bluuebunny/crossref_metadata_2025 huggingface dataset:
Current status of platelet manufacturing in 3D or bioreactors
Authors: Kweon Soonho , Kim Suyeon , Choi Hye Sook , Jo Kyeongwon , Park Ju Mi , Baek Eun Jung
Published: June 2023

Blood shortages for transfusion are global issues of grave concern. As in vitro manufactured platelets are promising substitutes for blood donation, recent research has shown progresses including different cell sources, different bioreactors, and three‐dimensional materials. The first‐in‐human clinical trial of cultured platelets using induced pluripotent stem cell‐derived platelets began in Japan and demonstrated its quality, safety, and efficacy. A novel bioreactor with fluid motion for platelet production has been reported. Herein, we discuss various cell sources for blood cell production, recent advances in manufacturing processes, and clinical applications of cultured blood.
Design, Characterization and Evaluation of a Lab‐made Photoreactor: A First Step Towards Standardized Procedures in Photocatalysis**
Authors: Aubineau Thomas , Laurent Justine , Olanier Ludovic , Guérinot Amandine
Published: June 2023

For the last fifteen years, photochemistry has known a renewal with the emergence of new photoredox approaches, along with the development of new powerful artificial sources of light. However, the described procedures often lack information about the characteristics of the setups (wavelength, actual received light power, distance from the source) even when commercial apparatuses are used. This lacunar information hampers the development of standardized procedures which would guarantee the reproducibility of the reactions. With the objective of furnishing a standardized setup, a lab‐made reactor was designed. The use of 3D‐printing technology makes it easily accessible to most laboratories. Its characterization showed the critical effect of the environmental conditions upon the light power received and how crucial they are for reproducibility of photochemical reactions. At last, the setup was evaluated against experiments taken from recent literature.
Recovery of lithium salt from spent lithium‐ion battery by less polar solvent wash and water extraction
Authors: Du Hao , Kang Yuqiong , Li Chenglei , Zhao Yun , Tian Yao , Lu Jian , Chen Zhaoyang , Gao Ning , Li Zhike , Wozny John , Li Tao , Wang Li , Tavajohi Naser , Kang Feiyu , Li Baohua
Published: June 2023

The lithium hexafluorophosphate (LiPF6) in spent lithium‐ion batteries (LIBs) is a potentially valuable resource and a significant environmental pollutant. Unfortunately, most of the LiPF6 in a spent LIB is difficult to extract because the electrolyte is strongly adsorbed by the cathode, anode, and separator. Storing extracted electrolyte is also challenging because it contains LiPF6, which promotes the decomposition of the solvent. Here we show that electrolytes in spent LIBs can be collected by a less polar solvent dimethyl carbonate (DMC) wash, and LiPF6 can be concentrated by simple aqueous extraction by lowering ethylene carbonate (EC) content in the recycled electrolyte. Due to the similar dielectric constant of EC and water, reducing the content of EC in LIB electrolytes, or even eliminating it, facilitates the separation of water and electrolyte, thus enabling the lithium salts in the electrolyte to be separated from the organic solvent. The lithium salt extracting efficiency achieved in this way can be as high as 99.8%, and fluorine and phosphorus of LiPF6 can be fixed in the form of stable metal fluoride and phosphate by hydrothermal method. The same strategy can be used in industrial waste electrolyte recycling by diluting the waste with DMC and extracting the resulting solution with water. This work thus reveals a new route for waste electrolyte treatment and will also support the development of advanced EC‐free electrolytes for high‐performance, safe, and easily recyclable LIBs.
A π‐Extension Process from 9‐Phosphaanthracene Leading to Phosphatetraphenes and Phosphatetracenes
Authors: Yasuda Kohei , Ito Shigekazu
Published: June 2023

Extension of π‐system with phosphinine (phosphorine, phosphabenzene) has been of interest because of the expected higher HOMO and lower LUMO levels compared with the corresponding carbon congeners. In this paper, a π‐extension process based on the 9‐phosphaanthracene skeleton was demonstrated by synthesizing 12‐phosphatetraphene and 9‐phosphabenzo[f]tetraphene by utilizing the deaminative aromatization pathway. Starting from 3,5‐bis(trifluoromethyl)aniline, we developed the dibromotriarylmethane precursors containing the 3,5‐bis(trifluoromethyl)‐2‐bromophenyl unit, which would be slightly effective to increase the steric congestion around the fragile P=C bonds incorporated in the fused polyaromatic skeletons. The bis‐trifluoromethyl 12‐phosphatetraphenes have been synthesized together with the mono‐trifluoromethyl derivative, and the planar 12‐phosphatetraphene skeleton was confirmed. On the other hand, the CF3‐substituted 9‐phosphabenzo[f]tetraphene displayed a remarkably twisted fused five ring system leading to the wavy structures incorporating phosphinine. Also, synthetic study of 5‐phosphatetracene using the bis(trifluoromethyl)phenyl unit was attempted and the incomplete elimination of the amine indicated labile characters of the observed phosphorus congener of tetracene. The findings of this study would be informative for developing heavier congeners of polyaromatic hydrocarbons (PAHs) as well as the trifluromethyl effects.
Can rooted apical cuttings complement seed systems to improve availability of quality seed potato in Africa?—The case of Kenya
Authors: Wauters Pieter , Hutchings James , Munguti Florence , Borus Dinah , Nyawade Shadrack , Atieno Elly O. , Sharma Kalpana , Parker Monica L.
Published: June 2023

Limited availability and access to quality seed is a major challenge faced by the Kenyan potato subsector. Smallholder farmers cultivate the bulk of potato mainly planting seed from informal sources without any quality assurance which contributes to low yields. In recent years, private sector businesses have engaged in certified seed potato production with positive impact on the volumes available, relying on minitubers to multiply in the field over three to four generations. Rooted apical cuttings (RACs) provide a productive alternative starter material that can further boost the Kenyan seed systems. Stokman Rozen Kenya Ltd (SRK) is a private sector business that has embraced this technology in 2017. Also, small‐scale nurseries have recently started the commercial production of cuttings. They both sell RACs mainly to seed growers for further bulking, but ware potato farmers can also produce quality seed on‐farm for their own use from RACs when applying good agricultural practices. This paper examines the initial experiences of both SRK and small‐scale nurseries in the production and marketing of RACs as well as their performance during subsequent field multiplications. Producing and selling RACs offers a profitable business opportunity, especially when productivity and sales increase. Compared to other rapid multiplication technologies, RACs also allow to significantly increase the volumes of early generation seed produced. Key recommendations are to create awareness and to develop adequate marketing strategies to promote their uptake, and to ensure RACs are adequately multiplied into commercial seed to improve its availability to smallholder farmers in Kenya.
Modeling interactions of planting date and phenology in Louisiana rice under current and future climate conditions
Authors: Jamshidi Sajad , Murgia Teresa , Morales‐Ona Ana G. , Cerioli Tommaso , Famoso Adam N. , Cammarano Davide , Wang Diane R.
Published: June 2023

The performance of novel genetic combinations under untested environmental scenarios and management practices can be virtually examined using process‐based crop models. Indeed, there has been a long‐standing interest in the crop modeling community to expand the utility of process‐based models to broader germplasm panels (e.g., breeding lines or diversity panels). Yet, there is often a misalignment between data needed to parameterize process‐based crop models and data routinely collected by breeding programs. To address this gap, we leverage a dataset from a long‐term trial on advanced experimental lines and released varieties from the Louisiana rice breeding program to calibrate and evaluate the decision support for agrotechnology transfer (DSSAT) CSM‐CERES‐Rice model. Next, we use data collected by the same program on a large collection of breeding lines to generate numerous in silico genotypes and evaluate their performance across different management practices (different planting dates) and three climatic conditions (current climate and two future scenarios based on CMIP6‐SSP5‐8.5 climate projections). Our simulations indicate that shifting the current planting date (i.e., March) back by 1–2 months (to January) under moderate warming conditions (+1.3°C warmer and 41% higher CO2 level), and 2–3 months (to December) under extreme warming conditions (+4.1°C warmer and 133% higher CO2 level) could potentially offset the negative impacts of the increased future temperature. Given earlier planting, shorter duration varieties (i.e., those with shorter growing degree day requirements during the vegetative and grain filling periods) are found to be more favorable for supporting high yields. Such varieties with a shorter thermal time to anthesis are found to remain just outside of the current pool of variation for this trait. Opportunities and challenges for leveraging breeding data in process‐based modeling to derive insights into adaptation strategies for future climates are further discussed.
Droplet impact on a wettability‐patterned woven mesh
Authors: Catsoulis Sotiris , Sen Uddalok , Walther Jens H. , Megaridis Constantine M.
Published: June 2023

Droplet impact and breakup on meshes are relevant to a number of applications involving filters, textiles, and other spatially inhomogeneous media encountering gas‐dispersed liquids. This study presents high‐resolution simulation results of mm‐size droplets striking wettability‐patterned meshes with the goal of (a) replicating prior physical experiments, (b) identifying sensitivities to the initial conditions and wettability of the mesh wires, and (c) studying the fluid‐field dynamics when droplets strike such meshes. The insights from the present model may help to advance understanding of droplet atomization on meshes, which depends on a number of parameters that are nontrivial to control in an experimental setting. The analysis is carried out by benchmarking the numerical methods used in a commercial software package for orthogonal droplet impact on a flat smooth surface, followed by a convergence analysis, and finally, simulation of specific experiments and case studies involving wettability‐patterned mesh targets. We show that the wettability contrast between the hydrophilic and hydrophobic domains on the mesh as well as the contact angle hysteresis on each side play a critical role in determining whether liquid pinch‐off occurs. The three‐dimensional computational framework constructed in this work is a step toward predicting the postimpact behavior of droplets that strike woven meshes and other porous inhomogeneous media consisting of materials with different wetting properties.
Ultrafast Laser‐Induced Excellent Thermoelectric Performance of PEDOT:PSS Films
Authors: Wang Xuewen , Feng Yuzhe , Sun Kaili , Chai Nianyao , Mai Bo , Li Sheng , Chen Xiangyu , Zhao Wenyu , Zhang Qingjie
Published: June 2023

Because poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) is water processable, thermally stable, and highly conductive, PEDOT:PSS and its composites have been considered to be one of the most promising flexible thermoelectric materials. However, the PEDOT:PSS film prepared from its commercial aqueous dispersion usually has very low conductivity, thus cannot be directly utilized for TE applications. Here, a simple environmental friendly strategy via femtosecond laser irradiation without any chemical dopants and treatments was demonstrated. Under optimal conditions, the electrical conductivity of the treated film is increased to 803.1 S cm−1 from 1.2 S cm−1 around three order of magnitude higher, and the power factor is improved to 19.0 μW m−1 K−2, which is enhanced more than 200 times. The mechanism for such remarkable enhancement was attributed to the transition of the PEDOT chains from a coil to a linear or expanded coil conformation, reduction of the interplanar stacking distance, and the removal of insulating PSS with increasing the oxidation level of PEDOT, facilitating the charge transportation. This work presents an effective route for fabricating high‐performance flexible conductive polymer films and wearable thermoelectric devices.
Emotion regulation and disordered eating behaviour in youths: Two daily‐diary studies
Authors: Dworschak Christine , Polack Reuma Gadassi , Winschel Julia , Joormann Jutta , Kober Hedy
Published: June 2023

Objective

Disordered eating cognitions and behaviours in childhood and adolescence have been identified as precursors for the development of eating disorders. Another important contributor to eating disorder risk is maladaptive emotion regulation. However, while the regulation of negative affect has been the focus of much research, the literature on the role of positive emotion regulation in eating pathology is extremely limited. The present study extends previous research by examining the regulation of both positive and negative affect in disordered eating using two waves of a daily diary design.

Method

Every evening for 21 days, 139 youths (8–15 years) reported their use of rumination, dampening, and disordered eating cognitions and behaviours. 1 year later, during the onset of the COVID‐19 pandemic, 115 of these youths were followed‐up.

Results

As predicted, higher levels of rumination and dampening were found to be associated with a higher frequency of weight concerns and restrictive eating on person‐level (both Waves) and day‐level (Wave 2). Further, a higher frequency of rumination at Wave 1 predicted increases in the frequency of restrictive eating 1 year later.

Conclusions

Our findings underline the importance of examining regulation of both positive and negative emotion in order to understand eating disorder risk.
Targeting mitochondrial quality control in muscle aging: Natural dietary products as potential interventions
Authors: Chen Qi , Huang Weisu , Capanoglu Esra , Amrouche Amel Thanina , Lu Baiyi
Published: June 2023

Mitochondria are the main sources of energy production for muscle tissues, including skeletal, cardiac, or smooth muscle, to support their activities. Mitochondrial dysfunction and dysregulation of their quality control systems are significant characteristics in aged muscle. Increasing evidence indicates that natural products, especially phytochemicals, can prevent or improve age‐related muscle disorders. Among them, some dietary components specifically regulate mitochondrial quality control (MQC) to play their efficacy. However, the content of related studies is currently not systematically reviewed. In this review, composition, changes, and associated regulators in the MQC network during muscle aging were summarized by comprehensive literature retrieval. Subsequently, the effects and mechanisms of dietary active ingredients on this control network were described. This review showed that mitochondrial dysfunction is a common feature in different types of muscle aging. And four main ways of MQC are involved in maintaining mitochondrial homeostasis and they form a tight and integral system, for muscle‐healthy aging. The benefits of specific endogenous metabolites and exogenous components on aged muscle health are mediated in the above ways. Dietary phytochemicals including phenols, terpenoids, and alkaloids, unfold their influential roles in delaying muscle aging via promoting mitochondrial biogenesis and mitophagy. These findings suggest that MQC is a promising action site against muscle aging and food or herbal‐derived natural products are representative potential interventions. More clinical studies in the future are worthy of future investigation of these natural products.
BRAFmutations and concurrent alterations in patients with soft tissue sarcoma
Authors: Kobayashi Hiroshi , Zhang Liuzhe , Okajima Koichi , Ishibashi Yuki , Hirai Toshihide , Tsuda Yusuke , Ikegami Masachika , Kage Hidenori , Shinozaki‐Ushiku Aya , Oda Katsutoshi , Tanaka Sakae
Published: June 2023

BRAFalterations, including V600E and non‐V600E mutations and fusions, in soft tissue sarcoma (STS) have been identified in a limited case series. Here, we aimed to evaluate the frequency ofBRAFmutations and concurrent alterations in STS to understand their therapeutic action. In this retrospective analysis, we included data from 1964 patients with advanced STS who underwent comprehensive genomic profiling tests at hospitals in Japan between June 2019 and March 2023. The prevalence ofBRAFand recurrent concurrent gene alterations were also investigated.BRAFmutations were detected in 24 (1.2%) of 1964 STS patients, with a median age of 47 (range 1–69) years.BRAFV600E was detected in 11 (0.6%) of the 1964 patients with STS,BRAFnon‐V600E mutations in 9 (4.6%), andBRAFfusions were detected in 4 (0.2%).BRAFV600E was identified in 4 (0.2%) cases of malignant peripheral nerve sheath tumors. The most common concurrent alteration wasCDKN2A(11 cases, 45.8%), and the frequency was equivalent to that of theBRAFV600E (5/11 cases, 45.5%) and non‐V600E (5/9 cases, 55.6%) groups. Recurrent concurrent alterations, such asTERTpromoter mutations (7 cases, 29.2%), were detected at the same frequency in the V600E and non‐V600E groups. In contrast,TP53alterations (4/9 cases, 44.4%) and mitogen‐activated protein kinase (MAPK)‐activating genes, includingNF1,GNAQ, andGNA11(3/9 cases, 33.3%), were identified as relatively higher in the non‐V600E group than in the V600E group (each 1/11 case, 9.1%). We identifiedBRAFalterations at a rate of 1.2% in all patients with advanced STS. Among them,BRAFV600E andBRAFfusions account for 45.8% and 16.7%, respectively. Collectively, our findings support the clinical characteristics and therapeutic strategies for patients withBRAF‐altered advanced STS.
Microglia morphotyping in the adult mouse CNS using hierarchical clustering on principal components reveals regional heterogeneity but no sexual dimorphism
Authors: van Weering Hilmar R. J. , Nijboer Tjalling W. , Brummer Maaike L. , Boddeke Erik W. G. M. , Eggen Bart J. L.
Published: June 2023

Microglia are the resident macrophages of the central nervous system (CNS) and play a pivotal role in immune surveillance and CNS homeostasis. Morphological transitions in microglia are indicative for local changes in the CNS microenvironment and serve as a proxy for the detection of alterations in the CNS, both in health and disease. Current strategies to ‘measure’ microglia combine advanced morphometrics with clustering approaches to identify and categorize microglia morphologies. However, these studies are labor intensive and clustering approaches are often subject to relevant feature selection bias. Here, we provide a morphometrics pipeline with user‐friendly computational tools for image segmentation, automated feature extraction and morphological categorization of microglia by means of hierarchical clustering on principal components (HCPC) without the need for feature inclusion criteria. With this pipeline we provide new and detailed insights in the distribution of microglia morphotypes across sixteen CNS regions along the rostro‐caudal axis of the adult C57BL/6J mouse CNS. Although regional variations in microglia morphologies were evident, we found no evidence for male–female dimorphism at any CNS region investigated, indicating that ‐ by and large ‐ microglia in adult male and female mice are morphometrically indistinguishable. Taken together, our newly developed pipeline provides valuable tools for objective and unbiased identification and categorization of microglia morphotypes and can be applied to any CNS (disease) model.
Advances in positron emission tomography and radiomics
Authors: Barrington Sally F.
Published: June 2023

Positron emission tomography is established for staging and response evaluation in lymphoma using visual evaluation and semi‐quantitative analysis. Radiomic analysis involving quantitative imaging features at baseline, such as metabolic tumor volume and markers of disease dissemination and changes in the standardized uptake value during treatment are emerging as powerful biomarkers. The combination of radiomic features with clinical risk factors and genomic analysis offers the potential to improve clinical risk prediction. This review discusses the state of current knowledge, progress toward standardization of tumor delineation for radiomic analysis and argues that radiomic features, molecular markers and circulating tumor DNA should be included in clinical trial designs to enable the development of baseline and dynamic risk scores that could further advance the field to facilitate testing of novel treatments and personalized therapy in aggressive lymphomas.
Are we reaching the maximum cure rate for Hodgkin lymphoma?
Authors: Johnson Peter W. M.
Published: June 2023

The treatment of Hodgkin lymphoma, using cytotoxic chemotherapy and selective radiotherapy, has resulted in progressively increasing cure rates over the last 40 years. Recent studies have been directed at using response‐adapted approaches to modulate treatment according to the responses seen using functional imaging, with the aim of balancing the probability of cure against the toxicity of more extensive treatments, in particular the risks of infertility, second malignancy and cardiovascular disease. The results of these studies suggest that we have reached the limits of what might be expected from the conventional treatments, but the arrival of antibody‐based therapies, specifically antibody‐drug conjugates and immune checkpoint blocking antibodies, now holds out the prospect of further improvements. The next challenge will be to select those groups for whom they are most needed.
CAR T‐cell therapy in large B cell lymphoma
Authors: Boardman Alexander P. , Salles Gilles
Published: June 2023

CD19‐targeted chimeric antigen receptor (CAR) T‐cells have revolutionized the treatment of lymphoid malignancies, including large B cell lymphoma (LBCL). Following seminal early phase multicenter clinical trials published between 2017 and 2020, three CD19‐CAR T‐cell products received FDA and EMA approval designations in lymphoma in the third‐line setting, paving the way for follow‐up studies in the second‐line. Meanwhile, investigations into the applications of CAR T‐cell therapy have further broadened to treating high‐risk patients even prior to completion of first‐line conventional chemo‐immunotherapy. Furthermore, as early trials excluded patients with central nervous system involvement with lymphoma, several studies have recently shown promising efficacy of CD19‐CAR T‐cells in primary and secondary CNS lymphoma. Here we provide a detailed overview on clinical data supporting the use of CAR T‐cells in patients with LBCL.
Implementing innovative teaching strategies to promote student academic engagement in a critical care elective
Authors: Shoulders Bethany R. , Alexander Kaitlin M. , Allen John M. , Voils Stacy A. , Feild Carinda J.
Published: June 2023

Introduction

Learner engagement can be challenging to manage in multiple learning environments. The multi‐campus delivery and remote learning aspect of a Critical Care Pharmacy elective course led faculty to strategically design multimodal innovations to promote student academic engagement.

Objective

This article aims to describe and define the impact of teaching and learning innovations implemented in a Critical Care Pharmacy elective course through objective and student‐reported learning‐associated outcomes.

Methods

This study evaluates course innovations implemented in a Critical Care Pharmacy elective. Performance on individual readiness assurance tests (iRATs) was tracked to evaluate learning preparation, in addition to overall course grades and exams. Learning outcomes were compared between the pre‐intervention year (2018) and the intervention years (2019–2022). Individual time spent in the virtual intensive care unit (VICU) environment was tracked via in‐class questions. Voluntary pre‐ and post‐course self‐assessment surveys were utilized to assess student understanding, comfort, and preparedness resulting from the teaching innovations. In 2019 and 2020, the survey was repeated following advanced pharmacy practice experiences. In addition, university course evaluations were analyzed.

Results

Students' academic engagement and performance were maintained, even during remote learning years. An increase in mean iRAT scores after implementing innovations to the rapid response and trauma intensive care unit (ICU) modules was observed. Course evaluations reflected a gain in student understanding and comfort, and students performed consistently well on exams and in the course throughout each course iteration. Time spent in the VICU environment also increased compared with the initial delivery of the content. Most students reported that innovations “somewhat” or “greatly improved” learning, and this was also reflected in the follow‐up feedback.

Conclusion

Multimodal innovations maintained student academic engagement in a Critical Care Pharmacy elective, despite variations in content delivery. Students expressed progression in learning outcomes which was supported by assessments and course grades.
Investigations of hybrid infill pattern in additive manufactured tablets: A novel approach towards tunable drug release
Authors: Durga Prasad Reddy R. , Sharma Varun
Published: June 2023

The significance of 3D printing has risen exponentially in biomedical and pharmaceutical applications. Its potential in the field of fabricating drug delivery systems, by virtue of processing biocompatible polymers, has been very lucrative. This work aims to tap the interstitial drug delivery kinetics that are often inaccessible through machine‐specific infill patterns in additive manufactured tablets fabricated using PVA biopolymer as an excipient. In this regard, a myo‐inositol containing tablet has been printed using Fused Deposition Modeling preceded by Hot Melt Extrusion drug loading route. Two machine‐specific infill patterns were taken, namely straight and grid. Later, these two distinct patterns were juxtaposed to obtain novel hybrid infill patterns in the tablets. Then, these tablets and their filament were subjected to various thermal, mechanical, imaging and pharmaceutical characterization tests to assess the feasibility of the research attempt. Finally, dissolution tests were conducted to evaluate their dissolution behavior over a time period. The characterization tests proved the scientific viability of this attempt along with amorphous existence of drug in the polymeric filament. The dissolution results showed favorable drug release by achieving interstitial dissolution timings with surface area/volume (SA/V) ratio being found to be the principal factor.
Associations of Type 2 Diabetes, Body Composition, and Insulin Resistance with Bone Parameters: The Dubbo Osteoporosis Epidemiology Study
Authors: Sheu Angela , Blank Robert D. , Tran Thach , Bliuc Dana , Greenfield Jerry R. , White Christopher P. , Center Jacqueline R.
Published: June 2023

Type 2 diabetes (T2D) may be associated with increased risk of fractures, despite preserved bone mineral density (BMD). Obesity and insulin resistance (IR) may have separate effects on bone turnover and bone strength, which contribute to skeletal fragility. We characterized and assessed the relative associations of obesity, body composition, IR, and T2D on bone turnover markers (BTMs), BMD, and advanced hip analysis (AHA). In this cross‐sectional analysis of Dubbo Osteoporosis Epidemiology Study, 525 (61.3% women) participants were grouped according to T2D, IR (homeostasis model assessment insulin resistance [HOMA‐IR] </≥2.5), and BMI (</≥25 kg/m2): insulin‐sensitive lean (IS‐L), insulin‐sensitive overweight/obese (IS‐O), insulin‐resistant (IR), and T2D. BMD, AHA, and body composition, including visceral adipose tissue (VAT) (on dual‐energy x‐ray absorptiometry scan) and fasting BTMs, were assessed. Analyses performed using Bayesian model averaging and principal component analysis. T2D was associated with low BTMs (by 26%–30% [95% confidence interval [CI] 11%–46%] in women, 35% [95% CI 18%–48%] in men compared to IS‐L), which persisted after adjustment for VAT. BTMs were similar among IR/IS‐O/IS‐L. BMD was similar among T2D/IR/IS‐O; BMD was low only in IS‐L. All groups were similar after adjustment for BMI. Similarly, AHA components were lowest in IS‐L (attenuated following adjustment). On multivariate analysis, T2D was independently associated with BTMs. IR was also associated with C‐terminal telopeptide of type 1 collagen in men. Age and body size were the strongest independent contributors to BMD and AHA. VAT was inversely associated with section modulus, cross‐sectional area, cross‐sectional moment of inertia in women, and hip axis length in men. Low bone turnover is associated with T2D and IR (in men), while BMD and hip strength/geometry are predominantly associated with body size. VAT, indicative of dysglycemia, is also associated with impaired bone geometry. Establishing the role of BTMs and AHA fracture risk may improve skeletal assessment in T2D people. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Carbamazepine‐Induced Severe Cutaneous Adverse Drug Reactions: A 21‐Year Comparison Between Children and Adults in Malaysia
Authors: Hariraj Vidhya , Wo Wee Kee , Lee Sing Chet , Ramli Azuana
Published: June 2023

Severe cutaneous adverse drug reactions (SCARs) are a life‐threatening condition. We aimed to identify all carbamazepine‐induced SCARs voluntarily reported to the Malaysian pharmacovigilance database and to compare between children and adults. Adverse drug reaction reports for carbamazepine were extracted from 2000 to 2020, and divided into 2 groups, that is, children (aged 0–17 years) and adults (aged 18 years and above). Age, sex, race, and carbamazepine dose were analyzed using multiple logistic regression. Of 1102 carbamazepine adverse drug reaction reports, 416 reports were SCARs (99 children, 317 adults). Stevens–Johnson syndrome and toxic epidermal necrolysis were the main SCAR types for both age groups. Median time‐to‐onset for any type of SCAR was 13 days, regardless of age. In children, Malay individuals were 3.6 times more likely to report SCARs (95% confidence interval, 1.356–9.546; P = .010) compared to the Chinese population. In adults, carbamazepine‐induced SCARs were reported as 3.6 times higher in those with a daily dose of 200 mg or less as compared to a daily dose of 400 mg or more. (95% confidence interval, 2.257–5.758; P < .001) Carbamazepine‐induced SCARs reported in Malaysia were predominantly Stevens–Johnson syndrome or toxic epidermal necrolysis, with the majority in Malay individuals. Initiation therapy needs close monitoring between 2 weeks and 1 month.
Population Pharmacokinetics of Ranibizumab Delivered via the Port Delivery System Implanted in the Eye in Patients with Neovascular Age‐Related Macular Degeneration
Authors: Kågedal Matts , Alskär Oskar , Petersson Klas , Hanze Eva , Maia Mauricio , Lu Tong , Vakhavkar Shweta , Quartino Angelica , Willis Jeffrey R. , Jin Jin Y. , Maass Katie F.
Published: June 2023

The port delivery system with ranibizumab (PDS) is designed to continuously deliver ranibizumab to maintain therapeutic drug concentrations in the vitreous of the eye for an extended duration. The PDS has been evaluated for the treatment of neovascular age‐related macular degeneration in the Ladder (PDS 10, 40, and 100 mg/mL, with refill exchanges as needed, versus monthly intravitreal ranibizumab 0.5 mg), Archway (PDS 100 mg/mL with 24‐week refill exchanges, versus monthly intravitreal ranibizumab 0.5 mg), and ongoing Portal (PDS 100 mg/mL with 24‐week refill exchanges) clinical trials. Data from Ladder, Archway, and Portal were used to develop a population pharmacokinetics (PK) model to estimate the ranibizumab release rate from the PDS implant, describe ranibizumab PK in serum and aqueous humor, and predict the concentration in vitreous humor. A model was developed to adequately describe the serum and aqueous humor PK data, as suggested by goodness‐of‐fit plots as well as visual predictive checks. In the final model, the first‐order implant release rate was estimated to be 0.00654 (1/day), corresponding to a half‐life of 106 days, consistent with the implant release rate determined in vitro. The model‐predicted vitreous concentrations achieved with PDS 100 mg/mL given every 24 weeks were below the intravitreal peak concentration and above the intravitreal trough concentration of ranibizumab over the entire 24‐week refill interval. The results demonstrate a durable release of ranibizumab from the PDS with a half‐life of 106 days, providing vitreous exposure to ranibizumab for at least 24 weeks that is within the range of exposure for monthly intravitreal treatment.
The effect of periprosthetic bone loss on the failure risk of tibial total knee arthroplasty
Authors: Soltanihafshejani Navid , Bitter Thom , Verdonschot Nico , Janssen Dennis
Published: June 2023

The effect of long‐term periprosthetic bone loss on the process of aseptic loosening of tibial total knee arthroplasty (TKA) is subject to debate. Contradicting studies can be found in literature, reporting either bone resorption or bone formation before failure of the tibial tray. The aim of the current study was to investigate the effects of bone resorption on failure of tibial TKA, by simulating clinical postoperative bone density changes in finite element analysis (FEA) models and FEA models were created of two tibiae representing cases with good and poor initial bone quality which were subjected to a walking configuration and subsequently to a traumatic stumbling load. Bone failure was simulated using a crushable foam model incorporating progressive yielding. Repetitive loading under a level walking load did not result in failure of the periprosthetic bone in neither the good nor poor bone quality tibia at the baseline bone densities. When applying a stumble load, a collapse of the tibial reconstruction was noticed in the poor bone quality model. Incorporating postoperative bone loss led to a significant increase of the failure risk, particularly for the poor bone quality model in which subsidence of the tibial component was substantial. Our results suggest bone loss can lead to an increased risk of a collapse of the tibial component, particularly in case of poor bone quality at the time of surgery. The study also examined the probability of medial or lateral subsidence of the implant and aimed to improve clinical implications. The FEA model simulated plastic deformation of the bone and implant subsidence, with further validation required via mechanical experiments.
Patient and procedure characteristics associated with postoperative pain after prophylactic versus therapeutic ambulatory bilateral breast surgery
Authors: Simon Natalie B. , Assel Melissa , Serafin Joanna , McCready Taylor M. , Nelson Jonas A. , Vickers Andrew J. , Moo Tracy‐Ann , Tokita Hanae K.
Published: June 2023

Background and Objectives

We investigated whether age, body mass index (BMI), and tissue expander placement were related to postoperative opioid requirement for patients undergoing therapeutic versus prophylactic breast surgery.

Methods

Postoperative opioid consumption was evaluated for patients who underwent bilateral mastectomy with immediate implant‐based reconstruction at a freestanding ambulatory cancer surgery center between 2016 and 2021. Ordinal regression tested whether surgical indication was associated with increased postoperative opioid requirements after adjusting for age, BMI, and tissue expander placement.

Results

Of 2447 patients, 6% underwent prophylactic surgeries. Therapeutic mastectomy patients had lower postoperative opioid requirement (OR = 0.67; 95% CI: 0.50−0.91; p = 0.030), but this was not significant after adjusting for covariates (OR = 0.75; 95% CI: 0.53−1.07; p = 0.2). Opioid use increased with higher BMI (OR = 1.06; 95% CI: 1.05−1.08; p < 0.001) and decreased with age (OR = 0.97; 95% CI: 0.96−0.98; p < 0.001) with therapeutic mastectomy patients being older (median 46 vs. 39). The subpectoral tissue expander group had nearly double the postoperative opioid requirement compared to prepectoral placement (OR = 1.86; 95% CI: 1.55−2.23; p < 0.001).

Conclusions

Increased postoperative opioid requirement in women undergoing prophylactic procedures is best explained by age. Mastectomy patients should be counseled similarly about postoperative pain irrespective of indication. A larger prophylactic mastectomy sample is required to provide more precise estimates.
Paraprofessional delivery of online narrative exposure therapy for firefighters
Authors: Olthuis Janine V. , Kaltenbach Elisa , Giberson Emma , Saryeddine Tina , Asmundson Gordon J. G. , Carleton R. Nicholas , Cramm Heidi , Crombach Anselm , Devlin Julie , Mack Jeff , Lingley‐Pottie Patricia , Rao Sanjay , Sullivan Michael , Wozney Lori , McGrath Patrick J.
Published: June 2023

Firefighters are at increased risk for developing posttraumatic stress disorder (PTSD) and face numerous barriers to accessing mental health care. Innovative ways to increase access to evidence‐based interventions are needed. This study was a case series testing the acceptability, feasibility, and preliminary effectiveness of a paraprofessional‐delivered, virtual narrative exposure therapy (eNET) intervention for PTSD. Participants were 21 firefighters who met the criteria for clinical or subclinical probable PTSD and completed 10–12 sessions of eNET via videoconference. Participants completed self‐report measures pre‐ and postintervention and at 2‐ and 6‐month follow‐ups as well as a postintervention qualitative interview. Paired samples t tests evidenced statistically significant decreases in PTSD, anxiety, and depressive symptom severity and functional impairment from pre‐ to postintervention, ds = 1.08–1.33, and in PTSD and anxiety symptom severity and functional impairment from preintervention to 6‐month follow‐up, ds = 0.69–1.10. The average PTSD symptom severity score fell from above to below the clinical cutoff for probable PTSD at postintervention and follow‐ups. Qualitative interviews indicated that paraprofessionals were considered central to participants’ success and experience with the intervention. No adverse events or safety concerns were raised. This study is an important step in demonstrating that appropriately trained and supervised paraprofessionals can effectively deliver eNET to firefighters with PTSD.
Multi‐imaging approach to analyze bioactive compounds in Abelmoschus moschatus and Cinnamomum zeylanicum via planar chromatography hyphenated with effect‐directed assays and high‐resolution mass spectrometry
Authors: Chandana N.G.A.S. Sumudu , Morlock Gertrud
Published: June 2023

Citizens in developing countries rely on indigenous knowledge and practices and use locally available medicinal plants for different treatments. Due to limited instrumentation for chemical and biological characterization, most studies investigating the bioactive properties of Sri Lankan medicinal plants rarely progress to the molecular level. While for some plants, the whole plant extracts have been tested, most of the individual active compounds and their effect mechanisms have still not been identified. The separation of bioactive compounds from natural sources is a challenging task. Multi‐imaging high‐performance thin‐layer chromatography (HPTLC‐UV/Vis/FLD) combined with biological/biochemical assays (effect‐ directed analysis, EDA) and high‐resolution mass spectrometry (HRMS) provide the straightforward identification of natural products without prior tedious fractionation and compound isolation. Separating complex plant extracts into individual compounds, and still on the same adsorbent surface, studying their effects highlighted their potential. These findings can be used to substantiate current traditional medicinal knowledge and to evaluate their benefits, risks, and limitations. The developed hyphenated HPTLC‐UV/Vis/FLD‐EDA‐HESI‐ HRMS methods for identification of single compound effects in Sri Lankan Abelmoschus moschatus and Cinnamomum zeylanicum included (1) non‐target screening, (2) assignment of prominent individual bioactive compounds, and (3) comparison of product profiles to check the quality of commercial products. Both studies revealed not only the phytochemical profiles but also prioritized bioactive constituents. Diverse antimicrobials, antioxidants, and inhibitors of glucosidase, tyrosinase, and cholinesterase were detected. Running reference standards in parallel to identified compounds, confirmed the assignments and bioactivities. The sustainable and environmentally friendly technique can be used in developing countries for profiling and valorization of plant‐based preparations.
Biocatalytic Production of Bioactive Dipeptides
Authors: Bordewick Sven Ingo , Berger Ralf G.
Published: June 2023

Dipeptides are a promising substance class with a large variety of bioactivities. N‐terminal ar‐ ginyl dipeptides (Arg‐X) have been shown to exhibit both salt‐taste enhancing (Arg‐Ser among others) and antihypertensive properties (Arg‐Phe). A novel biocatalytic strategy for the specific synthesis of these dipeptides is the application of L‐amino acid ligases like RizA from B. subtilis, which enables production of Arg‐X dipeptides directly from their amino acids. However, challenges for an industrial application are the dependence on the expensive cofactor ATP (adenosine triphosphate), low product yields, formation of the undesired side product Arg Arg and the potentially high enzyme costs.

In order to reduce the need for ATP, a strategy for ATP regeneration from acetyl phosphate was established using acetate kinase from E. coli (AckA). Up to 5.9 g/L Arg‐Ser were produced, corresponding to an ATP efficiency of 23 g Arg‐Ser per gram ATP (without regeneration max. 0.5 g Arg‐Ser/g ATP). Next, variants of RizA were created to alter the substrate specificity. A total of 21 RizA variants were created by site‐directed mutagenesis of eight positions in the substrate binding pocket. Additional 14 variants were created by combination of different mutations. Variants with improved activity and specificity were identified for all five examined amino acid combinations (Arg + Arg, Asp, Ser, Ala, Phe). The largest change was observed for K83F_S156A, which improved the product formation of Arg‐Phe six‐fold and improved specificity more than tenfold. Finally, co immobilization of RizA and selected variants with AckA was performed to enable reusability of this biocatalytic system. Immobilisates of T81F_A158S produced up to 3.0 g/L Arg Ser and immobilisates of K83F_S156A produced up to 3.8 g/L Arg‐Phe and could both be reused several times.

This thesis represents the first extensive scientific investigation into establishing ATP regeneration for an L‐amino acid ligase and co‐immobilization of such a biocatalytic system, and substantially expanded the knowledge about engineering the substrate specificity of L amino acid ligases.
Using machine learning to achieve simultaneous, georeferenced surveys of fish and benthic communities on shallow coral reefs
Authors: Miller Scott D. , Dubel Alexandra K. , Adam Thomas C. , Cook Dana T. , Holbrook Sally J. , Schmitt Russell J. , Rassweiler Andrew
Published: June 2023

Surveying coastal systems to estimate distribution and abundance of fish and benthic organisms is labor‐intensive, often resulting in spatially limited data that are difficult to scale up to an entire reef or island. We developed a method that leverages the automation of a machine learning platform, CoralNet, to efficiently and cost‐effectively allow a single observer to simultaneously generate georeferenced data on abundances of fish and benthic taxa over large areas in shallow coastal environments. Briefly, a researcher conducts a fish survey while snorkeling on the surface and towing a float equipped with a handheld GPS and a downward‐facing GoPro, passively taking ~ 10 photographs per meter of benthos. Photographs and surveys are later georeferenced and photographs are automatically annotated by CoralNet. We found that this method provides similar biomass and density values for common fishes as traditional scuba‐based fish counts on fixed transects, with the advantage of covering a larger area. Our CoralNet validation determined that while photographs automatically annotated by CoralNet are less accurate than photographs annotated by humans at the level of a single image, the automated approach provides comparable or better estimations of the percent cover of the benthic substrates at the level of a minute of survey (~ 50 m2 of reef) due to the volume of photographs that can be automatically annotated, providing greater spatial coverage of the site. This method can be used in a variety of shallow systems and is particularly advantageous when spatially explicit data or surveys of large spatial extents are necessary.
Diffraction Neural Network for Multi‐Source Information of Arrival Sensing
Authors: Huang Min , Zheng Bin , Li Ruichen , Li Xiaofeng , Zou Yijun , Cai Tong , Chen Hongsheng
Published: June 2023

All‐optical diffractive neural networks (DNNs) based on passive structures have been shown to perform complicated functions by optical acceleration, thus reforming in situ applications requiring digital computing processing. Its stable, compact, and passive features make it suitable for many conventional applications in complex electromagnetic environments. Here, a DNN based on a multilayer passive metasurface array is presented to estimate the information of arrival (IOA) over a wide range of frequency bands and incident angles. Unlike traditional methods, multiple correlated or coherent electromagnetic signals interfere with each other, resulting in difficult separation which is a fundamental obstacle in multi‐source IOA detection. Here, the proposed diffraction system creates separate virtual channels to isolate and process different incoming waves. It recognizes and classifies the beams, focuses them on the output plane divided by the arrival angle and working frequency, and displays the IOA and number of sources in real time at the speed of light. Furthermore, the massive‐parallelism and data‐post‐processing‐free strategy allows for broader applications in harsh environments, such as seismic detection and underwater circumstances.