bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Associations Between Exposure to Violent Pornography and Teen Dating Violence Among Female Sexual Minority High School Students
Authors: Herbitter Cara , Norris Alyssa L. , Nelson Kimberly M. , Orchowski Lindsay M.
Published: July 2021

Previous research indicates that teen dating violence (TDV) is more common among sexual minority than heterosexual adolescents, with approximately half of female sexual minority adolescents (SMA) endorsing TDV victimization in the last year. In samples of adolescents without regard to sexual orientation, exposure to violent pornography is associated with TDV, but this relationship has not been assessed in female SMA. The current study sample consisted of 10th-grade high school students aged 14–17 who identified as cisgender females ( N = 1,276). Data were collected from a baseline survey prior to the delivery of a sexual assault prevention intervention. Female SMA had 2.54 times the odds (95%CI [1.75, 3.69]) of being exposed to violent pornography and 2.53 times the odds (95%CI [1.72, 3.70)]) of TDV exposure compared to heterosexual girls. Exposure to violent pornography was not associated with involvement in TDV among female SMA, controlling for episodic heavy drinking ( aOR = 2.25, 95%CI [0.88,6.22]).

Given the relatively higher rates of violent pornography and TDV exposure among female SMA compared to heterosexual girls, it is critical that sex education curricula address these experiences and meet the needs of adolescents of all sexual orientations. Future research can assess how these TDV interventions might be tailored for female SMA. Although we did not find that exposure to violent pornography was associated with TDV among female SMA, these investigations should be replicated with larger data sets, given that the association between exposure to violent pornography and engagement in TDV was in the expected direction.
Error correction technique for numerical control machine tools based on the simplex method
Authors: Liu Hongwei , Yang Rui , Wang Pingjiang , Chen Jihong , Xiang Hua
Published: July 2021

The objective of this research is to develop a novel correction mechanism to reduce the fluctuation range of tools in numerical control (NC) machining. Error compensation is an effective method to improve the machining accuracy of a machine tool. If the difference between two adjacent compensation data is too large, the fluctuation range of the tool will increase, which will seriously affect the surface quality of the machined parts in mechanical machining. The methodology used in compensation data processing is a simplex method of linear programming. This method reduces the fluctuation range of the tool and optimizes the tool path. The important aspect of software error compensation is to modify the initial compensation data by using an iterative method, and then the corrected tool path data are converted into actual compensated NC codes by using a postprocessor, which is implemented on the compensation module to ensure a smooth running path of the tool. The generated, calibrated, and amended NC codes were immediately fed to the machine tool controller. This technique was verified by using repeated measurements. The results of the experiments demonstrate efficient compensation and significant improvement in the machining accuracy of the NC machine tool.
Design and experimental investigation of a novel spiral microfluidic chip to separate wide size range of micro-particles aimed at cell separation
Authors: Tabatabaei Seyed Ali , Zabetian Targhi Mohammad
Published: July 2021

Isolation of microparticles and biological cells on microfluidic chips has received considerable attention due to their applications in numerous areas such as medical and engineering fields. Microparticles separation is of great importance in bioassays due to the need for smaller sample and device size and lower manufacturing costs. In this study, we first explain the concepts of separation and microfluidic science along with their applications in the medical sciences, and then, a conceptual design of a novel inertial microfluidic system is proposed and analyzed. The PDMS spiral microfluidic device was fabricated, and its effects on the separation of particles with sizes similar to biological particles were experimentally analyzed. This separation technique can be used to separate cancer cells from the normal ones in the blood samples. These components required for testing were selected, assembled, and finally, a very affordable microfluidic kit was provided. Different experiments were designed, and the results were analyzed using appropriate software and methods. Separator system tests with polydisperse hollow glass particles (diameter 2–20 µm), and monodisperse Polystyrene particles (diameter 5 & 15 µm), and the results exhibit an acceptable chip performance with 86% of efficiency for both monodisperse particles and polydisperse particles. The microchannel collects particles with an average diameter of 15.8, 9.4, and 5.9 μm at the proposed reservoirs. This chip can be integrated into a more extensive point-of-care diagnostic system to test blood samples.
Topical Review: Bone Marrow Aspirate Concentrate and Its Clinical Use in Foot and Ankle Surgery
Authors: Glenn Rachel , Johns William , Walley Kempland , Jackson J. Benjamin , Gonzalez Tyler
Published: July 2021

Bone marrow aspirate concentrate (BMAC) is now commonly used in orthopedic surgery. Animal studies showed promising results for cartilage, bone, and soft tissue healing; however, many of these outcomes have yet to be translated to human models. While there has been an increase in the use of BMAC in foot and ankle procedures, the associated clinical evidence is limited. The purpose of this review is to analyze the existing literature in order to evaluate the safety and efficacy of BMAC in foot and ankle surgery.
Organizing the precarious: Autonomous work, real democracy and ecological precarity
Authors: Graham Janna , Papadopoulos Dimitris
Published: July 2021

In 2008, just as the movement of the precarious seemed to be winning one political battle after the next, the fight against precarization suddenly dwindled. The cycle of struggles of the precarious that began in 2000 had seemingly come to an end. Ironically this was also the moment that precarity as a concept became widely known in popular opinion, media commentary and academia. This paper focuses on the movement of the precarious from its inception in the early 2000s to its decline in 2008 and its reappearance in response to the economic crisis through the widespread mobilizations for “real democracy” between 2008 and 2014. Drawing from our experience as participants in the movement of the precarious, and theoretical discussions that have shaped the politics of the movement, the paper adopts a retrospective approach to investigate the metamorphoses of a consciousness of precarity and of the underlying organizing practices that lead to its demise and subsequent incarnations. It reconstructs precarity as theory in action that lives through the organizational ontologies of the movement of the precarious.
Flexural strengthening of pre-cracked RC slabs with prestressed NSM CFRP laminates and evaluation of strain loss
Authors: Mostakhdemin Hosseini M.R. , Dias Salvador J.E. , Barros Joaquim A.O.
Published: July 2021

The strengthening intervention of RC structures often involves already cracked concrete. To evaluate the effect of the level of damage prior to the strengthening (pre-cracks) on the behavior of the flexurally strengthened RC slabs with prestressed NSM CFRP laminates, an experimental research was carried out. Two pre-cracking levels of damage were analyzed and, for each one, three levels of prestress were tested (0%, 20% and 40%). The obtained results showed that the strengthening of damaged RC slabs with prestressed NSM CFRP laminates results in a significant increase on the load carrying capacity at serviceability limit states. Pre-cracked RC slabs strengthened with prestressed NSM CFRP laminates presented a load carrying capacity almost similar to the corresponding uncracked strengthened slabs. To determine the effective prestress level in CFRP laminates, the variation of strain over the length of the CFRP and over time was experimentally recorded. The prestress transfer length was also evaluated. The experimental results revealed that the transfer length of CFRP laminates was less than 150 mm, and the maximum value of strain loss out of transfer length (around 14%) was measured close to the cracked section of the damaged RC slabs. Significant part of strain loss in CFRP laminates occurred during 24 h after releasing the prestress load.
Exploring how residential care facilities can enhance the autonomy of people with dementia and improve informal care
Authors: Boumans Jogé , van Boekel Leonieke C , Verbiest Marjolein EA , Baan Caroline A , Luijkx Katrien G
Published: July 2021

Background and objectives

Residential care facilities (RCFs) strive to enhance autonomy for people with dementia and to enhance informal care provision, although this is difficult. This study explored how RCF staff can enhance autonomy and improve informal care by looking at the influence of interactions (contact and approachability between residents, staff members and informal caregivers) and the physical environment, including the use of technologies.

Research design and methods

A realist evaluation multiple-case study was conducted using document analyses, eight semi-structured interviews with staff members and relatives and 56 hours of observations of residents across two RCFs aiming to provide person-centred care. Realist logic of analysis was performed, involving Context-Mechanism-Outcome configurations.

Findings

The behaviour, attitudes and interactions of staff members with residents and informal caregivers appeared to contribute to the autonomy of people with dementia and enhance informal care provision. The physical environment of the RCFs and the use of technologies were less relevant to enhancing autonomy and informal care provision, although they can support staff members in providing person-centred care in daily practice.

Discussion and implications

The findings add to those of other studies regarding the importance of interaction between residents, staff members and informal caregivers. The findings provide insight for other RCFs on how successfully to enhance autonomy for their residents and to improve informal care provision, as well as, more broadly, how to implement person-centred care.
Diet in Dermatology: Review of Diet’s Influence on the Conditions of Rosacea, Hidradenitis Suppurativa, Herpes Labialis, and Vitiligo
Authors: Jamgochian Marielle , Alamgir Mahin , Rao Babar
Published: July 2021

The influence of dietary patterns on cutaneous disease has been an oft-posed question to dermatologists by patients in a clinical setting. Similarly, the popularity of nutritional supplementation with vitamins, minerals, and nutraceutical blends has been increasing. Dermatologists, primary care physicians, and other providers should be familiar with dietary interventions that are evidence-based and those that are more marketable than efficacious. In this review, the modification of diet, including dietary exclusion and dietary supplementation for the treatment of rosacea, hidradenitis suppurativa (HS), herpes labialis, and vitiligo was investigated. Despite abundant anecdotal evidence, the literature search found no high-quality evidence that an elimination diet for rosacea “trigger foods” improved rosacea symptoms though these elimination diets (of hot, spicy, alcohol-containing, or cinnamaldehyde-containing foods) had low risk of harm. There is evidence that zinc supplementation and vitamin D supplementation in deficient patients is helpful for treating HS. For herpes labialis, L-lysine supplementation was found to be effective for prophylaxis but not for decreasing duration of active lesions. For vitiligo, the use of the herb Polypodium leucotomos in conjunction with phototherapy was found to increase repigmentation, as well as vitamin D supplementation in deficient patients.
Sonoelastographic Findings of Mucocele-Like Lesion in Breast Due to AQUAfilling® Gel Injection
Authors: Basara Akin Isil , Ozgul Hakan , Guray Durak Merih , Gurel Duygu , Sevinc Ali Ibrahim , Balci Pinar
Published: July 2021

AQUAfilling® gel has been described as human tissue biocompatible sterile synthetic material. In the literature, there are some cases presenting the complications of gel application. Rupture of implant, leakage, and migration of the gel are the most common complications. The radiologic findings due to gel leaking may mask many breast lesions including malignancy. In this case, the aim was to present the sonographic findings and elastographic features of a histopathologic-proven mucocele-like lesion in breast, due to AQUAfilling® gel injection. This appears to be a rather unique case in the literature.
A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis
Authors: Disatham Joshua , Brennan Lisa , Chauss Daniel , Kantorow Jason , Afzali Behdad , Kantorow Marc
Published: July 2021

Background

During eye lens development the embryonic vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia and the master regulator of the hypoxic response, hypoxia-inducible transcription factor 1 (HIF1), in the regulation of genes required for lens fiber cell differentiation, structure and transparency. Here, we employed a multiomics approach combining CUT&RUN, RNA-seq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes.

Results

CUT&RUN analysis revealed 8375 HIF1α-DNA binding complexes in the chick lens genome. One thousand one hundred ninety HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ2 test p < 1 × 10− 55) identified by ATACseq. Formation of the identified HIF1α-DNA complexes paralleled the activation or repression of 526 genes, 116 of which contained HIF1α binding sites within 10kB of the transcription start sites. Some of the identified HIF1α genes have previously established lens functions while others have novel functions never before examined in the lens. GO and pathway analysis of these genes implicate HIF1α in the control of a wide-variety of cellular pathways potentially critical for lens fiber cell formation, structure and function including glycolysis, cell cycle regulation, chromatin remodeling, Notch and Wnt signaling, differentiation, development, and transparency.

Conclusions

These data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens fiber cell formation, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues.
Genome sequencing identified novel mechanisms underlying virescent mutation in upland cotton Gossypiuma hirsutum
Authors: Gao Jin , Shi Yang , Wang Wei , Wang Yong-Hui , Yang Hua , Shi Qing-Hua , Chen Jian-Ping , Sun Yan-Ru , Cai Li-Wang
Published: July 2021

Background

Virescent mutation broadly exists in plants and is an ideal experimental material to investigate regulatory mechanisms underlying chlorophyll synthesis, photosynthesis and plant growth. Up to date, the molecular mechanisms in two virescent mutations have been clarified in cottons (Gossypiuma hirsutum). A virescent mutation has been found in the cotton strain Sumian 22, and the underlying molecular mechanisms have been studied.

Methods

The virescent mutant and wild type (WT) of Sumian 22 were cross-bred, and the F1 population were self-pollinated to calculate the segregation ratio. Green and yellow leaves from F2 populations were subjected to genome sequencing and bulked-segregant analysis was performed to screen mutations. Real-time quantitative PCR (RT-qPCR) were performed to identify genes in relations to chlorophyll synthesis. Intermediate products for chlorophyll synthesis were determined to validate the RT-qPCR results.

Results

The segregation ratio of green and virescent plants in F2 population complied with 3:1. Compared with WT, a 0.34 Mb highly mutated interval was identified on the chromosome D10 in mutant, which contained 31 genes. Among them, only ABCI1 displayed significantly lower levels in mutant than in WT. Meanwhile, the contents of Mg-protoporphyrin IX, protochlorophyllide, chlorophyll a and b were all significantly lower in mutant than in WT, which were consistent with the inhibited levels of ABCI1. In addition, a mutation from A to T at the -317 bp position from the start codon of ABCI1 was observed in the genome sequence of mutant.

Conclusions

Inhibited transcription of ABCI1 might be the mechanism causing virescent mutation in Sumian 22 cotton, which reduced the transportation of protoporphyrin IX to plastid, and then inhibited Mg-protoporphyrin IX, Protochlorophyllide and finally chlorophyll synthesis. These results provided novel insights into the molecular mechanisms underlying virescent mutation in cotton.
Identification of long noncoding RNAs reveals the effects of dinotefuran on the brain in Apis mellifera (Hymenopptera: Apidae)
Authors: Huang Minjie , Dong Jie , Guo Haikun , Xiao Minghui , Wang Deqian
Published: July 2021

Background

Dinotefuran (CAS No. 165252–70-0), a neonicotinoid insecticide, has been used to protect various crops against invertebrate pests and has been associated with numerous negative sublethal effects on honey bees. Long noncoding RNAs (lncRNAs) play important roles in mediating various biological and pathological processes, involving transcriptional and gene regulation. The effects of dinotefuran on lncRNA expression and lncRNA function in the honey bee brain are still obscure.

Results

Through RNA sequencing, a comprehensive analysis of lncRNAs and mRNAs was performed following exposure to 0.01 mg/L dinotefuran for 1, 5, and 10 d. In total, 312 lncRNAs and 1341 mRNAs, 347 lncRNAs and 1458 mRNAs, and 345 lncRNAs and 1155 mRNAs were found to be differentially expressed (DE) on days 1, 5 and 10, respectively. Gene set enrichment analysis (GSEA) indicated that the dinotefuran-treated group showed enrichment in carbohydrate and protein metabolism and immune-inflammatory responses such as glycine, serine and threonine metabolism, pentose and glucuronate interconversion, and Hippo and transforming growth factor-β (TGF-β) signaling pathways. Moreover, the DE lncRNA TCONS_00086519 was shown by fluorescence in situ hybridization (FISH) to be distributed mainly in the cytoplasm, suggesting that it may serve as a competing endogenous RNA and a regulatory factor in the immune response to dinotefuran.

Conclusion

This study characterized the expression profile of lncRNAs upon exposure to neonicotinoid insecticides in young adult honey bees and provided a framework for further study of the role of lncRNAs in honey bee growth and the immune response.
A mixed-methods study describing behavioral factors that influenced general practitioners’ experiences using triage during the COVID-19 pandemic
Authors: Lackey Shaun , Schmidtke Kelly Ann , Vlaev Ivo
Published: July 2021

Background

Early in the COVID-19 pandemic, general practices were asked to expand triage and to reduce unnecessary face-to-face contact by prioritizing other consultation modes, e.g., online messaging, video, or telephone. The current study explores the potential barriers and facilitators general practitioners experienced to expanding triage systems and their attitudes towards triage during the COVID-19 pandemic.

Method

A mixed-method study design was used in which a quantitative online survey was conducted along with qualitative interviews to gain a more nuanced appreciation for practitioners’ experiences in the United Kingdom. The survey items were informed by the Theoretical Domains Framework so they would capture 14 behavioral factors that may influence whether practitioners use triage systems. Items were responded to using seven-point Likert scales. A median score was calculated for each item. The responses of participants identifying as part-owners and non-owners (i.e., “partner” vs. “non-partner” practitioners) were compared. The semi-structured interviews were conducted remotely and examined using Braun and Clark’s thematic analysis.

Results

The survey was completed by 204 participants (66% Female). Most participants (83%) reported triaging patients. The items with the highest median scores captured the ‘Knowledge,’ ‘Skills,’ ‘Social/Professional role and identity,’ and ‘Beliefs about capabilities’ domains. The items with the lowest median scores captured the ‘Beliefs about consequences,’ ‘Goals,’ and ‘Emotions’ domains. For 14 of the 17 items, partner scores were higher than non-partner scores. All the qualitative interview participants relied on a phone triage system. Six broad themes were discovered: patient accessibility, confusions around what triage is, uncertainty and risk, relationships between service providers, job satisfaction, and the potential for total digital triage. Suggestions arose to optimize triage, such as ensuring there is sufficient time to conduct triage accurately and providing practical training to use triage efficiently.

Conclusions

Many general practitioners are engaging with expanded triage systems, though more support is needed to achieve total triage across practices. Non-partner practitioners likely require more support to use the triage systems that practices take up. Additionally, practical support should be made available to help all practitioners manage the new risks and uncertainties they are likely to experience during non-face-to-face consultations.
How one treats lateral epicondylitis – a survey among Brazilian orthopedists
Authors: Lazarini Rafael Fuchs , Zan Renato Arouca , Belloti João Carlos , de Almeida Filho Ildeu Afonso , Centenaro Luiz Fernando Sartori , Matsunaga Fabio Teruo , Tamaoki Marcel Jun Sugawara
Published: July 2021

Background

Lateral epicondylitis (LE), also known as tennis elbow, is the most common painful elbow condition. It affects approximately 1–3% of adults. There are various possible treatments described in the literature, but evidence to support a gold standard management protocol is lacking. Therefore, the objective of this study was to evaluate how Brazilian orthopaedists diagnose and treat lateral epicondylitis and compare these results with the available evidence.

Methods

This is an observational, analytical, cross-sectional study. A questionnaire was prepared to obtain information from the participants with eight specific questions (2 on diagnosis and 6 on treatment). These questions were answered voluntarily by participants at 3 major congresses of orthopaedists in Brazil in 2018. The results were analysed in accordance with the overall number of responses and were evaluated among groups according to subspecialty.

Results

We obtained a total of 501 questionnaires. Of these, 33 were excluded. The mean age was 38.67 years. The majority of respondents (91%) were male. We obtained 26.7% from specialists in hand surgery (Hand group), 36.5% from subspecialists in shoulder and elbow (Shoulder and Elbow group), and 36.8% from generalists in orthopaedics or from other subspecialties (General Orthopaedists group). For diagnosis, 24.4% did not initially request any imaging method. The most requested exam was ultrasonography (54.9%). The most prominent indication for initial treatment was physical therapy. For refractory cases, 78.3% of the respondents preferred doing a local infiltration. The most commonly used substance for local infiltrations was corticosteroids (89.6%). With respect to the surgical treatment option, 75.8% of those who recommend it prefer open techniques, and 24.2% prefer arthroscopic treatment. Of the total respondents, 12.8% did not recommend surgical treatment for LE.

Conclusion

Among Brazilian orthopaedists, the Cozen test is most frequently chosen, and ultrasound is the most commonly used imaging tool. Nonsurgically, oral nonsteroidal anti-inflammatory drugs (NSAIDs) plus physiotherapy is the most popular initial therapy, and corticosteroids are the most popular type of infiltration agent. Most surgeons recommended surgery after 6 months of nonsurgical treatment, and 75.8% preferred the open technique.
Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis
Authors: Wang Xin-Yang , Li Xin-Yu , Wu Cheng-Hua , Hao Yu , Fu Pan-Han , Mei Hong-Xia , Chen Fang , Gong Yu-Qiang , Jin Sheng-Wei , Li Hui
Published: July 2021

Background

Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits.

Methods

PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration.

Results

In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1.

Conclusion

PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.
Multi-responsive nanofibers composite gel for local drug delivery to inhibit recurrence of glioma after operation
Authors: Zhu Yufu , Jia Jun , Zhao Gang , Huang Xuyang , Wang Lansheng , Zhang Yongkang , Zhang Long , Konduru Naveena , Xie Jun , Yu Rutong , Liu Hongmei
Published: July 2021

Background

The postoperative recurrence of malignant gliomas has presented a clinical conundrum currently. Worse, there is no standard treatment for these recurrent tumours. Therefore, novel promising methods of clinical treatment are urgently needed.

Methods

In this study, we synthesized reactive oxygen species (ROS)-triggered poly(propylene sulfide)60 (PPS60) mixed with matrix metalloproteinases (MMPs)-responsive triglycerol monostearate (T) lipids and TMZ. The mixed solution could self-assemble at 50 ℃ to generate hydrogels with MMPs- and ROS-responsiveness. We explored whether the T/PPS + TMZ hydrogel could achieve the MMP- and ROS-responsive delivery of TMZ and exert anti-glioma regrowth effects in vitro and in vivo. These results demonstrated that the T/PPS + TMZ hydrogel significantly improved the curative effect of TMZ to inhibit postsurgical recurrent glioma.

Results

The results confirmed the responsive release of TMZ encapsulated in the T/PPS + TMZ hydrogel, and the hydrogel showed excellent performance against glioma in an incomplete glioma operation model, which indicated that the T/PPS + TMZ hydrogel effectively inhibited the growth of recurrent glioma.

Conclusion

In summary, we successfully developed injectable MMPs- and ROS-responsive hydrogels that could achieve the sustained release of TMZ in the surgical cavity to inhibit local recurrent glioma after surgery.

Graphic abstract
Cartilage-targeting poly(ethylene glycol) (PEG)-formononetin (FMN) nanodrug for the treatment of osteoarthritis
Authors: Xiong Wei , Lan Qiumei , Liang Xiaonan , Zhao Jinmin , Huang Hanji , Zhan Yanting , Qin Zainen , Jiang Xianfang , Zheng Li
Published: July 2021

Intra-articular (IA) injection is an efficient treatment for osteoarthritis, which will minimize systemic side effects. However, the joint experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with an average diameter about 218 nm. The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide a reference for clinical OA therapy.
JMJD3: a critical epigenetic regulator in stem cell fate
Authors: Ding Yuanjie , Yao Yuanchun , Gong Xingmu , Zhuo Qi , Chen Jinhua , Tian Miao , Farzaneh Maryam
Published: July 2021

The Jumonji domain-containing protein-3 (JMJD3) is a histone demethylase that regulates the trimethylation of histone H3 on lysine 27 (H3K27me3). H3K27me3 is an important epigenetic event associated with transcriptional silencing. JMJD3 has been studied extensively in immune diseases, cancer, and tumor development. There is a comprehensive epigenetic transformation during the transition of embryonic stem cells (ESCs) into specialized cells or the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). Recent studies have illustrated that JMJD3 plays a major role in cell fate determination of pluripotent and multipotent stem cells (MSCs). JMJD3 has been found to enhance self-renewal ability and reduce the differentiation capacity of ESCs and MSCs. In this review, we will focus on the recent advances of JMJD3 function in stem cell fate.
ALKBH3 partner ASCC3 mediates P-body formation and selective clearance of MMS-induced 1-methyladenosine and 3-methylcytosine from mRNA
Authors: Wollen Kristian Lied , Hagen Lars , Vågbø Cathrine B. , Rabe Renana , Iveland Tobias S. , Aas Per Arne , Sharma Animesh , Sporsheim Bjørnar , Erlandsen Hilde O. , Palibrk Vuk , Bjørås Magnar , Fonseca Davi M. , Mosammaparast Nima , Slupphaug Geir
Published: July 2021

Background

Reversible enzymatic methylation of mammalian mRNA is widespread and serves crucial regulatory functions, but little is known to what degree chemical alkylators mediate overlapping modifications and whether cells distinguish aberrant from canonical methylations.

Methods

Here we use quantitative mass spectrometry to determine the fate of chemically induced methylbases in the mRNA of human cells. Concomitant alteration in the mRNA binding proteome was analyzed by SILAC mass spectrometry.

Results

MMS induced prominent direct mRNA methylations that were chemically identical to endogenous methylbases. Transient loss of 40S ribosomal proteins from isolated mRNA suggests that aberrant methylbases mediate arrested translational initiation and potentially also no-go decay of the affected mRNA. Four proteins (ASCC3, YTHDC2, TRIM25 and GEMIN5) displayed increased mRNA binding after MMS treatment. ASCC3 is a binding partner of the DNA/RNA demethylase ALKBH3 and was recently shown to promote disassembly of collided ribosomes as part of the ribosome quality control (RQC) trigger complex. We find that ASCC3-deficient cells display delayed removal of MMS-induced 1-methyladenosine (m1A) and 3-methylcytosine (m3C) from mRNA and impaired formation of MMS-induced P-bodies.

Conclusions

Our findings conform to a model in which ASCC3-mediated disassembly of collided ribosomes allows demethylation of aberrant m1A and m3C by ALKBH3. Our findings constitute first evidence of selective sanitation of aberrant mRNA methylbases over their endogenous counterparts and warrant further studies on RNA-mediated effects of chemical alkylators commonly used in the clinic.
Alterations in intermuscular coordination underlying isokinetic exercise after a stroke and their implications on neurorehabilitation
Authors: Park Jeong-Ho , Shin Joon-Ho , Lee Hangil , Roh Jinsook , Park Hyung-Soon
Published: July 2021

Background

Abnormal intermuscular coordination limits the motor capability of stroke-affected upper limbs. By evaluating the intermuscular coordination in the affected limb under various biomechanical task constraints, the impact of a stroke on motor control can be analyzed and intermuscular coordination-based rehabilitation strategies can be developed. In this study, we investigated upper limb intermuscular coordination after a stroke during isokinetic movements.

Methods

Sixteen chronic stroke survivors and eight neurologically intact individuals were recruited. End-point forces and electromyographic activities of the shoulder and elbow muscles were measured while the participants performed isokinetic upper limb movements in a three-dimensional space. Intermuscular coordination of the stroke survivors and the control participants was quantified in the form of muscle synergies. Then, we compared the number, composition, and activation coefficients of muscle synergies and the end-point force between the groups. The correlation between the alteration of muscle synergies and the level of motor impairment was investigated.

Results

Four and five muscle synergies in the stroke and control groups were observed, respectively. The composition of muscle synergies was comparable between the groups, except that the three heads of the deltoid muscle were co-activated and formed one synergy in the stroke group, whereas those muscles formed two synergies in the control group. When the number of muscle synergies between the groups matched, the comparable composition of muscle synergies was observed in both groups. Alternatively, the modulation of synergy activation coefficients was altered after a stroke. The severity of motor impairments was negatively correlated with the similarity of the post-stroke synergies with respect to the mean control synergies.

Conclusions

Stroke-affected upper limbs seemed to modularize the activation of the shoulder and elbow muscles in a fairly similar way to that of neurologically intact individuals during isokinetic movements. Compared with free (i.e., unconstrained) movement, exercise under biomechanical constraints including the isokinetic constraint might promote the activation of muscle synergies independently in stroke survivors. We postulated the effect of biomechanical constraints on the intermuscular coordination and suggested a possible intermuscular coordination-based rehabilitation protocol that provides the biomechanical constraint appropriate to a trainee throughout the progress of rehabilitation.
Key factors to facilitate locally driven family planning programming: a qualitative analysis of urban stakeholder perspectives in Africa and Asia
Authors: Mwaikambo Lisa , Brittingham Sarah , Ohkubo Saori , Salem Ruwaida , Sama Denis Joel , Sow Fatimata , Mathur Deepti , Anieto Nneoma Nonyelum
Published: July 2021

Background

There has been greater recognition of the importance of country ownership in global health and development. However, operationalising country ownership to ensure the scale up and sustainability of proven interventions remains elusive at best. To address this challenge, we undertook a thematic analysis of interviews collected from representatives of local governments, public health systems, and communities in poor urban areas of East Africa, Francophone West Africa, India, and Nigeria, supported by The Challenge Initiative (TCI), aiming to rapidly and sustainably scale up evidence-based reproductive health and family planning solutions.

Methods

The main objective of this study was to explore critical elements needed for implementing and scaling evidence-based family planning interventions. The research team conducted thematic analysis of 96 stories collected using the Most Significant Change (MSC) technique between July 2018 and September 2019. After generating 55 unique codes, the codes were grouped into related themes, using TCI’s model as a general analytical framework.

Results

Five key themes emerged: (1) strengthening local capacity and improving broader health systems, (2) shifting mindsets of government and community toward local ownership, (3) institutionalising the interventions within existing government structures, (4) improving data demand and use for better planning of health services, and (5) enhancing coordination of partners.

Conclusion

While some themes feature more prominently in a particular region than others, taken together they represent what stakeholders perceive to be essential elements for scaling up locally-driven health programmes in urban areas in Africa and Asia.
A highly efficient regeneration, genetic transformation system and induction of targeted mutations using CRISPR/Cas9 in Lycium ruthenicum
Authors: Wang Wang , Liu Jiangmiao , Wang Hai , Li Tong , Zhao Huien
Published: July 2021

Background

CRISPR/Cas9 is a rapidly developing genome editing technology in various biological systems due to its efficiency, portability, simplicity and versatility. This editing technology has been successfully applied in in several important plants of Solanaceae such as tomato, tobacco, potato, petunia and groundcherry. Wolfberry ranked the sixth among solanaceous crops of outstanding importance in China following potato, tomato, eggplant, pepper and tobacco. To date, there has been no report on CRISPR/Cas9 technology to improve Lycium ruthenicum due to the unknown genome sequencing and the lack of efficient regeneration and genetic transformation systems.

Results

In this study, we have established an efficientregeneration and genetic transformation system of Lycium ruthenicum. We have used this system to validate target sites for fw2.2, a major fruit weight quantitative trait locus first identified from tomato and accounted for 30% of the variation in fruit size. In our experiments, the editing efficiency was very high, with 95.45% of the transgenic lines containing mutations in the fw2.2 target site. We obtained transgenic wolfberry plants containing four homozygous mutations and nine biallelic mutations in the fw2.2 gene.

Conclusions

These results suggest that CRISPR-based gene editing is effective for the improvement of black wolfberry traits, and we expect this approach to be routinely applied to this important economic fruit.
Quantitative parameters of lymphocyte nuclear morphology in bronchoalveolar lavage fluid as novel biomarkers for sarcoidosis
Authors: Horimasu Yasushi , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Masuda Takeshi , Miyamoto Shintaro , Nakashima Taku , Iwamoto Hiroshi , Fujitaka Kazunori , Hamada Hironobu , Hattori Noboru
Published: July 2021

Background

Bronchoalveolar lavage (BAL) is one of the fundamental examinations for the differential diagnosis of interstitial lung diseases (ILDs), and lymphocytosis strongly indicates alternative diagnoses rather than idiopathic pulmonary fibrosis. However, the BALF lymphocytosis is observed in several ILDs. We considered that quantitative evaluation of the BALF lymphocyte nuclear morphology would be useful in the differential diagnosis of ILDs with increased BALF lymphocyte fraction.

Results

One hundred and twenty-one patients with ILDs having increased BALF lymphocyte fraction were recruited (68 in the development cohort and 53 in the validation cohort). In the development cohort, BALF lymphocyte nuclei in sarcoidosis patients showed significantly smaller areas, shorter perimeters, lower radius ratios, and increased roundness than those of other ILD patients (p < 0.001 for each). Next, the fractions of lymphocytes with small areas, short perimeters, low radius ratios, and increased roundness, which were determined based on receiver operating characteristic (ROC) analyses-based thresholds, were demonstrated to be higher in sarcoidosis patients than in the other ILD patients (p < 0.001 for each). Furthermore, when we combined size-representing parameters with shape-representing parameters, the fraction of lymphocytes with small and round nuclei showed approximately 0.90 of area under the ROC curve in discriminating sarcoidosis both in the development cohort and the validation cohort.

Conclusion

This study is the first to demonstrate the usefulness of quantitative parameters of BALF lymphocyte nuclear morphology as novel biomarkers for sarcoidosis.
Characterization of the clinical and genetic spectrum of autoimmune polyendocrine syndrome type 1 in Chinese case series
Authors: Wang Ya-Bing , Wang Ou , Nie Min , Jiang Yan , Li Mei , Xia Wei-Bo , Xing Xiao-Ping
Published: July 2021

Background

Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital.

Results

In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison’s disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1.

Conclusion

We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1.
Admixture mapping reveals the association between Native American ancestry at 3q13.11 and reduced risk of Alzheimer’s disease in Caribbean Hispanics
Authors: Horimoto Andréa R. V. R. , Xue Diane , Thornton Timothy A. , Blue Elizabeth E.
Published: July 2021

Background

Genetic studies have primarily been conducted in European ancestry populations, identifying dozens of loci associated with late-onset Alzheimer’s disease (AD). However, much of AD’s heritability remains unexplained; as the prevalence of AD varies across populations, the genetic architecture of the disease may also vary by population with the presence of novel variants or loci.

Methods

We conducted genome-wide analyses of AD in a sample of 2565 Caribbean Hispanics to better understand the genetic contribution to AD in this population. Statistical analysis included both admixture mapping and association testing. Evidence for differential gene expression within regions of interest was collected from independent transcriptomic studies comparing AD cases and controls in samples with primarily European ancestry.

Results

Our genome-wide association study of AD identified no loci reaching genome-wide significance. However, a genome-wide admixture mapping analysis that tests for association between a haplotype’s ancestral origin and AD status detected a genome-wide significant association with chromosome 3q13.11 (103.7–107.7Mb, P = 8.76E−07), driven by a protective effect conferred by the Native American ancestry (OR = 0.58, 95%CI = 0.47−0.73). Within this region, two variants were significantly associated with AD after accounting for the number of independent tests (rs12494162, P = 2.33E−06; rs1731642, P = 6.36E−05). The significant admixture mapping signal is composed of 15 haplotype blocks spanning 5 protein-coding genes (ALCAM, BBX, CBLB, CCDC54, CD47) and four brain-derived topologically associated domains, and includes markers significantly associated with the expression of ALCAM, BBX, CBLB, and CD47 in the brain. ALCAM and BBX were also significantly differentially expressed in the brain between AD cases and controls with European ancestry.

Conclusion

These results provide multiethnic evidence for a relationship between AD and multiple genes at 3q13.11 and illustrate the utility of leveraging genetic ancestry diversity via admixture mapping for new insights into AD.
Energetic dysfunction in sepsis: a narrative review
Authors: Preau Sebastien , Vodovar Dominique , Jung Boris , Lancel Steve , Zafrani Lara , Flatres Aurelien , Oualha Mehdi , Voiriot Guillaume , Jouan Youenn , Joffre Jeremie , Uhel Fabrice , De Prost Nicolas , Silva Stein , Azabou Eric , Radermacher Peter
Published: July 2021

Background

Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.

Main text

Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.

Conclusions

Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.