated. Based on the hypotheses of potential effects of passion for work (e.g., subjects’ inclination for an activity, which becomes integrated into the person’s identity) on flow experience (e.g., positive and transient state that can promote total absorption, enjoyment, and intrinsic motivation) and job satisfaction (e.g., state of positive emotions, resulting from continuous experiences in the workplace), this research aimed to assess the association among the dualistic model of passion (harmonious and obsessive), flow, and job satisfaction in sports coaches. The sample consisted of 172 Brazilian coaches from different sports (69.60% male). Structural equation modeling demonstrated that both forms of passion were positively associated with absorption and intrinsic motivation experience; however, only harmonious passion showed a significant relationship with enjoyment and job satisfaction. Furthermore, a mediating role of flow (work enjoyment and intrinsic motivation) in the relationship between harmonious passion and coaches’ job satisfaction was observed. The results suggest that coaches who demonstrate harmonious passion for the profession tend to have a greater perception of positive experiences at work and feel more satisfied with these activities.
BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging
Authors: Blesa Javier , Pineda-Pardo José A. , Inoue Ken-ichi , Gasca-Salas Carmen , Balzano Tiziano , Del Rey Natalia López-González , Reinares-Sebastián Alejandro , Esteban-García Noelia , Rodríguez-Rojas Rafael , Márquez Raquel , Ciorraga María , del Álamo Marta , García-Cañamaque Lina , Ruiz de Aguiar Santiago , Rachmilevitch Itay , Trigo-Damas Inés , Takada Masahiko , Obeso José A.
Published: April 2023

Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson’s disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson’s disease. In these patients and in one monkey, blood-brain barrier opening was followed by
18
F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders.
Structural basis for the assembly of the DNA polymerase holoenzyme from a monkeypox virus variant
Authors: Li Yaning , Shen Yaping , Hu Ziwei , Yan Renhong
Published: April 2023

The ongoing global pandemic caused by a variant of the monkeypox (or mpox) virus (MPXV) has prompted widespread concern. The MPXV DNA polymerase holoenzyme, consisting of F8, A22, and E4, is vital for replicating the viral genome and represents a crucial target for the development of antiviral drugs. However, the assembly and working mechanism for the DNA polymerase holoenzyme of MPXV remains elusive. Here, we present the cryo–electron microscopy (cryo-EM) structure of the DNA polymerase holoenzyme at an overall resolution of 3.5 Å. Unexpectedly, the holoenzyme is assembled as a dimer of heterotrimers, of which the extra interface between the thumb domain of F8 and A22 shows a clash between A22 and substrate DNA, suggesting an autoinhibition state. Addition of exogenous double-stranded DNA shifts the hexamer into trimer exposing DNA binding sites, potentially representing a more active state. Our findings provide crucial steps toward developing targeted antiviral therapies for MPXV and related viruses.
Primate-conserved carbonic anhydrase IV and murine-restricted LY6C1 enable blood-brain barrier crossing by engineered viral vectors
Authors: Shay Timothy F. , Sullivan Erin E. , Ding Xiaozhe , Chen Xinhong , Ravindra Kumar Sripriya , Goertsen David , Brown David , Crosby Anaya , Vielmetter Jost , Borsos Máté , Wolfe Damien A. , Lam Annie W. , Gradinaru Viviana
Published: April 2023

The blood-brain barrier (BBB) presents a major challenge for delivering large molecules to study and treat the central nervous system. This is due in part to the scarcity of targets known to mediate BBB crossing. To identify novel targets, we leverage a panel of adeno-associated viruses (AAVs) previously identified through mechanism-agnostic directed evolution for improved BBB transcytosis. Screening potential cognate receptors for enhanced BBB crossing, we identify two targets: murine-restricted LY6C1 and widely conserved carbonic anhydrase IV (CA-IV). We apply AlphaFold-based in silico methods to generate capsid-receptor binding models to predict the affinity of AAVs for these identified receptors. Demonstrating how these tools can unlock target-focused engineering strategies, we create an enhanced LY6C1-binding vector, AAV-PHP.eC, that, unlike our prior PHP.eB, also works in
Ly6a
-deficient mouse strains such as BALB/cJ. Combined with structural insights from computational modeling, the identification of primate-conserved CA-IV enables the design of more specific and potent human brain–penetrant chemicals and biologicals, including gene delivery vectors.
Corrected and Republished from: “Isolation and Characterization of the First Freshwater Cyanophage Infecting
Pseudanabaena
”
Authors: Zhang Dong , You Fang , He Yiliang , Te Shu Harn , Gin Karina Yew-Hoong
Published: April 2023

This study presents the isolation of the very first freshwater cyanophage, PA-SR01, that infects
Pseudanabaena
, and fills an important knowledge gap on freshwater cyanophages as well as cyanophages infecting
Pseudanabaena
.
Rational Discourse on Virology and Pandemics
Authors: Bahry David
Published: April 2023

A group of 156 virologists, including American Society of Microbiology journal editors-in-chief, has recently published across three ASM journals a “call for rational discourse” on such important topics as the origin of SARS-CoV-2 and gain of function research (e.g., F. Goodrum et al.,
mBio
14:e0018823, 2023,
https://doi.org/10.1128/mbio.00188-23
).
Evaluating the Reproducibility of Amplicon Sequencing Data Derived from Deep-Sea Cold Seep Sediment-Associated Microbiota
Authors: Kong Jie , Feng Jingchun , Sun Liwei , Zhang Si
Published: April 2023

The reproducibility of amplicon sequencing is vital for whether the diversities of microbial communities could be accurately estimated. Thus, reproducibility influences the drawing of sound ecological conclusions.
P32 To evaluate prophylactic posaconazole prescribing in children under 12 years with primary immunodeficiency
Authors: Watson Mairi , Young Helen , Greener Sinead
Published: April 2023

Aim

Current prescribing in our trust, in the absence of a guideline and licensing for prophylactic posaconazole in children under 12 years, is based on a paper by Boonsathorn et al. 20181The purpose of this audit is to evaluate the extent to which prescribing and monitoring of prophylactic oral posaconazole prescribed within our paediatric inpatient population is in line with published recommendations.1Targets were 100% of patients were dosed as recommended1; 100% of trough concentrations for posaconazole were taken within 5–10 days after initial administration; and if trough concentrations are not in range (>0.7 mg/L) was corrective action taken.

Method

Patients between the ages of 2 months to 12 years with primary immunodeficiency recorded on their health record as being initiated on prophylactic posaconazole in the last 2 years were identified. Where patients met the inclusion criteria; age, weight, posaconazole formulation, date of initiation of posaconazole, trough concentration, date of trough concentration and dose adjustments were collected. Data was collated and analysed using MS Excel. Caldicott Guardian approval (ID: 9378) was granted by our trust and was added to the clinical effectiveness register (ID: 13451).

Results

23 patients were included with the mean age of 3.7 years. 84% of patients were dosed as recommended by Boonsathorn et al. 52% of all patients got a trough concentration taken within the 5–10 days and 75% of those patients had a trough concentration of >0.7 mg/L. 25% of patients had concentrations taken in 5–10 days that were <0.7 mg/L and doses were increased. These increased doses were not as recommended.133% of patients had concentrations taken in 5–10 days that greatly exceeded 0.7 mg/L and had dose reductions.

Conclusion

The majority of the patients were dosed as recommended and had a trough concentration >0.7 mg/L. Recommendations could be translated into a guideline to include; advising trough concentrations are taken 5–10 days of initial administration to get an accurate picture of the posaconazole concentration. To include recommendations of dose adjustments following <0.7 mg/L trough concentrations to get consistent optimal prescribing. There was no maximum trough concentration for prescribers to adhere so the addition of a maximum trough concentration and recommendations of dose reductions would improve the clinical safety of prescribing prophylactic posaconazole. Limitations of this audit included the limited number of patients that fitted the criteria and results cannot be generalised for all oral formulations as only one patient was prescribed tablets.

Reference

Boonsathorn, S, Cheng I, Kloprogge F,et al. Clinical pharmacokinetics and dose recommendations for posaconazole in infants and children.Clinical Pharmacokinetics2018;58:53–61.
Topical dilation as first-line treatment for fibrin membrane pupillary-block glaucoma following uncomplicated cataract surgery
Authors: Bennett Sashia , Studsgaard Anne , Telinius Niklas
Published: April 2023

Fibrin membrane pupillary-block glaucoma is an uncommon complication after phacoemulsification cataract surgery. We present a case treated successfully by pharmacological dilation of the pupil. Previous case reports have recommended the use of Nd:YAG peripheral iridotomy, Nd:YAG membranotomy and intracameral tissue plasminogen activator.

The patient presented with intraocular pressure (IOP) of 45 mmHg 2 days after uneventful phacoemulsification cataract surgery. Anterior segment optical coherence tomography revealed that a fibrinous membrane-filled space had formed between the pupillary plane and the implanted intraocular lens.

The diagnosis of fibrin membrane pupillary-block glaucoma was made. Initial treatment consisted of IOP-lowering medication and topical pupillary dilation (atropine 1%, phenylephrine hydrochloride 10% and tropicamide 1%). Within 30 min, the dilation broke the pupillary block and the IOP was 15 mmHg. The inflammation was treated with topical dexamethasone, nepafenac and tobramycin. Within a month, the patient reached a visual acuity of 1.0.
What is the cost-effectiveness of menu calorie labelling on reducing obesity-associated cancer burdens? An economic evaluation of a federal policy intervention among 235 million adults in the USA
Authors: Du Mengxi , Griecci Christina F , Cudhea Frederick , Eom Heesun , Wong John B , Wilde Parke , Kim David D , Michaud Dominique S , Wang Y Claire , Mozaffarian Dariush , Zhang Fang Fang
Published: April 2023

Objective

To assess the impact of menu calorie labelling on reducing obesity-associated cancer burdens in the USA.

Design

Cost-effectiveness analysis using a Markov cohort state-transition model.

Setting

Policy intervention.

Participants

A modelled population of 235 million adults aged ≥20 years in 2015–2016.

Interventions

The impact of menu calorie labelling on reducing 13 obesity-associated cancers among US adults over a lifetime was evaluated for: (1) effects on consumer behaviours; and (2) additional effects on industry reformulation. The model integrated nationally representative demographics, calorie intake from restaurants, cancer statistics and estimates on associations of policy with calorie intake, dietary change with body mass index (BMI) change, BMI with cancer rates, and policy and healthcare costs from published literature.

Main outcome measures

Averted new cancer cases and cancer deaths and net costs (in 2015 US$) among the total population and demographic subgroups were determined. Incremental cost-effectiveness ratios from societal and healthcare perspectives were assessed and compared with the threshold of US$150 000 per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analyses incorporated uncertainty in input parameters and generated 95% uncertainty intervals (UIs).

Results

Considering consumer behaviour alone, this policy was associated with 28 000 (95% UI 16 300 to 39 100) new cancer cases and 16 700 (9610 to 23 600) cancer deaths averted, 111 000 (64 800 to 158 000) QALYs gained, and US$1480 (884 to 2080) million saved in cancer-related medical costs among US adults. The policy was associated with net cost savings of US$1460 (864 to 2060) million and US$1350 (486 to 2260) million from healthcare and societal perspectives, respectively. Additional industry reformulation would substantially increase policy impact. Greater health gains and cost savings were predicted among young adults, Hispanic and non-Hispanic Black individuals.

Conclusions

Study findings suggest that menu calorie labelling is associated with lower obesity-related cancer burdens and reduced healthcare costs. Policymakers may prioritise nutrition policies for cancer prevention in the USA.
Prevalence of cognitive frailty among older adults in China: a systematic review and meta-analysis
Authors: Liu Jian , Xu Shengjia , Wang Jiurui , Yan Zeping , Wang Zhiwei , Liang Qian , Luan Xiaorong
Published: April 2023

Objective

This study aimed to investigate the prevalence of cognitive frailty among older adults in China.

Design

Systematic review and meta-analysis.

Methods

We searched the Cochrane Library, PubMed, Web of Science, Embase, China National Knowledge Infrastructure(CNKI), Wanfang, Chinese Biomedical Literature and Weipu (VIP) databases to collect information on the epidemiology of cognitive frailty among older adults in China. The study period was from the establishment of the database to March 2022. Two researchers independently screened the literature, extracted the data and assessed the risk of bias in the included studies. All statistical analyses were performed using Stata V.15.0.

Results

We screened 522 records, of which 28 met the inclusion criteria. The results of the meta-analysis showed that the prevalence of cognitive frailty among older adults in China was 15%(95%CI (0.13%,0.17%)). The prevalence of cognitive frailty was higher in hospitals and nursing homes than in communities. Moreover, the prevalence of cognitive frailty was higher in women than in men. Furthermore, the prevalence rates of cognitive frailty in North China Hospital, older adults aged≥80 years, and illiterate individuals were 25%, 29%, and 55%, respectively.

Conclusions

In conclusion, in China, the prevalence of cognitive frailty is higher among older adults, is higher in women than in men, is higher in hospitals and nursing homes than in communities, and is higher in North China than other regions. Moreover, the higher the educational level, the lower the prevalence of cognitive frailty. Multimodal interventions for cognitive frailty, including increased exercise, nutritional support, increased socialisation opportunities and multifactorial strategies, may be effective in preventing cognitive frailty. These findings have important implications for adjusting healthcare and social care systems.

PROSPERO registration number

CRD42023390486.
Negative and protective experiences influencing the well-being of refugee children resettling in Germany: a qualitative study
Authors: Abdelhamid Shaymaa , Lindert Jutta , Fischer Joachim , Steinisch Maria
Published: April 2023

Objective

Conflict, forced migration and searching for safety in a foreign land are all experiences common to refugee children. They experience potentially traumatic events that are distinct from the general population, yet current adverse childhood experience (ACE) studies do not cover these events. Studies that do examine refugee children’s experiences typically focus on a single stage of migration or adversities from the community, offering insight into only a fraction of their realities. This study aimed to identify potentially traumatising and protective experiences subjectively perceived as influencing refugee children’s well-being from all stages of migration and all socio-ecological levels.

Design

Qualitative study with thematic analysis of semi-structured individual and group interviews. Themes were organised within a socio-ecological model.

Setting

Non-profit organisations, youth welfare facilities and societies that organise civic engagement for refugee families in the Rhine-Neckar region in Germany provided rooms where interviews could be conducted.

Participants

Refugee parents and children who spoke one of the four most common languages of those seeking asylum in Germany in 2018 were included. This study excluded refugees who were not fleeing a conflict area. Forty-seven refugee parents and 11 children (aged 8–17 years) from Syria, Iraq, Palestine, Afghanistan and Eritrea participated.

Results

Eight major themes emerged from interviews including six reflecting potentially negative experiences and two potentially protective themes. These themes evolved from experiences such as family dispersion, displacement, rigorous immigration and national policies, as well as constructive parenting and community support.

Conclusion

It is increasingly important to identify these diverse experiences as the refugee population continues to grow, and the increased prevalence of poor health outcomes in refugee children continues to be widely documented. Identifying ACEs specifically relevant to refugee children could contribute to understanding potential pathways and could further serve as a starting point for tailored interventions.
Completion and publication of clinical trials in a cooperative group: a cohort study of trials of the Swiss Group for Clinical Cancer Research (SAKK)
Authors: Hayoz Stefanie , Kasenda Benjamin , Schenker Annina Lea , Kopp Christoph , Schär Sämi , Thürlimann Beat , von Moos Roger , Pless Miklos
Published: April 2023

Background

Premature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.

Objectives

To investigate trial completion and publication rate of cancer trials conducted within the Swiss Group for Clinical Cancer Research (SAKK).

Design

Cohort study of clinical trials.

Setting

Cohort of interventional cancer trials conducted in Switzerland with accrual closure between 1986 and 2021 identified from the SAKK trial management system.

Outcomes

Premature trial discontinuation and publication in peer-reviewed journal.

Results

We included 261 trials; median number of recruited patients was 150.5 (range 1–8028). Most trials (67.0%) were randomised. Overall, 76 of 261 (29.1%) trials were prematurely closed for accrual. The three main reasons for premature closure were insufficient accrual in 28 trials, followed by stopping for futility in 17 or efficacy in 8 trials. We included 240 trials for the publication status (21 excluded, because 8 still in follow-up, for 10 the primary completion date was less than a year ago and for 3 the manuscript was submitted, but to accepted yet). 216 of 240 (90.0%) were published as a full article, 14 were published in other formats, leading to an overall publication rate of 95.8%. The rate of premature discontinuation declined over time, with 34.2%, 27.8% and 23.5% in trials activated before 2000, between 2000 and 2009, and since 2010, respectively. We observed an increasing publication rate in peer-reviewed journals over time: 79.2% (closed before 2000), 95.7% (closed between 2000 and 2009) and 93.2% (closed after 2010).

Conclusion

Insufficient patient recruitment is still the major reason for premature trial discontinuation. SAKK has continuously improved its quality management of trial conduct over time leading to increased successful trial completion and publication. However, there is still room for improvement to increase the number of trials reaching their target sample size.