bluuebunny/crossref_metadata_2025 huggingface dataset:
Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal
Authors: He Jianrong , Cheng Yuda , Ruan Yan , Wang Jiali , Tian Yanping , Wang Jiaqi , Wang Fengsheng , Zhang Chen , Xu Yixiao , Liu Lianlian , Yu Meng , Wang Jiangjun , Zhao Binyu , Zhang Yue , Yang Yi , Liu Gaoke , Wu Wei , He Ping , Xiong Jiaxiang , Huang He , Zhang Junlei , Jian Rui
Published: July 2021

Dax1(also known as Nr0b1) is regarded as an important component of the transcription factor network in mouse embryonic stem cells (ESCs). However, the role and the molecular mechanism of Dax1 in the maintenance of different pluripotency states are poorly understood. Here, we constructed a stable Dax1 knockout (KO) cell line using the CRISPR/Cas9 system to analyze the precise function of Dax1. We reported that 2i/LIF-ESCs had significantly lower Dax1 expression than LIF/serum-ESCs. Dax1KO ES cell lines could be established in 2i/LIF and their pluripotency was confirmed. In contrast, Dax1-null ESCs could not be continuously passaged in LIF/serum due to severe differentiation and apoptosis. In LIF/serum, the activities of the Core module and Myc module were significantly reduced, while the PRC2 module was activated after Dax1KO. The expression of most proapoptotic genes and lineage-commitment genes were drastically increased, while the downregulated expression of antiapoptotic genes and many pluripotency genes was observed. Our research on the pluripotent state-dependent role of Dax1 provides clues to understand the molecular regulation mechanism at different stages of early embryonic development.
High Submandibular Anteroparotid Approach for Open Reduction and Internal Fixation of Condylar Fracture
Authors: Hayashi Kamichika , Onda Takeshi , Honda Hirona , Takata Mitsuru , Matsuda Hiroyuki , Tamura Hidetoshi , Takano Masayuki
Published: July 2021

Aim. There are several techniques for the treatment of mandibular condylar fractures. This is the first report of the high submandibular anteroparotid approach for open reduction and internal fixation of condylar fracture. Materials and Methods. A 41-year-old woman fell indoors and injured her face. She was referred to our department for detailed examination and treatment of a suspected mandibular fracture. X-ray and computed tomography showed a right mandibular condylar base fracture and lateral dislocation of the fracture fragment. Open reduction and internal fixation procedures were performed for a right mandibular condylar fracture under general anesthesia. The mandibular ramus was reached by approaching from the inferior margin of the mandible, delaminating the masseter fascia posteriorly, and bypassing the anterior margin of the parotid gland. Once the fractured bone was reached, reduction and fixation were performed. Results. We have achieved good results by the high submandibular anteroparotid approach, which is minimally invasive and simple, to reduce and fix condylar fractures. With this approach, no facial artery or retromandibular vein was encountered, and the mental stress for the surgeon was minimal. Postoperative wound infection, parotid gland complications such as parotitis and salivary fistula, facial nerve dysfunction such as facial paralysis, and esthetic disorders such as scarring were not observed. Conclusions. Although it is necessary to examine more cases in the future, the high submandibular anteroparotid approach may be useful as a new approach for open reduction and internal fixation of condylar fractures.
The Success of Topical Treatment of Onychomycosis Seems to Be Influenced by Fungal Features
Authors: Vasconcellos-Pontello Vanessa , Veiga Flávia Franco , Gadelha Marina Cristina , Ribeiro Marielen , Negri Melyssa , Estivalet Svidzinski Terezinha Inez
Published: July 2021

Aim. To evaluate the topical treatment of onychomycosis using a 10% hydroalcoholic propolis extract (PE) in two aleatorily chosen patients and analyze possible risk factors from hosts including some particularities of the isolated fungi that may justify the outcomes achieved. Materials and Methods. A topical treatment, with PE, was started in two cases of toe onychomycosis due to T. rubrum. The in vitro PE antifungal activity against these isolates was confirmed. Moreover, the ability of the fungi to infect the human nail was evaluated also in an ex vivo study, analyzed by histopathology. Results. Within four months, both patients showed evident improvement, but with different outcomes. The possible host-related risk factors justifying the poorer outcome in patient 1 include a longer duration time of onychomycosis (50 years). Some particularities in the T. rubrum strain isolated from this patient in relation to that found in patient 2 were observed: (1) the hypha morphology suggesting a major adaptation of the fungus to the host; (2) a 16 times greater propolis concentration was required in vitro; and (3) a faster ability to start a growth using the nail as the only nutritional source. Additionally, this isolate was more efficient in producing a biofilm on the nail surface. Conclusions. A partial clinical and complete mycological cure for the two patients was achieved after four months of PE daily use. Despite a complete recovery, a different outcome was observed between both cases. A more persistent onychomycosis, added to greater fungal potential to produce biofilm on the nail, seems to influence greatly the success of a topical treatment with PE.
Vector Appropriate Distraction and Reduction of a Neglected Trimalleolar Fracture-Dislocation Performed with a Temporary Intraoperative External Fixator
Authors: Brand Jordan , Moran Jay , Yoo Brad
Published: July 2021

Traumatic fractures of the ankle can occur with concomitant tibiotalar dislocations, necessitating complex treatment. These injuries have higher rates of loose bodies, open injuries, postoperative complications, and worse patient reported outcomes compared to ankle fractures without dislocation. Patients with neglected or delayed presentations are associated with even higher rates of postoperative complications and worse outcomes compared to acute injuries. The chronicity of the injury leads to soft tissue contractures and malunited fractures, obligating a care plan which involves gradual reduction with a multiplanar external fixator with or without internal fixation at a later date. We discuss a 60-year-old homeless man who presented four weeks after an open trimalleolar fracture-dislocation and was definitely treated with an acute one-stage procedure. Anatomic reduction and stable fixation was achieved through a lateral malleolus osteotomy, soft tissue releases, TAL, and a temporary intraoperative external fixator. This technique was advantageous in this instance of anticipated patient noncompliance. We advocate for the judicious use of the described technique in similar challenging situations.
Experimental Research of the Influence of Microfracture Morphology on Permeability of Shale Rock
Authors: Huang Xiaohe , Long Yunqian , Wang Yuyi , Yue Ming
Published: July 2021

Hydraulic fracturing is currently one of the main technical methods of shale gas exploitation. The permeability variation of shale gas reservoir after fracturing is inevitable, while the influence of fracture length and fracture width on permeability and seepage characteristics of shale rock is a mystery. Besides, the stress sensitivity characteristics of shale rock, derived from different initial permeability, with the same permeability after fracturing are also ambiguous. To this end, a series of seepage characteristic experiments related to different fracture parameters are carried out with the black shale of the Longmaxi Formation in Sichuan gas field as the research target. The results show that the fracture length and fracture width have a good exponential relationship with the corresponding permeability of the reformed shale rock, and the contribution of the fracture width to shale permeability is much greater than that of the fracture length. In addition, the nonlinear seepage characteristics of shale rock are gradually significant with the reduction of fracture length and fracture width. Taking the primitive effective stress (10 MPa) as a critical point, the permeability of shale with large initial permeability decreased by 26.4%, which is about twice as much as that of shale rock with small initial permeability (14.9%) in the selected pressure loading stage, owing to the difference of fracture width inside the shale rock. The permeability of the shale rock with a large initial permeability is restored by 14.7%, while the shale rock with a small initial permeability is only recovered to 5.2% in the pressure unloading stage, which is attributed to the closure of fractures, especially the loss of fracture width. This research can provide some new insights for the production prediction of shale gas reservoir after fracturing.
The Diagnosis and Treatment of Local Complications of Acute Necrotizing Pancreatitis in China: A National Survey
Authors: Dong Xiaowu , Mao Wenjian , Ke Lu , Gao Lin , Zhou Jing , Ye Bo , Li Gang , Phillips Anthony , Tong Zhihui , Windsor John , Li Weiqin , Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)
Published: July 2021

Background. The optimal management strategy in acute necrotizing pancreatitis (ANP) is debated, and compliance with current guidelines in China is not known. In this study, we performed a national survey on this topic in China. Methods. An online questionnaire about the diagnosis and treatment of local complications of ANP was distributed through a national collaborative network. The local and systemic complications were defined according to the Revised Atlanta Classification. Results. There were 321 survey respondents from the 394 who opened the link (response rate 81%) from 208 hospitals located in 30/34 provinces across China. There was a lack of consensus in terms of early diagnosis of infected pancreatic necrosis (IPN) as the respondents chose to depend on clinical symptoms (70/321, 22%), organ failure (82/321, 26%), imaging changes (84/321, 26%), and fine needle aspiration (51/321, 16%), respectively. A “step-up” approach has been widely adopted in patients with IPN (294/321, 92%). The decision for initial intervention (without confirmed/suspected infection) was based on clinical condition, CT imaging, or laboratory indicators for most respondents (229/321, 71%). Conclusion. While the “step-up” approach has been widely adopted, there is still significant variation in regard to the diagnosis of infection, the best timing for drainage, and the indications for early intervention.
The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Jantarato Attapon , Vachatimanont Sira , Boonkawin Natphimol , Yaset Sukanya , Kunawudhi Anchisa , Promteangtrong Chetsadaporn , Assanasen Jintana , Mahanonda Nithi , Chotipanich Chanisa
Published: July 2021

Background. Some studies have reported the effectiveness of [18F]PI-2620 as an effective tau-binding radiotracer; however, few reports have applied semiquantitative analysis to the tracer. Therefore, this study’s aim was to perform a semiquantitative analysis of [18F]PI-2620 in individuals with normal cognition and patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods. Twenty-six cognitively normal (CN) subjects, 7 patients with AD, and 36 patients with MCI were enrolled. A dynamic positron emission tomography (PET) scan was performed 30–75 min postinjection. PET and T1-weighted magnetic resonance imaging scans were coregistered. The standardized uptake value ratio (SUVr) was used for semiquantitative analysis. The P-Mod software was applied to create volumes of interest. The ANOVA and post hoc Tukey HSD were used for statistical analysis. Results. In the AD group, the occipital lobe had a significantly higher mean SUVr ([Formula: see text]) than in the CN and MCI groups. Compared with the CN group, the AD group showed significantly higher mean SUVr in the fusiform gyrus ([Formula: see text] vs. [Formula: see text]), inferior temporal ([Formula: see text] vs. [Formula: see text]), parietal lobe, lingual gyrus, and precuneus regions. Similarly, the AD group demonstrated a higher mean SUVr than the MCI group in the precuneus, lingual, inferior temporal, fusiform, supramarginal, orbitofrontal, and superior temporal regions. The remaining observed regions, including the striatum, basal ganglia, thalamus, and white matter, showed a low SUVr across all groups with no statistically significant differences. Conclusion. A significantly higher mean SUVr of [18F]PI-2620 was observed in the AD group; a significant area of the brain in the AD group demonstrated tau protein deposit in concordance with Braak Stages III–V, providing useful information to differentiate AD from CN and MCI. Moreover, the low SUVr in the deep striatum and thalamus could be useful for excluding primary tauopathies.
Anticariogenic Effect of Selenium Nanoparticles Synthesized Using Brassica oleracea
Authors: Dhanraj Ganapathy , Rajeshkumar Shanmugam
Published: July 2021

Selenium is a trace element in the human body present in various enzymes with antioxidant activities and several functional proteins. This study is aimed at synthesizing selenium nanoparticles using Brassica oleracea (broccoli) and characterizing and assessing the antioxidant and antimicrobial effectiveness against cariogenic microorganisms. UV-visible spectrum displayed a peak at 370 nm which confirms the formation of SeNPs. TEM images of synthesized selenium nanoparticles showed polydisperse nanoparticles, spherical. The size of the particles ranged from 10 to 25 nm, and the average particle size obtained was15.2±1.9 nm. SEM images of nanoparticles were spherical and ranged in size from 10 to 28 nm. The SeNPs showed effective antimicrobial activity against cariogenic pathogens. The SeNPs synthesized with Brassica oleracea extract can be incorporated in toothpaste, gums, and mouthwashes that are cost-effective and biocompatible and used for the prevention of dental caries.
Semiautomatic Generation of Code Ontology Using ifcOWL in Compliance Checking
Authors: Li Yuchao , Zhao Qin , Liu Yunhe , Hei Xinhong , Li Zongjian
Published: July 2021

Code compliance checking is a very important step in engineering construction, but most of code compliance checking relies on manual review at present. With the development of semantic web technology, ontology can be used to represent code information and check the code automatically. However, code ontology is established manually by researchers who have sufficient domain knowledge, in which it is easy to cause poor hierarchical structure of classes. It is also possible for code ontology not being suitable for compliance check. This paper proposes a semiautomatic construction method of railway code ontology based on ifcOWL. The railway code ontology is developed by converting ifcOWL which extends semantic information of railway code. This method can ensure the completeness of the hierarchical relationship of the classes in code ontology with good scalability, which makes use of taxonomy in ifcOWL. The establishment of ontology is divided into two processes with low coupling, namely, extension and conversion, which reduces the domain knowledge requirements of the researchers. Finally, a practical specification is selected to generate a code ontology that achieves some clauses checking.
Isolation and Characterization of Urease-Producing Soil Bacteria
Authors: Mekonnen Eshetu , Kebede Ameha , Nigussie Asefa , Kebede Gessese , Tafesse Mesfin
Published: July 2021

Urease is an enzyme produced by ureolytic microorganisms which hydrolyzes urea into ammonia and carbon dioxide. Microbial urease has wide applications in biotechnology, agriculture, medicine, construction, and geotechnical engineering. Urease-producing microbes can be isolated from different ecosystems such as soil, oceans, and various geological formations. The aim of this study was to isolate and characterize rapid urease-producing bacteria from Ethiopian soils. Using qualitative urease activity assay, twenty urease-producing bacterial isolates were screened and selected. Among these, three expressed urease at high rates as determined by a conductivity assay. The isolates were further characterized with respect to their biochemical, morphological, molecular, and exoenzyme profile characteristics. The active urease-producing bacterial isolates were found to be nonhalophilic to slightly halophilic neutrophiles and aerobic mesophiles with a range of tolerance towards pH (4.0–10.0), NaCl (0.25—5%), and temperature (20–40°C). According to the API ZYM assays, all three isolates were positive for alkaline phosphatase, leucine aryl amidase, acid phosphatase, and naphthol_AS_BI_phosphohydrolase. The closest described relatives of the selected three isolates (Isolate_3, Isolate_7, and Isolate_11) were Bacillus paramycoides, Citrobacter sedlakii, and Enterobacter bugandensis with 16S rRNA gene sequence identity of 99.0, 99.2, and 98.9%, respectively. From the study, it was concluded that the three strains appear to have a relatively higher potential for urease production and be able to grow under a wider range of growth conditions.
[Retracted] Effect of lncRNA PVT1/miR186/KLF5 Axis on the Occurrence and Progression of Cholangiocarcinoma
Authors: Sun Qiang , Gong Xueyi , Wu Jianlong , Hu Zhipeng , Zhang Qiao , Gong Jingling , Zhu Xiaofeng
Published: July 2021

This study primarily focused on the effect of the long noncoding RNA (lncRNA) PVT1/miR186/KLF5 axis on the occurrence and progression of cholangiocarcinoma (CCA). miR186 was found both in the lncRNA PVT1 targeting miRNAs and KLF5 targeting miRNAs using bioinformatic analysis. The expression of lncRNA PVT1 and KLF5 in the TFK‐1, QBC939, and HuCCT1 cell lines and normal biliary epithelial HIBEpiC cells was detected by RT‐qPCR. The significance of lncRNA PVT1 and KLF5 on cell proliferation was analyzed using the MTT assay and clone formation assay in lncRNA PVT1 and KLF5 silencing HuCCT1 cell lines and lncRNA PVT1and KLF5 overexpressing TFK‐1 and QBC939 cell lines, respectively. The potential role of lncRNA PVT1 and KLF5 in cell migration was detected using the transwell invasion assay in CCA cell lines and tumor formation assay. Additionally, lncRNA PVT1 and KLF5 were proved to be highly expressed in CCA tissues and cell lines. Silencing and overexpressing of lncRNA PVT1 or KLF5 markedly inhibited or increased the cell proliferation and cell invasion in CCA cell lines, respectively. Silencing and overexpressing of lncRNA PVT1 significantly inhibited and increased the expression of KLF5 in CCA cell lines, respectively. Silencing of lncRNA PVT1 increased the expression of miR186, and silencing of miR186 increased the expression of KLF5 in CCA cell lines. Cotransfection of lncRNA PVT1 and miR186 increased the expression of KLF5 compared with controls. Overall, these results demonstrated that the lncRNA PVT1/miR186/KLF5 axis might exert a key role in the occurrence and progression of CCA, and this axis might provide a new target for treating CCA.
Optimal Financing Decision in a Contract Food Supply Chain with Capital Constraint
Authors: Luo Ying , Deng Tianyu , Wei Qiang , Xiao Guoan , Ling Qihui
Published: July 2021

To solve the financing problem of the food producers, we consider a two‐echelon contract food supply chain composed of a family farm with capital constraints and a food processing enterprise. With no capital constraints as the benchmark model, we analyze optimal decisions of the family farm and the food processing enterprise in the case of bank financing with bank participation only and bank financing with “government, bank, and insurance” coparticipation. Then, we discuss how the risk of yield uncertainty influences the optimal decisions and profits of the family farm and the food processing enterprise under different financing situation. Meanwhile, the reason why the government subsidizes agriculture is explored, and the policy of minimum purchase price of the food is initiated when the market price is too low. Finally, the numerical examples and sensitivity analysis are presented. The results show that the bank financing with “government, bank, and insurance” coparticipation improves the welfare of supply chain members more obviously than the bank financing with bank participation only; when the rice price is too low, the policy of minimum purchase price of food is initiated, which increases the revenue and the growing enthusiasm of the family farm; the profits of the family farm and the food processing enterprise will decrease as the risk of yield uncertainty increases in the case of bank financing, and the risk of yield uncertainty will be reduced for the family farm when bank financing with “government, bank, and insurance” coparticipation.
A Stochastic Holling-Type II Predator-Prey Model with Stage Structure and Refuge for Prey
Authors: Shi Wanying , Huang Youlin , Wei Chunjin , Zhang Shuwen
Published: July 2021

In this paper, we study a stochastic Holling-type II predator-prey model with stage structure and refuge for prey. Firstly, the existence and uniqueness of the global positive solution of the system are proved. Secondly, the stochastically ultimate boundedness of the solution is discussed. Next, sufficient conditions for the existence and uniqueness of ergodic stationary distribution of the positive solution are established by constructing a suitable stochastic Lyapunov function. Then, sufficient conditions for the extinction of predator population in two cases and that of prey population in one case are obtained. Finally, some numerical simulations are presented to verify our results.
Numerical Simulation Study on Compression Characteristics of Gravelly Soil Mixture Based on Soft Servo Method
Authors: Ning Yu , Huang Qingfu , Shi Chong , Meng Qingxiang
Published: July 2021

Because of complex mechanical properties and deformation mechanism, gravel soil mixture is an important medium of concern in the field of geotechnical engineering. Based on the continuous-discontinuous coupling algorithm formed by the structure shell elements and the particle discrete element method (PFC3D), the soft servo loading of the sample is realized, and the typical triaxial compression test data are used to calibrate mesoscale parameters. Furthermore, the numerical tests under different rock contents and confining pressure are carried out. The change rule of shear strength of mixed medium is discussed. It shows that the continuous-discontinuous coupling algorithm achieves a good effect in reflecting the deformation process. Under the mechanism of the flexible servo, the failure mode of the sample takes on drum-failure mode, and the internal of the damaged sample forms an obvious asymmetric X-shaped shear band. With the increase of stone content, the internal friction angle and cohesive force distribution of the sample have certain discreteness, but on the whole, the internal friction angle and cohesive force increase with the increase of stone content. The results can provide a reference for the parameter determination of mixed mediums such as gravel soil.
The Snowden Phone: A Comparative Survey of Secure Instant Messaging Mobile Applications
Authors: Johansen Christian , Mujaj Aulon , Arshad Hamed , Noll Josef
Published: July 2021

In recent years, it has come to attention that governments have been doing mass surveillance of personal communications without the consent of the citizens. As a consequence of these revelations, developers have begun releasing new protocols for end-to-end encrypted conversations, extending and making popular the old Off-the-Record protocol. New implementations of such end-to-end encrypted messaging protocols have appeared, and several popular chat applications have been updated to use such protocols. In this survey, we compare six existing applications for end-to-end encrypted instant messaging, namely, Signal, WhatsApp, Wire, Viber, Riot, and Telegram, most of them implementing one of the recent and popular protocols called Signal. We conduct five types of experiments on each of the six applications using the same hardware setup. During these experiments, we test 21 security and usability properties specially relevant for applications (not protocols). The results of our experiments demonstrate that the applications vary in terms of the usability and security properties they provide, and none of them are perfect. In consequence, we make 12 recommendations for improvement of either security, privacy, or usability, suitable for one or more of the tested applications.
Experimental Analysis of Neural Approaches for Synthetic Angle-of-Attack Estimation
Authors: Lerro Angelo , Gili Piero , Fravolini Mario Luca , Napolitano Marcello
Published: July 2021

Synthetic sensors enable flight data estimation without devoted physical sensors. Within modern digital avionics, synthetic sensors can be implemented and used for several purposes such as analytical redundancy or monitoring functions. The angle of attack, measured at air data system level, can be estimated using synthetic sensors exploiting several solutions, e.g., model-based, data-driven, and model-free state observers. In the class of data-driven observers, multilayer perceptron neural networks are widely used to approximate the input-output mapping angle-of-attack function. Dealing with experimental flight test data, the multilayer perceptron can provide reliable estimation even though some issues can arise from noisy, sparse, and unbalanced training domain. An alternative is offered by regularization networks, such as radial basis function, to cope with training domain based on real flight data. The present work’s objective is to evaluate performances of a single-layer feed-forward generalized radial basis function network for AoA estimation trained with a sequential algorithm. The proposed analysis is performed comparing results obtained using a multilayer perceptron network adopting the same training and validation data.
Single-Cell Analyses Reveal Diverse Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer
Authors: Kashima Yukie , Shibahara Daisuke , Suzuki Ayako , Muto Kyoko , Kobayashi Ikei S. , Plotnick David , Udagawa Hibiki , Izumi Hiroki , Shibata Yuji , Tanaka Kosuke , Fujii Masanori , Ohashi Akihiro , Seki Masahide , Goto Koichi , Tsuchihara Katsuya , Suzuki Yutaka , Kobayashi Susumu S.
Published: July 2021

Tumor heterogeneity underlies resistance to tyrosine kinase inhibitors (TKI) in lung cancers harboring EGFR mutations. Previous evidence suggested that subsets of preexisting resistant cells are selected by EGFR-TKI treatment, or alternatively, that diverse acquired resistance mechanisms emerge from drug-tolerant persister (DTP) cells. Many studies have used bulk tumor specimens or subcloned resistant cell lines to identify resistance mechanism. However, intratumoral heterogeneity can result in divergent responses to therapies, requiring additional approaches to reveal the complete spectrum of resistance mechanisms. Using EGFR-TKI-resistant cell models and clinical specimens, we performed single-cell RNA-seq and single-cell ATAC-seq analyses to define the transcriptional and epigenetic landscape of parental cells, DTPs, and tumor cells in a fully resistant state. In addition to AURKA, VIM, and AXL, which are all known to induce EGFR-TKI resistance, CD74 was identified as a novel gene that plays a critical role in the drug-tolerant state. In vitro and in vivo experiments demonstrated that CD74 upregulation confers resistance to the EGFR-TKI osimertinib and blocks apoptosis, enabling tumor regrowth. Overall, this study provides new insight into the mechanisms underlying resistance to EGFR-TKIs.

Significance:

Single-cell analyses identify diverse mechanisms of resistance as well as the state of tolerant cells that give rise to resistance to EGFR tyrosine kinase inhibitors.
Caregiver Health‐Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL
Authors: Gilotra Nisha A. , Pamboukian Salpy V. , Mountis Maria , Robinson Shawn W. , Kittleson Michelle , Shah Keyur B. , Forde‐McLean Rhondalyn C. , Haas Donald C. , Horstmanshof Douglas A. , Jorde Ulrich P. , Russell Stuart D. , Taddei‐Peters Wendy C. , Jeffries Neal , Khalatbari Shokoufeh , Spino Catherine A. , Richards Blair , Yosef Matheos , Mann Douglas L. , Stewart Garrick C. , Aaronson Keith D. , Grady Kathleen L.
Published: July 2021

Background

Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health‐related quality of life (HRQOL) and burden in ambulatory advanced HF are limited.

Methods and Results

Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow‐up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow‐up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (
P
=0.007) and less burden by both time spent (
P
<0.0001) and difficulty (
P
=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (
P
=0.034) and being a married caregiver (
P
=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03–1.99;
P
=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29–6.96;
P
=0.011).

Conclusions

Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient‐caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.
Activation of Glucagon‐Like Peptide‐1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism‐Independent Pathway
Authors: Li Qiang , Jia Mengxiao , Yan Zhencheng , Li Qiang , Sun Fang , He Chengkang , Li Yingsha , Zhou Xunmei , Zhang Hexuan , Liu Xiaoli , Bu Xiaona , Gao Peng , He Hongbo , Zhao Zhigang , Zhu Zhiming
Published: July 2021

Background

Patients with hypertension and diabetes mellitus are susceptible to dementia, but regular therapy fails to reduce the risk of dementia. Glucagon‐like peptide‐1 receptor agonists have neuroprotective effects in experimental studies. We aimed to assess the effect of liraglutide, a glucagon‐like peptide‐1 receptor agonist, on cognitive function and whether its effect was associated with metabolic changes in patients with type 2 diabetes mellitus.

Methods and Results

Fifty patients with type 2 diabetes mellitus were recruited in this prospective study. All patients underwent cognitive assessment and brain activation monitoring by functional near‐infrared spectroscopy. At 12 weeks, patients in the glucagon‐like peptide‐1 group acquired better scores in all cognitive tests and showed remarkable improvement in memory and attention (
P
=0.040) test compared with the control group after multivariable adjustment. Compared with the control group, liraglutide significantly increased activation of the dorsolateral prefrontal cortex and orbitofrontal cortex brain regions (
P
=0.0038). After liraglutide treatment, cognitive scores were significantly correlated with changes in these activating brain regions (
P
<0.05), but no correlation was observed between the changes in cognitive function and changes of body mass index, blood pressure, and glycemic levels.

Conclusions

We concluded that liraglutide improves cognitive decline in patients with type 2 diabetes mellitus. This beneficial effect is independent of its hypoglycemic effect and weight loss. The optimal intervention should be targeted to cognitive decline in the early stages of dementia.

Registration

URL:
https://www.ClinicalTrials.gov
; Unique identifier: NCT03707171.
Radical Tense-Indexical Historicality and the De Se
Authors: Humphries Carl
Published: July 2021

“Being is said in many ways,” claimed Aristotle, initiating a discussion about existential commitment that continues today. Might there not be reasons to say something similar about “having been,” or “having happened,” where these expressions denote something’s being located in the past? Moreover, if history – construed not only as an object of inquiry (actual events, etc.) but also as a way of casting light on certain matters – is primarily concerned with “things past,” then the question just posed also seems relevant to the question of what historical understanding amounts to. While the idea that ‘being’ may mean different things in different contexts has indisputable importance, the implications of other, past-temporal expressions are elusive. In what might any differences of substantive meaning encountered there consist? One starting point for responding – the one that provides the subject matter explored here – is furnished by the question of whether or not a certain way of addressing matters relating to the past permits or precludes forms of intelligibility that could be said to be ‘radically historical.’

After arguing that the existing options for addressing this issue remain unsatisfactory, I set out an alternative view of what it could mean to endorse or reject such an idea. This involves drawing distinctions and analogies connected with notions of temporal situatedness, human practicality and historicality, which are then linked to a further contrast between two ways of understanding the referential significance of what is involved when we self-ascribe a relation to a current situation in a manner construable as implying that we take ourselves to occupy a unique, yet circumstantially defined, perspective on that situation. As regards the latter, on one reading, the specific kind of indexically referring language we use – commonly labelled “de se” – is something whose rationale is exhausted by its practical utility as a communicative tool. On the other, it is viewed as capturing something of substantive importance about how we can be thought of as standing in relation to reality. I claim that this second reading, together with the line of thinking about self-identification and self-reference it helps foreground, can shed light on what it would mean to affirm or deny the possibility of radically historical forms of intelligibility – and thus also on what it could mean to ascribe a plurality of meanings to talk concerning things being ‘in the past.’
The Potential of Application of the ECHR in Climate Change Related Cases
Authors: Siwior Przemysław
Published: July 2021

The purpose of this article is to analyse the existing case-law of the European Court of Human Rights (ECtHR) in environmental cases in order to determine whether the European Convention on Human Rights (ECHR) ensures protection in cases related to climate change and its adverse impacts. Due to the fact that to date the ECtHR has not yet ruled on the issue of climate change, the article analyses environmental cases addressed by the ECtHR based on article 8 (right to respect for private and family life) and article 2 (right to life) of the ECHR taking into account potential application of their conclusions to climate change.
Biodiversity and Climate Change
Authors: Fitzmaurice Malgosia
Published: July 2021

This article analyses the question of a relationship between biodiversity and climate change. The legal framework for the protection of biodiversity from climate change is contained in the climate change system of treaties, i.e. the 1992 United Nations Framework Convention on Climate Change; the 1997 Kyoto Protocol; the 2015 Paris Agreement, on one hand; and the 1992 Convention on Biological Diversity on the other. There are also important global Conventions which contribute to combating of impacts of climate change on biodiversity, such as the Desertification Convention and the Ramsar Convention. The article discusses the principle of common but differentiated responsibilities within the context of climate change and biodiversity. The case study is the Arctic, which illustrates the impact of climate change on biodiversity.
Ship Energy Efficiency Measures and Climate Protection
Authors: Pyć Dorota
Published: July 2021

This paper addresses the importance of the implementation and enforcement of the energy efficiency measures for ships. These measures are frequently referred to and used as a tool for carbon mitigation by reducing greenhouse gas emissions from ships in order to protect the Earth’s climate. Moreover, these measures can also play an important role in climate adaptation. The purpose of this paper is to look briefly at the current and expected impact of the ships’ energy efficiency measures developed under auspices of the International Maritime Organization, i.e.: the Energy Efficiency Design Index (EEDI) and the Ship Energy Efficiency Management Plan (SEEMP) on climate change mitigation. Both of them, EEDI and SEEMP became mandatory measures after the adoption of amendments to the Annex VI of the International Convention for the Prevention of Pollution from Ships (MARPOL), and their entry into force in 2013. Furthermore, those measures were also the first legally binding tools relating to climate change, adopted since the Kyoto Protocol.
The Participation of the Council of the European Union and the European Commission in the Process of Concluding International Agreements on Climate Protection
Authors: Bukowska Joanna , Świat Piotr , Sosnowska Anna
Published: July 2021

For many years the European Union has aspired to be the leader of global climate protection policy. By setting increasingly ambitious challenges in its efforts against global warming, the EU has tried to encourage other countries to compete in this field at international level. In this article, the authors present the roles of the Council of the European Union and the European Commission in the process of concluding international agreements on climate protection. The division of competences between the two institutions is important in the situation when the agreements are concluded within Union’s non-exclusive competence such as the one in the field of environmental protection. In case of such agreements both the Union and its Member States are contracting parties. However, not only the division of competences is at the centre of the EU external action, but also the development of appropriate solutions that will ensure the effective achievement of climate policy objectives.
Candra Aditya’s Dewi pulang
Authors: Fox Richard
Published: July 2021

Short films have proven an important medium for social commentary in contemporary Indonesia. As an example of the genre, this special issue of BKI presents Candra Aditya’s (2016) short film, Dewi pulang (Dewi goes home), which follows a young Javanese woman as she travels from Jakarta to her natal home in Central Java to attend her father’s funeral. A critically annotated transcript and translation of the film’s dialogue is followed by four essays on various aspects of the film and a conversation with the filmmaker. Issues addressed include the changing nature of short films and ‘indie’ cinema in post-authoritarian Indonesia; the filmmaking practices specific to Dewi pulang; the interplay of absence and presence in Dewi’s movement between Jakarta and her natal home in Central Java; and the juxtaposition of Indonesian-, English- and Javanese-language dialogue, and the forms of sociality they respectively embody. Taken as a whole, the special issue offers at once a window onto short filmmaking in Indonesia and new primary materials for further analysis.
Landscape of Possibility
Authors: Engchuan Rosalia Namsai
Published: July 2021

This essay is driven by the question of how Candra, the writer and director of Dewi pulang (2017), is able to sustain his cinematic practice, despite the controversial nature of his films. Considering the notion of landscape of possibility, this essay traces processes that precede and go beyond the production of a particular film, but which are nevertheless constitutive of its becoming. These entanglements are explored through concrete stories in dialogical engagement with film practitioners in Indonesia. Adding these to the conversation of what constitutes a film conceptually and analytically, the desired gesture of this essay is less a representation or documentation of Candra’s practice or Indonesian film communities but rather a provocation to approaches in film studies that operate on binary assumptions of landscape as an external backdrop (of text and context, film and maker, state and film production). I will argue that the evolution of film communities in Indonesia challenges commonly held assumptions about the role of the state in ‘independent’ film, and the linear ‘assembling logic’ from ‘grassroots’ to ‘mainstream’.
Back for Good
Authors: Low Choo Chin
Published: July 2021

This article suggests that legalization and amnesty programmes have not been able to reduce undocumented migration in Malaysia for two reasons. First, the programmes merely serve as a registration tool that provides foreign workers with short-term work permits and as a surveillance tool to keep track of foreign workers. Second, the temporary work permits granted are no substitute for a migrant-labour management policy in addressing the acute shortage of low-skilled workers. Despite the introduction of these programmes, undocumented migrants have continued to exist because employers prefer to hire undocumented workers in their ‘race to the bottom’ in terms of costs, and the workers are dependent on their employers and agents as the gatekeepers of their legal immigration status. In 2016 and 2019, the Malaysian government introduced two reforms to its legalization and amnesty programmes: it eliminated outsourcing of the process in the Rehiring Programme (2016) and barred repatriated migrants from re-entering the country under the Back for Good amnesty programme (2019). Though these reforms have partially addressed the limitations of the previous programmes, they have not addressed the root cause of migrant labourers working without proper documentation.
MiR-144-3p Regulates Lipopolysaccharide-Stimulated Chondrocyte Biological Behavior via Wingless-Related Integration Site/Beta-Catenin
Authors: Zhang Nanxin , Li Kuangda , Han Qiong , Wu Maohou , Li Qiang
Published: July 2021

Osteoarthritis (OA) gradually affects all joint tissues. Chondrocytes participate in osteoarthritis. However, the role and mechanism of MiR-144-3p on chondrocytes during the development of OA has not been elucidated. OA patients and normal bone and articular cartilage tissues were collected
to measure MiR-144-3p level by Real-time PCR. Chondrocytes were divided into control group, LPS group (1 μg/ml lipopolysaccharide (LPS) was added to establish an osteoarthritis (OA) stimulation model, and MiR-144-3p inhibitor group which was transfected with MiR-144-3p inhibitor
followed by analysis of cell proliferation by MTT, Caspase 3 activity, Wnt/β-catenin signaling protein expression by Western blot and TNF-α and IL-6 secretion by ELISA. MiR-144-3p was significantly upregulated in OA patients (P <0.05). In LPS group, MiR-144-3p
was significantly upregulated, chondrocyte proliferation decreased, Caspase 3 activity increased, Wnt/β-catenin signaling protein decreased, and TNF-α and IL-6 secretion increased (P <0.05). MiR-144-3p inhibitor transfection can significantly down-regulate
MiR-144-3p, promote cell proliferation, reduce Caspase 3 activity, increase Wnt/β-catenin signaling protein expression, and reduce TNF-α and IL-6 secretion (P <0.05). MiR-144-3p is upregulated in osteoarthritis cartilage tissue. Inhibition of MiR-144-3p can
inhibit articular chondrocytes apoptosis under inflammatory condition, promote cell proliferation, and alleviate joint inflammation by regulating Wnt/β-catenin signaling pathway.
Overexpression of miR-145 in Bone Marrow Mesenchymal Stem Cells Improves Myocardial Injury in Rats
Authors: Chen Lian , Ruan Zhengwen
Published: July 2021

Ischemia/reperfusion injury (IRI) causes myocardial damage. Bone marrow mesenchymal stem cells (BMSCs) exert protection on damaged hearts. We studied the effect of BMSCs with highly expressed miR-145 on repairing damaged heart caused by IRI in rats. SD rats were selected to isolate
BMSCs which were assigned into negative control group, BMSCs group or miR-145-BMSCs (transfected with a lentivirus carrying pLVX-miR-145) followed by analysis of cell proliferation and apoptosis, and level of miR-145, Bcl2, Bax and VEGF by qRT-PCR. BMSCs overexpressing miR-145 showed elevated
proliferation and decreased apoptotic activity. The cardiac function of miR-145-BMSCs and BMSCs rats was improved significantly, Bcl-2 and VEGF expression was enhanced, and Bax was decreased with more significant improvement in miR-145-BMSCs group. miR-145 overexpression has a regulatory effect
on the biological behavior of BMSCs, and upregulates Bcl-2, VEGF and other key factors to repair the heart damage caused by IRI and restore heart function.
Bone Marrow Mesenchymal Stem Cells (BMSCs) with High Expression miR-155 Affect the Proliferation and Metastasis of Oral Squamous Cell Carcinoma by Regulating Phosphatase and Tensin Homolog 12 (PTEN12)
Authors: Ma Guowu , Hou Jia , Qiu Jiezi , Fan Jianlin , Yang Jianxin
Published: July 2021

Oral squamous cell carcinoma (OSCC) had the poor prognosis. miR-155 was involved in some diseases. However, whether BMSCs with high expression miR-155 affect the proliferation and metastasis of OSCC is unclear. Our study aims to assess BMSCs’ effect on OSCC cells. miR-155 level
in OSCC tumor tissues was analyzed. BMSCs were transfected with miR-155 followed by analysis of cell proliferation by MTT assay, cell apoptosis and migration, and MMP-9 level by ELISA and PTEN12 level. In the tumor tissue, miR-155 level was significantly increased (P <0.05). Co-culture
of BMSCs with high expression miR-155 with OSCC cells could significantly promote OSCC cell proliferation and reduced cell apoptotic activity, increased cell migration and MMP-9 secretion as well as downregualted PTEN12 expression (P <0.05). In conclusion, miR-155 was increased in
the OSCC patients and BMSCs of high expression miR-155 could promote the proliferation and metastasis of OSCC by regulating PTEN12.
Exosomal MicroRNA-1257 from Bone Marrow Stem Cells (BMSCs) Suppresses Cell Proliferation and Induces Cell Apoptosis in Ovarian Cancer
Authors: Lin Lin , Li Jiang , Yang Hua , Wang Xinlu , Xin Bing , Jiang Tao , Feng Xiaoyu
Published: July 2021

The role of bone marrow stem cell (BMSC)-derived exosomal microRNA-1257 (miR-1257) in ovarian cancer (OC) was explored in this research. BMSCs were cultured and the exosomes (exo) were isolated from BMSCs. OC cells were co-cultured with BMSC-exo or BMSC-exo transfected with miR-1257
inhibitor. Cell apoptosis was analyzed by flow cytometry, cell proliferative ability was tested by MTT assay, and apoptotic protein Bax and anti-apoptotic proteins Bcl-2 were assessed by Western blot. MiR-1257 was downregulated in OC cells and tissues, which was closely related to the poor
prognosis. The co-culture of BMSC-exo with OC cells upregulated the transcription level of miR-1257, inhibited cell proliferation, and enhanced apoptosis. After silencing of miR-1257, the effects of BMSC-exo on apoptosis and proliferation were eliminated, Bax expression increased, and Bcl-2
level decreased. MiR-1257 from BMSC-exo inhibits the progression of OC.