bluuebunny/crossref_metadata_2025 huggingface dataset:
Studi Pengaruh Silinder Pori Pada Saluran Drainase Terhadap Debit Infiltrasi Pada Tanah Lempung
Authors: Sindagamanik Fenti Daud , Antaria Sukmasari , Nenny Nenny
Published: December 2020

Usaha penanggulangan banjir perlu dilakukan secara dini, dimana salah satunya adalah melakukan perbaikan pada sistim drainase. Penanggulangan banjir  memerlukan desain drainase efektif, berwawasan lingkungan , yang berfungsi menampung, dan mengalirkan air dari badan jalan ke lapisan tanah yang ada di bawahnya . penelitian skala laboratorium sangat diperlukan untuk mengetahui : dimensi, rasio luas, bahan dan kedalaman lubang pori yang efektif untuk meresapkan air dari badan saluran drainase ke lapisan tanah di bawah saluran. Penelitian ini dilakukan dengan Studi eksperimental dengan menggunakan model saluran drainase bersilinder pori. Pengujian dilakukan dengan 3 variasi diameter lubang, ,3 variasi ketinggian muka air di saluran. Sebagai media infiltrasi digunakan  tanah jenis Lempung yang dimodelkan berdasarkan sampel tanah yang diambil pada lokasi yang sering mengalami banjir atau genangan . Dari pengamatan dan uji laboratorium diharapkan dapat di hasilkan dimensi silinder pori yang seseuai dengan kondisi tanah Lempung pada bagian bawah saluran drainase. Makalah ini merupakan bagian dari penelitian  Saluran Bersilinder Pori Berwawasan Lingkungan Pereduksi Genangan banjir Perkotaan, yaitu mengenai Pengaruh Silinder Pori Terhadap debit Infiltrasi Pada Tanah Lempung
Kerusakan Perkerasan Lentur Dengan Metode Bina Marga STA 140 + 000 – STA 150 + 000 Batas Sumatera Barat – Riau
Authors: Prayitno Eko , Triana Era
Published: December 2020

Metode bina marga adalah metode yang dipakai untuk menentukan jenis kerusakan, yang perlu diperhatikan saat melakukan survei visual adalah kekasaran permukaan, lubang, tambalan, retak, alur dan amblas. Retak adalah suatu gejala kerusakan atau pecahnya permukaan perkerasan sehingga akan menyebabkan air pada permukaan perkerasan masuk ke lapisan dibawahnya. Penentuan nilai kondisi jalan dilakukan dengan menjumlahkan setiap angka dan nilai untuk masing-masing keadaan kerusakan. untuk mengetahui jenis kerusakan jalan dan menganalisa tingkat kerusakan jalan dengan metode bina marga serta bentuk penanganannya, maka harus diadakan pemilihan terhadap jenis dan luas kerusakan yang terjadi. Jenis kerusakan yang dapat ditemukan pada ruas jalan batas Sumatera Barat – Riau STA 140 + 000 – STA 150 + 000 antara lain retak buaya, retak memanjang, tambalan, lubang, amblas dan alur. Tingkat kerusakan jalan dengan metode bina marga serta jenis penanganannya adalah tingkat atau nilai prioritas kerusakan batas Sumatera Barat – Riau STA 140 + 000 – STA 150 + 000 dengan menggunakan metode bina marga adalah 5, menandakan bahwa jalan perlu dimasukkan ke dalam program pemeliharaan berkala.
Analisis Perilaku Lalu Lintas Jalan Perkotaan Kota Baubau Dengan Membandingkan Metode MKJI 1997 Dan PKJI 2014
Authors: Hajia Muhammad Chaiddir
Published: December 2020

Transportasi mempunyai peran penting terhadap pergerakan manusia terkhususnya di Kota Baubau. Peningkatan volume lalu lintas Kota Baubau dari tahun ke tahun mengalami peningkatan sehingga kinerja lalu lintas mengalami penurunan. Salah satu lokasi yang mengalami dampak berkurangnya kinerja lalu lintas yaitu Jalan Anoa Kota Baubau. Untuk menganalisis perilaku lalu lintas dapat dilakukan dengan dua metode yaitu dengan metode MKJI 1997 dan PKJI 2014. Tujuan dilakukan penelitian ini adalah untuk menganalisis perilaku lalu lintas dengan membandingan kedua metode tersebut. Penelitian ini dilakukan selama 3 hari dimulai dari jam 08.00 – 16.00 WITA dengan interval waktu penelitian diambil selama 15 menit dan tipe jalan yaitu 2/2 UD. Hasil penelitian didapatkan dari dua metode tersebut memberikan hasil yang sama dimana perilaku lalu lintas di Jalan Anoa memiliki tingkat pelayanan jalan tipe B dengan nilai V/C adalah 0,38 < 0,75 sehingga pada ruas jalan tersebut tidak perlu dilakukan pelebaran jalan, ataupun penambahan jalur. Kedua metode tersebut juga memberikan hasil sama untuk nilai derajat kejenuhannya sehingga untuk untuk menganalisis perilaku lalu lintas bisa dengan menggunakan metode MKJI 1997 ataupun PKJI 2014.
Characterising seabird vessel interactions associated with demersal ocean trawling: vessel attendance by birds depends on intrinsic and extrinsic predictors
Authors: Barnes TC , Candy SG , Johnson D
Published: December 2020

Seabirds are declining on a global scale, and this trend is concerning as they play an important role in the marine ecosystem. The decline is due to multiple reasons, but harvest fisheries are a major contributor. The impact of fisheries, however, appears to vary; demersal trawlers cause mortality of many birds in some areas and very few in others. Fishery-dependent monitoring is required to understand this impact on seabirds, and particularly to better understand the variable impact of demersal trawling. We employed a targeted observer program to gather data on seabird assemblages, catastrophic interactions with trawl vessels and predictors of vessel attendance by the seabirds. The latter is a useful proxy for catastrophic interactions and provides information on potential mitigation. Throughout the program period, 1040942 seabirds from ~21 species attended New South Wales (NSW) ocean demersal trawlers. These species included 7 species of petrel and albatross listed by the IUCN, including the flesh footed shearwater Ardenna carneipes and wandering albatross Diomedea exulans. Two catastrophic interactions were recorded, and intrinsic and extrinsic predictors of vessel attendance (e.g. offal discharge and wind, respectively) were characterised. The results of the study will provide information to managers, with the goal of ensuring the sustainability of NSW ocean trawling—in particular its coexistence with threatened seabirds. The NSW Ocean Trawl fishery appears to directly harm very few seabirds which is not always the case when considering worldwide trawl fisheries. Predictors of attendance such as space, time and offal discharge can potentially be used to mitigate the attractiveness of trawlers to seabirds.
Intertidal ecosystem engineer species promote benthic-pelagic coupling and diversify trophic pathways
Authors: Jones AG , Dubois SF , Desroy N , Fournier J
Published: December 2020

Ecosystem engineering is a ubiquitous process by which the biological activity of a species shapes habitat diversity and often creates local biodiversity hotspots. The honeycomb-worm Sabellaria alveolata, an intertidal ecosystem engineer, actively builds reefs across Europe by aggregating sand. Here, we used carbon and nitrogen isotopic compositions measured on basal resources and bentho-demersal consumers (fish, mega- and macroinvertebrates) to empirically investigate how non-trophic interactions (ecosystem engineering) modify food web structure and functioning. Three sediment types corresponding to different substrata and species assemblages were sampled: a control soft sediment (medium to muddy sand, before the establishment of S. alveolata), the sediment engineered by S. alveolata (hardened 3D structures), and the soft sediment under the influence of S. alveolata (associated sediment). Using consumer community isotopic biplots (biomass-weighted), niche metrics (standard ellipse area), and mixing models, we found that S. alveolata, through the physical structure it creates, the stimulation of basal resources (microphytobenthos and Ulva), and the diversification of suspension-feeding species, promotes benthic-pelagic coupling and a habitat-wide form of ‘gardening,’ which further leads to trophic pathway diversification and limits trophic competition between the engineer species and associated suspension-feeders. Furthermore, our results help to refine the definition of S. alveolata reefs as the sum of the engineered and associated sediments since they are part of a single reef food web coupled by the stimulated basal resources and consumers. Finally, the non-trophic and trophic interactions mediated by S. alveolata and the associated macrofauna seem to promote the establishment of a temporally stable and probably highly resilient reef habitat.
EFFECT OF DISTRIBUTION CHANNEL TO SALES VOLUME IN PT HONDA POWER PRODUCT INDONESIA
Authors: Rahman Faisal , Vikaliana Resista
Published: December 2020

This research was conducted at PT. Honda Power Products Indonesia, with the aim to determine the effect of distribution channels on sales volume at PT. Honda Power Products Indonesia. This research approach is a quantitative approach with correlational research type. Data were collected by distributing questionnaires to 80 samples. From the calculation and data analysis, the linear regression equation is Y = 13.134 + 0.195 X1 + e. The correlation coefficient obtained is 0.694, which means that the Distribution Channel variable has a strong influence on the Sales Volume variable. While the coefficient of determination obtained is 0.489, or 48.9%. This shows that the distribution channel has an influence of 48.9% on volume, while the remaining 51.1% is influenced by other variables not included in the model or not examined by the author. The results of the t hypothesis test show that the Distribution Channel variable has a positive and significant effect on the Sales Volume variable.
A Novel Nanosystem Realizing Curcumin Delivery Based on Fe3O4@Carbon Dots Nanocomposite for Alzheimer’s Disease Therapy
Authors: Kuang Ying , Zhang Jingwen , Xiong Mogao , Zeng Weijia , Lin Xiaofeng , Yi Xiaoqing , Luo Yan , Yang Min , Li Feng , Huang Qitong
Published: December 2020

Alzheimer’s disease (AD) is the most common neurodegenerative disease, which seriously affects human health but lacks effective treatment methods. Amyloid β (Aβ) aggregates are considered a possible target for AD treatment. Evidence is increasingly showing that curcumin (CUR) can partly protect cells from Aβ-mediated neurotoxicity by inhibiting Aβ aggregation. However, the efficiency of targeted cellular uptake and bioavailability of CUR is very low due to its poor stability and water-solubility. In order to better improve the cell uptake efficiency and bioavailability of CUR and reduce the cytotoxicity of high-dose CUR, a novel CUR delivery system for AD therapy has been constructed based on the employment of the Fe3O4@carbon dots nanocomposite (Fe3O4@CDs) as the carrier. CUR-Fe3O4@CDs have a strong affinity toward Aβ and effectively inhibit extracellular Aβ fibrillation. In addition, CUR-Fe3O4@CDs can inhibit the production of reactive oxygen species (ROS) mediated by Aβ fibrils and the corresponding neurotoxicity in PC12 cells. More importantly, it can restore nerve damage and maintained neuronal morphology. These results indicate that the application of CUR-Fe3O4@CDs provides a promising platform for the treatment of AD.
Strategic Decision Making in Construction Supply Chains: A Comparison of Reverse Logistics Strategies
Authors: Pushpamali NNC , Agdas Duzgun , Rose Timothy M.
Published: December 2020

Most of the construction materials still go to landfill after structures are demolished. This causes issues in human health, ecosystem preservation, and excessive resource consumption compared to RL options. Hence, recovering material value through reverse logistics (RL) is important to lessen the environmental and social burden. Embodying RL practices into strategic level decisions derives long-term and sustainable advantages. Although the most common RL option in construction seems to be recycling, it requires an additional energy and material intensive process. Therefore, recycling should be the last preference among other RL options. The hypothesis of this study is that alternative RL strategies provide more environmental benefits than recycling, the most common RL method, and traditional landfilling. The hypothesis was tested through assessment of the environmental impact of RL options in the construction sector. A life cycle assessment (LCA) with ReCipe2016 Midpoint and Endpoint assessment method was conducted for a bridge construction supply chain. Different end-of-life scenarios such as reuse, remanufacture, recycle, and landfill scenarios were assessed using SimaPro software. This paper addresses a key knowledge gap on the environmental impact of reverse logistics strategies from a construction supply chain perspective. The research results reveal that “reuse” strategy has the least environmental impact, remanufacturing has a lesser impact on the environment than other options, recycling has the second highest environmental impact, with landfill assessed as the least environmentally friendly end-of-life option. Consequently, this paper emphasizes the importance of informed strategic supply chain decisions for reverse logistics to obtain the best outcome from environmentally friendly practices. Since there is no relevant previous research conducted to examine the environmental impact of different reverse logistics options from a construction supply chain perspective, the findings of this study provide crucial input in RL decision making and can extend to contributing to practice. Industry stakeholders, especially the government agencies and regulatory bodies, should encourage practitioners to adopt the most effective RL approaches, including reuse and remanufacturing, rather than focusing only on material recycling. The motivation of supportive designs for more environmentally friendly RL options from the researchers, designers, architects, and planners are required in this process.
Nesfatin-1 Promotes the Osteogenic Differentiation of Tendon-Derived Stem Cells and the Pathogenesis of Heterotopic Ossification in Rat Tendons via the mTOR Pathway
Authors: Xu Kai , Zhang Zhanfeng , Chen Mengyao , Moqbel Safwat Adel Abdo , He Yuzhe , Ma Chiyuan , Jiang Lifeng , Xiong Yan , Wu Lidong
Published: December 2020

Heterotopic ossification (HO) is a pathological condition involved in tendinopathy. Adipokines are known to play a key role in HO of tendinopathy. Nesfatin-1, an 82-amino acid adipokine is closely reportedly associated with diabetes mellitus (DM), which, in turn, is closely related to tendinopathy. In the present study, we aimed to investigate the effects of nesfatin-1 on the osteogenic differentiation of tendon-derived stem cells (TDSCs) and the pathogenesis of tendinopathy in rats. In vitro, TDSCs were incubated in osteogenic induction medium for 14 days with different nesfatin-1 concentration. In vivo, Sprague Dawley rats underwent Achilles tenotomy to evaluate the effect of nesfatin-1 on tendinopathy. Our results showed that the expression of nesfatin-1 expression in tendinopathy patients was significantly higher than that in healthy subjects. Nesfatin-1 affected the cytoskeleton and reduced the migration ability of TDSCs in vitro. Furthermore, nesfatin-1 inhibited the expression of Scx, Mkx, and Tnmd and promoted the expression of osteogenic genes, such as COL1a1, ALP, and RUNX2; these results suggested that nesfatin-1 inhibits cell migration, adversely impacts tendon phenotype, promotes osteogenic differentiation of TDSCs and the pathogenesis of HO in rat tendons. Moreover, we observed that nesfatin-1 suppressed autophagy and activated the mammalian target of rapamycin (mTOR) pathway both in vitro and in vivo. The suppression of the mTOR pathway alleviated nesfatin-1-induced HO development in rat tendons. Thus, nesfatin-1 promotes the osteogenic differentiation of TDSC and the pathogenesis of HO in rat tendons via the mTOR pathway; these findings highlight a new potential therapeutic target for tendinopathy.
Biological Behavioral Alterations of the Post-neural Differentiated Dental Pulp Stem Cells Through an in situ Microenvironment
Authors: Luo Lihua , Wang Xiaoyan , Zhang Yanni , Wu Yuwei , Hu Fengting , Xing Zhenjie , Wang Lei , Xiao Jian , Guastaldi Fernando , He Yan , Ye Qingsong
Published: December 2020

Transplantation of undifferentiated dental pulp stem cells (DPSCs) may suffer from tumorigenesis. Neuronal differentiated DPSCs (d-DPSCs) have emerged as an ideal source to treat central nervous system (CNS) disorders. Moreover, different components of culture medium functioned on the characteristics of d-DPSCs in vitro. In this study, d-DPSCs were cultured in three types of medium: Neurobasal®®-A medium supplemented with 2% B27 (the 2% B27 NM group), Neurobasal® -A medium supplemented with 2% B27 and 5% FBS (the 2% B27 + 5% FBS NM group), and α-MEM containing 10% FBS (the 10% FBS α-MEM group). We found that d-DPSCs in the 2% B27 + 5% FBS NM group had lower proliferation and reduced expression of transient receptor potential canonical 1 (TRPC1) and CD146, whereas up-regulated Nestin and microtubule-associated protein-2 (MAP-2). Notably, d-DPSCs in the 10% FBS α-MEM group possessed high proliferative capacity, decreased expression of neuron-like markers and partially restored stemness. It was demonstrated that d-DPSCs cultured in the 2% B27 + 5% FBS NM could maintain their neuron-like characteristics. Besides, d-DPSCs cultivated in the 10% FBS α-MEM could partially recover their stem cells properties, indicating that neural differentiation of DPSCs was reversible and could open novel avenues for exploring the pluripotency of DPSCs.
The Current Process for the Recycling of Spent Lithium Ion Batteries
Authors: Zhou Li-Feng , Yang Dongrun , Du Tao , Gong He , Luo Wen-Bin
Published: December 2020

With the development of electric vehicles involving lithium ion batteries as energy storage devices, the demand for lithium ion batteries in the whole industry is increasing, which is bound to lead to a large number of lithium ion batteries in the problem of waste, recycling and reuse. If not handled properly, it will certainly have a negative impact on the environment and resources. Current commercial lithium ion batteries mainly contain transition metal oxides or phosphates, aluminum, copper, graphite, organic electrolytes containing harmful lithium salts, and other chemicals. Therefore, the recycling and reuse of spent lithium ion batteries has been paid more and more attention by many researchers. However, due to the high energy density, high safety and low price of lithium ion batteries have great differences and diversity, the recycling of waste lithium ion batteries has great difficulties. This paper reviews the latest development of the recovery technology of waste lithium ion batteries, including the development of recovery process and products. In addition, the challenges and future economic and application prospects are described.
Freshwater Testate Amoebae (Arcellinida) Response to Eutrophication as Revealed by Test Size and Shape Indices
Authors: Macumber Andrew L. , Roe Helen M. , Prentice Stephen V. , Sayer Carl D. , Bennion Helen , Salgado Jorge
Published: December 2020

We review the potential for applying traits-based approaches to freshwater testate amoeba, a diverse protist group that are abundant in lakes and are valuable ecological indicators. We investigated the efficacy of geometric morphometric analysis to define Arcellinida test size and shape indices that could summarize freshwater testate amoeba community dynamics along a temporal gradient of eutrophication in Loch Leven, Scotland (United Kingdom). A cluster analysis of test size and shape indices yielded three clusters, each dominated by a single shape: elongate, spherical and ovoid. When plotted stratigraphically, we observed increases in spherical tests, decreases in elongate tests and shrinking of test size coeval with eutrophication in Loch Leven. Decreases in the elongate cluster may reflect benthic conditions with reduced oxygen levels, while increases in the spherical cluster are likely associated with an expanding macrophyte community that promoted pelagic and epibiotic life habits. Shrinking of test size may be a stress response to eutrophication and/or warming temperatures. Tracking community dynamics using test size and shape indices was found to be as effective as using species-based approaches to summarize key palaeolimnological changes, with the added benefits of being free from taxonomic bias and error. The approach thus shows significant potential for future studies of aquatic community change in nutrient impacted lakes.
Tumor-Associated Macrophages in Tumor Immunity
Authors: Pan Yueyun , Yu Yinda , Wang Xiaojian , Zhang Ting
Published: December 2020

Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. The former typically exerts anti-tumor functions, including directly mediate cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; the latter can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis, and lead to tumor progression. Both M1 and M2 macrophages have high degree of plasticity and thus can be converted into each other upon tumor microenvironment changes or therapeutic interventions. As the relationship between TAMs and malignant tumors becoming clearer, TAMs have become a promising target for developing new cancer treatment. In this review, we summarize the origin and types of TAMs, TAMs interaction with tumors and tumor microenvironment, and up-to-date treatment strategies targeting TAMs.
Protein Biomarkers in Uveitis
Authors: Bansal Reema , Gupta Amod
Published: December 2020

The diseases affecting the retina or uvea (iris, ciliary body, or choroid) generate changes in the biochemical or protein composition of ocular fluids/tissues due to disruption of blood-retinal barrier. Ocular infections and inflammations are sight-threatening diseases associated with various infectious and non-infectious etiologies. Several etiological entities cause uveitis, a complex intraocular inflammatory disease. These causes of uveitis differ in different populations due to geographical, racial, and socioeconomic variations. While clinical appearance is sufficiently diagnostic in many diseases, some of the uveitic entities manifest nonspecific or atypical clinical presentation. Identification of biomarkers in such diseases is an important aid in their diagnostic armamentarium. Different diseases and their different severity states release varying concentrations of proteins, which can serve as biomarkers. Proteomics is a high throughput technology and a powerful screening tool for serum biomarkers in various diseases that identifies proteins by mass spectrometry and helps to improve the understanding of pathogenesis of a disease. Proteins determine the biological state of a cell. Once identified as biomarkers, they serve as future diagnostic and pharmaceutical targets. With a potential to redirect the diagnosis of idiopathic uveitis, ocular proteomics provide a new insight into the pathophysiology and therapeutics of various ocular inflammatory diseases. Tears, aqueous and vitreous humor represent potential repositories for proteomic biomarkers discovery in uveitis. With an extensive proteomics work done on animal models of uveitis, various types of human uveitis are being subjected to proteome analysis for biomarker discovery in different ocular fluids (vitreous, aqueous, or tears).
Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2
Authors: Salamanna Francesca , Maglio Melania , Landini Maria Paola , Fini Milena
Published: December 2020

The explosion of the new coronavirus (SARS-CoV-2) pandemic has brought the role of the angiotensin converting enzyme 2 (ACE2) back into the scientific limelight. Since SARS-CoV-2 must bind the ACE2 for entering the host cells in humans, its expression and body localization are critical to track the potential target organ of this infection and to outline disease progression and clinical outcomes. Here, we mapped the physiological body distribution, expression, and activities of ACE2 and discussed its potential correlations and mutal interactions with the disparate symptoms present in SARS-CoV-2 patients at the level of different organs. We highlighted that despite during SARS-CoV-2 infection ACE2-expressing organs may become direct targets, leading to severe pathological manifestations, and subsequent multiple organ failures, the exact mechanism and the potential interactions through which ACE2 acts in these organs is still heavily debated. Further scientific efforts, also considering a personalized approach aimed to consider specific patient differences in the mutual interactions ACE2-SARS-CoV-2 and the long-term health effects associated with COVID-19 are currently mandatory.
Outcomes of COVID-19 Among Hospitalized Patients With Non-dialysis CKD
Authors: Coca Armando , Burballa Carla , Centellas-Pérez Francisco Javier , Pérez-Sáez María José , Bustamante-Munguira Elena , Ortega Agustín , Dueñas Carlos , Arenas María Dolores , Pérez-Martínez Juan , Ruiz Guadalupe , Crespo Marta , Llamas Francisco , Bustamante-Munguira Juan , Pascual Julio
Published: December 2020

Background:Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Corona Virus 2 has generated significant impact on global health worldwide. COVID-19 can cause pneumonia and organ injury. Chronic kidney disease (CKD) has been associated with increased mortality in previous epidemics, but there is a paucity of data regarding actual risks for non-dialysis CKD patients with COVID-19.

Methods:Multicenter, observational cohort study including 136 non-dialysis CKD patients and 136 age- and sex-matched controls that required hospitalization due to COVID-19. Patients with end-stage renal disease, a kidney transplant or without registered baseline glomerular filtration rate prior to COVID-19 infection were excluded. CKD and acute kidney injury (AKI) were defined according to KDIGO criteria.

Results:CKD patients had higher white blood cell count and D-dimer and lower lymphocyte percentage. No differences were found regarding symptoms on admission. CKD was associated with higher rate of AKI (61 vs. 24.3%) and mortality (40.4 vs. 24.3%). Patients with AKI had the highest hazard for death (AKI/non-CKD HR:7.04, 95% CI:2.87–17.29; AKI/CKD HR:5.25, 95% CI: 2.29–12.02), followed by CKD subjects without AKI (HR:3.39, 95% CI:1.36–8.46). CKD status did not condition ICU admission or length of in-hospital stay.

Conclusions:CKD patients that require hospitalization due to COVID-19 are exposed to higher risk of death and AKI.
Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets?
Authors: Cupisti Adamasco , Giannese Domenico , Moriconi Diego , D'Alessandro Claudia , Torreggiani Massimo , Piccoli Giorgina B.
Published: December 2020

Sodium-glucose-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs that in large trials such as CREDENCE have shown also a reduction of glomerular hyperfiltration and albuminuria in type 2 diabetic patients. Hence, the interest toward SGLT2i is focused toward this potential nephroprotective effect, in order to reduce the progression to overt nephropathy, and it seems to be confirmed in the most recent DAPA-CKD trial. This is the reason why the indication for SGLT2i treatment has been extended to chronic kidney disease (CKD) patients with eGFR up to 30 ml/min, namely with CKD stage 1–3. In patients with CKD stage 3 to 5, the most recent KDIGO guidelines recommend low-protein diet and plant-based regimens to delay end-stage kidney disease (ESKD) and improve quality of life. Similarly to SGLT2i, low-protein diets exert renal-protective effects by reducing single nephron hyperfiltration and urinary protein excretion. Beyond the glomerular hemodynamic effects, both protein restriction and SGLT2i are able to restore autophagy and, through these mechanisms, they may exert protective effects on diabetic kidney disease. In this perspective, it is likely that diet may modulate the effect of SGLT2i in CKD patients. Unfortunately, no data are available on the outcomes of the association of SGLT2i and low-protein and/or vegan diets. It is therefore reasonable to investigate whether CKD patients receiving SGLT2i may have further advantages in terms of nephroprotection from the implementation of a low-protein and/or plant-based diet or whether this association does not result in an additive effect, especially in vascular nephropathies.
Prevalence, Virulence, Antimicrobial Resistance, and Molecular Characterization of Pseudomonas aeruginosa Isolates From Drinking Water in China
Authors: Wei Lei , Wu Qingping , Zhang Jumei , Guo Weipeng , Gu Qihui , Wu Huiqing , Wang Juan , Lei Tao , Xue Liang , Zhang Youxiong , Wei Xianhu , Zeng Xiaocong
Published: December 2020

Pseudomonas aeruginosa is an important opportunistic pathogen and remains a major threat to the microbial safety of drinking water. There is a lack of comprehensive data on P. aeruginosa contamination in drinking water in China. Therefore, this study aimed to determine the prevalence, genetic diversity, virulence genes, and antimicrobial resistance of P. aeruginosa isolated from mineral water and spring water in China. From January 2013 to January 2014, 314 drinking water samples were collected from 23 cities in China. Of the collected samples, 77 (24.5%) were contaminated with P. aeruginosa, and these comprised 34 raw water (30.4%), 39 activated carbon-filtered water (30.6%), and four final water product (3.9%). A total of 132 P. aeruginosa isolates were obtained, and all of them showed the presence of virulence genes, with the detection rates of ExoU, ExoS, phzM, toxA, and lasB genes being 7.6, 86.3, 95.5, 89.4, and 100%, respectively. All isolates were sensitive to the 14 antibiotics (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, gentamicin, tobramycin, amikacin, polymyxin B, imipenem, meropenem, aztreonam, ceftazidime, cefepime, and piperacillin/tazobactam) tested. The 132 isolates were categorized into 42 sequence types according to multilocus sequence typing, and ST235 accounted for 8.3% (11) of the total isolates. Thus, this study provides comprehensive data on the prevalence and characteristics of P. aeruginosa in drinking water in China and can aid in developing preventive measures against contamination during the drinking water treatment process.
Aberrant Amplitude of Low-Frequency Fluctuations in Different Frequency Bands in Patients With Parkinson’s Disease
Authors: Wang Zhaoxiu , Liu Yanjun , Ruan Xiuhang , Li Yuting , Li E. , Zhang Guoqin , Li Mengyan , Wei Xinhua
Published: December 2020

Previous studies reported abnormal spontaneous neural activity in Parkinson’s disease (PD) patients using resting-state functional magnetic resonance imaging (R-fMRI). However, the frequency-dependent neural activity in PD is largely unknown. Here, 35 PD patients and 35 age- and education-matched healthy controls (HCs) underwent R-fMRI scanning to investigate abnormal spontaneous neural activity of PD using the amplitude of low-frequency fluctuation (ALFF) approach within the conventional band (typical band: 0.01–0.08 Hz) and specific frequency bands (slow-5: 0.010–0.027 Hz and slow-4: 0.027–0.073 Hz). Compared with HCs, PD patients exhibited increased ALFF in the parieto-temporo-occipital regions, such as the bilateral inferior temporal gyrus/fusiform gyrus (ITG/FG) and left angular gyrus/posterior middle temporal gyrus (AG/pMTG), and displayed decreased ALFF in the left cerebellum, right precuneus, and left postcentral gyrus/supramarginal gyrus (PostC/SMG) in the typical band. PD patients showed greater increased ALFF in the left caudate/putamen, left anterior cingulate cortex/medial superior frontal gyrus (ACC/mSFG), left middle cingulate cortex (MCC), right ITG, and left hippocampus, along with greater decreased ALFF in the left pallidum in the slow-5 band, whereas greater increased ALFF in the left ITG/FG/hippocampus accompanied by greater decreased ALFF in the precentral gyrus/PostC was found in the slow-4 band (uncorrected). Additionally, the left caudate/putamen was positively correlated with levodopa equivalent daily dose (LEDD), Hoehn and Yahr (HY) stage, and disease duration. Our results suggest that PD is related to widespread abnormal brain activities and that the abnormalities of ALFF in PD are associated with specific frequency bands. Future studies should take frequency band effects into account when examining spontaneous neural activity in PD.
Astrocytic Sonic Hedgehog Alleviates Intracerebral Hemorrhagic Brain Injury via Modulation of Blood-Brain Barrier Integrity
Authors: Xing Gebeili , Zhao Tianman , Zhang Xiyue , Li He , Li Xiuping , Cui Pan , Li Minshu , Li Daojing , Zhang Nan , Jiang Wei
Published: December 2020

Background: Intracerebral hemorrhage (ICH) is a fatal subtype of stroke that lacks effective therapy. Blood-brain barrier (BBB) damage is a hallmark of ICH-induced brain injury that leads to edema formation, leukocytes infiltration, influx of blood components into the perihematomal (PHE) region, and eventually brain injury. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted molecules that contribute to the association between these cells. Sonic hedgehog (SHH) derived from astrocytes promotes the maturity and integrity of the BBB by upregulating tight junctions (TJs) in brain capillary endothelial cells (ECs). However, the effect of SHH on BBB in ICH has not been investigated.

Methods: Cyclopamine (CYC) is a potent, selective inhibitor that specifically blocks the SHH signaling pathway. Here, we used pharmacological inhibitions (CYC and its derivatives) to determine a critical role of the SHH signaling pathway in promoting BBB integrity after ICH by mechanisms of regulating the TJ proteins in vivo and in vitro.

Results: The expression of astrocytic SHH was upregulated in mouse brains after ICH. Compared with the vehicle-treated group, inhibition of the SHH signaling pathway with CYC and its derivatives treatments aggravated neurological function deficits, brain edema, hematoma volume, and BBB impairment by downregulating TJs in ECs through the SHH-Gli-1 axis in vivo and in vitro.

Conclusions: SHH signaling pathway at the level of the BBB provides a barrier-promoting effect, suggesting that the SHH signaling pathway may function as a potential therapeutic target for restoring BBB function in ICH.
Challenges in Modeling Human Neural Circuit Formation via Brain Organoid Technology
Authors: Matsui Takeshi K. , Tsuru Yuichiro , Kuwako Ken-ichiro
Published: December 2020

Human brain organoids are three-dimensional self-organizing tissues induced from pluripotent cells that recapitulate some aspects of early development and some of the early structure of the human brain in vitro. Brain organoids consist of neural lineage cells, such as neural stem/precursor cells, neurons, astrocytes and oligodendrocytes. Additionally, brain organoids contain fluid-filled ventricle-like structures surrounded by a ventricular/subventricular (VZ/SVZ) zone-like layer of neural stem cells (NSCs). These NSCs give rise to neurons, which form multiple outer layers. Since these structures resemble some aspects of structural arrangements in the developing human brain, organoid technology has attracted great interest in the research fields of human brain development and disease modeling. Developmental brain disorders have been intensely studied through the use of human brain organoids. Relatively early steps in human brain development, such as differentiation and migration, have also been studied. However, research on neural circuit formation with brain organoids has just recently began. In this review, we summarize the current challenges in studying neural circuit formation with organoids and discuss future perspectives.
Association Between Amyloid Accumulation and Sleep in Patients With Idiopathic REM Sleep Behavior Disorder
Authors: Lee Hanul , Cho Hyunjin , Choe Yeong Sim , Seo Sang Won , Joo Eun Yeon
Published: December 2020

Background and Objectives: Amyloid-beta protein may lead to sleep disturbance and eventually develop cognitive impairment. Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a predictor of neurodegeneration, yet there have been limited studies evaluating the relationship between cognitive decline and amyloid accumulation in iRBD patients. The aim of this study is to investigate the clinical and sleep characteristics of iRBD patients and its association with amyloid deposition.

Methods: We enroll 23 iRBD patients (mean age, 65.8 years; male, 73.9%), and their mean history of clinically suspected RBD was 6.5 years. All underwent 18F-flutemetamol amyloid PET completed polysomnography (PSG) and questionnaires. Patients were classified into two groups according to amyloid deposition as amyloid positive and negative. Clinical and sleep parameters were compared between groups and were correlated with amyloid deposition, calculated as a standardized uptake value ratio (SUVR).

Results: Four patients (17.4%) were revealed to be amyloid positive, and they showed increased percentage of wake after sleep onset (WASO), stage N1, and stage N2 sleep and worse on the Stroop Word Color Test compared to amyloid negative patients. Global SUVR was correlated with total sleep time, sleep efficiency, WASO, and N1 sleep, and these sleep parameters were associated with a part of default mode network of brains such as orbitofrontal, dorsolateral pre-frontal, and left temporal areas.

Conclusion: iRBD patients with amyloid deposition have worse sleep quality than patients without amyloid. Relationship between fragmented sleep and amyloid deposition in the default mode network may be crucial to elucidate the disease progress of iRBD.
Cerebellar Direct Current Stimulation (ctDCS) in the Treatment of Huntington's Disease: A Pilot Study and a Short Review of the Literature
Authors: Bocci Tommaso , Baloscio Davide , Ferrucci Roberta , Sartucci Ferdinando , Priori Alberto
Published: December 2020

Introduction: In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques as a putative treatment in Huntington's Disease (HD). Our aim was to evaluate the effects of cerebellar transcranial Direct Current Simulation (ctDCS) on the motor outcome in patients affected by HD, encompassing at the same time the current knowledge about the effects of NIBS both on motor and non-motor dysfunctions in HD.

Materials and Methods: Four patients (two females) were enrolled and underwent ctDCS (both anodal or sham, elapsed by at least 3 months: 2.0 mA, 20 min per day, 5 days a week). Clinical scores were assessed by using the Unified Huntington's Disease Rating Scale – part I (UHDRS-I), immediately before ctDCS (T0), at the end of the 5-days treatment (T1) and 4 weeks later (T2).

Results: Anodal ctDCS improved motor scores compared to baseline (p = 0.0046), whereas sham stimulation left them unchanged (p = 0.33, Friedman test). In particular, following anodal ctDCS, UHDRS-I score significantly improved, especially regarding the subitem “dystonia,” both at T1 and T2 compared to sham condition (p < 0.05; Wilcoxon matched-pairs signed test).

Conclusions: ctDCS improved motor scores in HD, with effects lasting for about 4 weeks after tDCS completion. This is the first study discussing the putative role of cerebellar non-invasive simulation for the treatment of HD.
Individual Differences in Brain Responses: New Opportunities for Tailoring Health Communication Campaigns
Authors: Huskey Richard , Turner Benjamin O. , Weber René
Published: December 2020

Prevention neuroscience investigates the brain basis of attitude and behavior change. Over the years, an increasingly structurally and functionally resolved “persuasion network” has emerged. However, current studies have only identified a small handful of neural structures that are commonly recruited during persuasive message processing, and the extent to which these (and other) structures are sensitive to numerous individual difference factors remains largely unknown. In this project we apply a multi-dimensional similarity-based individual differences analysis to explore which individual factors—including characteristics of messages and target audiences—drive patterns of brain activity to be more or less similar across individuals encountering the same anti-drug public service announcements (PSAs). We demonstrate that several ensembles of brain regions show response patterns that are driven by a variety of unique factors. These results are discussed in terms of their implications for neural models of persuasion, prevention neuroscience and message tailoring, and methodological implications for future research.
Altered Gray Matter Volume and Functional Connectivity in Human Immunodeficiency Virus-Infected Adults
Authors: Liu Dan , Zhao Cui , Wang Wei , Wang Yuanyuan , Li Ruili , Sun Jun , Liu Jiaojiao , Liu Mingming , Zhang Xu , Liang Ying , Li Hongjun
Published: December 2020

People living with human immunodeficiency virus (HIV) (PLWH) are at high risk of neurocognitive impairment. The pathogenesis of neurocognitive impairment remains unclear, and there is still no diagnostic biomarker. By coupling three-dimensional T1-weighted imaging and resting-state functional imaging, we explored structural and functional alterations in PLWH and examined whether such imaging alterations had the potential to denote neurocognitive function. A total of 98 PLWH and 47 seronegative controls aged 20–53 years were recruited. Structural alterations were first explored between HIV-negative controls and PLWH. Subsequently, brain regions showing gray matter alterations were used as seeds for separate whole-brain functional connectivity (FC) analysis. Finally, the relationships between imaging alterations and cognitive function were explored. PLWH suffered from thalamus, occipital lobe, and hippocampus/parahippocampus atrophy. Visual cortices in PLWH showed decreased anticorrelation with the posterior cingulate cortex and left angular gyrus of the default mode network. FC within the visual cortices (between the left calcarine and right calcarine) and in the thalamic prefrontal circuit and between the thalamus and somatosensory association cortex were also altered. In addition, FC between the left thalamus and right dorsolateral prefrontal cortex in the cognitively impaired group was significantly different from that in the cognitively normal group in PLWH. Partial correlation analysis uncorrected for multiple comparisons suggested that some imaging alterations can be associated with neurocognition. Our study supports the presence of brain atrophy and functional reconfiguration in PLWH. Imaging alterations can be associated with neurocognitive function. We hold that neuroimaging is a promising approach in evaluating PLWH and might have the potential to clarify the pathogenesis of HIV-associated neurocognitive disorder.
Immune Checkpoint Inhibitors in Advanced Acral Melanoma: A Systematic Review
Authors: Zheng Qingyue , Li Jiarui , Zhang Hanlin , Wang Yuanzhuo , Zhang Shu
Published: December 2020

Introduction

Acral melanoma (AM) has different biological characteristics from cutaneous melanoma. Although systemic therapeutic strategies for advanced AM resemble those for advanced cutaneous melanoma, the evidence of the clinical use of immune checkpoint inhibitors (ICIs) for AM is still inadequate. We aimed to systematically analyze the therapeutic effects and safety profile of ICI treatments in advanced AM.

Methods

This systematic review was conducted in line with a previously registered protocol. Three electronic databases, conference abstracts, clinical trial registers, and reference lists of included articles were searched for eligible studies. The primary outcomes were therapeutic effects, and the secondary outcomes were the safety profiles.

Results

This systematic review included six studies investigating anti-CTLA-4 immunotherapy, 12 studies investigating anti-PD-1 immunotherapy, one study investigating the combination therapy of anti-CTLA-4 and anti-PD-1, and one study investigating anti-PD-1 immunotherapy in combination with radiotherapy. In most studies investigating ipilimumab, the anti-CTLA-4 antibody, the objective response rate ranged from 11.4 to 25%, the median progression-free survival ranged from 2.1 to 6.7 months, and the median overall survival was more than 7.16 months. For studies discussing anti-PD-1 immunotherapy with nivolumab, pembrolizumab, or JS001, the objective response rate ranged from 14 to 42.9%, the median progression-free survival ranged from 3.2 to 9.2 months, and the median overall survival was more than 14 months. The combination therapy of anti-CTLA-4 and anti-PD-1 immunotherapy showed better efficacy with an objective response rate of 42.9% than single-agent therapy. The retrospective study investigating the combination therapy of anti-PD-1 immunotherapy and radiation showed no overall response. Few outcomes regarding safety were reported in the included studies.

Conclusions

ICIs, especially anti-CTLA-4 monoclonal antibodies combined with anti-PD-1 antibodies, are effective systematic treatments in advanced AM. However, there remains a lack of high-level evidence to verify their efficacy and safety and support their clinical application.
Multiple Microinvasion Foci in Ductal Carcinoma In Situ Is Associated With an Increased Risk of Recurrence and Worse Survival Outcome
Authors: Si Jing , Guo Rong , Pan Huan , Lu Xiang , Guo Zhiqin , Han Chao , Xue Li , Xing Dan , Wu Wanxin , Chen Caiping
Published: December 2020

Background

Ductal carcinoma in situ with microinvasion (DCISM) was defined as one or more foci of invasion beyond the basement membrane within 1 mm. The size of primary lesion is associated with axillary status and prognosis in patients with invasive breast cancer; thus, it is of interest to determine whether multiple foci of microinvasion are associated with a higher risk of positive axillary status or worse long-term outcomes in patients with DCISM.

Methods

This study identified 359 patients with DCISM who had undergone axillary evaluation at our institute from January 2006 to December 2015. Patients were categorized as one focus or multiple foci (≥2 foci) according to the pathological results. Clinicopathological features, axillary status, and disease-free survival rate were obtained and analyzed.

Results

Of 359 patients, 233 (64.90%) had one focus of microinvasion and 126 (35.10%) had multiple foci. Overall, 242 (67.41%) and 117 (32.59%) patients underwent sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Isolated tumor cells were found in four (1.11%) patients and axillary metastasis rate was 2.51%. Neither axillary evaluation methods (P = 0.244) nor axillary metastasis rate (P = 0.559) was significantly different between patients with one focus and multiple foci. In univariate analysis, patients with multiple foci tended to have larger tumor size (P < 0.001), higher nuclear grade (P = 0.001), and higher rate of lymphatic vascular invasion (P = 0.034). Also, the proportion of positive HER2 (P = 0.027) and Ki67 level (P = 0.004) increased in patients with multiple foci, while in multivariate analysis, only tumor size showed significant difference (P = 0.009). Patients with multiple foci were more likely to receive chemotherapy (56.35 vs 40.77%; P = 0.028). At median 5.11 years follow-up, overall survival rate was 99.36%. Patients with multiple microinvasive foci had worse disease-free survival rate compared with one-focus patients (98.29 vs 93.01%, P = 0.032).

Conclusion

Even though the numbers of microinvasion were different and patients with multiple foci of microinvasion tended to have larger tumor size, there was no higher risk of axillary involvement compared with patients with one focus of microinvasion, while patients with multiple microinvasive foci had worse DFS rate. Thus, DCISM patients with multiple foci of microinvasion may be the criterion for more aggressive local–regional treatment. Optimization of adjuvant therapy in DCISM patients is required.