bluuebunny/crossref_metadata_2025 huggingface dataset:
CLN-978, a novel half-life extended CD19/CD3/HSA-specific T cell-engaging antibody construct with potent activity against B-cell malignancies with low CD19 expression
Authors: Meetze Kristan , Mehta Naveen K , Li Bochong , Findlay Hannah M , London Timothy B , Patakas Agapitos , Michaelson Jennifer S , Baeuerle Patrick A
Published: August 2023

Background

Despite significant progress in the development of T cell-engaging therapies for various B-cell malignancies, a high medical need remains for the refractory disease setting, often characterized by suboptimal target levels.

Methods

To address this issue, we have developed a 65-kDa multispecific antibody construct, CLN-978, with affinities tuned to optimize the killing of low-CD19 expressing tumor cells. CLN-978 bound to CD19 on B cells with picomolar affinity, and to CD3ε on T cells with nanomolar affinity. A serum albumin binding domain was incorporated to extend serum half-life. In this setting, we biophysically characterize and report the activities of CLN-978 in cell co-culture assays, multiple mouse models and non-human primates.

Results

Human T cells redirected by CLN-978 could eliminate target cells expressing less than 300 copies of CD19 on their surface. The half-life extension and high affinity for CD19 led to significant antitumor activity in murine lymphoma models at very low doses of CLN-978. In primates, we observed a long serum half-life, deep and sustained depletion of normal B cells, and remarkable tolerability, in particular, reduced cytokine release when CLN-978 was administered subcutaneously.

Conclusions

CLN-978 warrants further exploration. An ongoing clinical phase 1 trial is investigating safety, pharmacokinetics, pharmacodynamics, and the initial therapeutic potential of subcutaneously administered CLN-978 in patients with non-Hodgkin’s lymphoma.
Genetic and phenotypic spectrum of non-21-hydroxylase-deficiency primary adrenal insufficiency in childhood: data from 111 Chinese patients
Authors: Duan Ying , Zheng Wanqi , Xia Yu , Zhang Huiwen , Liang Lili , Wang Ruifang , Yang Yi , Zhang Kaichuang , Lu Deyun , Sun Yuning , Han Lianshu , Yu Yongguo , Gu Xuefan , Sun Yu , Xiao Bing , Qiu Wenjuan
Published: August 2023

Background

Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. Differential diagnosis of numerous causes of PAI requires a thorough understanding of the condition.

Methods

To describe the genetic composition and presentations of PAI. The following data were collected retrospectively from 111 patients with non-21OHD with defined genetic diagnoses: demographic information, onset age, clinical manifestations, laboratory findings and genetic results. Patients were divided into four groups based on the underlying pathogenesis: (1) impaired steroidogenesis, (2) adrenal hypoplasia, (3) resistance to adrenocorticotropic hormone (ACTH) and (4) adrenal destruction. The age of onset was compared within the groups.

Results

Mutations in the following genes were identified:NR0B1(n=39),STAR(n=33),CYP11B1(n=12),ABCD1(n=8),CYP17A1(n=5),HSD3B2(n=4),POR(n=4),MRAP(n=2),MC2R(n=1),CYP11A1(n=1),LIPA(n=1) andSAMD9(n=1). Frequent clinical manifestations included hyperpigmentation (73.0%), dehydration (49.5%), vomiting (37.8%) and abnormal external genitalia (23.4%). Patients with adrenal hypoplasia typically presented manifestations earlier than those with adrenal destruction but later than those with impaired steroidogenesis (both p<0.01). The elevated ACTH (92.6%) and decreased cortisol (73.5%) were the most common laboratory findings. We generated a differential diagnosis flowchart for PAI using the following clinical features: 17-hydroxyprogesterone, very-long-chain fatty acid, external genitalia, hypertension and skeletal malformation. This flowchart identified 84.8% of patients with PAI before next-generation DNA sequencing.

Conclusions

STARandNR0B1were the most frequently mutated genes in patients with non-21OHD PAI. Age of onset and clinical characteristics were dependent on aetiology. Combining clinical features and molecular tests facilitates accurate diagnosis.
Colchicine in patients with heart failure and preserved left ventricular ejection fraction: rationale and design of a prospective, randomised, open-label, crossover clinical trial
Authors: Shchendrygina Anastasia , Rachina Svetlana , Cherkasova Natalia , Suvorov Aleksandr , Komarova Irina , Mukhina Nadezhda , Ananicheva Natalia , Gasanova Diana , Sitnikova Violetta , Koposova Aleksandra , Smirnova Julia , Moiseewa Elizaveta , Drogashevskaya Daria
Published: August 2023

Introduction

Systemic low-grade inflammation is a fundamental pathophysiological mechanism of heart failure with preserved left ventricular ejection fraction (HFpEF). The efficacy of anti-inflammatory therapy in HFpEF is largely understudied. The aim of the study is to assess the anti-inflammatory effect of colchicine in HFpEF by looking at inflammatory biomarkers: high-sensitivity C reactive protein (hsCRP) and soluble suppression of tumorigenicity 2 (sST2).

Methods and analysis

This is a single-centre, prospective, randomised controlled, open-label, blinded-endpoint crossover clinical trial of stable but symptomatic patients with HFpEF. Patients will be randomised to either colchicine treatment 0.5 mg two times per day or usual care for 12 weeks followed by a 2-week washout period and crossover to 12 weeks of treatment with the alternate therapy. The primary objective is to investigate if administration of colchicine compared with usual care reduces inflammation in patients with HFpEF measured by primary endpoint sST2 and co-primary endpoint hsCRP at baseline and 12-week follow-up. Secondary objective is to determine if treatment with colchicine influences N-terminal pro-B-type natriuretic peptide levels, left ventricular diastolic function and remodelling, right ventricular systolic function and left atrial volumetric characteristics. We are aiming to enrol a total of 40 participants. This trial will answer the question if colchicine treatment reduces systemic low-grade inflammation and influences left ventricular diastolic function and remodelling with patients with HFpEF.

Ethics and dissemination

Ethical approval was obtained from the Ethics Committee of Sechenov University (reference: 03-22).

Trial registration number

NCT05637398.
Exercise regimens for improved sleep quality in adult breast cancer survivors: systematic review and network meta-analysis
Authors: Hasan Faizul , Tu Yu-Kang , Lin Chia-Chin , Yuliana Lia Taurussia , Romadlon Debby Syahru , Chiu Hsiao-Yean
Published: August 2023

Objective

The relative efficacy of exercise regimens for improving sleep quality in adult breast cancer survivors remains unknown. This network meta-analysis aimed to compare the efficacy of various exercise regimens for improving sleep quality in adult breast cancer survivors.

Methods

This study searched four electronic databases for relevant literature from inception to 18 July 2023. Randomised controlled trials reporting the effects of exercise on sleep quality in adults with breast cancer were included. A random-effects network meta-analysis based on the frequentist framework was performed.

Results

In total, 35 trials including 3374 breast cancer survivors were included. Compared with usual care, endurance training combined with resistance training significantly improved sleep quality (standardised mean differences (SMDs) = −0.97; 95% CI = −1.50 to −0.43; certainty of evidence=moderate) (p<0.05). Endurance training combined with resistance training (SMDs: −1.42; 95% CIs: −2.31 to −0.53; moderate) achieved superior sleep quality results compared with stretching exercises (p<0.05). The surface under the cumulative ranking curve analysis indicated that endurance training combined with resistance training was ranked as the top effective treatment among other exercise regimens for improving sleep quality in breast cancer survivors (71%).

Conclusions

Endurance training combined with resistance training is effective in improving sleep quality in adult breast cancer survivors. Our results provide evidence that exercise can improve sleep quality in adult breast cancer survivors.
Impact of unilateral dual-brachial arteries on endothelial-dependent and endothelial-independent vasodilation: a case study
Authors: Courish Molly K. , Shivgulam Madeline E. , MacLeod Jessica R. , Kimmerly Derek S. , O'Brien Myles W.
Published: August 2023

Brachial artery bifurcation has been documented in ∼5%–10% of cadaver models, but our understanding of arterial function in these rare cases is unknown. This case study examined vasodilatory responses between a right bifurcated (right superficial brachial artery, right deep brachial artery) versus a left nonbifurcated brachial artery in a 28-year-old healthy female. Vasodilatory functions were assessed via flow-mediated dilation and nitroglycerin-mediated dilation (0.4 mg sublingual spray) techniques. Bifurcation of the brachial artery promotes lower endothelial-dependent vasodilation and possibly reduced vascular smooth muscle responsiveness to nitric oxide.

Take home message

Our case study indicated that a bifurcated brachial artery exhibited worse vasodilatory responses relative to an intact contralateral artery.
Microhabitat use of northern and southern flying squirrels in a recent hybrid zone
Authors: O'Brien Paul P. , Bowman Jeff , Newar Sasha , Garroway Colin J.
Published: August 2023

Secondary contact of closely related species may lead to hybridization if reproductive isolation is incomplete. We examined the role of habitat use as a factor contributing to reproductive isolation of northern ( Glaucomys sabrinus (Shaw, 1801)) and southern ( Glaucomys volans (Linnaeus, 1758)) flying squirrels in an area of secondary contact in Ontario, Canada. Specifically, we looked at summer microhabitat use within sites of sympatry and allopatry to test for evidence of reinforcement due to diverging habitat use. We also examined differences in broad-scale habitat features at woodlots to determine predictors of species occurrence across sites. We used 18 years (2002–2019) of flying squirrel summer capture data from six sites along a north–south transect and microhabitat data from vegetation surveys conducted during summer 2016. We found microhabitat variables to be weak predictors of trap-level flying squirrel presence, and we found no evidence of divergence in microhabitat use over the 18 years. Further, we found latitude, not broad-scale habitat, was the strongest predictor of site-level flying squirrel occurrence. Overall, our findings suggest that microhabitat-based isolation is not being reinforced between flying squirrels; however, hybridization may be limited to areas where climate and habitat are suitable for both species.
Bodylab
Authors: Zeidler Daniel , McGinity Matthew
Published: August 2023

Bodylab is a virtual reality system for creating full-body virtual reality avatars. It provides anatomically realistic mannequins as canvases, which can be painted and textured, sculpted and deformed, adorned with objects and animated with particle effects. The artist can work from a first or third person perspective, and variety of interaction modalities are made available. To assess the system, we invite costume designers and theatrical artists to provide expert reviews. We also describe the use of Bodylab in a live dance performance. We believe Bodylab to be the first virtual reality tool for in virtuo painting and sculpting of full-body avatars.
The Power of Robot-mediated Play: Forming Friendships and Expressing Identity
Authors: Ahumada-Newhart Verónica , Schneider Margaret , Riek Laurel D.
Published: August 2023

Tele-operated collaborative robots are used by many children for academic learning. However, as child-directed play is important for social-emotional learning, it is also important to understand how robots can facilitate play. In this article, we present findings from an analysis of a national, multi-year case study, where we explore how 53 children in grades K–12 (
n
= 53) used robots for self-directed play activities. The contributions of this article are as follows. First, we present empirical data on novel play scenarios that remote children created using their tele-operated robots. These play scenarios emerged in five categories of play: physical, verbal, visual, extracurricular, and wished-for play. Second, we identify two unique themes that emerged from the data—robot-mediated play as a foundational support of general friendships and as a foundational support of self-expression and identity. Third, our work found that robot-mediated play provided benefits similar to in-person play. Findings from our work will inform novel robot and HRI design for tele-operated and social robots that facilitate self-directed play. Findings will also inform future interdisciplinary studies on robot-mediated play.
Generative Adversarial Networks: A Survey on Attack and Defense Perspective
Authors: Zhang Chenhan , Yu Shui , Tian Zhiyi , Yu James J. Q.
Published: August 2023

Generative Adversarial Networks (GANs) are a remarkable creation with regard to deep generative models. Thanks to their ability to learn from complex data distributions, GANs have been credited with the capacity to generate plausible data examples, which have been widely applied to various data generation tasks over image, text, and audio. However, as with any powerful technology, GANs have a flip side: their capability to generate realistic data can be exploited for malicious purposes. Many recent studies have demonstrated the security and privacy (S&P) threats brought by GANs, especially the attacks on machine learning (ML) systems. Nevertheless, so far as we know, there is no existing survey that has systematically categorized and discussed the threats and strategies of these GAN-based attack methods. In this article, we provide a comprehensive survey of GAN-based attacks and countermeasures. We summarize and articulate: (1) what S&P threats of GANs expose to ML systems; (2) why GANs are useful for certain attacks; (3) what strategies can be used for GAN-based attacks; and (4) what countermeasures can be effective to GAN-based attacks. Finally, we provide several promising research directions combining the existing limitations of GAN-based studies and the prevailing trend in the associated research fields.
The Extraordinary Alkali Bee, Nomia melanderi (Halictidae), the World's Only Intensively Managed Ground-Nesting Bee
Authors: Cane James H.
Published: August 2023

Among the ground-nesting bees are several proven crop pollinators, but only the alkali bee ( Nomia melanderi) has been successfully managed. In <80 years, it has become the world's most intensely studied ground-nesting solitary bee. In many ways, the bee seems paradoxical. It nests during the torrid, parched midsummer amid arid valleys and basins of the western United States, yet it wants damp nesting soil. In these basins, extensive monocultures of an irrigated Eurasian crop plant, alfalfa (lucerne), subsidize millions of alkali bees. Elsewhere, its polylectic habits and long foraging range allow it to stray into neighboring crops contaminated with insecticides. Primary wild floral hosts are either non-native or poorly known. Kleptoparasitic bees plague most ground nesters, but not alkali bees, which do, however, host other well-studied parasitoids. Building effective nesting beds requires understanding the hydraulic conductivity of silty nesting soils and its important interplay with specific soil mineral salts. Surprisingly, some isolated populations endure inhospitably cold climates by nesting amid hot springs. Despite the peculiarities and challenges associated with its management, the alkali bee remains the second most valuable managed solitary bee for US agriculture and perhaps the world.
Inverse Problems for Physics-Based Process Models
Authors: Bingham Derek , Butler Troy , Estep Don
Published: August 2023

We describe and compare two formulations of inverse problems for a physics-based process model in the context of uncertainty and random variability: the Bayesian inverse problem and the stochastic inverse problem. We describe the foundations of the two problems in order to create a context for interpreting the applicability and solutions of inverse problems important for scientific and engineering inference. We conclude by comparing them to statistical approaches to related problems, including Bayesian calibration of computer models.
Cross-species comparison of pregnancy-induced GDF15
Authors: Klein Anders Bue , Ranea-Robles Pablo , Nicolaisen Trine Sand , Gil Cláudia , Johann Kornelia , Quesada Júlia Prats , Pistolevij Nina , Hviid Kathrine V.R. , Fich Line , Offersen Simone M. , Helge Jørn Wulff , Nielsen Henriette Svarre , Bakker Jaco , Kleinert Maximilian , Clemmensen Christoffer
Published: August 2023

In the present study pregnancy-induced changes in circulating growth differentiation factor 15 (GDF15) in rodents, rhesus macaques, and humans are mapped. In sum, it is demonstrated that humans and macaques exhibit a tremendous increase in placental and circulating GDF15 during pregnancy. In contrast, GDF15 is negligibly increased in pregnant mice and rats, questioning a physiological role for GDF15 in pregnancy in rodents.
Application of Ketamine in Pain Management and the Underlying Mechanism
Authors: Ma Xiaofan , Yan Jia , Jiang Hong
Published: August 2023

Since ketamine was approved by the FDA as an intravenous anesthetic, it has been in clinical use for more than 50 years. Apart from its anesthetic effects, ketamine is one of the few intravenous anesthetics with potent analgesic properties. As part of the effort to develop pain management, renewed interest has focused on the use of ketamine for the treatment of acute and chronic pain. Ketamine is commonly used to treat various kinds of chronic pain syndromes and is also applied to control perioperative pain and reduce the consumption of postoperative analgesics. However, its precise mechanisms of action remain mysterious for a large part. Despite extensive research in the field, the mechanism of ketamine is still unclear. Its analgesic effect appears to be largely mediated by blockade of NMDARs, but opioid, GABA, and monoaminergic system seem to partly participate in the pain transmission procedure. Its metabolites also have an analgesic effect, which may prolong pain relief. More recently, the antidepressant effect of ketamine has been considered to reduce pain-related aversion to relieve chronic pain. Overall, the analgesic mechanism of ketamine seems to be a complex combination of multiple factors. Due to its potent analgesic properties, ketamine is an analgesic with great clinical application prospects. Exploring the precise mechanism of action of ketamine will help guide clinical medication and confirm indications for ketamine analgesia. This review aims to list the application of ketamine in pain management and discuss its analgesic mechanism.
Mesenchymal Stem Cell‐Derived Exosomal miRNA‐222‐3p Increases Th1/Th2 Ratio and Promotes Apoptosis of Acute Myeloid Leukemia Cells
Authors: Yuan Yuan , Tan Shengfen , Wang Huanhuan , Zhu Junfeng , Li Jiajia , Zhang Pingping , Wang Meng , Zhang Feng
Published: August 2023

Interferon regulatory factor 2 (IRF2) participates in the differentiation of immune T cells. Bone marrow mesenchymal stem cell (BM‐MSC)‐derived exosomes can secret mRNA, miRNAs, and proteins to regulate tumor microenvironment. The present study focused on the miRNA/IRF2 axis in regulating Th1/Th2 ratio and cell apoptosis in acute myeloid leukemia (AML). The flow cytometry analysis was performed to examine the Th1/Th2 ratio and AML apoptosis in vivo and in vitro. The contents of Interferon γ (IFN‐γ) and Interleukin‐4 (IL‐4) were measured using enzyme‐linked immunosorbent assay. StarBase was used to predict the potential binding site between miR‐222‐3p and the 3′ untranslated region of IRF2. Luciferase reporter assay was applied for validating the combination of miR‐222‐3p and IRF2. BM‐MSC exosomes were successfully isolated. BM‐MSC exosomes increased Th1/Th2 ratio and promoted apoptosis of AML cells. Further analysis showed that IRF2 was targeted by miR‐222‐3p. Overexpression of miR‐222‐3p promoted Th1/Th2 ratio and AML cell apoptosis. IRF2 partially reversed the effect that is exerted by miR‐222‐3p on Th1/Th2 ratio and AML cell apoptosis. Overexpression of miR‐222‐3p promoted Th1/Th2 ratio and caspase 3 expression in vivo. To sum up, miR‐222‐3p promotes Th1/Th2 ratio and AML cell apoptosis by regulating IRF2 expression, which provided crucial targets for the treatment of AML.
Characteristics and Health Service Use of a Longitudinal Cohort of Carers Aged over 45 in Central and Eastern Sydney, Australia
Authors: Harris-Roxas Ben , Kabir Alamgir , Kearns Rachael , Webster Gurdive , Woodland Lisa , Barr Margo
Published: August 2023

Carers are a large portion of the Australian community. In 2018, 2.65 million Australians identified as carers, and almost one-third (32.6%) of this group were primary carers. There is currently a lack of understanding of the impact of being a carer on a person’s health and wellbeing compared to non-carers. This research was undertaken to understand the health status, health risks, and health outcomes for carers in Central and Eastern Sydney, Australia (CES), who are 45 years of age or over. A record linkage study using data from the 45 and Up Study, Medicare Benefit Scheme claims, hospitalisations, and deaths was undertaken on participants in CES (n = 29,489). Characteristics of carers were described and outcomes over an eight-year period were also calculated. Around 12% of the cohort was carers at a given time, though most transitioned in and out of caring roles over a five-year period. Compared with non-carers, carers in CES had higher rates of self-reported smoking, anxiety, psychological distress, heart disease, and self-rated poor quality of life. Carers had higher rates of general practitioner use than non-carers (Adj. HR (95% CI): 1.21 (1.13, 1.30)). However, hospital admissions and mortality were not significantly different. This study confirms that a small proportion of carers remain in carer roles for many years. Caring often starts suddenly, and people need to quickly adapt to their new role. The finding that carers are well-engaged with GPs suggests they may play an important role in identifying carers who are struggling, and delivering interventions for carers.
lnc-MRGPRF-6:1 Promotes ox-LDL-Induced Macrophage Ferroptosis via Suppressing GPX4
Authors: You Zhihuan , Ye Xiaotian , Jiang Meihua , Gu Ning , Liang Caihong
Published: August 2023

Background. Ferroptosis, a newly discovered mode of cell death, emerges as a new target for atherosclerosis (AS). Long noncoding RNAs (lncRNAs) are involved in the regulation of ferroptosis. In our previous study, lnc-MRGPRF-6:1 was highly expressed in patients with coronary atherosclerotic disease (CAD) and closely associated with macrophage-mediated inflammation in AS. In the present study, we aim to investigate the role of lnc-MRGPRF-6:1 in oxidized-low-density lipoprotein (ox-LDL)-induced macrophage ferroptosis in AS. Methods. Firstly, ox-LDL-treated macrophages were used to simulate macrophage injury in AS. Then, ferroptosis-related biomarkers and mitochondrial morphology were detected and observed in ox-LDL-treated macrophages. Subsequently, we constructed lnc-MRGPRF-6:1 knockdown and overexpression of THP-1-derived macrophages and investigated the role of lnc-MRGPRF-6:1 in ox-LDL-induced ferroptosis. Then human monocytes were isolated successfully and were used to explore the role of lnc-MRGPRF-6:1 in macrophage ferroptosis. Likely, we constructed lnc-MRGPRF-6:1 knockdown and overexpression of human monocyte-derived macrophages and detected the expression levels of ferroptosis-related biomarkers. Then, transcriptome sequencing, literature searching, and following quantitative real-time polymerase chain reaction and western blot were implemented to explore specific signaling pathway in the process. It was demonstrated that lnc-MRGPRF-6:1 may regulate ox-LDL-induced macrophage ferroptosis through glutathione peroxidase 4 (GPX4). Eventually, the correlation between lnc-MRGPRF-6:1 and GPX4 was measured in monocyte-derived macrophages of CAD patients and controls. Results. The ox-LDL-induced injury in macrophages was involved in ferroptosis. The knockdown of lnc-MRGPRF-6:1 could alleviate ox-LDL-induced ferroptosis in macrophages. Meanwhile, the overexpression of lnc-MRGPRF-6:1 could intensify ox-LDL-induced ferroptosis. Furthermore, the knockdown of lnc-MRGPRF-6:1 could alleviate the decrease of GPX4 induced by RAS-selective lethal compounds 3 (RSL-3). These indicated that lnc-MRGPRF-6:1 may suppress GPX4 to induce macrophage ferroptosis. Eventually, lnc-MRGPRF-6:1 was highly expressed in the monocyte-derived macrophages of CAD patients and was negatively correlated with the expression of GPX4. Conclusion. lnc-MRGPRF-6:1 can promote ox-LDL-induced macrophage ferroptosis through inhibiting GPX4.
Assessing the Professional Personality of College Counselors: A Student-Oriented Psychological Scale
Authors: Cheng Haiyun , Liu Wei , Dong Mingniu , Zhou Cheng
Published: August 2023

This study is aimed at identifying the structure and traits of college counselors’ professional personality. Following existing methodology in conducting face-to-face and open-ended interviews, specialist evaluations, and a literature review, we develop a pilot test questionnaire measuring college counselors’ professional personality traits (79 questions) based on salient data collected from a random sample of 2372 university/college students across China. We also conduct explorative factor analysis and confirmatory factor analysis to construct the formal “scale for college counselors’ professional personality traits” (SCCPPT, 45 terms) using SPSS 20.0 and LISREL 8.80 software. The results show that this scale features a second-order, 5-factor structure covering the following five dimensions of professional personality: dutifulness, loyalty, affinity, dedication, and innovation. The findings indicate that the reliability (Cronbach’s alpha coefficient) of these five factors ranges from 0.741 to 0.952 and that their validity is supported. Identifying their professional personality enables college counselors to have a more sustainable career and promote the faster growth and higher quality development of students, and the SCCPPT can be used as a measurement tool, supporting research on college counselors’ professional personality. Thus, this study expands both the theoretical and practical literature concerning professional personality traits. It can also provide a novel perspective, which can help global educators understand Chinese higher education; it is also a reference with international implications for professional groups of student affair administrators or instructors.
Metric Dimension of Line Graphs of Bakelite and Subdivided Bakelite Network
Authors: Farooq Muhammad Umer , Rehman Atiq ur , Ibrahim Tabarek Qasim , Hussain Muhammad , Ali Ali Hasan , Rashwani Badr
Published: August 2023

Graph theory is considered one of the major subjects, and it also plays a significant role in the digital world. It has numerous uses in computer science, robot navigation, and chemistry. Graph theory is employed in forming the structures of different chemical networks, locating robots on a network, and troubleshooting computer networks. Additionally, it finds applications in scheduling airplanes and studying diffusion mechanisms. The current work investigates the metric dimension of the line graphs of the Bakelite and subdivided Bakelite networks. The results prove that these families of graphs do not have a constant metric dimension. The invention of Bakelite was influential in the development of modern plastics, and it has various applications in fields such as jewelry, clocks, toys, kitchenware, electrical, and sports industries.
Preparation of Eumelanin-Encapsulated Stereocomplex Polylactide Nano/Microparticles for Degradable Biocompatible UV-Shielding Products
Authors: Putri Oceu Dwi , Petchsuk Atitsa , Buchatip Suthawan , Supmak Wilairat , Kaewsaneha Chariya , Thananukul Kamonchanok , Nim Bunthoeun , Bayram Sinan , Thumanu Kanjana , Opaprakasit Pakorn
Published: August 2023

The role of eumelanin as a natural pigment in protecting human skin from ultraviolet (UV) light has drawn vast interest in the research and industrial community. Encapsulation of the compound by various shell materials has been extensively studied to optimize and prolong its shielding efficiency from UV penetration through the skin. Polylactide (PLA)-based copolymers have been widely used in the encapsulation of various active compounds due to their biocompatibility and biodegradability that facilitate sustained release of the active compounds. In this work, stereocomplex PLA (sc-PLA) derived from mixtures of poly(D-lactide-caprolactone-D-lactide), P(DLA-b-CL-b-DLA), a triblock copolymer with linear poly(L-lactide), and PLLA are employed to encapsulate eumelanin by an oil-in-water emulsion (O/W) technique. The effect of eumelanin distribution in PLA’s enantiomers and ultrasonication on the physicochemical properties, encapsulation efficiency, and release behavior of the nano/microparticles were evaluated. The potential application of the resulting particles for sunscreen products was assessed in terms of UV absorbance and in vitro sun protection factor (SPF). The nano/microparticles show a hollow spherical structure, whose size can be controlled by ultrasonication. The distribution of eumelanin and the ultrasonication process play a key role in the growth of sc-PLA and the crystalline structure of the particles. The highest encapsulation efficiency of 46.6% was achieved for sc-PLA2U particles. The high content of eumelanin and the hollow structure with a large surface area lead to improvement in the UV absorbance and sunscreen performance of the particles, as revealed by the increase in the SPF value from 9.7 to 16.5. The materials show high potential for various applications, especially in cosmetic and pharmaceutical fields, as UV-shielding products.
Magnetic Biochar by One-Step Impregnation Pyrolysis of Peganum harmala L. for Removal of Rhodamine B
Authors: Alharbi Abdulrahman F. , Alotaibi Abdullah A. , Gomaa Hassan E. M. , Abahussain Abdulaziz A. M. , Abdel Azeem Sami M.
Published: August 2023

A new magnetic P. harmala biochar/Mn-ZnFe2O4 material was prepared by the one-step pyrolysis approach and characterized by FT-IR, SEM, XRD, and BET techniques. The efficacy of removing rhodamine B (RhB) via adsorption and catalytic degradation was examined. Adsorption removal attained 82% of 10 mg·L-1 RhB at pH 4.0, 90 min of agitation, and 3.2 g·L-1 of adsorbent. The adsorption kinetics indicated a diffusion-limited mechanism and matched the second-order model. The equilibrium data are better suited by the Langmuir isotherm, and the maximum monolayer adsorption capacity ([Formula: see text]) was 34.5 mg·g-1. The D-R and Tempkin isotherms both showed an endothermic chemical adsorption process and negligible lateral repulsive forces, respectively. The catalytic removal by Fenton-like degradation was 40 and 99%, respectively, for the biochar/H2O2 and biochar/Mn-ZnFe2O4/H2O2. The prospective use of P. harmala biochar/Mn-ZnFe2O4 as an alternative material for RhB decontamination of water was validated by the successful removal of RhB from industrial wastewater of greater than 77% by adsorption and of 95% by the catalytic degradation.
Supplementary Figure S1 from Prediagnostic Prescription Antibiotics Use and Survival in Patients with Colorectal Cancer: A Swedish National Register-based Study
Authors: Lu Sai San Moon , Rutegård Martin , Ahmed Maghfoor , Häggström Christel , Gylfe Åsa , Harlid Sophia , Van Guelpen Bethany
Published: August 2023

Supplementary Figure S1: Model fitness test using Cox-snell residuals for different multivariable models for stage I-IIIcolorectal cancer.The variables included in the multivariate models (Model 1, Model 2 and Model 3) are presented in thestatistical methods text and in Supplementary Figure S4. To perform model fitness tests, we used the Statacommands available from: Introduction to survival analysis with Stata. UCLA: Statistical Consulting Group.https://stats.oarc.ucla.edu/stata/seminars/stata-survival/(accessed July 12, 2022).
CXCL10 Recruitment of γδ T Cells into the Hypoxic Bone Marrow Environment Leads to IL17 Expression and Multiple Myeloma Progression
Authors: Wang Jingya , Peng Ziyi , Guo Jing , Wang Yixuan , Wang Sheng , Jiang Hongmei , Wang Mengqi , Xie Ying , Li Xin , Hu Meilin , Xie Yangyang , Cheng Hao , Li Tiantian , Jia Linchuang , Song Jia , Wang Yafei , Hou Jian , Liu Zhiqiang
Published: August 2023

In multiple myeloma (MM), bone marrow stromal cells (BMSC) shape a unique niche within the bone marrow, promoting T-cell dysfunction and driving MM progression; however, the precise underlying mechanisms remain elusive. Here, we show that BMSC-mediated reprogramming of MM cells led to heightened production of CXCL10. CXCL10 orchestrated the recruitment of γδ T cells into the bone marrow, and this was observed in both the Vk*MYC and 5TGM1 mouse models of MM, as well as in patients experiencing refractory or relapsed MM. Furthermore, the dysfunctional γδ T cells in the MM bone marrow niche exhibited increased PD-1 expression and IL17 production. In the Vk*MYC mouse model, MM–associated bone lesions and mortality were markedly alleviated in Tcrd−/− mice, and MM disease progression could be rescued in these mice upon transplantation of γδ T cells expanded from wild-type mice, but not from Il17−/− mice. Mechanistically, the hypoxic microenvironment prevailing in the MM bone marrow niche stimulated the expression of steroid receptor coactivator 3 (SRC-3) in γδ T cells, which in turn interacted with the transcriptional factor RORγt, promoting Il17 transcription. Pharmacologic inhibition of SRC-3 utilizing SI-2 effectively suppressed Il17A expression in γδ T cells, leading to alleviation of MM progression in the murine models and enhancing the anti–multiple myeloma efficacy of bortezomib. Our results illuminated the bone marrow microenvironment's involvement in provoking γδ T-cell dysfunction throughout MM progression and suggest SRC-3 inhibition as a promising strategy to enhance the effectiveness of immunotherapies targeting γδ T cells.
Krebs von den Lungen-6 as a Potential Predictive Biomarker in Fibrosing Interstitial Lung Diseases
Authors: Lederer Christoph , Mayer Katharina , Somogyi Vivien , Kriegsmann Katharina , Kriegsmann Mark , Buschulte Katharina , Polke Markus , Findeisen Peter , Herth Felix , Kreuter Michael
Published: August 2023

Background: As fibrosing interstitial lung diseases (fILDs) are associated with high mortality, monitoring of disease activity under treatment is highly relevant. Krebs von den Lungen-6 (KL-6) is associated with the presence and severity of different fILDs, mainly in Asian patient populations. Objectives: Our aim was to evaluate KL-6 as a predictive biomarker in fILDs in Caucasian patients. Methods: Consecutive patients with fILDs were recruited prospectively and serum concentrations of KL-6 were measured at baseline (BL), after 6 and 12 months (6 Months, 12 Months). Clinical characteristics including pulmonary function tests were assessed at 6-monthly visits and correlated with KL-6 BL levels as well as with KL-6 level changes. Results: A total of 47 fILD patients were included (mean age: 65 years, 68% male). KL-6 levels at BL were significantly higher in fILD patients than in healthy controls (n = 44, mean age: 45, 23% male) (ILD: 1,757 ± 1960 U/mL vs. control: 265 ± 107 U/mL, p < 0.0001). However, no differences were noted between ILD subgroups. KL-6 decreased significantly under therapy (6M∆BL-KL6: −486 ± 1,505 mean U/mL, p = 0.032; 12M∆BL-KL6: −547 ± 1,782 mean U/mL, p = 0.041) and KL-6 level changes were negatively correlated with changes in pulmonary function parameters (forced vital capacity [FVC]: r = −0.562, p < 0.0001; DLCOSB: r = −0.405, p = 0.013). While neither absolute KL-6 levels at BL nor KL-6 level changes were associated with ILD progression (FVC decline ≥10%, DLCOSB decline ≥15% or death), patients with a stable FVC showed significantly decreasing KL-6 levels (p = 0.022). Conclusions: A decline of KL-6 under therapy correlated with a clinically relevant stabilization of lung function. Thus, KL-6 might serve as a predictive biomarker, which however must be determined by larger prospective cohorts.
IP10 and Anti-HBc can Predict Virological Relapse and HBsAg Loss in Chronic Hepatitis B Patients after Nucleos(t)ide Analog Discontinuation
Authors: Xie Yandi , Li Minghui , Ou Xiaojuan , Zheng Sujun , Gao Yinjie , Xu Xiaoyuan , Yang Ying , Ma Anlin , Li Jia , Nan Yuemin , Zheng Huanwei , Liu Juan , Wei Lai , Feng Bo
Published: August 2023

Introduction: To assess predictive ability of serum interferon-inducible protein 10 (IP10) and hepatitis B core antibody (anti-HBc) levels for virological relapse (VR) and hepatitis B surface antigen (HBsAg) loss after nucleos(t)ide analog (NA) discontinuation. Methods: In this multicenter prospective study, overall 139 patients were followed up for 24 months after NA discontinuation. Results: End of treatment (EOT) IP10 and anti-HBc were 29.2 (5.1–66.4) pg/mL and 193.6 (136.9–221.4) IU/mL. EOT IP10 and anti-HBc were independent predictors for VR and HBsAg loss in Cox regression analysis. Cumulative rates of VR in patients with EOT IP10 > 26.99 pg/mL was 31.9% (vs. 70.1%, hazard ratio [HR] 2.998, p < 0.001). Cumulative incidences of VR in patients with EOT anti-HBc ≤141.35 IU/mL was 49.1% (vs. 60.6%, HR 2.99, p < 0.001). Cumulative probabilities of VR was 16.7% in patients with EOT IP10 > 26.99 pg/mL plus anti-HBc ≤141.35 IU/mL (vs. 73.6%, HR 6.464, p < 0.001). Cumulative probabilities of HBsAg loss in patients with EOT IP10 > 93.5 pg/mL was 46.2% (vs. 4.7%, HR 10.94, p < 0.001). Cumulative probabilities of HBsAg loss in patients with EOT anti-HBc ≤78.42 IU/mL were 47.1% (vs. 5%, HR 12.27, p < 0.001). Patients with EOT IP10 > 93.5 pg/mL plus anti-HBc ≤78.42 IU/mL had the highest 24-month cumulative HBsAg loss rate (53.8% vs. 4%, HR 16.83, p < 0.001). Conclusion: High EOT IP10 and low EOT anti-HBc levels were related to both lower risk of VR and higher probability of HBsAg loss.
Central Retinal Artery Occlusion: A Review of Pathophysiological Features and Management
Authors: Dagra Abeer , Lucke‐Wold Brandon , McGrath Kyle , Mehkri Ilyas , Mehkri Yusuf , Davidson Caroline Grace , Gilberstadt Noah , Douglas Bobby W. , Hoh Brian
Published: August 2023

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke that results in painless vision loss attributable to retinal infarction. A keen understanding of clinical presentation and underlying pathophysiological features is key to timely intervention and development of new treatment modalities. In CRAO, the time between initial insult to presentation is significant because, analogous to ischemic stroke, the duration of ischemia is inversely related to viable retinal tissue. A major challenge in CRAO is delayed presentation, which reduces the amount of salvageable retina. In addition, imaging techniques to effectively identify a retinal penumbra, or retinal tissue that is reversibly damaged, are not well established. To compile this narrative review, we conducted a systematic search of the PubMed database to identify relevant articles on the pathophysiological features and treatment of CRAO, including reviews, meta‐analyses, clinical studies, observational trials, and randomized trials. The search strategy included the following keywords: central retinal artery occlusion, CRAO, treatment, management, review, meta‐analysis, clinical study, observational trial, and randomized trial. We also searched for ongoing clinical trials related to CRAO on ClinicalTrials.gov. The identified articles and studies were then carefully evaluated for their relevance to the topic and used in compiling this review. Intravenous thrombolysis is a compelling therapeutic approach, with current limited data suggesting early intervention (4.5 hours of symptom onset) results in better patient outcomes. However, ongoing trials assessing and comparing different fibrinolytic agents, routes of administration (venous versus arterial), and timing of intervention will provide further insight on the efficacy of this treatment modality. In parallel, development and testing of imaging techniques aimed at quantifying retinal blood flow and assessing tissue viability could improve risk stratification to guide treatment. These can then be used in conjunction to guide use of conventional therapies, neuroprotectants, and thrombolytics for the management of various CRAO presentations that can be effectively deployed in emergency settings. This article provides a narrative review of pathophysiological features, risk factors, and current and emerging management techniques of CRAO.
Reading Braille by Touch Recruits Posterior Parietal Cortex
Authors: Liu Yun-Fei , Rapp Brenda , Bedny Marina
Published: August 2023

Blind readers use a tactile reading system consisting of raised dot arrays: braille/⠃⠗⠇. How do human brains implement reading by touch? The current study looked for signatures of reading-specific orthographic processes in braille, separate from low-level somatosensory responses and semantic processes. Of specific interest were responses in posterior parietal cortices (PPCs), because of their role in high-level tactile perception. Congenitally blind, proficient braille readers read real words and pseudowords by touch while undergoing fMRI. We leveraged the system of contractions in English braille, where one braille cell can represent multiple English print letters (e.g., “ing” ⠬, “one” ⠐⠕), making it possible to separate physical and orthographic word length. All words in the study consisted of four braille cells, but their corresponding Roman letter spellings varied from four to seven letters (e.g., “con-c-er-t” ⠒⠉⠻⠞. contracted: four cells; uncontracted: seven letters). We found that the bilateral supramarginal gyrus in the PPC increased its activity as the uncontracted word length increased. By contrast, in the hand region of primary somatosensory cortex (S1), activity increased as a function of a low-level somatosensory feature: dot-number per word. The PPC also showed greater response to pseudowords than real words and distinguished between real and pseudowords in multivariate-pattern analysis. Parieto-occipital, early visual and ventral occipito-temporal, as well as prefrontal cortices also showed sensitivity to the real-versus-pseudoword distinction. We conclude that PPC is involved in orthographic processing for braille, that is, braille character and word recognition, possibly because of braille's tactile modality.
Conditional Generation with a Question-Answering Blueprint
Authors: Narayan Shashi , Maynez Joshua , Amplayo Reinald Kim , Ganchev Kuzman , Louis Annie , Huot Fantine , Sandholm Anders , Das Dipanjan , Lapata Mirella
Published: August 2023

The ability to convey relevant and faithful information is critical for many tasks in conditional generation and yet remains elusive for neural seq-to-seq models whose outputs often reveal hallucinations and fail to correctly cover important details. In this work, we advocate planning as a useful intermediate representation for rendering conditional generation less opaque and more grounded. We propose a new conceptualization of text plans as a sequence of question-answer (QA) pairs and enhance existing datasets (e.g., for summarization) with a QA blueprint operating as a proxy for content selection (i.e., what to say) and planning (i.e., in what order). We obtain blueprints automatically by exploiting state-of-the-art question generation technology and convert input-output pairs into input-blueprint-output tuples. We develop Transformer-based models, each varying in how they incorporate the blueprint in the generated output (e.g., as a global plan or iteratively). Evaluation across metrics and datasets demonstrates that blueprint models are more factual than alternatives which do not resort to planning and allow tighter control of the generation output.
The Iranian Sound Change *w- > *γw- in the Indo-Iranian Borderlands and a New Etymology for Gāndhārī and Sanskrit guśura(ka)-
Authors: Schoubben Niels
Published: August 2023

It is generally accepted that the etymology of the Gāndhārī and Sanskrit official title guśura(ka)- has to be sought within the Iranian sphere, but the details remain debatable. In this article, I first give an overview of recently discovered evidence for an early sound change of *w- > *γw- in some Iranian dialects from the Indo-Iranian borderlands. On this basis, I then propose to derive guśura(ka)- from a dialect form such as *γwazurg / *γwuzurg / *γuzurg < *wazr̥ka- ‘strong’. Two by-products of this article are a new Bactrian etymology for the Gāndhārī personal name G̱aṇavhryaka and some notes on the etymology of the Gāndhārī title sturaka-*.
The Role of Local and Remote Processes for Wintertime Surface Energy Budget Extremes over Arctic Sea Ice
Authors: Papritz Lukas , Murto Sonja , Röthlisberger Matthias , Caballero Rodrigo , Messori Gabriele , Svensson Gunilla , Wernli Heini
Published: August 2023

Arctic warm extremes and anomalous sea ice melting have been linked to episodic injections of warm and moist air from midlatitudes, as well as airmass transformations inside the Arctic. However, the relative importance of remote and local processes for such events remains unclear. Here, we focus on events with extreme positive daily-mean surface energy budget (SEB) anomalies over Arctic sea ice in ERA5 data during extended winters (November–March during 1979–2020). Kinematic backward trajectories from the tropospheric column collocated with the SEB anomalies show that near-surface air is of Arctic origin, whereas air farther aloft is transported poleward from the midlatitudes and ascends. Despite the different origin of the air, the entire tropospheric column shows pronounced potential temperature anomalies (on the order of 10 K) building up along air-parcel trajectories over 2–4 days. Quantifying the contributions of horizontal and vertical transport as well as diabatic processes to the generation of these potential temperature anomalies emphasizes the relevance of horizontal advection across the climatological potential temperature gradient for the generation of the anomalies at all levels. Anomalies aloft are further enhanced by latent heating and those near the surface by subsidence, respectively. Surface heat fluxes over subpolar and polar oceans are key for warming and moistening the near-surface air of predominantly Arctic origin and maintaining a positive potential temperature anomaly, which due to its proximity to the surface unfolds the strongest impact on the SEB. This suggests that Arctic airmasses and their local transformations are crucial for generating the most extreme SEB anomalies.