bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of Coco-Biodiesel from CNO (Coconut Natural Oil) for Small Scale Industries/Coconut Farmers Using Static Mixer and Dry Washing
Authors: Alamsyah Rizal , Solikhah Maharani Dewi , Kismanto Agus , Heryani Susi
Published: September 2023

Coco-biodiesel is a derivative product of coconut (copra) and is a substitute for diesel fuel. The production of coco-biodiesel is a solution when the price of fossil fuels is uncertain and increasing. In addition, producing coco-biodiesel for coconut farmers will increase the added value of coconut, ensure the availability of local fuel, and support integrated coconut processing. The objective of the study is to introduce a process and equipment prototype for processing coco-biodiesel that can be operated on a small scale which is suitable for coconut farmers, especially in remote areas. Coconut natural oil (CNO) was mixed with 0.1% phosphoric acid in a tank, heated for 2 hours at 80°C, and settled for 4 hours. After that, the transesterification reaction was carried out by reacting coconut oil with methanol with a molar ratio variation of 1: 10, 1: 6, and 1: 4. The process was conducted at a temperature of 65°C and a flow speed of 1.25 m/s (on a static mixer) and using methanol 98 % and 1% KOH catalyst. The crude coco-biodiesel washing was done using dry washing (membrane filter), the results of which were compared with washing using hot water. The type of membrane filter used was ultra-filtration membrane with a membrane area of 0.0055 m2, length of 1200 mm, and porous size of 0.2-1.2 micrometers. The optimum condition of triglycerides synthesis into fatty acid methyl esters (coco-biodiesel) to produce a 96.5% content (requirement) was obtained at a molar ratio of 1: 6. Acid numbers, total glycerol, free glycerol, density, viscosity, and Iodine number of coco-biodiesel produced were <0.5, 0.1%, 0.02%, 855 kg/m3, 3.6 cSt, respectively. The values of these parameters meet the Indonesian biodiesel standards. The performance of dry washing exhibited the capacity of biodiesel washing of 0.56 kg/minute or 0.65 l/min, an energy consumption of 315 kJ/kg which was less than the energy consumption of water washing (1361 kJ/kg).
Adaptive Strategies for expansion of coconut cultivation into marginal areas under the challenge of climate change
Authors: Peries R R A
Published: September 2023

It is predicted that by the year 2050, zonal borders could change in coconut-growing regions in South and Southeast Asia, with rainfall either decreasing in the traditional coconut-growing regions or rainfall increasing in non-traditional drier regions where the soil lacks adequate capacity to store extra soil water. An innovative technology is presented that can ameliorate heavy clay subsoil which can be beneficial in extending coconut cultivation under both of the above scenarios. The practice can lead to the aggregation of heavy clay thereby improving the resilience of soil to capture, store and provide increased amounts of plant-available water. The practice known as subsoil manuring has the potential for an adaptive strategy to a warming and drying climate.
Picosecond laser microvia drilling of ABF material using MHz burst mode
Authors: Franz Daniel , Häfner Tom , Bischoff Kay , Helm Jonas , Kunz Tim , Rung Stefan , Esen Cemal , Hellmann Ralf
Published: September 2023

We report on a comprehensive study of laser percussion microvia drilling of Ajinomoto build-up film (ABF) material using an ultrashort pulsed laser in MHz burst mode. After laser processing, microvia drilling quality is being evaluated by the fabricated diameter and taper using laser scanning microscopy and metallography. The influences of the incubation effect, heat accumulation and shielding effects as a result of pulse to pulse interactions are being discussed on the ablation threshold, penetration depth and laser microvia drilling quality. We find that an increasing heat accumulation in MHz burst mode processing is responsible for the void formation and delamination of the insulating ABF layer. Therefore, the parameter clearance is introduced to evaluate these effects on the microvia sidewalls. For a comparable clearance, applying 2 intra-burst pulses achieves an average reduced taper of down to 19.5% compared to single pulse mode. At the same time, a reduced laser drilling time of 16.7% per microvia highlights the enormous potential of the MHz burst mode for laser drilling of ABF material in printed circuit board fabrication.
Recent advances of mussel-inspired materials in osteoarthritis therapy
Authors: Xiao Fujie , Yan Liwei , Ding Yonghui , Lu Xiong , Xie Chaoming
Published: September 2023

Osteoarthritis (OA) is a common chronic joint disease that significantly affects the quality of life and can lead to disability. Oral and intra-articular administration are the main clinical treatments used to alleviate inflammation and pain. However, the therapeutic efficiency of these approaches is limited by burst drug release, poor retention time, and undesirable toxic effects. In recent years, mussel-inspired materials with strong interfacial adhesiveness have been considered as promising candidates for the treatment of OA. These materials can act as delivery platforms to enhance drug availability; moreover, they display multiple non-pharmacological pathways that alleviate OA. In this review, we introduce the pathological features of OA, summarize the fabrication methods for mussel-inspired materials, and highlight their superiority in response to recent therapeutic strategies for OA.
Skin Perfusion After Hemostatic Net: An Anatomic and Radiologic Study in a Cadaver Model
Authors: Henry Guillaume , Auersvald Andre , Auersvald Luiz A , Ospital Caroline , Boucher Fabien , Mojallal Ali
Published: September 2023

Background

The hemostatic net is a recent technique initially developed to reduce the occurrence of postoperative hematomas following facelift procedures. Its applications have expanded to include skin redraping, deep plane fixation, and other areas beyond the face. However, no experimental study has investigated its effect on skin blood supply.

Objectives

The aim of this study was to analyze facial skin vascularization after applying a hemostatic net to fresh cadavers.

Methods

Fourteen hemifaces from fresh adult cadavers were examined. The study model involved a deep plane facelift procedure with the use of a hemostatic net. The first step, involving 4 hemifaces, included dissections and two-/three-dimensional angiographies by digital microangiography and computed tomography scan, respectively. The purpose was to evaluate the influence of the hemostatic net on vascular perfusion. The second step involved a sequential dye perfusion study performed on 10 other hemifaces that underwent facelift procedures with the hemostatic net to determine its impact on skin perfusion.

Results

The anatomic and radiologic techniques enabled visualization of skin, and showed the arterial system reaching the subdermal vascular plexus and branching between the vascular territories, without interference from the net. The sequential dye perfusion study showed staining after injection in each facelift flap, with comparable coloration distributions before and after the application of the net.

Conclusions

The hemostatic net did not affect the skin blood supply, correlating with no clinical increases in ischemia and necrosis rates in the facelift flap. This study provides additional evidence supporting the safety of the hemostatic net in clinical practice.

Level of Evidence: 5
Estimation of prediction error in time series
Authors: Aue Alexander , Burman Prabir
Published: September 2023

The accurate estimation of prediction errors in time series is an important problem, which has immediate implications for the accuracy of prediction intervals as well as the quality of a number of widely used time series model selection criteria such as the Akaike information criterion. Except for simple cases, however, it is difficult or even impossible to obtain exact analytical expressions for one-step and multi-step predictions. This may be one of the reasons that, unlike in the independent case (see Efron, 2004), up to now there has been no fully established methodology for time series prediction error estimation. Starting from an approximation to the bias-variance decomposition of the squared prediction error, a method for accurate estimation of prediction errors in both univariate and multivariate stationary time series is developed in this article. In particular, several estimates are derived for a general class of predictors that includes most of the popular linear, nonlinear, parametric and nonparametric time series models used in practice, with causal invertible autoregressive moving average and nonparametric autoregressive processes discussed as lead examples. Simulations demonstrate that the proposed estimators perform quite well in finite samples. The estimates may also be used for model selection when the purpose of modelling is prediction.
Imperial lag: some spatial-temporal politics of music streaming’s global expansion
Authors: Sprengel Darci
Published: September 2023

This article takes the music industry in Egypt as an empirical case study for understanding some imperial politics of music streaming’s global expansion. Based on accounts of industry professionals, it suggests that the digitization of the music industry in line with the logics of global streaming technologies is characterized by a spatial-temporal regime of “being behind,” which I refer to as “lag.” Lag is marked by a perpetual striving for that which is always just out of reach, and it demonstrates how streaming can act as a technology of temporal recalibration. I argue that lag is the lived experience of imperial power by showing how it is rooted in longer histories of colonial dominance and control in Egypt. Most broadly, this article suggests that theorizing digitization from the Global South invites greater attention to history and culture to avoid universalizing theories of streaming that uphold Western histories and ideologies as normative.
Technology Transfer of a Validated RP-HPLC Method for the Simultaneous Estimation of Andrographolide and Paclitaxel in Application to Pharmaceutical Nanoformulation
Authors: Kumar Abhiram , Rana Rafquat , Saklani Ravi , Kumar Madhaw , Yadav Pavan Kumar , Tiwari Amrendra , Chourasia Manish Kumar
Published: September 2023

Many analytical methods are reported for simultaneous estimation of pharmaceutical dosages form. However, only a few are reproducible at an industrial scale. The proposed research aims to establish a technology transfer (TT) protocol between two laboratories (Lab-X, originator) with binary and (Lab-Y, receiver) with quaternary high-performance liquid chromatography (HPLC) system. Thus, utilizing reverse-phase HPLC (RP-HPLC), a robust, sensitive and repeatable analytical method has been developed, validated and TT between two laboratories for simultaneous estimation of Andrographolide (AG) and Paclitaxel (PTX). The method has been developed on a Phenomenex Luna C18 column (150 x 4.6, 5) sustained at 40°C and validated under the International Conference on Harmonisation (ICH) Q2 (R1) regulatory guideline and TT USP chapter 1224. The mobile phase consisted of MilliQ (pH = 3) and a combination of acetonitrile and methanol (1:1) in the ratio 50:50 with a flow rate of 0.45 mL/min, linear gradient elution in both labs. The AG and PTX were detected on the PDA detector at 224 and 227 nm wavelength with retention time of 4.5 ± 0.34 and 8.2 ± 0.02 min and limit of detection was found 0.028 ± 0.004 μg/mL, and 0.028 ± 0.0007 μg/mL, whereas limit of quantification as 0.086 ± 0.011 μg/mL and 0.088 ± 0.0014 μg/mL respectively in both labs. Throughout, this approach we have proved that proposed method is repeatable in both labs, and it can be used to quantify AG and PTX in developed pharmaceutical nano-formulations.
Patchy and Pink: Dynamics of a Chlainomonas sp. (Chlamydomonadales, chlorophyta) algal bloom on Bagley Lake, North Cascades, WA
Authors: van Hees Dan , Hanneman Clare , Paradis Sophie , Camara A G , Matsumoto Maya , Hamilton Trinity , Krueger-Hadfield Stacy A , Kodner Robin B
Published: September 2023

Snow algal blooms frequently occur throughout alpine and polar environments during spring and summer months; however, our understanding of bloom dynamics is limited. We tracked a recurrent bloom of Chlainomonas sp. on Upper Bagley Lake in the North Cascade Mountains, USA, to assess the spatiotemporal dynamics in bloom color intensity, community photophysiology, and community composition over eight weeks. We found that the algae biomass had a dynamic patchy distribution over space and time, which was decoupled from changes in community composition and life-cycle progress averaged across the bloom. The proportional representation of Chlainomonas sp. remained consistent throughout the study while the overall community composition shows a progression through the bloom. We found that community photophysiology, measured by the maximum quantum yield of PSII (Fv/Fm), decreased on average throughout the bloom. These findings suggest that the Chlainomonas sp. community on Bagley Lake is not simply an algal bloom with rapid increase in biomass followed by a population crash, as is often seen in aquatic systems, though there is a physiological trajectory and sensitivity to environmental stress. These results contribute to our understanding of the biology of Chlainomonas sp. and its response to environmental stress, specifically an extreme warming event.
Evolution of an Alternative Genetic Code in the Providencia Symbiont of the Hematophagous Leech Haementeria acuecueyetzin
Authors: Manzano-Marín Alejandro , Kvist Sebastian , Oceguera-Figueroa Alejandro
Published: September 2023

Strict blood-feeding animals are confronted with a strong B-vitamin deficiency. Blood-feeding leeches from the Glossiphoniidae family, similarly to hematophagous insects, have evolved specialized organs called bacteriomes to harbor symbiotic bacteria. Leeches of the Haementeria genus have two pairs of globular bacteriomes attached to the esophagus which house intracellular “Candidatus Providencia siddallii” bacteria. Previous work analyzing a draft genome of the Providencia symbiont of the Mexican leech Haementeria officinalis showed that, in this species, the bacteria hold a reduced genome capable of synthesizing B vitamins. In this work, we aimed to expand our knowledge on the diversity and evolution of Providencia symbionts of Haementeria. For this purpose, we sequenced the symbiont genomes of three selected leech species. We found that all genomes are highly syntenic and have kept a stable genetic repertoire, mirroring ancient insect endosymbionts. Additionally, we found B-vitamin pathways to be conserved among these symbionts, pointing to a conserved symbiotic role. Lastly and most notably, we found that the symbiont of H. acuecueyetzin has evolved an alternative genetic code, affecting a portion of its proteome and showing evidence of a lineage-specific and likely intermediate stage of genetic code reassignment.
α-tubulin regulation by 5′ introns in Saccharomyces cerevisiae
Authors: Wethekam Linnea C , Moore Jeffrey K
Published: September 2023

Across eukaryotic genomes, multiple α- and β-tubulin genes require regulation to ensure sufficient production of tubulin heterodimers. Features within these gene families that regulate expression remain underexplored. Here, we investigate the role of the 5′ intron in regulating α-tubulin expression in Saccharomyces cerevisiae. We find that the intron in the α-tubulin, TUB1, promotes α-tubulin expression and cell fitness during microtubule stress. The role of the TUB1 intron depends on proximity to the TUB1 promoter and sequence features that are distinct from the intron in the alternative α-tubulin isotype, TUB3. These results lead us to perform a screen to identify genes that act with the TUB1 intron. We identified several genes involved in chromatin remodeling, α/β-tubulin heterodimer assembly, and the spindle assembly checkpoint. We propose a model where the TUB1 intron promotes expression from the chromosomal locus and that this may represent a conserved mechanism for tubulin regulation under conditions that require high levels of tubulin production.
The Possibility of Paraphrase
Authors: Leth Palle
Published: September 2023

It is often claimed that, in at least some areas of language use, the relation between form and content is such that any attempt at reformulation or paraphrase amounts to a distortion of the significance of the original wording. In this article, I set out to vindicate an undemanding yet nontrivial conception of paraphrase. According to the rhetorical relations account of textual cohesion proposed, the meaning specifications required by a collection of sentences in order to constitute a text pave the way for a kind of reformulation which is in solidarity with the possibility of paraphrase. I substantiate my approach with prosaic and poetic examples from Woolf and Dickinson, respectively.
Single-cell transcriptomics of Treg reveals hallmarks and trajectories of immunological aging
Authors: Yang Kevin Y , Liao Jinyue , Ma Zhangjing , Tse Hung Fat , Lu Liwei , Graca Luis , Lui Kathy O
Published: September 2023

Age-related immunosenescence is characterized by progressive dysfunction of adaptive immune response and increased autoimmunity. Nevertheless, the impact of aging on CD4+ regulatory T cells that are master regulators of the immune system remains largely unclear. Here, we report cellular and molecular hallmarks of regulatory T cells derived from murine lymphoid and adipose tissues at 3, 18, and 24 mo of age, respectively, by analyzing their heterogeneity that displays dynamic changes in transcriptomic effector signatures at a single-cell resolution. Although the proportion of regulatory T cells among total Cd4+ T cells, as well as their expression levels of Foxp3, did not show any global change with time, we have identified 6 transcriptomically distinct clusters of regulatory T cells with cross-tissue conserved hallmarks of aging, including increased numbers of proinflammatory regulatory T cells, reduced precursor cells, increased immature and mature T follicular regulatory cells potentially supported by a metabolic switch from oxidative phosphorylation to glycolysis, a gradual loss of CD150hi regulatory T cells that support hematopoiesis, and increased adipose tissue-specific regulatory T cells that are associated with metabolic disease. To dissect the impact of immunosenescence on humoral immunity, we propose some potential mechanisms underlying T follicular regulatory cell–mediated dysfunction by interactome analysis on T follicular regulatory cells, T follicular helper cells, and B cells during aging. Lastly, spatiotemporal analysis further revealed trajectories of regulatory T-cell aging that demonstrate the most significant changes in marrow and adipose tissues that might contribute to the development of age-related immunosenescence and type 2 diabetes. Taken together, our findings could provide a better understanding of age-associated regulatory T-cell heterogeneity in lymphoid and adipose tissues, as well as regulatory T-cell hallmarks during progressive adaptation to aging that could be therapeutically targeted for rejuvenating the aging immune system in the future.
Surplus embryos in IVF units in Israel: patients’ attitude towards various dispositions—a bioethical analysis of empirical findings
Authors: Tamir Sivan , Gilbar Roy
Published: September 2023

Owing to its pro-natalist approach, Israel is considered as an in-vitro fertilization (IVF) superpower. With the high number of state-funded IVF treatments, IVF units find themselves stranded with around a million cryopreserved ‘surplus’ embryos; namely, embryos neglected or forgotten by patients, or abandoned due to personal or familial circumstances. The accumulation of such a vast number of surplus embryos creates operational and economic burdens for IVF units. Attempting to better comprehend this predicament, we conducted a survey. Its findings serve as a basis for the theoretical analysis provided in this article, which is based on the tension between reproductive autonomy on the one hand, and solidarity and personal responsibility, on the other. The survey examined present and former IVF patients’ attitudes towards relevant dispositions for surplus embryos in Israel. Our findings indicated that patients express an individualistic approach to autonomy, which was reflected, for example in reluctance to donate their surplus embryos to research or discard them, even years after completing their IVF treatments. These findings and others led us to conclude that a solidarity-based policy should be imposed. We also argue that personal responsibility, via the constructs of ‘participatory patienthood’—the notion of self-empowered patients taking initiative with respect to their health—should be encouraged in supporting an ethical imperative to choose a disposition for one’s surplus embryos.
Landmine Injury Resulting in Comminuted Lumbar Facet Fracture as a Cause of Lumbar Stenosis and Spondylolisthesis
Authors: Chen Jason A , Mooney Michael A , Rachlin Jacob R
Published: September 2023

Lumbar facet fractures are rarely reported and have been linked to sports and spine surgery. We describe the case of a 77-year-old patient who sustained an injury from multiple landmine blasts during the Vietnam War. He had low back pain since that time, which was initially managed conservatively. However, the pain progressed over decades to severe neurogenic claudication that greatly restricted his quality of life. Neuroimaging revealed the presence of bone fragments impinging on the spinal canal at the L5/6 level (transitional anatomy) that resulted from a comminuted fracture of the lumbar facet at the inferior articular process. We performed an L5/6 decompressive laminectomy, with removal of these fragments, and posterior instrumented fusion, with substantial improvement in symptoms. This case illustrates a unique mechanism of lumbar facet fracture and the biomechanic origination, natural history, and optimal treatment of this entity. We expand on the spectrum of lumbosacral injuries associated with the combat blast injury that have only increased in prevalence in recent conflicts.
CASCO: Cosmological and AStrophysical parameters from Cosmological simulations and Observations – I. Constraining physical processes in local star-forming galaxies
Authors: Busillo V , Tortora C , Napolitano N R , Koopmans L V E , Covone G , Gentile F , Hunt. L K
Published: September 2023

We compare the structural properties and dark matter content of star-forming galaxies taken from the Cosmology and Astrophysics with MachinE Learning Simulations (camels) cosmological simulations to the observed trends derived from the SPARC sample in the stellar mass range $[10^{9}, 10^{11}]\, \textrm {M}_{\odot }$, to provide constraints on the value of cosmological and astrophysical (supernova- and active galactic nucleus-related) parameters. We consider the size–, internal DM fraction–, internal DM mass–, and total–stellar mass relations for all the 1065 simulations, all having different cosmological and astrophysical parameters, from the IllustrisTNG, SIMBA, and ASTRID suites of camels, and search for the parameters that minimize the χ2 with respect to the observations. For the IllustrisTNG suite, we find the following constraints for the cosmological parameters: $\Omega _{\textrm {m}} = 0.27_{-0.05}^{+0.01}$, $\sigma _{8} = 0.83_{-0.11}^{+0.08}$, and $S_{8} = 0.78_{-0.09}^{+0.03}$, which are consistent within 1σ with the results from the 9-yr WMAP observations. SN feedback-related astrophysical parameters, which describe the departure of outflow wind energy per unit star formation rate and wind velocity from the reference IllustrisTNG simulations, assume the following values: $A_{\textrm {SN1}} = 0.48_{-0.16}^{+0.25}$ and $A_{\textrm {SN2}} = 1.21_{-0.34}^{+0.03}$, respectively. Therefore, simulations with a lower value of outflow wind energy per unit star formation rate with respect to the reference illustrisTNG simulation better reproduce the observations. Variation of active galactic nucleus feedback parameters, on the other hand, shows negligible effects on the scaling relation trends in the mass range probed. Simulations based on SIMBA and ASTRID suites predict central dark matter masses substantially larger than those observed in real galaxies, which can be reconciled with observations only by requiring values of Ωm inconsistent with cosmological constraints for SIMBA, or simulations characterized by unrealistic galaxy mass distributions for ASTRID.
P03.03.A T2-FLUID-ATTENUATED INVERSION RECOVERY MISMATCH SIGN IN LOWER-GRADE GLIOMAS: CORRELATION WITH PATHOLOGICAL AND MOLECULAR FINDINGS
Authors: Yamashita S , Takeshima H , Kadota Y , Azuma M , Fukushima T , Watanabe T , Yokogami K
Published: September 2023

BACKGROUND

After the new molecular-based classification was reported to be useful for predicting prognosis, the T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign has gained interest as one of the promising methods for detecting lower-grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutations and chromosome 1p/19q non-codeletion (IDH mut-Noncodel) with high specificity. Although all institutions could use T2-FLAIR mismatch sign without any obstacles, this sign was not completely helpful because of its low sensitivity. In this study, we attempted to uncover the mechanism of T2-FLAIR mismatch sign for clarifying the cause of this sign’s low sensitivity.

MATERIAL AND METHODS

In this study, data on 101 consecutive and unselected patients with LGGs (WHO grades 2 and 3) admitted to Miyazaki University Hospital between November 2005 and January 2021 were collected. The inclusion criteria were as follows: (1) obtained molecular information on IDH mutation and chromosome 1p/19q codeletion status and (2) obtained preoperative MRI data, including T2-weighted imaging and FLAIR sequences. In this study, 99 patients were enrolled and then classified into three groups based on IDH mutation and chromosome 1p/19q codeletion status: (1) IDH-mutant, 1p/19q-codeleted LGGs (IDH mut-codel); (2) IDH-mutant, 1p/19q-noncodeleted LGGs (IDH mut-Noncodel); and (3) IDH wild-type LGGs (IDH wt).

RESULTS

Among 99 patients with LGGs, 22 were T2-FLAIR mismatch sign-positive (22%), and this sign as a marker of IDH mut-Noncodel showed a sensitivity of 55.6% and specificity of 96.8%. Via pathological analyses, we could provide evidence that not only microcystic changes but the enlarged intercellular space was associated with T2-FLAIR mismatch sign (p =0.017). As per the molecular analyses, overexpression of mTOR-related genes (m-TOR, RICTOR) were detected as the molecular events correlated with T2-FLAIR mismatch sign (p = 0.020, 0.030. respectively).

CONCLUSION

We suggested that T2-FLAIR mismatch sign could pick up the IDH mut-Noncodel LGGs with enlarged intercellular space or that with overexpression of mTOR-related genes.
P06.19.A BEYOND T CELL TOXICITY - INTRATHECAL CXCL13 ELEVATION INDICATES B-CELL INVOLVEMENT IN NEUROLOGICAL IMMUNE-RELATED ADVERSE EVENTS FOLLOWING IMMUNE CHECKPOINT INHIBITION: 2 CASE OBSERVATIONS AND COMPREHENSIVE REVIEW
Authors: Bieler L , Otto F , Seiberl M , Moser T , Kleindienst W , Wipfler P , Kölblinger P , Harrer A
Published: September 2023

BACKGROUND

Neurological immune-related adverse events (nirAE) can occur following cancer treatment with immune checkpoint inhibitors (ICI). Mainly attributed to autoreactive T-cells, nirAE usually respond to first line therapy with high-dose steroids (GC). Severe or fatal outcomes are rare & most frequently reported in clinically overlapping syndromes with accumulating evidence of B cell autoimmunity.

MATERIAL AND METHODS

We present 2 patients who developed grade 3-4 nirAE with evidence suggestive for B cell involvement.

RESULTS

Case 1: A 75y female with metastatic melanoma developed double vision & general weakness 2 weeks after the 1st cycle of ipilimumab & nivolumab. Diagnostic workup showed pleocytosis (27 cells/µl) with elevated CXCL13 (316 pg/ml) in cerebrospinal fluid (CSF). Increases of creatine kinase, troponin T, elevated levels of anti-acetylcholine receptor antibodies & positive anti-titin antibodies led to the diagnosis of myocarditis & myositis/myasthenia gravis overlap syndrome. The patient received pulsed high-dose GC with tapering. CSF flow cytometry revealed intrathecal recruitment of CXCL13-responsive B cell helper T cells of a predominant inflammatory phenotype & a highly increased pathological CD4/CD8 T cell ratio in peripheral blood. Clinically non-responding to GC, the patient received additional therapy with immunoglobulins (IVIG). 2 weeks later she was readmitted due to generalized myopathy with dropped head & received a second cycle of high-dose GC since she refused plasmapheresis. Further escalation with rituximab could not be realized because the patient rapidly deteriorated & deceased. Case 2: A 75y female with metastatic invasive enteric adenocarcinoma of the lung developed gait ataxia & ataxia of the lower limbs 5 months after pembrolizumab therapy. CSF analysis showed a pleocytosis (248 cells/µl) with plasma cells, pronounced CXCL13 elevation (>488 pg/ml) & positive screening for anti-neuronal cerebellar antibodies, suggesting ICI-mediated cerebellitis. The patient received high-dose GC & IVIG for 5 days each, was discharged but readmitted 5 months later due to subacute onset of spastic paraparesis. Magnetic resonance imaging of the spine revealed thoracic myelopathy & CSF showed mild pleocytosis (5 cells/µl), intrathecal immunoglobulin synthesis & mild CXCL13 elevation (33 pg/ml). The patient completed a second cycle of steroids followed by rituximab targeting B-cell involvement & currently 4 months later is clinically stable.

CONCLUSION

Intrathecal CXCL13 may serve as diagnostic tool of B cell involvement, here supported by intrathecal immunoglobulin synthesis, presence of plasma cells and/or severely altered immune cell compositions. Early treatment escalation with B cell depleting agents such as rituximab may help prevent fatal clinical courses.
P13.01.A POST-OPERATIVE MRI SYNTHESIS FROM PRE-OPERATIVE MRI AND POST-OPERATIVE CT USING CONDITIONAL GAN FOR THE ASSESSMENT OF DEGREE OF RESECTION
Authors: Miao X , Chen H , Tang M , Chen Y
Published: September 2023

BACKGROUND

Magnetic resonance imaging (MRI) is an essential part of assessing the extension of resection after craniotomy, allowing for accurate assessment of the brain. However, the application of MRI within 72 hours after surgery is limited, owing to its high cost, long time duration, and patients’ limited mobility. Besides, MRI excludes people with contraindications, including implantable electronic devices or artificial limbs, in which sceneries computerized tomography (CT) is the only available choice. To overcome these limitations, we investigated the use of a deep learning model for synthesizing post-operative MRI images.

MATERIAL AND METHODS

We aim to employ Cross-domain Correspondence Learning for Exemplar-based Image Translation Network (CoCosNet), an exemplar-based image translation model to synthesize T1 contrast-enhanced (T1ce) MRI images by combining post-operative T1ce and post-operative CT images. 233 cases were retrospectively collected at Sun Yat-sen University Cancer Center, who underwent complete MRI and CT scans.

RESULTS

After 200 epochs and a batch size of 10, CoCosNet achieved comparable results compared to other existing models, with objective indicators structural similarity index = 0.75, peak signal-to-noise ratio = 21.68, and mean absolute error = 0.007. Furthermore, assessments of the extent of resection between the true and synthesized T1ce images achieve great consistency.

CONCLUSION

Our study demonstrates the effectiveness of the CoCosNet deep learning model in synthesizing post-operative MRI images from pre-operative MRI and post-operative CT scans. Our quantitative analysis indicates that the synthesized images have comparable quality to real MRI images and are able to accurately assess the extent of resection. This approach has a promising future by providing a reliable alternative to traditional post-operative MRI.
Aqueous batteries: from laboratory to market
Authors: Zhang Xikun , Xing Pengcheng , Madanu Thomas L , Li Jing , Shu Jie , Su Bao-Lian
Published: September 2023

This perspective discusses the fundamental benefits and drawbacks of aqueous batteries and the challenges of the development of such battery technology from laboratory scale to industrial applications.
Impact of Fluoroquinolone Susceptibility Suppression on Discharge Prescribing for Acute Uncomplicated Cystitis
Authors: Hayden Dillon A , White Bryan P , Neely Stephen , Bennett Kiya K
Published: September 2023

Background

Fluoroquinolones (FQs) are associated with adverse effects and increasing resistance. However, uncomplicated cystitis remains a frequent reason for FQ use. Selective reporting involves withholding susceptibilities for select antimicrobial agents on microbiology reports, in hopes of dissuading use by providers. The purpose of this study was to investigate the impact of FQ susceptibility suppression on discharge prescribing for hospitalized patients with uncomplicated cystitis.

Methods

This retrospective quasi-experimental analysis was conducted among adult patients at a 350-bed academic medical center. Its aim was to compare the incidence of FQ prescribing for cystitis at hospital discharge, one year before and after implementation (1 March 2017–31 March 2019) of a policy to suppress FQ urinary susceptibility results for pansusceptible Klebsiella spp and Escherichia coli. FQ appropriateness and risk factors for FQ use were also examined.

Results

There was a relative risk reduction of 39% in discharge FQ prescribing when adjusted for discharge team (adjusted risk ratio, 0.61; 95% CI, .40–.93). Almost all FQ use was inappropriate, largely due to organisms’ susceptibility to a guideline-preferred agent (n = 61). In multivariate analysis, odds ratios of discharge FQ prescribing were 0.22 (95% CI, .12–.39) for insured patients, 0.43 (95% CI, .21–.86) for patients with antibiotic allergy, and 57.8 (95% CI, 13.7–244) for those receiving inpatient FQ. Discharge from a medicine team was protective against discharge FQ prescribing.

Conclusions

With multidisciplinary inpatient medicine services and avoidance of inpatient FQ use, suppression of FQ susceptibilities on pansusceptible urine isolates for Klebsiella spp and E coli may represent an attractive strategy for antibiotic stewardship at hospital discharge.
Lower Quadrant Edema Patient-Reported Outcome Measure Is Reliable, Valid, and Efficient for Patients With Lymphatic and Venous Disorders
Authors: Deutscher Daniel , Kallen Michael A , Hayes Deanna , Werneke Mark W , Mioduski Jerome E , Levenhagen Kim , Pfarr Megan , Cook Karon F
Published: September 2023

Objective

The main aims of this study were: (1) to create a patient-reported outcome measure (PROM) item bank for measuring the impact of lower quadrant edema (LQE) on physical function using item response theory and (2) to assess reliability, validity, and administration efficiency of LQE PROM scores based on computerized adaptive test (CAT) and the reliability of a 10-item short form (SF).

Methods

This retrospective study included data from patients treated in outpatient rehabilitation clinics for lower quadrant edema who responded to all 30 candidate items at intake. Item response theory model assumptions of unidimensionality, local item independence, item fit, and presence of differential item functioning (DIF) were evaluated. LQE-CAT-generated scores were assessed for reliability, validity, and administration efficiency. LQE-SF-generated scores were assessed for reliability.

Results

The total cohort included 4894 patients (mean [SD] age = 65 [14] years; range = 14–89 years). A set of 20 items was selected for the item bank based on support for its unidimensionality and fit to the item response theory model, with reliability estimates greater than 0.92 for CAT and SF administration modes. No items demonstrated DIF with respect to tested variables. After controlling for scores at intake, scores discriminated among multiple patient groups in clinically logical ways with better outcomes observed for patients who were younger with less chronic symptoms and fewer comorbidities. Scores were responsive to change but the effect size was small (0.4). There were negligible floor and ceiling effects. CAT administration of the item bank required an average of 6.1 items (median = 5). Scores correlated highly with full-bank scores (Pearson correlation coefficient = 0.98).

Conclusion

Scores on the LQE PROM were reliable, valid, and efficient for assessing perceived physical function of patients with lower quadrant edema. The LQE, CAT, and SF are suitable for research and routine clinical care. Reasons for the small effect size for change scores should be studied.

Impact

The newly developed LQE PROM was reliable and valid and offered efficient administration modes for assessing perceived physical function of patients with LQE, both for research and routine clinical care in busy outpatient rehabilitation settings. As an item response theory-based measure, the LQE PROM allows administration of condition-specific functional questions with low response burden for patients. The 10-item LQE-SF offers a feasible alternative administration mode when CAT administration is not available. This study supports a transition to PROMs that are based on modern measurement approaches to achieve the combined benefits of high accuracy and efficiency.
Chondrogenic medium in combination with a c-Jun N-terminal kinase inhibitor mediates engineered cartilage regeneration by regulating matrix metabolism and cell proliferation
Authors: Zhang Peiling , Wang Qianyi , Chen Jie , Ci Zheng , Zhang Wei , Liu Yu , Wang Xiaoyun , Zhou Guangdong
Published: September 2023

Cartilage tissue engineering is a promising strategy for repairing cartilage defects. However, achieving satisfactory cartilage regeneration in vitro and maintaining its stability in vivo remains a challenge. The key to achieving this goal is establishing an efficient cartilage regeneration culture system to retain sufficient active cells with physiological functions, generate abundant cartilage extracellular matrix (ECM) and maintain a low level of cartilage ECM degradation. The current chondrogenic medium (CM) can effectively promote cartilage ECM production; however, it has a negative effect on cell proliferation. Meanwhile, the specific c-Jun N-terminal kinase pathway inhibitor SP600125 promotes chondrocyte proliferation but inhibits ECM synthesis. Here, we aimed to construct a three-dimensional cartilage regeneration model using a polyglycolic acid/polylactic acid scaffold in combination with chondrocytes to investigate the effect of different culture modes with CM and SP600125 on in vitro cartilage regeneration and their long-term outcomes in vivo systematically. Our results demonstrate that the long-term combination of CM and SP600125 made up for each other and maximized their respective advantages to obtain optimal cartilage regeneration in vitro. Moreover, the long-term combination achieved stable cartilage regeneration after implantation in vivo with a relatively low initial cell-seeding concentration. Therefore, the long-term combination of CM and SP600125 enhanced in vitro and in vivo cartilage regeneration stability with fewer initial seeding cells and thus optimized the cartilage regeneration culture system.
A construct of adipose-derived mesenchymal stem cells—laden collagen scaffold for fertility restoration by inhibiting fibrosis in a rat model of endometrial injury
Authors: Dai Yangyang , Xin Liaobing , Hu Sentao , Xu Shiqian , Huang Dong , Jin Xiaoying , Chen Jianmin , Chan Rachel Wah Shan , Ng Ernest Hung Yu , Yeung William Shu Biu , Ma Lie , Zhang Songying
Published: September 2023

Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion, resulting in uterine factor infertility. Mesenchymal stem cell (MSC) therapy is a promising strategy in endometrial repair; yet, exogenous MSCs still raise concerns for safety and ethical issues. Human adipose-derived mesenchymal stem cells (ADMSCs) residing in adipose tissue have high translational potentials due to their autologous origin. To harness the high translation potentials of ADMSC in clinical endometrium regeneration, here we constructed an ADMSCs composited porous scaffold (CS/ADMSC) and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury model. We found that CS/ADMSC intrauterine implantation (i) promoted endometrial thickness and gland number, (ii) enhanced tissue angiogenesis, (iii) reduced fibrosis and (iv) restored fertility. We ascertained the pro-proliferation, pro-angiogenesis, immunomodulating and anti-fibrotic effects of CS/ADMSC in vitro and revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic analysis. Our results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.
Fixed Effects and the Generalized Mundlak Estimator
Authors: Arkhangelsky Dmitry , Imbens Guido W
Published: September 2023

We develop a new approach for estimating average treatment effects in observational studies with unobserved group-level heterogeneity. We consider a general model with group-level unconfoundedness and provide conditions under which aggregate balancing statistics—group-level averages of functions of treatments and covariates—are sufficient to eliminate differences between groups. Building on these results, we re-interpret commonly used linear fixed-effect regression estimators by writing them in the Mundlak form as linear regression estimators without fixed effects but including group averages. We use this representation to develop Generalized Mundlak Estimators that capture group differences through group averages of (functions of) the unit-level variables and adjust for these group differences in flexible and robust ways in the spirit of the modern causal literature.
Emotion regulation of social pain: double dissociation of lateral prefrontal cortices supporting reappraisal and distraction
Authors: Mo Licheng , Li Sijin , Cheng Si , Li Yiwei , Xu Feng , Zhang Dandan
Published: September 2023

The dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) are both crucial regions involved in voluntary emotion regulation. However, it remains unclear whether the two regions show functional specificity for reappraisal and distraction. This study employed transcranial magnetic stimulation (TMS) to explore, in a real social interactive scenario, whether different lateral prefrontal regions play relatively specific roles in downregulating social pain via reappraisal and distraction. Participants initially took part in a social interactive game, followed by receiving either active (the DLPFC- or VLPFC-activated group, n = 100 per group) or control (the vertex-activated group, n = 100) TMS session. They were then instructed to use both distraction and reappraisal strategies to downregulate any negative emotions evoked by the social evaluation given by their peers who interacted with them previously. Results demonstrated that the TMS-activated DLPFC has a greater beneficial effect during distraction, whereas the activated VLPFC has a greater beneficial effect during reappraisal. This result investigated the direct experience of social pain and extended previous findings on empathy-related responses to affective pictures while also controlling for confounding factors such as empathic concern. Therefore, we are now confident in the double dissociation proposal of the DLPFC and VLPFC in distraction and reappraisal.
Understanding the divergent evolution and epidemiology of H3N8 influenza viruses in dogs and horses
Authors: Wasik Brian R , Rothschild Evin , Voorhees Ian E H , Reedy Stephanie E , Murcia Pablo R , Pusterla Nicola , Chambers Thomas M , Goodman Laura B , Holmes Edward C , Kile James C , Parrish Colin R
Published: September 2023

Cross-species virus transmission events can lead to dire public health emergencies in the form of epidemics and pandemics. One example in animals is the emergence of the H3N8 equine influenza virus (EIV), first isolated in 1963 in Miami, FL, USA, after emerging among horses in South America. In the early 21st century, the American lineage of EIV diverged into two ‘Florida’ clades that persist today, while an EIV transferred to dogs around 1999 and gave rise to the H3N8 canine influenza virus (CIV), first reported in 2004. Here, we compare CIV in dogs and EIV in horses to reveal their host-specific evolution, to determine the sources and connections between significant outbreaks, and to gain insight into the factors controlling their different evolutionary fates. H3N8 CIV only circulated in North America, was geographically restricted after the first few years, and went extinct in 2016. Of the two EIV Florida clades, clade 1 circulates widely and shows frequent transfers between the USA and South America, Europe and elsewhere, while clade 2 was globally distributed early after it emerged, but since about 2018 has only been detected in Central Asia. Any potential zoonotic threat of these viruses to humans can only be determined with an understanding of its natural history and evolution. Our comparative analysis of these three viral lineages reveals distinct patterns and rates of sequence variation yet with similar overall evolution between clades, suggesting epidemiological intervention strategies for possible eradication of H3N8 EIV.
Questioning the monophyly of Anthroherponina (Coleoptera: Leiodidae: Cholevinae: Leptodirini) and description of three new, ecologically ultraspecialized subterranean species
Authors: Delić Teo , Lohaj Roman , Brestovanský Jiří , Čáha Daniel , Jalžić Branko
Published: September 2023

The beetle subtribe Anthroherponina (Coleoptera: Leiodidae), including also ecologically specialized and semi-aquatic hygropetricolous genera, presents one of the most illustrative examples of morphological variability in cave-adapted animals. However, phylogenetic relations within the tribe remain dubious. Recent exploration of deep-phreatic caves of the Western Balkans Dinaric Karst enabled us to collect all known Anthroherponina genera and access new populations of hygropetricolous beetles, representatives of the iconic Hadesia and elusive Nauticiella. We studied the taxonomic structure of newly collected semi-aquatic beetle populations by using traditional morphology and deploying uni- and multilocus molecular species delimitation. In addition, we tested the monophyly of the subtribe Anthroherponina and set the group’s evolutionary development into a palaeogeographic context by reconstructing a multilocus calibrated phylogeny. As a result, three new species of specialized semi-aquatic beetles are described. The morphologically based monophyly of Anthroherponina was shown to be an artefact of evolutionary convergences, while the evolutionary development of the monophylum seems to be paired with the orogeny of the Dinarides. Finally, the new results raise more questions about our understanding of evolution in subterranean beetles and their adaptation to special ecological niches.