bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Pelaksanaan Peraturan Bupati Merangin Nomor 70 Tahun 2018 Tentang Tambahan Penghasilan Karyawan dalam Peningkatan Disiplin Dinas PNS di Dinas Pekerjaan Publik dan Tata Ruang Kabupaten Merangin
Authors: Hidayat Farid
Published: October 2021

Penelitian ini bertujuan untuk menganalisis dan mengetahui implementasi penerapan Tambahan Penghasilan Pegawai di lingkungan Dinas Pekerjaan Umum dan Penataan Ruang Kabupaten Merangin. Penelitian ini  menggunakan pendekatan kualitatif, data diperoleh dengan cara wawancara, sedangkan populasi dalam penelitian ini adalah Pegawai Dinas Pekerjaan Umum danPenataan Ruang Kabupaten Merangin, dengan informan berjumlah 10 orang. Dipilih dengan metode purposive sampling. Data dianalisis dengan menggunakan metode triungulasi, hasil penelitian ini dapat disimpulkan bahwa penerapan Peraturan Bupati Merangin Nomor 70 Tahun 2018 tentang pemberian Tambahan Penghasilan Pegawai telah dapat diimplementasikan dengan baik oleh implementor sehingga terjadi peningkatan disiplin dan kinerja. Dari penjelasan diatas penulis menyarankan bahwa TPP yang diberikan  tehadap Pegawai perlu dievaluasi jumlah besaran yang diberikan, sehingga bukan saja disiplin menjadi baik, tetapi semangat dalam bekerja tentu juga akan meningkat sehingga pekerjaan yang telah direncanakan sebelumnya dapat terlaksana dan apa yang menjadi visi dan misi organisasi dapat terlaksanakan dengan baik.
Nilai-Nilai Publik dalam Kebijakan Pelestarian Cendana (Santalum Album L) di Kabupaten Timor Tengah Selatan
Authors: Nursalam Nursalam
Published: October 2021

Nilai-nilai publik adalah nilai yang memberikan konsensus normatif tentang:  hak, manfaat, dan hak prerogatif; kewajiban warga negara kepada masyarakat, negara, dan satu sama lain; serta prinsip-prinsip yang menjadi landasan pemerintah dan kebijakan (Bozeman: 2007). nilai publik sebagai cara untuk memahami aktivitas pemerintah, menginformasikan pembuatan kebijakan dan membangun penyampaian layanan (O’Flynn, 2007)

Penelitian ini bertujuan untuk mengetahui penerapan nilai-nilai publik dalam kebijakan  pelestarian Cendana (santalum album L) di kabupaten Timor Tengah Selatan. Metode yang digunakan adalah metode penelitian kualitatif dengan teknik pengumpulan data melalui wawancara, observasi, dan dokumentasi. Pemilihan informan ditetapkan dengan menggunakan teknik purposif kepada tokoh-tokoh masyarakat sebagai pemangku kepentingan adat, pengambil kebijakan dan pelaksana kebijakan.

Hasil penelitian menunjukkan bahwa nilai publik sangat penting dijadikan sebagai landasan dalam proses perumusan dan pelaksanaan kebijakan pelestarian Cendana. Nilai-nilai seperti nilai keadilan sosial, akuntabiltas, dan nilai keberlanjutan, belum maksimal diakomodir pada kebijakan pelestarian Cendana. Beberapa implikasi yang muncul akibat terabaikannya nilai adalah; masyarakat (publik) tidak mempunyai semangat untuk ikut terlibat dalam upaya pelestarian dan masih adanya pandangan bahwa Cendana sebagai sumber daya alam lokal yang bernilai tinggi, namun menuai juga banyak masalah.

Rekomendasi penelitian adalah perlunya revitalisasi nilai-nilai publik (public values) agar kebijakan pelestarian dapat meningkatkan populasi cendana.
ХОЗЯЙСТВЕННЫЙ УКЛАД ЖИТЕЛЕЙ ДЕРЕВЕНЬ ГОРЕНДУ, БОНГУ И ГУМБУ (НОВАЯ ГВИНЕЯ) В СОВРЕМЕННЫХ РЕАЛИЯХ (ПО МАТЕРИАЛАМ ПОЛЕВЫХ ИССЛЕДОВАНИЙ)
Authors: Чининов И.В.
Published: October 2021

В апреле–мае 2019 г. научно-исследовательская экспедиция Фонда им. Миклухо-Маклая (под руководством директора Фонда Н.Н. Миклухо-Маклая-младшего) продолжила комплексные полевые работы в провинции Маданг Независимого Государства Папуа – Новая Гвинея – в деревнях Горенду, Бонгу и Гумбу на Берегу Маклая (на северо-востоке о-ва Новая Гвинея), где проживают представители папуасскоязычной этнической группы бонгу (самоназвание бонгуанцы). Этнографическая часть программы предусматривала изучение различных сторон современной хозяйственной деятельности и их корреляций с традиционными занятиями бонгу минувших веков. Во второй половине XIX столетия в этом регионе проводил свои научные изыскания выдающийся русский ученый-гуманист Николай Николаевич Миклухо-Маклай, в 1971 и 1977 гг. здесь работали советские, а в 2017 и 2019 гг. российские этнографы. Проведенные автором статьи – участником двух последних экспедиций – исследования позволили выявить прочную сохранность аутентичных элементов в хозяйственной деятельности бонгу. Приходящие извне инновации не только не трансформируют в корне традиционный уклад жизни папуасов, но, органично на него наслаиваясь, придают ему еще большую устойчивость.
In April–May 2019, the research expedition of the Miklouho-Maclay Foundation (led by N. N. Miklouho-Maclay, Jr. – the Director of the Foundation) continued comprehensive fieldwork in the villages of Gorendu, Bongu, and Gumbu on the Maklay Coast (the north-east of the New Guinea island) in the Madang Province of the independent State of Papua New Guinea. The ethnographic part included studying various aspects of the economic activity of the Papuan-speaking ethnic group Bongu (Bonguans) living in these villages and their associations with the corresponding traditional occupations of the past centuries recorded in the works of Russian scientists. In the second half of the XIX century, the outstanding Russian scientist-humanist Nikolai Nikolayevich Miklouho-Maclay conducted his long-term scientific research in this region. Soviet ethnographers worked there in 1971 and 1977. The research conducted by the author revealed the strong preservation of authentic elements in this sphere of life, which, in turn, is reflected in other cultural aspects. The innovations emerging from the outside world do not fundamentally transform the economic life of the Bongu Papuans but are organically incorporated, giving it even greater stability.
K-Neighbourhood Analysis: A Method for Understanding SMLM Images as Compositions of Local Neighbourhoods
Authors: Feher Kristen , Graus Matthew S. , Coelho Simao , Farrell Megan V. , Goyette Jesse , Gaus Katharina
Published: October 2021

Single molecule localisation microscopy (SMLM) is a powerful tool that has revealed the spatial arrangement of cell surface signalling proteins, producing data of enormous complexity. The complexity is partly driven by the convolution of technical and biological signal components, and partly by the challenge of pooling information across many distinct cells. To address these two particular challenges, we have devised a novel algorithm called K-neighbourhood analysis (KNA), which emphasises the fact that each image can also be viewed as a composition of local neighbourhoods. KNA is based on a novel transformation, spatial neighbourhood principal component analysis (SNPCA), which is defined by the PCA of the normalisedK-nearest neighbour vectors of a spatially random point pattern. Here, we use KNA to define a novel visualisation of individual images, to compare within and between groups of images and to investigate the preferential patterns of phosphorylation. This methodology is also highly flexible and can be used to augment existing clustering methods by providing clustering diagnostics as well as revealing substructure within microclusters. In summary, we have presented a highly flexible analysis tool that presents new conceptual possibilities in the analysis of SMLM images.
Cardiomyocyte-Specific RIP2 Overexpression Exacerbated Pathologic Remodeling and Contributed to Spontaneous Cardiac Hypertrophy
Authors: Yang Jing-jing , Zhang Nan , Zhou Zi-ying , Ni Jian , Feng Hong , Li Wen-jing , Mou Shan-qi , Wu Hai-ming , Deng Wei , Liao Hai-han , Tang Qi-zhu
Published: October 2021

This study aimed to investigate the role and mechanisms of Receptor interacting protein kinase 2 (RIP2) in pressure overload-induced cardiac remodeling. Human failing or healthy donor hearts were collected for detecting RIP2 expression. RIP2 cardiomyocyte-specific overexpression, RIP2 global knockout, or wild-type mice were subjected to sham or aortic banding (AB) surgery to establish pressure overload-induced cardiac remodeling in vivo. Phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) were used for further investigation in vitro. The expression of RIP2 was significantly upregulated in failing human heart, mouse remodeling heart, and Ang II-treated NRCMs. RIP2 overexpression obviously aggravated pressure overload-induced cardiac remodeling. Mechanistically, RIP2 overexpression significantly increased the phosphorylation of TAK1, P38, and JNK1/2 and enhanced IκBα/p65 signaling pathway. Inhibiting TAK1 activity by specific inhibitor completely prevented cardiac remodeling induced by RIP2 overexpression. This study further confirmed that RIP2 overexpression in NRCM could exacerbate PE-induced NRCM hypertrophy and TAK1 silence by specific siRNA could completely rescue RIP2 overexpression-mediated cardiomyocyte hypertrophy. Moreover, this study showed that RIP2 could bind to TAK1 in HEK293 cells, and PE could promote their interaction in NRCM. Surprisingly, we found that RIP2 overexpression caused spontaneous cardiac remodeling at the age of 12 and 18 months, which confirmed the powerful deterioration of RIP2 overexpression. Finally, we indicated that RIP2 global knockout attenuated pressure overload-induced cardiac remodeling via reducing TAK1/JNK1/2/P38 and IκBα/p65 signaling pathways. Taken together, RIP2-mediated activation of TAK1/P38/JNK1/2 and IκBα/p65 signaling pathways played a pivotal role in pressure overload-induced cardiac remodeling and spontaneous cardiac remodeling induced by RIP2 overexpression, and RIP2 inhibition might be a potential strategy for preventing cardiac remodeling.
WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity
Authors: Zhong Guohui , Zhao Dingsheng , Li Jianwei , Liu Zifan , Pan Junjie , Yuan Xinxin , Xing Wenjuan , Zhao Yinglong , Ling Shukuan , Li Yingxian
Published: October 2021

Cardiac muscle is extremely sensitive to changes in loading conditions; the microgravity during space flight can cause cardiac remodeling and function decline. At present, the mechanism of microgravity-induced cardiac remodeling remains to be revealed. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is an important activator of pressure overload-induced cardiac remodeling by stabilizing disheveled segment polarity proteins 2 (DVL2) and activating the calcium-calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 4 (HDAC4)/myocyte-specific enhancer factor 2C (MEF2C) axis. However, the role of WWP1 in cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether WWP1 was also involved in the regulation of cardiac remodeling caused by microgravity. Firstly, we detected the expression of WWP1 and DVL2 in the heart from mice and monkeys after simulated microgravity using western blotting and immunohistochemistry. Secondly, WWP1 knockout (KO) and wild-type (WT) mice were subjected to tail suspension (TS) to simulate microgravity effect. We assessed the cardiac remodeling in morphology and function through a histological analysis and echocardiography. Finally, we detected the phosphorylation levels of CaMKII and HDAC4 in the hearts from WT and WWP1 KO mice after TS. The results revealed the increased expression of WWP1 and DVL2 in the hearts both from mice and monkeys after simulated microgravity. WWP1 deficiency alleviated simulated microgravity-induced cardiac atrophy and function decline. The histological analysis demonstrated WWP1 KO inhibited the decreases in the size of individual cardiomyocytes of mice after tail suspension. WWP1 KO can inhibit the activation of the DVL2/CaMKII/HDAC4 pathway in the hearts of mice induced by simulated microgravity. These results demonstrated WWP1 as a potential therapeutic target for cardiac remodeling and function decline induced by simulated microgravity.
Outcome Comparison Between Open and Endovascular Aortic Repair for Retrograde Type A Intramural Hematoma With Intimal Tear in the Descending Thoracic Aorta: A Retrospective Observational Study
Authors: Yang Kelvin Jeason , Chi Nai-Hsin , Yu Hsi-Yu , Chen Yih-Sharng , Wang Shoei-Shen , Wu I-Hui
Published: October 2021

Objective: The optimal treatment modality for retrograde type A intramural hematoma (IMH) remains debatable. This study evaluated and compared surgical outcomes and aortic remodeling after open aortic repair and thoracic endovascular aortic repair (TEVAR) in patients with retrograde type A IMH with a primary intimal tear or ulcer like projection in the descending aorta.

Methods: A single center, retrospective observational study was performed on patients with retrograde type A IMH undergoing either open aortic repair and TEVAR. From June 2009 and November 2019, 46 patients with retrograde type A IMH who received either open aortic repair or TEVAR at our institution were reviewed for clinical outcomes, including post-operative mortality/morbidity, re-intervention rate and aortic remodeling.

Results: 33 patients underwent open aortic repair and 13 underwent TEVAR. Median age was 68 years (interquartile range [IQR] 15.2 years) and 63 years (IQR 22.5 years) for the open repair group and TEVAR group, respectively. The median duration of follow-up for TEVAR patients was 37.6 months and 40.3 months for open aortic repair. No difference in the 5-year estimated freedom from all-cause mortality (82.1 vs. 87.8%, p = 0.34), re-intervention (82.5 vs. 93.8%, p = 0.08), and aortic-related mortality (88.9 vs. 90.9%, p = 0.88) were observed between the TEVAR and open repair group, respectively; however, the open repair group had a significantly higher 30-day composite morbidity (39.4 vs. 7.7%, p = 0.037). All patients from both treatment groups had complete resolution of the IMH in the ascending aorta. With regard to the descending thoracic aorta, TEVAR group had a significantly greater regression in the diameter of the false lumen or IMH thickness when compared to the open repair group [median 14mm (IQR 10.1) vs. 5mm (IQR 9.5), p < 0.001].

Conclusion: TEVAR and open aortic repair were both effective treatments for retrograde type A IMH, in which no residual ascending aortic IMH was observed during follow-up. TEVAR was also associated with lower post-operative composite morbidities and better descending aortic remodeling. In selected patients with retrograde type A IMH, TEVAR might be a safe, effective alternative treatment modality.
A Comparative Transcriptional Landscape of Two Castor Cultivars Obtained by Single-Molecule Sequencing Comparative Analysis
Authors: Zhou Yaxing , Zhu Guoli , Wang Yun , He Zhibiao , Zhou Wei
Published: October 2021

Background and Objectives: Castor (Ricinus communis L.) is an important non-edible oilseed crop. Lm-type female strains and normal amphiprotic strains are important castor cultivars, and are mainly different in their inflorescence structures and leaf shapes. To better understand the mechanisms underlying these differences at the molecular level, we performed a comparative transcriptional analysis.

Materials and Methods: Full-length transcriptome sequencing and short-read RNA sequencing were employed.

Results: A total of 76,068 and 44,223 non-redundant transcripts were obtained from high-quality transcripts of Lm-type female strains and normal amphiprotic strains, respectively. In Lm-type female strains and normal amphiprotic strains, 51,613 and 20,152 alternative splicing events were found, respectively. There were 13,239 transcription factors identified from the full-length transcriptomes. Comparative analysis showed a great variety of gene expression of common and unique transcription factors between the two cultivars. Meanwhile, a functional analysis of the isoforms was conducted. The full-length sequences were used as a reference genome, and a short-read RNA sequencing analysis was performed to conduct differential gene analysis. Furthermore, the function of DEGs were performed to annotation analysis.

Conclusion: The results revealed considerable differences and expression diversity between the two cultivars, well beyond what was reported in previous studies and likely reflecting the differences in architecture between these two cultivars.
Development of a 3 RNA Binding Protein Signature for Predicting Prognosis and Treatment Response for Glioblastoma Multiforme
Authors: Sun Ruohan , Pan Yujun , Mu Long , Ma Yaguang , Shen Hong , Long Yu
Published: October 2021

Purpose: Glioblastoma multiforme (GBM) is the most widely occurring brain malignancy. It is modulated by a variety of genes, and patients with GBM have a low survival ratio and an unsatisfactory treatment effect. The irregular regulation of RNA binding proteins (RBPs) is implicated in several malignant neoplasms and reported to exhibit an association with the occurrence and development of carcinoma. Thus, it is necessary to build a stable, multi-RBPs signature-originated model for GBM prognosis and treatment response prediction.

Methods: Differentially expressed RBPs (DERBPs) were screened out based on the RBPs data of GBM and normal brain tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx) datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses on DERBPs were performed, followed by an analysis of the Protein-Protein Interaction network. Survival analysis of the DERBPs was conducted by univariate and multivariate Cox regression. Then, a risk score model was created on the basis of the gene signatures in various survival-associated RBPs, and its prognostic and predictive values were evaluated through Kaplan-Meier analysis and log-rank test. A nomogram on the basis of the hub RBPs signature was applied to estimate GBM patients’ survival rates. Moreover, western blot was for the detection of the proteins.

Results: BICC1, GNL3L, and KHDRBS2 were considered as prognosis-associated hub RBPs and then were applied in the construction of a prognostic model. Poor survival results appeared in GBM patients with a high-risk score. The area under the time-dependent ROC curve of the prognostic model was 0.723 in TCGA and 0.707 in Chinese Glioma Genome Atlas (CGGA) cohorts, indicating a good prognostic model. What was more, the survival duration of the high-risk group receiving radiotherapy or temozolomide chemotherapy was shorter than that of the low-risk group. The nomogram showed a great discriminating capacity for GBM, and western blot experiments demonstrated that the proteins of these 3 RBPs had different expressions in GBM cells.

Conclusion: The identified 3 hub RBPs-derived risk score is effective in the prediction of GBM prognosis and treatment response, and benefits to the treatment of GBM patients.
Anti-gout Medications and Risk of Cardiovascular Disease: A Nested Case-Control Study
Authors: Chuang Tsung-Ju , Wang Yu-Hsun , Wei James Cheng-Chung , Yeh Chih-Jung
Published: October 2021

Introduction: Gout is the leading cause of inflammatory arthritis and is also correlated with multiple comorbidities, including cardiovascular disease (CVD), whose future risk can be lowered by urate-lowering therapy (ULT) in gout patients. It is, however, still not clear whether its effect is associated with the days of usage and the adherence rate of ULT.

Methods: Data were collected from Taiwan's National Health Insurance Research Database. The study period was from 1999/1/1 to 2013/12/31. In addition, patients with newly diagnosed gout from 2000 to 2012 and usage of antigout preparations (allopurinol or benzbromarone) within half a year among age ≥20 years old were enrolled in the study. The outcome of interest is CVD. New diagnosis of CVD after half a year of diagnosis of gout was included in the CVD group. Moreover, conditional logistic regression was used to evaluate the odds ratio of CVD in relation to the days of usage and to the adherence rate of ULT after the adjustment for potentially confounding variables.

Results: A total of 3,706 gout patients with and without CVD have been included in the final analysis after a 1:1 propensity score that matched for age, sex, comorbidities, aspirin, and statin. The days of usage of allopurinol was <180 days and benzbromarone, in its turn, presupposed a higher risk of CVD. The adherence rate of allopurinol and benzbromarone at ≥ 0.7 both have a lower CVD risk: allopurinol (adjusted OR: 0.66 95% CI: 0.46–0.96), benzbromarone (adjusted OR: 0.68 95% CI: 0.50–0.91). The subgroup analysis revealed an adherence rate of ≥0.7 of ULT with a lower CVD was only found to be present in males and at age <65. Furthermore, the correlations were more pronounced in the ischemic heart disease subgroup than in the cerebrovascular disease group.

Conclusion: This study reveals that gout patients taking ULT (allopurinol and benzbromarone) with an adherence rate of ≥0.7 are at a lower risk of developing CVD, especially with a younger age (<65) and if they are male. On top of this, the benefit is more pronounced in ischemic heart disease. Despite further prospective trials needing to be warranted to confirm our findings, health care providers may, bearing these conclusions in mind, emphasize the importance of adherence to ULT in gout patients.
Sharp-Wave Ripple Frequency and Interictal Epileptic Discharges Increase in Tandem During Thermal Induction of Seizures in a Mouse Model of Genetic Epilepsy
Authors: Cheah Christine S. , Beckman Megan A. , Catterall William A. , Oakley John C.
Published: October 2021

Dravet Syndrome (DS) is a genetic, infantile-onset epilepsy with refractory seizures and severe cognitive impairment. While network level pathophysiology is poorly understood, work in genetic mouse models of DS reveals selective reduction of inhibitory interneuron excitability, a likely mechanism of seizures and comorbidities. Consistent with the critical role of interneurons in timing and recruitment of network activity, hippocampal sharp wave ripples (SPW-R)—interneuron dependent compound brain rhythms essential for spatial learning and memory—are less frequent and ripple frequency is slower in DS mice, both likely to impair cognitive performance. Febrile seizures are characteristic of DS, reflecting a temperature-dependent shift in excitation–inhibition balance. DS interneurons are sensitive to depolarization block and may fall silent with increased excitation precipitating epileptic transformation of ripples. To determine the temperature dependence of SWP-R features and relationship of SPW-R to hippocampal interictal activity, we recorded hippocampal local field potentials in a DS mouse model and wildtype littermate controls while increasing core body temperature. In both genotypes, temperature elevation speeds ripple frequency, although DS ripples remain consistently slower. The rate of SPW-R also increases in both genotypes but subsequently falls in DS mice as interictal epileptic activity simultaneously increases preceding a thermally-evoked seizure. Epileptic events occur intermixed with SPW-R, some during SPW-R burst complexes, and transiently suppress SPW-R occurrence suggesting shared network elements. Together these data demonstrate a temperature dependence of SPW-R rate and ripple frequency and suggest a pathophysiologic mechanism by which elevated temperature transforms a normal brain rhythm into epileptic event.
Wearable Reduced-Channel EEG System for Remote Seizure Monitoring
Authors: Frankel Mitchell A. , Lehmkuhle Mark J. , Spitz Mark C. , Newman Blake J. , Richards Sindhu V. , Arain Amir M.
Published: October 2021

Epitel has developed Epilog, a miniature, wireless, wearable electroencephalography (EEG) sensor. Four Epilog sensors are combined as part of Epitel's Remote EEG Monitoring platform (REMI) to create 10 channels of EEG for remote patient monitoring. REMI is designed to provide comprehensive spatial EEG recordings that can be administered by non-specialized medical personnel in any medical center. The purpose of this study was to determine how accurate epileptologists are at remotely reviewing Epilog sensor EEG in the 10-channel “REMI montage,” with and without seizure detection support software. Three board certified epileptologists reviewed the REMI montage from 20 subjects who wore four Epilog sensors for up to 5 days alongside traditional video-EEG in the EMU, 10 of whom experienced a total of 24 focal-onset electrographic seizures and 10 of whom experienced no seizures or epileptiform activity. Epileptologists randomly reviewed the same datasets with and without clinical decision support annotations from an automated seizure detection algorithm tuned to be highly sensitive. Blinded consensus review of unannotated Epilog EEG in the REMI montage detected people who were experiencing electrographic seizure activity with 90% sensitivity and 90% specificity. Consensus detection of individual focal onset seizures resulted in a mean sensitivity of 61%, precision of 80%, and false detection rate (FDR) of 0.002 false positives per hour (FP/h) of data. With algorithm seizure detection annotations, the consensus review mean sensitivity improved to 68% with a slight increase in FDR (0.005 FP/h). As seizure detection software, the automated algorithm detected people who were experiencing electrographic seizure activity with 100% sensitivity and 70% specificity, and detected individual focal onset seizures with a mean sensitivity of 90% and mean false alarm rate of 0.087 FP/h. This is the first study showing epileptologists' ability to blindly review EEG from four Epilog sensors in the REMI montage, and the results demonstrate the clinical potential to accurately identify patients experiencing electrographic seizures. Additionally, the automated algorithm shows promise as clinical decision support software to detect discrete electrographic seizures in individual records as accurately as FDA-cleared predicates.
Theta and Alpha Oscillatory Activity During Working Memory Maintenance in Long-Term Cannabis Users: The Importance of the Polydrug Use Context
Authors: Binkowska Alicja Anna , Jakubowska Natalia , Krystecka Klaudia , Galant Natalia , Piotrowska-Cyplik Agnieszka , Brzezicka Aneta
Published: October 2021

Background: Impairments in various subdomains of memory have been associated with chronic cannabis use, but less is known about their neural underpinnings, especially in the domain of the brain’s oscillatory activity.

Aims: To investigate neural oscillatory activity supporting working memory (WM) in regular cannabis users and non-using controls. We focused our analyses on frontal midline theta and posterior alpha asymmetry as oscillatory fingerprints for the WM’s maintenance process.

Methods: 30 non-using controls (CG) and 57 regular cannabis users—27 exclusive cannabis users (CU) and 30 polydrug cannabis users (PU) completed a Sternberg modified WM task with a concurrent electroencephalography recording. Theta, alpha and beta frequency bands were examined during WM maintenance.

Results: When compared to non-using controls, the PU group displayed increased frontal midline theta (FMT) power during WM maintenance, which was positively correlated with RT. The posterior alpha asymmetry during the maintenance phase, on the other hand, was negatively correlated with RT in the CU group. WM performance did not differ between groups.

Conclusions: Both groups of cannabis users (CU and PU), when compared to the control group, displayed differences in oscillatory activity during WM maintenance, unique for each group (in CU posterior alpha and in PU FMT correlated with performance). We interpret those differences as a reflection of compensatory strategies, as there were no differences between groups in task performance. Understanding the psychophysiological processes in regular cannabis users may provide insight on how chronic use may affect neural networks underlying cognitive processes, however, a polydrug use context (i.e., combining cannabis with other illegal substances) seems to be an important factor.
Increased Signal Delays and Unaltered Synaptic Input Pattern Recognition in Layer III Neocortical Pyramidal Neurons of the rTg4510 Mouse Model of Tauopathy: A Computer Simulation Study With Passive Membrane
Authors: Somogyi Attila , Wolf Ervin
Published: October 2021

Abnormal tau proteins are involved in pathology of many neurodegenerative disorders. Transgenic rTg4510 mice express high levels of human tau protein with P301L mutation linked to chromosome 17 that has been associated with frontotemporal dementia with parkinsonism. By 9 months of age, these mice recapitulate key features of human tauopathies, including presence of hyperphosphorylated tau and neurofibrillary tangles (NFTs) in brain tissue, atrophy and loss of neurons and synapses, and hyperexcitability of neurons, as well as cognitive deficiencies. We investigated effects of such human mutant tau protein on neuronal membrane, subthreshold dendritic signaling, and synaptic input pattern recognition/discrimination in layer III frontal transgenic (TG) pyramidal neurons of 9-month-old rTg4510 mice and compared these characteristics to those of wild-type (WT) pyramidal neurons from age-matched control mice. Passive segmental cable models of WT and TG neurons were set up in the NEURON simulator by using three-dimensionally reconstructed morphology and electrophysiological data of these cells. Our computer simulations predict leakage resistance and capacitance of neuronal membrane to be unaffected by the mutant tau protein. Computer models of TG neurons showed only modest alterations in distance dependence of somatopetal voltage and current transfers along dendrites and in rise times and half-widths of somatic Excitatory Postsynaptic Potential (EPSPs) relative to WT control. In contrast, a consistent and statistically significant slowdown was detected in the speed of simulated subthreshold dendritic signal propagation in all regions of the dendritic surface of mutant neurons. Predictors of synaptic input pattern recognition/discrimination remained unaltered in model TG neurons. This suggests that tau pathology is primarily associated with failures/loss in synaptic connections rather than with altered intraneuronal synaptic integration in neurons of affected networks.
The Arch Electrode: A Novel Dry Electrode Concept for Improved Wearing Comfort
Authors: Vasconcelos Beatriz , Fiedler Patrique , Machts René , Haueisen Jens , Fonseca Carlos
Published: October 2021

Electroencephalography (EEG) is increasingly used for repetitive and prolonged applications like neurofeedback, brain computer interfacing, and long-term intermittent monitoring. Dry-contact electrodes enable rapid self-application. A common drawback of existing dry electrodes is the limited wearing comfort during prolonged application. We propose a novel dry Arch electrode. Five semi-circular arches are arranged parallelly on a common baseplate. The electrode substrate material is a flexible thermoplastic polyurethane (TPU) produced by additive manufacturing. A chemical coating of Silver/Silver-Chloride (Ag/AgCl) is applied by electroless plating using a novel surface functionalization method. Arch electrodes were manufactured and validated in terms of mechanical durability, electrochemical stability, in vivo applicability, and signal characteristics. We compare the results of the dry arch electrodes with dry pin-shaped and conventional gel-based electrodes. 21-channel EEG recordings were acquired on 10 male and 5 female volunteers. The tests included resting state EEG, alpha activity, and a visual evoked potential. Wearing comfort was rated by the subjects directly after application, as well as at 30 min and 60 min of wearing. Our results show that the novel plating technique provides a well-adhering electrically conductive and electrochemically stable coating, withstanding repetitive strain and bending tests. The signal quality of the Arch electrodes is comparable to pin-shaped dry electrodes. The average channel reliability of the Arch electrode setup was 91.9 ± 9.5%. No considerable differences in signal characteristics have been observed for the gel-based, dry pin-shaped, and arch-shaped electrodes after the identification and exclusion of bad channels. The comfort was improved in comparison to pin-shaped electrodes and enabled applications of over 60 min duration. Arch electrodes required individual adaptation of the electrodes to the orientation and hairstyle of the volunteers. This initial preparation time of the 21-channel cap increased from an average of 5 min for pin-like electrodes to 15 min for Arch electrodes and 22 min for gel-based electrodes. However, when re-applying the arch electrode cap on the same volunteer, preparation times of pin-shaped and arch-shaped electrodes were comparable. In summary, our results indicate the applicability of the novel Arch electrode and coating for EEG acquisition. The novel electrode enables increased comfort for prolonged dry-contact measurement.
Metabolic Molecule PLA2G2D Is a Potential Prognostic Biomarker Correlating With Immune Cell Infiltration and the Expression of Immune Checkpoint Genes in Cervical Squamous Cell Carcinoma
Authors: Liu Hong , Xu Ruiyi , Gao Chun , Zhu Tong , Liu Liting , Yang Yifan , Zeng Haihong , Huang Yafei , Wang Hui
Published: October 2021

Cervical squamous cell carcinoma (CSCC) is the major pathological type of cervical cancer (CC), the second most prevalent reproductive system malignant tumor threatening the health of women worldwide. The prognosis of CSCC patients is largely affected by the tumor immune microenvironment (TIME); however, the biomarker landscape related to the immune microenvironment of CSCC and patient prognosis is less characterized. Here, we analyzed RNA-seq data of CSCC patients from The Cancer Genome Atlas (TCGA) database by dividing it into high- and low-immune infiltration groups with the MCP-counter and ESTIMATE R packages. After combining weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis, we found that PLA2G2D, a metabolism-associated gene, is the top gene positively associated with immune infiltration and patient survival. This finding was validated using data from The Cancer Genome Characterization Initiative (CGCI) database and further confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, multiplex immunohistochemistry (mIHC) was performed to confirm the differential infiltration of immune cells between PLA2G2D-high and PLA2G2D-low tumors at the protein level. Our results demonstrated that PLA2G2D expression was significantly correlated with the infiltration of immune cells, especially T cells and macrophages. More importantly, PLA2G2D-high tumors also exhibited higher infiltration of CD8+ T cells inside the tumor region than PLA2G2D-low tumors. In addition, PLA2G2D expression was found to be positively correlated with the expression of multiple immune checkpoint genes (ICPs). Moreover, based on other immunotherapy cohort data, PLA2G2D high expression is correlated with increased cytotoxicity and favorable response to immune checkpoint blockade (ICB) therapy. Hence, PLA2G2D could be a novel potential biomarker for immune cell infiltration, patient survival, and the response to ICB therapy in CSCC and may represent a promising target for the treatment of CSCC patients.
Long-Term Use of Statins Lowering the Risk of Rehospitalization Caused by Ischemic Stroke Among Middle-Aged Hyperlipidemic Patients: A Population-Based Study
Authors: Yin Jiu-Haw , Peng Giia-Sheun , Chen Kang-Hua , Chu Chi-Ming , Chien Wu-Chien , Kao Li-Ting , Wu Chia-Chao , Yang Chih-Wei , Tsai Wen-Chiuan , Lin Wei-Zhi , Wu Yi-Syuan , Lin Hung-Che , Chang Yu-Tien
Published: October 2021

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis.

Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model.

Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29–1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users.

Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.
Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation
Authors: Liu Yun-zi , Xu Ming-yuan , Dai Xiao-yu , Yan Lang , Li Lei , Zhu Rui-zhen , Ren Li-jun , Zhang Ji-qian-zhu , Zhang Xiao-fang , Li Jin-feng , Tian Yi-jun , Shi Wen-jing , Liu Ye-qiang , Jiang Chun-lei , Zhu Jiang-bo , Chen Ji-kuai
Published: October 2021

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.
Explore the Bereavement Needs of Families of Children With Cancer From the Perspective of Health Caregivers: A Qualitative Study
Authors: Pakseresht Maryam , Rassouli Maryam , Rejeh Nahid , Rostami Shahnaz , Barasteh Salman , Molavynejad Shahram
Published: October 2021

Introduction: The experience of bereavement is associated with severe physical, psychological, social and spiritual reactions in the parents of children with cancer. Because of that, the families of these children need to receive bereavement services. The aim of this study was to explore the bereavement needs of families of children with cancer from the perspective of health caregiver as people who have a close relationship with the child and the family.

Methods: This qualitative descriptive study design in. In total 15 semi-structured interviews were conducted using a purposive sampling in 2018. Interviews were recorded and transcribed and conventional content analysis was used to analysis the data. The Trustworthiness of the data were assessed according to the criteria of Lincoln and Guba.

Results: From the data analysis, needs of the bereaved family were categorized in three dimension including “achieving peace,” “Abandoned family access to care,” and “continuing care.” The category of “achieving peace” includes spiritual and existential support, companionship with the family, contact with other bereaved families, support in passing and accepting the bereaved and continuing empathetic communication with the family, the category “Abandoned family access to care” includes the promotion of family self-control, awareness of end-of-life care to the family, and the category of “continuing care,” includes formal and informal family care and individualized care.

Conclusion: It is necessary for the care team to pay special focus to family considering the needs of the family about the death of the patient and the challenges of the family bereavement period. It is recommended that members of the health care team should be trained in assessing family needs, identifying risks of adverse outcomes, continuing care, and providing resources during bereavement. The needs of the bereaved family should also be addressed in their care plan.
Impact of Internet Use on Multi-dimensional Health: An Empirical Study Based on CGSS 2017 Data
Authors: Han Junhui , Zhao Xiaoqiong
Published: October 2021

Based on the data of the Chinese General Social Survey (CGSS) in 2017, the paper divides overall health into physical, mental, and social health, using the ordered probit model to examine the impact of Internet use on multi-dimensional health. It then discusses the possible heterogeneity in different groups and underlying mechanism. Results found that using the Internet can improve the health level in multiple dimensions. After endogenous and robustness tests, the results remain robust. Heterogeneity analysis shows that Internet use has more obvious effects on the health of senior high school education or above, the elderly, and men. Further analysis of the mediating effect model found that information, leisure, and social preferences are important path mechanisms for Internet use to promote physical, mental, and social health, respectively.
The Design and Rationale of a Multicentre Randomised Controlled Trial Comparing Transperineal Percutaneous Laser Ablation With Transurethral Resection of the Prostate for Treating Benign Prostatic Hyperplasia
Authors: Zhang Wei , Zhang Weituo , Guo Qian , Chen Lei , Meng Zheying , Xu Yanjun , Cao Nailong , Hu Bing , Qian Biyun
Published: October 2021

Background: Transurethral resection of the prostate (TURP) is regarded as the “gold standard” for the treatment of benign prostatic hyperplasia (BPH) in elderly men. However, ~15% of patients who had undergone TURP had intraoperative and postoperative complications, such as bleeding, urinary incontinence and urethral stricture. Transperineal percutaneous laser ablation (TPLA) is a method that places the optical fibre directly into the prostate with the guidance of ultrasound imaging, and the percutaneous transperineal approach is performed distal to the urethra and rectum to protect these structures and reduce urethral or postoperative infection. Several studies on TPLA for BPH treatment have been reported recently; however, high-quality randomised controlled trial (RCT) to evaluate its efficacy, safety, and long-term follow up remain absent.

Methods: This study is a multicentre, open-label RCT to assess the efficacy and safety of TPLA vs. TURP to treat BPH. We hypothesise that the TPLA has non-inferior efficacy to TURP in the International Prostate Symptom Score (IPSS) at 3 months changing from the baseline and lower incidence of post-surgery complications. One hundred and fourteen patients with BPH will be recruited at 19 sites and randomly assigned at 1:1 to TPLA or TURP groups. The patients will be followed up at 1, 3, 6, 12, and 24 months after the procedure.

Discussion: The study will be the first multicentre clinical trial including 16 participating centres in China, Italy, Switzerland, and Poland with relatively large sample size 114. By comprehensively compare the safety and efficacy of TPLA with TURP in patients with BPH, especially concerning the improvement of lower urinary tract symptoms (LUTS) and complication incidence, the study will help to illustrate the clinical value of TPLA and provide a beneficial alternative treatment for BPH patients.

Clinical Trial Registration: The study has been registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn), identifier [ChiCTR1900022739].
Nutrient Release and Ammonia Volatilization from Biochar-Blended Fertilizer with and without Densification
Authors: Lee Yit Leng , Ahmed Osumanu Haruna , Wahid Samsuri Abdul , Jalloh Mohamadu Boyie , Muzah Adiza Alhassan
Published: October 2021

Blending fertilizer with biochar followed by densification to make it into a tablet can enhance the adsorption of fertilizer on the biochar surface and reduce the nutrient loss during handling. However, the nutrient release and ammonia volatilization from biochar-blended fertilizer with and without densification are not well understood. The objectives of this study were to determine the nutrient release and ammonia volatilization from an acid soil applied with biochar-blended NPK fertilizer with and without densification. The nutrient release of biochar-blended NPK was determined using water incubation for 30 days, whereas daily loss of ammonia was measured using a closed dynamic air flow system for 10 days. The densified biochar-blended NPK caused stronger physical binding of the nutrients within the tablet in addition to stronger chemical bondings between the nutrients with the biochar’s functional groups. As a result, nutrient release in the water incubation from the biochar-blended NPK fertilizer tablet was slower. However, blending the biochar with the NPK fertilizer increased soil ammonia volatilization relative to the NPK fertilizer alone. This demonstrates that the biochar-blended fertilizer tablet has the potential to serve as a slow release fertilizer for crop cultivation.
Automatic Segmentation and Classification Methods Using Optical Coherence Tomography Angiography (OCTA): A Review and Handbook
Authors: Meiburger Kristen M. , Salvi Massimo , Rotunno Giulia , Drexler Wolfgang , Liu Mengyang
Published: October 2021

Optical coherence tomography angiography (OCTA) is a promising technology for the non-invasive imaging of vasculature. Many studies in literature present automated algorithms to quantify OCTA images, but there is a lack of a review on the most common methods and their comparison considering multiple clinical applications (e.g., ophthalmology and dermatology). Here, we aim to provide readers with a useful review and handbook for automatic segmentation and classification methods using OCTA images, presenting a comparison of techniques found in the literature based on the adopted segmentation or classification method and on the clinical application. Another goal of this study is to provide insight into the direction of research in automated OCTA image analysis, especially in the current era of deep learning.