bluuebunny/crossref_metadata_2025 huggingface dataset:
POLA MAKAN TERHADAP KEJADIAN OBESITAS PADA ANAK
Authors: Sriwahyuni  , - Junaidin , - Noyumala , .A Alfiah , Tangkelayuk Vitarianti
Published: September 2021

Obesitas merupakan masalah utama bagi tubuh karena efeknya akan membuat tubuh menjadi lambat bergerak. Penyebab obesitas bersifat multifaktorial. Peningkatan konsumsi makanan cepat saji (fast food), terutama di kota besar, bergeser dari pola makan tradisional ke pola makan barat (terutama dalam bentuk fast food). Prevalensi gizi lebih pada anak usia sekolah dengan jenis kelamin laki-laki adalah 9,5% sedangkan perempuan adalah 6,4%. Prevalensi status gizi lebih nasional pada anak sekolah (6-12 tahun) yaitu 9,2%. Padatahun 2013 prevalensi gizi lebih juga mengalami peningkatan menjadi 18,8 %. Tujuan penelitian ini untuk mengetahui pola makan fast food terhadap kejadian obesitas pada anak di SD Frater Bakti Luhur Makassar. Metode penelitian ini menggunakan deskritif analitik dengan pendekatan cross sectional. Populasi berjumlah 30 orang. Pengambilan sampel dengan teknik total sampling. Pengumpulan data menggunakan kuesioner danlembar observasi (pengukuran antropometri) kemudian dianalisis dengan uji chi-square (p<0,05). Didapatkan hasil analisis bivariate menunjukkan adanya hubungan pola makan fast food terhadap kejadian obesitas pada anak dengan nilai p=0,031 < alpha=0,05. Kesimpulan dalam penelitian ini adalah pola makan fast food dapat meningkatkan beratbadan jika dikomsumsi lebih dari 2 kali seminggu. Saran agar memperhatikan pola makan fast food yang dikomsumsi oleh anak yang dapat menyebabkan terjadinya obesitas.
PEMBERIAN EMOLIEN MINYAK ZAITUN DALAM MENURUNKAN SKALA PRURITUS PADA PASIEN HEMODIALISIS
Authors: Muliani Rizki , Lestari Syifa Asih , HHK Nur Intan
Published: September 2021

Toksik uremia dan hemodialisis sebagai penatalaksanaan Penyakit Ginjal Kronis (PGK)dapat menimbulkan pruritus. Pruritus mengakibatkan luka pada kulit, infeksi danmengganggu kenyamanan pasien sehingga dibutuhkan terapi topikal tambahan olehpasien. Minyak zaitun merupakan salah satu jenis emolien topikal yang alami, tidakada efek samping dan mudah didapat tanpa resep dokter. Tujuan penelitian ini untukmengetahui pengaruh pemberian emolien minyak zaitun terhadap skala pruritus padapasien yang menjalani hemodialisis. Jenis penelitian menggunakan preeksperimen denganpendekatan one group pre-post-test design. Sampel dalam penelitian ini sebanyak 23pasien yang diambil dengan teknik purposive sampling. Instrumen yang digunakan yaituNumerical Rating Scale (NRS) pruritus dan prosedur pemberian minyak zaitun. Analisisdata menggunakan uji t-test sampel berpasangan. Hasil penelitian menunjukkan 30,4% (7orang) mengalami pruritus dengan skala 7 sebelum diberikan emolien minyak zaitun dandidapatkan 34,8% (8 orang) mengalami pruritus dengan skala 3 setelah diberikan emolienminyak zaitun. Hasil analisis t-test didapat p-value = 0,000 sehingga disimpulkan adapengaruh pemberian emolien minyak zaitun terhadap skala pruritus pada pasien yangmenjalani hemodialisis. Penurunan skor pruritus setelah diberikan minyak zaitun karenaminyak zaitun mengisi ruang keratin kulit sehingga melembabkan, mencegah kulit gatal,mengobati luka dan infeksi. Oleh karena itu, perlu dilakukan terapi tambahan berupapenggunaan minyak zaitun untuk mengatasi pruritus pada pasien PGK.
PERILAKU SELF CARE MANAGEMENT PENDERITA HIPERTENSI: STUDI KUALITATIF
Authors: Salami
Published: September 2021

Hipertensi membutuhkan manajemen penyakit jangka panjang oleh penderitanya.Manajemen perawatan diri (self care management) ini berhubungan erat denganperilaku penderita. Kegagalan melakukan self care akan berdampak terhadap terjadinyakomplikasi yang mematikan. Penelitian ini bertujuan untuk mengeksplorasi perilakuself care manajement penderita hipertensi di Puskesmas Kota Bandung. Manfaatpenelitian ini sebagai data dasar untuk petugas kesehatan dan pengambil kebijakanterkait perspektif pasien hipertensi dalam pengelolaan penyakitnya. Metode penelitianyang digunakan adalah deskriptif kualitatif. Partisipan pada penelitian berjumlahtujuh orang sesuai dengan kriteria inklusi dan eksklusi. Pemilihan partisipan denganmenggunakan Teknik Purposive Sampling. Pengumpulan data berdasarkan wawancaraterstruktur menggunakan pedoman wawancara. Hasil wawancara dibuat verbatim. Datadianalisis dengan Model Miles Huberman. Untuk memenuhi prinsip keandalan datapenelitian (Trustworthiness) dilakukan credibility, dependeability, confirmability, dantransferability. Hasil penelitian didapatkan tiga tema yaitu: pengobatan yang dilakukan,upaya self care management, dan persepsi terhadap penyakit. Petugas kesehatandisarankan untuk memberikan intervensi yang tepat pada penderita hipertensi terkaitpersepsi penyakit, terutama tentang efek samping pengobatan. Dengan ersepsi yangtepat diharapkan penderita menjadi lebih patuh minum obat
Flexible Biosensors Based on Colorimetry, Fluorescence, and Electrochemistry for Point-of-Care Testing
Authors: Yan Tingyi , Zhang Guangyao , Chai Huining , Qu Lijun , Zhang Xueji
Published: September 2021

With the outbreak and pandemic of COVID-19, point-of-care testing (POCT) systems have been attracted much attention due to their significant advantages of small batches of samples, user-friendliness, easy-to-use and simple detection. Among them, flexible biosensors show practical significance as their outstanding properties in terms of flexibility, portability, and high efficiency, which provide great convenience for users. To construct highly functional flexible biosensors, abundant kinds of polymers substrates have been modified with sufficient properties to address certain needs. Paper-based biosensors gain considerable attention as well, owing to their foldability, lightweight and adaptability. The other important flexible biosensor employs textiles as substrate materials, which has a promising prospect in the area of intelligent wearable devices. In this feature article, we performed a comprehensive review about the applications of flexible biosensors based on the classification of substrate materials (polymers, paper and textiles), and illustrated the strategies to design effective and artificial sensing platforms, including colorimetry, fluorescence, and electrochemistry. It is demonstrated that flexible biosensors play a prominent role in medical diagnosis, prognosis, and healthcare.
Tumor Immune Microenvironment Landscape in Glioma Identifies a Prognostic and Immunotherapeutic Signature
Authors: Zhang Chunyu , Guo Lirui , Su Zhongzhou , Luo Na , Tan Yinqiu , Xu Pengfei , Ye Liguo , Tong Shiao , Liu Haitao , Li Xiaobin , Chen Qianxue , Tian Daofeng
Published: September 2021

The tumor immune microenvironment (TIME) has been recognized to be associated with sensitivity to immunotherapy and patient prognosis. Recent research demonstrates that assessing the TIME patterns on large-scale samples will expand insights into TIME and will provide guidance to formulate immunotherapy strategies for tumors. However, until now, thorough research has not yet been reported on the immune infiltration landscape of glioma. Herein, the CIBERSORT algorithm was used to unveil the TIME landscape of 1,975 glioma observations. Three TIME subtypes were established, and the TIMEscore was calculated by least absolute shrinkage and selection operator (LASSO)–Cox analysis. The high TIMEscore was distinguished by an elevated tumor mutation burden (TMB) and activation of immune-related biological process, such as IL6-JAK-STAT3 signaling and interferon gamma (IFN-γ) response, which may demonstrate that the patients with high TIMEscore were more sensitive to immunotherapy. Multivariate analysis revealed that the TIMEscore could strongly and independently predict the prognosis of gliomas [Chinese Glioma Genome Atlas (CGGA) cohort: hazard ratio (HR): 2.134, p < 0.001; Gravendeel cohort: HR: 1.872, p < 0.001; Kamoun cohort: HR: 1.705, p < 0.001; The Cancer Genome Atlas (TCGA) cohort: HR: 2.033, p < 0.001; the combined cohort: HR: 1.626, p < 0.001], and survival advantage was evident among those who received chemotherapy. Finally, we validated the performance of the signature in human tissues from Wuhan University (WHU) dataset (HR: 15.090, p = 0.008). Our research suggested that the TIMEscore could be applied as an effective predictor for adjuvant therapy and prognosis assessment.
Increased Nuclear Transporter Importin 7 Contributes to the Tumor Growth and Correlates With CD8 T Cell Infiltration in Cervical Cancer
Authors: Chen Jing , Hu Yan , Teng Yincheng , Yang BiKang
Published: September 2021

Background: Importin 7 (IPO7), a karyopherin-β protein, is involved in various tumorigenesis and progression abilities by mediating the nuclear import of oncoproteins. However, the exact biological functions of IPO7 remain to be further elucidated.

Materials and Methods: TCGA and GEO datasets were used to identify dysregulated expression of IPO7 in various cancers. Gain-of-function and loss-of-function analyses were used to identify the oncogenic functions of IPO7 in vitro and in vivo. Moreover, LC-MS/MS and parallel reaction monitoring analysis were used to comparatively profiled IPO7-related proteomics and potential molecular machinery.

Results: Our works demonstrated that the expression of IPO7 was upregulated and was correlated with a poor prognosis in cervical cancer. In vitro and in vivo experiments demonstrated that knockdown of IPO7 inhibited the proliferation of HeLa and C-4 I cells. LC-MS/MS analysis showed that IPO7-related cargo proteins mainly were enriched in gene transcription regulation. Then independent PRM analysis for the first time demonstrated that 32 novel IPO7 cargo proteins, such as GTF2I, RORC1, PSPC1, and RBM25. Moreover, IPO7 contributed to activating the PI3K/AKT-mTOR pathway by mediating the nuclear import of GTF2I in cervical cancer cells. Intriguingly, we found that the IPO7 expression was negatively correlated with CD8 T cell infiltration via regulating the expression of CD276 in cervical cancer.

Conclusion: This study enhances our understanding of IPO7 nuclear-cytoplasmic translocation and might reveal novel potential therapeutic targets. The results of a negative correlation between the IPO7 and CD8 T cell infiltration indicate that the IPO7 might play an important impact on the immune microenvironment of cervical cancer.
Conserved Mechanism of Bicarbonate-Induced Sensitization of CatSper Channels in Human and Mouse Sperm
Authors: Ferreira Juan J. , Lybaert Pascale , Puga-Molina Lis C. , Santi Celia M.
Published: September 2021

To fertilize an egg, mammalian sperm must undergo capacitation in the female genital tract. A key contributor to capacitation is the calcium (Ca2+) channel CatSper, which is activated by membrane depolarization and intracellular alkalinization. In mouse epididymal sperm, membrane depolarization by exposure to high KCl triggers Ca2+entry through CatSper only in alkaline conditions (pH 8.6) or afterin vitroincubation with bicarbonate (HCO3–) and bovine serum albumin (capacitating conditions). However, in ejaculated human sperm, membrane depolarization triggers Ca2+entry through CatSper in non-capacitating conditions and at lower pH (< pH 7.4) than is required in mouse sperm. Here, we aimed to determine the mechanism(s) by which CatSper is activated in mouse and human sperm. We exposed ejaculated mouse and human sperm to high KCl to depolarize the membrane and found that intracellular Ca2+concentration increased at pH 7.4 in sperm from both species. Conversely, intracellular Ca2+concentration did not increase under these conditions in mouse epididymal or human epididymal sperm. Furthermore, pre-incubation with HCO3–triggered an intracellular Ca2+concentration increase in response to KCl in human epididymal sperm. Treatment with protein kinase A (PKA) inhibitors during exposure to HCO3–inhibited Ca2+concentration increases in mouse epididymal sperm and in both mouse and human ejaculated sperm. Finally, we show that soluble adenylyl cyclase and increased intracellular pH are required for the intracellular Ca2+concentration increase in both human and mouse sperm. In summary, our results suggest that a conserved mechanism of activation of CatSper channels is present in both human and mouse sperm. In this mechanism, HCO3–in semen activates the soluble adenylyl cyclase/protein kinase A pathway, which leads to increased intracellular pH and sensitizes CatSper channels to respond to membrane depolarization to allow Ca2+influx. This indirect mechanism of CatSper sensitization might be an early event capacitation that occurs as soon as the sperm contact the semen.
Human Amniotic Epithelial Stem Cell-Derived Retinal Pigment Epithelium Cells Repair Retinal Degeneration
Authors: Li Jinying , Qiu Chen , Wei Yang , Yuan Weixin , Liu Jia , Cui Wenyu , Zhou Jiayi , Qiu Cong , Guo Lihe , Huang Liquan , Ge Zhen , Yu Luyang
Published: September 2021

Age-related macular degeneration (AMD), featured with dysfunction and loss of retinal pigment epithelium (RPE), is lacking efficient therapeutic approaches. According to our previous studies, human amniotic epithelial stem cells (hAESCs) may serve as a potential seed cell source of RPE cells for therapy because they have no ethical concerns, no tumorigenicity, and little immunogenicity. Herein, trichostatin A and nicotinamide can direct hAESCs differentiation into RPE like cells. The differentiated cells display the morphology, marker expression and cellular function of the native RPE cells, and noticeably express little MHC class II antigens and high level of HLA-G. Moreover, visual function and retinal structure of Royal College of Surgeon (RCS) rats, a classical animal model of retinal degeneration, were rescued after subretinal transplantation with the hAESCs-derived RPE like cells. Our study possibly makes some contribution to the resource of functional RPE cells for cell therapy. Subretinal transplantation of hAESCs-RPE could be an optional therapeutic strategy for retinal degeneration diseases.
Interplay Between BALL and CREB Binding Protein Maintains H3K27 Acetylation on Active Genes in Drosophila
Authors: Shaukat Ammad , Khan Muhammad Haider Farooq , Ahmad Hina , Umer Zain , Tariq Muhammad
Published: September 2021

CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report a previously unknown interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.
Characterization of Phytochemicals in Ulva intestinalis L. and Their Action Against SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain
Authors: Kulkarni Seema A. , Krishnan Sabari B.B. , Chandrasekhar Bavya , Banerjee Kaushani , Sohn Honglae , Madhavan Thirumurthy
Published: September 2021

Coronavirusdisease-2019 (COVID-19) has caused a severe impact on almost all aspects of human life and economic development. Numerous studies are being conducted to find novel therapeutic strategies to overcome COVID-19 pandemic in a much effective way.Ulva intestinalisL. (Ui), a marine microalga, known for its antiviral property, was considered for this study to determine the antiviral efficacy against severe acute respiratory syndrome-associatedCoronavirus-2 (SARS-CoV-2). The algal sample was dried and subjected to ethanolic extraction, followed by purification and analysis using gas chromatography-coupled mass spectrometry (GC-MS). Forty-three known compounds were identified and docked against the S1receptor binding domain (RBD) of the spike (S) glycoprotein. The compounds that exhibited high binding affinity to the RBD of S1protein were further analyzed for their chemical behaviour using conceptual density-functional theory (C-DFT). Finally, pharmacokinetic properties and drug-likeliness studies were carried out to test if the compounds qualified as potential leads. The results indicated that mainly phenols, polyenes, phytosteroids, and aliphatic compounds from the extract, such as 2,4-di-tert-butylphenol (2,4-DtBP), doconexent, 4,8,13-duvatriene-1,3-diol (DTD), retinoyl-β-glucuronide 6′,3′-lactone (RBGUL), and retinal, showed better binding affinity to the target. Pharmacokinetic validation narrowed the list to 2,4-DtBP, retinal and RBGUL as the possible antiviral candidates that could inhibit the viral spike protein effectively.
Various Nodal Lines in P63/mmc-type TiTe Topological Metal and its (001) Surface State
Authors: Lin Peng , Fang Fang , Zhang Li , Li Yang , Wang Kai
Published: September 2021

Searching for existing topological materials is a hot topic in quantum and computational chemistry. This study uncovers P63/mmc type TiTe compound—an existing material—is a newly discovered topological metal that hosts the various type of nodal line states. Different nodal line states normally exhibit different properties; they may have their individual applications. We report that TiTe hosts I, II, and hybrid type nodal line (NL) states at its ground state without chemical doping and strain engineering effects. Specifically, two type I NLs, two hybrid-type NLs, and one Γ—centered type II NL can be found in the kz = 0 plane. Moreover, the spin-orbit coupling induced gaps for these NLs are very small and within acceptable limits. The surface states of the TiTe (001) plane were determined to provide strong evidence for the appearance of the three types of NLs in TiTe. We also provide a reference for the data of the dynamic and mechanical properties of TiTe. We expect that the proposed NL states in TiTe can be obtained in future experiments.
Limitations of Remote Sensing in Assessing Vegetation Damage Due to the 2019–2021 Desert Locust Upsurge
Authors: Adams Emily C. , Parache Helen B. , Cherrington Emil , Ellenburg Walter L. , Mishra Vikalp , Lucey Ronan , Nakalembe Catherine
Published: September 2021

The 2019–2020 Desert Locust (DL) upsurge in East Africa threatened food security for millions in the region. This highlighted the need to track and quantify the damaging impacts of the swarming insects on cropland and rangelands. Satellite Earth observations (EO) data have the potential to contribute to DL damage assessments that can inform control measures, aid distribution and recovery efforts. EO can complement traditional ground based surveys (which are currently further limited due to COVID-19), by rapidly and cost effectively capturing the full spatial scale of the DL upsurge. However, EO-based techniques struggled to accurately quantify damage from this DL upsurge due to the sporadic and localized nature of infestations impacting scale, timing, and anomalous vegetation conditions. This study analyzed time series data from MODIS, the harmonized Landsat Sentinel-2 product, and C-band radar data from Sentinel-1 to distinguish DL damage from normal senescence or other confounding factors from January to June 2020. These data were compared to in situ locust swarm, band, and non locust observations collected by the Food and Agriculture Organization (FAO) and PlantVillage. The methods presented did not produce results that could confidently differentiate senescence from locust activity, and may represent a limitation of publicly available remotely sensed data to detect DL damage. However, the higher spatial resolution data sets showed promise, and there is potential to explore commercially available satellite products such as Planet Labs for damage assessment protocols.
A High-Resolution Regional Climate Model Physics Ensemble for Northern Sub-Saharan Africa
Authors: Laux Patrick , Dieng Diarra , Portele Tanja C. , Wei Jianhui , Shang Shasha , Zhang Zhenyu , Arnault Joel , Lorenz Christof , Kunstmann Harald
Published: September 2021

While climate information from General Circulation Models (GCMs) are usually too coarse for climate impact modelers or decision makers from various disciplines (e.g., hydrology, agriculture), Regional Climate Models (RCMs) provide feasible solutions for downscaling GCM output to finer spatiotemporal scales. However, it is well known that the model performance depends largely on the choice of the physical parameterization schemes, but optimal configurations may vary e.g., from region to region. Besides land-surface processes, the most crucial processes to be parameterized in RCMs include radiation (RA), cumulus convection (CU), cloud microphysics (MP), and planetary boundary layer (PBL), partly with complex interactions. Before conducting long-term climate simulations, it is therefore indispensable to identify a suitable combination of physics parameterization schemes for these processes. Using the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis product ERA-Interim as lateral boundary conditions, we derived an ensemble of 16 physics parameterization runs for a larger domain in Northern sub-Saharan Africa (NSSA), northwards of the equator, using two different CU-, MP-, PBL-, and RA schemes, respectively, using the Weather Research and Forecasting (WRF) model for the period 2006–2010 in a horizontal resolution of approximately 9 km. Based on different evaluation strategies including traditional (Taylor diagram, probability densities) and more innovative validation metrics (ensemble structure-amplitude-location (eSAL) analysis, Copula functions) and by means of different observation data for precipitation (P) and temperature (T), the impact of different physics combinations on the representation skill of P and T has been analyzed and discussed in the context of subsequent impact modeling. With the specific experimental setup, we found that the selection of the CU scheme has resulted in the highest impact with respect to the representation of P and T, followed by the RA parameterization scheme. Both, PBL and MP schemes showed much less impact. We conclude that a multi-facet evaluation can finally lead to better choices about good physics scheme combinations.
Revisiting China’s Sponge City Planning Approach: Lessons From a Case Study on Qinhuai District, Nanjing
Authors: Chen Shiyang , van de Ven Frans H. M. , Zevenbergen Chris , Verbeeck Simon , Ye Qinghua , Zhang Weijun , Wei Liang
Published: September 2021

Integrating sustainable urban water management into the urban planning process is essential for developing water-resilient cities. To this end, the central government of the People’s Republic of China initiated the “Sponge City” programme. However, challenges and gaps exist in current urban planning practice. The operationalizable planning approach to realise the multiple objectives of Sponge City is missing in the existing guidelines. Using a local example of Sponge City planning in Nanjing City as a case study, this paper outlines the current Sponge City approach from the perspectives of planning content and planning process. A qualitative comparative analysis between Nanjing’s Sponge City planning and Auckland Water Sensitive Design, as well as an evaluation of the Sponge City approach through the lens of Dutch urban water management, identified key missing elements that would enhance the current Sponge City planning approach. Examples include targets for pluvial flood protection, a strategy for planning interventions, and tools for interdisciplinary cooperation in the planning process. This enhanced approach was successfully applied in the Sponge City planning for Qinhuai District, Nanjing City. Nevertheless, challenges on data availability and the decision-makers’ mindsets called for more efforts on the interface of research and policy development for upscaling the Sponge City approach.
Global ex situ Conservation of Palms: Living Treasures for Research and Education
Authors: Griffith M. Patrick , Meyer Abby , Grinage Ayress
Published: September 2021

Under the old taxon Principes, palms were once the Princes of the Kingdom Plantae. First on Engler’s list, they occupy a cherished place to botanists, and remain treasured centerpieces of many gardens. In turn, botanic gardens have put forward a decades-long effort to conserve these widely admired plants, keeping a number of palm species from extinction. Living palm collections also have critical value for comparative ecological studies. In this paper we highlight successful ex situ conservation programs for palms, review how the promising new field of collections genetics can guide ex situ conservation of palms, conduct a family-wide gap analysis for living collections in the Arecaceae, and provide an in-depth case study of ex situ conservation of the genus Sabal. These analyses highlight ways in which gardens can advance palm conservation following four recommendations: collect, cultivate, communicate, and collaborate.
Case Report: Recurrent Variant c.298 TA in CCN6 Gene Found in Progressive Pseudorheumatoid Dysplasia Patients From Patni Community of Gujarat: A Report of Three Cases
Authors: Sheth Harsh , Shah Jhanvi , Nair Aadhira , Naik Premal , Sheth Jayesh
Published: September 2021

Biallelic mutations in the CCN6 gene are known to cause a rare genetic disorder—progressive pseudorheumatoid dysplasia (PPD). PPD is characterized by distinct joint deformities of interphalangeal joints, stiffness, gait disturbance, abnormal posture, and absence of inflammation, resulting in significant morbidity. The largest case series of PPD from India suggests c.233G>A and c.1010G>A to be the most common mutations in the CCN6 gene, although the distribution of these variants among endogamous communities in India has not been carried out. We here report three cases of PPD from three independent families belonging to the Patni community of Gujarat, a community known to practice endogamy. All three cases had short stature, gait disturbance, scoliosis, and interphalangeal joint deformities. Analysis by whole-exome sequencing in the first case showed the presence of a previously known, homozygous, missense variant c.298T>A (p.Cys100Ser) in exon 3 of the CCN6 gene in all cases. Due to all three families belonging to the same community, analysis by Sanger sequencing in the remaining two cases for the variant mentioned earlier showed both cases to be of homozygous mutant genotype. Unaffected family members, i.e., parents and siblings, were either heterozygous carriers or wildtype for the said variant. The present case series is the first report of a recurrent variant occurring across multiple PPD-affected individuals from unrelated families belonging to the same community from India.
Diagnosis of Ovarian Neoplasms Using Nomogram in Combination With Ultrasound Image-Based Radiomics Signature and Clinical Factors
Authors: Qi Lisha , Chen Dandan , Li Chunxiang , Li Jinghan , Wang Jingyi , Zhang Chao , Li Xiaofeng , Qiao Ge , Wu Haixiao , Zhang Xiaofang , Ma Wenjuan
Published: September 2021

Objectives: To establish and validate a nomogram integrating radiomics signatures from ultrasound and clinical factors to discriminate between benign, borderline, and malignant serous ovarian tumors.

Materials and methods: In this study, a total of 279 pathology-confirmed serous ovarian tumors collected from 265 patients between March 2013 and December 2016 were used. The training cohort was generated by randomly selecting 70% of each of the three types (benign, borderline, and malignant) of tumors, while the remaining 30% was included in the validation cohort. From the transabdominal ultrasound scanning of ovarian tumors, the radiomics features were extracted, and a score was calculated. The ability of radiomics to differentiate between the grades of ovarian tumors was tested by comparing benign vs borderline and malignant (task 1) and borderline vs malignant (task 2). These results were compared with the diagnostic performance and subjective assessment by junior and senior sonographers. Finally, a clinical-feature alone model and a combined clinical-radiomics (CCR) model were built using predictive nomograms for the two tasks. Receiver operating characteristic (ROC) analysis, calibration curve, and decision curve analysis (DCA) were performed to evaluate the model performance.

Results: The US-based radiomics models performed satisfactorily in both the tasks, showing especially higher accuracy in the second task by successfully discriminating borderline and malignant ovarian serous tumors compared to the evaluations by senior sonographers (AUC = 0.789 for seniors and 0.877 for radiomics models in task one; AUC = 0.612 for senior and 0.839 for radiomics model in task 2). We showed that the CCR model, comprising CA125 level, lesion location, ascites, and radiomics signatures, performed the best (AUC = 0.937, 95%CI 0.905–0.969 in task 1, AUC = 0.924, 95%CI 0.876–0.971 in task 2) in the training as well as in the validation cohorts (AUC = 0.914, 95%CI 0.851–0.976 in task 1, AUC = 0.890, 95%CI 0.794–0.987 in task 2). The calibration curve and DCA analysis of the CCR model more accurately predicted the classification of the tumors than the clinical features alone.

Conclusion: This study integrates novel radiomics signatures from ultrasound and clinical factors to create a nomogram to provide preoperative diagnostic information for differentiating between benign, borderline, and malignant ovarian serous tumors, thereby reducing unnecessary and risky biopsies and surgeries.
Relationship Between Inflammation and Metabolism in Patients With Newly Presenting Rheumatoid Arthritis
Authors: Jutley Gurpreet Singh , Sahota Kalvin , Sahbudin Ilfita , Filer Andrew , Arayssi Thurayya , Young Stephen P. , Raza Karim
Published: September 2021

Background

Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA.

Methods

Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation.

Results

Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP.

Conclusions

This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.
Transcriptional Changes in Pulmonary Phagocyte Subsets Dictate the Outcome Following Interaction With The Fungal Pathogen Cryptococcus neoformans
Authors: Hawkins Ashlee N. , Determann Brenden F. , Nelson Benjamin N. , Wozniak Karen L.
Published: September 2021

With over 220,000 cases and 180,000 deaths annually, Cryptococcus neoformans is the most common cause of fungal meningitis and a leading cause of death in HIV/AIDS patients in Sub-Saharan Africa. Either C. neoformans can be killed by innate airway phagocytes, or it can survive intracellularly. Pulmonary murine macrophage and dendritic cell (DC) subsets have been identified in the naïve lung, and we hypothesize that each subset has different interactions with C. neoformans. For these studies, we purified murine pulmonary macrophage and DC subsets from naïve mice – alveolar macrophages, Ly6c- and Ly6c+ monocyte-like macrophages, interstitial macrophages, CD11b+ and CD103+ DCs. With each subset, we examined cryptococcal association (binding/internalization), fungicidal activity, intracellular fungal morphology, cytokine secretion and transcriptional profiling in an ex vivo model using these pulmonary phagocyte subsets. Results showed that all subsets associate with C. neoformans, but only female Ly6c- monocyte-like macrophages significantly inhibited growth, while male CD11b+ DCs significantly enhanced fungal growth. In addition, cytokine analysis revealed that some subsets from female mice produced increased amounts of cytokines compared to their counterparts in male mice following exposure to C. neoformans. In addition, although cells were analyzed ex vivo without the influence of the lung microenviroment, we did not find evidence of phagocyte polarization following incubation with C. neoformans. Imaging flow cytometry showed differing ratios of cryptococcal morphologies, c-shaped or budding, depending on phagocyte subset. RNA sequencing analysis revealed the up- and down-regulation of many genes, from immunological pathways (including differential regulation of MHC class I in the antigen processing pathway and the cell adhesion pathway) and pathways relating to relating to metabolic activity (genes in the Cytochrome P450 family, genes related to actin binding, calcium voltage channels, serine proteases, and phospholipases). Future studies gaining a more in-depth understanding on the functionality of individual genes and pathways specific to permissive and non-permissive pulmonary phagocytes will allow identification of key targets when developing therapeutic strategies to prevent cryptococcal meningitis.
Evolution of Serum Acute-Phase Glycoproteins Assessed by 1H-NMR in HIV Elite Controllers
Authors: Malo Ana-Irene , Peraire Joaquim , Ruiz-Mateos Ezequiel , Masip Jenifer , Amigó Núria , Alcamí José , Moreno Santiago , Girona Josefa , García-Pardo Graciano , Reig Rosaura , Vidal Francesc , Castro Antoni , Masana Lluís , Rull Anna
Published: September 2021

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) who maintain undetectable viral loads (VLs) despite not being on antiretroviral therapy (ART). However, this phenotype is heterogeneous, with some of these subjects losing virological control over time. In this longitudinal retrospective study, serum acute-phase glycoprotein profile assessed by proton nuclear magnetic resonance (1H-NMR) was determined in 11 transient controllers (TCs) who spontaneously lost virological control and 11 persistent controllers (PCs) who persistently maintained virological control over time. Both PCs and TCs showed similar acute-phase glycoprotein profiles, even when TCs lost the virological control (GlycB, p = 0.824 and GlycA, p = 0.710), and the serum acute-phase glycoprotein signature in PCs did not differ from that in HIV-negative subjects (GlycB, p = 0.151 and GlycA, p = 0.243). Differences in serum glycoproteins A and B were significant only in ECs compared to HIV-typical progressors (TPs) with < 100 CD4+ T-cells (p < 0.001). 1H-NMR acute-phase glycoprotein profile does not distinguish TCs form PCs before the loss of viral control. ECs maintain a low-grade inflammatory state compared to TPs. PCs revealed a closer serum signature to HIV-negative subjects, reaffirming this phenotype as a closer model of functional control of HIV.
Human Wharton’s Jelly-Derived Mesenchymal Stromal Cells Primed by Tumor Necrosis Factor-α and Interferon-γ Modulate the Innate and Adaptive Immune Cells of Type 1 Diabetic Patients
Authors: Mrahleh Mairvat Al- , Matar Suzan , Jafar Hanan , Wehaibi Suha , Aslam Nazneen , Awidi Abdalla
Published: September 2021

The unique immunomodulation and immunosuppressive potential of Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) make them a promising therapeutic approach for autoimmune diseases including type 1 diabetes (T1D). The immunomodulatory effect of MSCs is exerted either by cell-cell contact or by secretome secretion. Cell-cell contact is a critical mechanism by which MSCs regulate immune-responses and generate immune regulatory cells such as tolerogenic dendritic cells (tolDCs) and regulatory T cell (Tregs). In this study, we primed WJ-MSCs with TNF-α and IFN-γ and investigated the immunomodulatory properties of primed WJ-MSCs on mature dendritic cells (mDCs) and activated T cells differentiated from mononuclear cells (MNCs) of T1D patient’s. Our findings revealed that primed WJ-MSCs impaired the antigen-mediated immunity, upregulated immune-tolerance genes and downregulated immune-response genes. We also found an increase in the production of anti-inflammatory cytokines and suppression of the production of pro-inflammatory cytokines. Significant upregulation of FOXP3, IL10 and TGFB1 augmented an immunosuppressive effect on adaptive T cell immunity which represented a strong evidence in support of the formation of Tregs. Furthermore, upregulation of many critical genes involved in the immune-tolerance mechanism (IDO1 and PTGES2/PTGS) was detected. Interestingly, upregulation of ENTPD1/NT5E genes express a strong evidence to switch immunostimulatory response toward immunoregulatory response. We conclude that WJ-MSCs primed by TNF-α and IFN-γ may represent a promising tool to treat the autoimmune disorders and can provide a new evidence to consider MSCs- based therapeutic approach for the treatment of TID.
Advances in Adoptive Cell Therapy Using Induced Pluripotent Stem Cell-Derived T Cells
Authors: Netsrithong Ratchapong , Wattanapanitch Methichit
Published: September 2021

Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR) T cells holds impressive clinical outcomes especially in patients who are refractory to other kinds of therapy. However, many challenges hinder its clinical applications. For example, patients who undergo chemotherapy usually have an insufficient number of autologous T cells due to lymphopenia. Long-termex vivoexpansion can result in T cell exhaustion, which reduces the effector function. There is also a batch-to-batch variation during the manufacturing process, making it difficult to standardize and validate the cell products. In addition, the process is labor-intensive and costly. Generation of universal off-the-shelf CAR T cells, which can be broadly given to any patient, prepared in advance and ready to use, would be ideal and more cost-effective. Human induced pluripotent stem cells (iPSCs) provide a renewable source of cells that can be genetically engineered and differentiated into immune cells with enhanced anti-tumor cytotoxicity. This review describes basic knowledge of T cell biology, applications in ACT, the use of iPSCs as a new source of T cells and current differentiation strategies used to generate T cells as well as recent advances in genome engineering to produce next-generation off-the-shelf T cells with improved effector functions. We also discuss challenges in the field and future perspectives toward the final universal off-the-shelf immunotherapeutic products.
Catch Pattern for Antarctic krill (Euphausia superba) of Different Commercial Trawls in Similar Times and Overlapping Fishing Grounds
Authors: Wang Zhongqiu , Tang Hao , Herrmann Bent , Xu Liuxiong
Published: September 2021

Antarctic krill (Euphausia superba) is harvested using different design midwater trawls. Knowing the selective properties between trawls is crucial information for the management of the krill resources. This study compared the catch patterns between different commercial krill trawls at similar times and overlapping fishing grounds based on scientific data collected by scientific observers onboard commercial trawlers Long Teng (LT) and Fu Rong Hai (FRH). The results showed significant differences in the length-dependent catch densities and cumulative catch densities of krill between the two trawls. The krill length range in catches from LT's trawl was wider than that of FRH's trawl. Furthermore, the catch would consist of a larger proportion of smaller krill in the LT's trawl. The LT's trawl caught significantly higher proportions of krill below 38 mm than FRH's trawl. Even, the LT's trawl caught substantial numbers of krill <30 mm, whereas the FRH's trawl caught very few of them. The main factors causing the difference between trawls in catch pattern were inferred to be related to gear design including differences in mesh sizes used. The results of this study enhance the quality of comparative analysis of scientific data from commercial trawls and the understanding of gear selectivity of different configuration trawls used for harvesting krill.
Evaluation of the Impacts of Climate Change on Albacore Distribution in the South Pacific Ocean by Using Ensemble Forecast
Authors: Chang Yi-Jay , Hsu Jhen , Lai Po-Kai , Lan Kuo-Wei , Tsai Wen-Pei
Published: September 2021

South Pacific albacore (Thunnus alalunga) is a highly migratory tuna species widely distributed throughout 0°–50°S in the South Pacific Ocean. Climate-driven changes in the oceanographic condition largely influence the albacore distribution, relative abundance, and the consequent availability by the longline fisheries. In this study, we examined the habitat preference and spatial distribution of south Pacific albacore using a generalized additive model fitted to the longline fisheries data from the Western and Central Pacific Fisheries Commission (WCPFC) and Inter-American Tropical Tuna Commission (IATTC). Future projections of albacore distributions (2020, 2050, and 2080) were predicted by using an ensemble modeling approach produced from various atmosphere-ocean general circulation models and anthropogenic emission scenarios (i.e., RCP 4.5 and RCP 8.5) to reduce the uncertainty in the projected changes. The dissolved oxygen concentration at 100 meters (DO100) and sea surface temperature (SST) were found to have the most substantial effects on the potential albacore distribution that the albacore preferred in the habitat with DO100 of 0.2–0.25 mmol L–1 and SST of 13–22°C. This study suggested that the northern boundary of albacore preferred habitat is expected to shift southward by about 5° latitudes, and the relative abundance is expected to gradually increase in the area south of 30°S from 2020 to 2080 for both RCP scenarios, especially with a higher degree of change for the RCP 8.5. Moreover, the albacore relative abundance is projected to decrease in the most exclusive economic zones (EEZs) of countries and territories in the South Pacific Ocean by 2080. These findings could lend important implications on the availability of tuna resources to the fisheries and subsequent evaluation of tuna conservation and management under climate change.
Clinicopathological Characteristics and Influencing Factors of Renal Vascular Lesions in Anti-neutrophil Cytoplasmic Autoantibody-Related Renal Vasculitis
Authors: Wang Ruiqiang , Wu Yunqi , Zhang Xiaofeng , An Dongyue , Guo Ningning , Guo Yuanyuan , Wang Jin , Tang Lin
Published: September 2021

The purpose of this study was to evaluate the clinicopathological features of different degrees of extraglomerular renal vascular lesions (RVLs) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis and explore their clinical determinants. This is a retrospective study of 186 patients with ANCA-associated renal vasculitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019. The patients who met the inclusion criteria were divided into non-renal RVLs, mild RVLs, moderate RVLs, and severe RVLs. It was found that there were significant differences in serum creatinine (SCR), estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate (ESR), high-density lipoprotein (HDL), systolic blood pressure (SBP), the prevalence rate of hypertension, the proportion of normal glomeruli, and the proportion of sclerotic glomeruli and interstitial fibrosis integral. SCR and ESR are independent risk factors for RVLs. The participants were followed up for 1 year, and the progression to end-stage renal disease (ESRD) and death was defined as endpoint events. We found that the survival rate of patients without RVLs was significantly higher than that of patients with RVLs and that the RVLs were an independent risk factor for ESRD or death. Early intervention in the progression of RVLs can improve the prognosis.
Sleeping, Smoking, and Kidney Diseases: Evidence From the NHANES 2017–2018
Authors: Wu Chia-Chao , Wang Han-En , Liu Yi-Chun , Zheng Cai-Mei , Chu Pauling , Lu Kuo-Cheng , Chu Chi-Ming , Chang Yu-Tien
Published: September 2021

Study Objectives: Smoking and sleep are modifiable factors associated with the chronic kidney diseases. However, the interaction of smoking and sleep on the renal function are still unclear. Therefore, we aimed to evaluate the interactive impacts of smoking and sleep on the renal function.

Methods: Data were obtained from the National Health and Nutrition Examination Survey. The study population were categorized into nine subgroups by smoking (smoking every day, sometimes, and non-smokers recently) and sleep duration (short duration ≤ 6 h, normal duration 6–9 h, and longer duration ≥ 9 h on the weekdays).

Results: The study group with a short sleep duration had significantly higher serum cotinine and hydrocotinine levels compared with the other two sleep groups. After adjusting the demographic characteristics (age, race, body mass index, and marital status), sleep quality (snoring or breathing cessation), and comorbidities (diabetes mellitus, hypertension, high cholesterol, anemia, congestive heart failure, coronary heart disease, and stroke), non-smokers with short or long sleep duration had significant lower estimated glomerular filtration rate (eGFR) levels than the study group who smoked every day and slept ≤ 6 h. The effects of sleep duration on eGFR levels varied with smoking status. For the study group smoking every day, eGFR levels increased as sleep duration decreased, whereas for the study group smoking sometimes, eGFR levels increased as sleep duration increased. The U-shaped effects of eGFR levels were observed among non-smokers whose normal sleep duration was associated with better eGFR levels. Normal sleep duration was an important protective factor of the renal function for non-smokers than smokers.

Conclusions: The effects of sleep duration on eGFR levels varied with smoking status. Normal sleep duration was a protective factor and more crucial for non-smokers than for smokers.