bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Learning: Challenges and Coping Mechanisms of Language Learners in Rural Areas
Authors: Francisco Rizalin
Published: October 2021

The sudden shift from face-to-face instruction to online-based learning was prompted by the urgent necessity to continue the delivery of instruction amidst the COVID outbreak. Since all the country’s institutions have opted to close schools and universities, students in both urban cities and rural towns have had to adjust to the new standard. Hence, this research study employed a descriptive-qualitative research design and conducted in-depth interviews to determine the challenges and coping mechanisms of language learners studying online in rural areas. Moreover, responses were transcribed and analyzed through thematic analysis. The participants of the study were seven language learners, two males and five females who study online in rural areas. It was discovered from the interviews that among the challenges encountered are problems with internet connectivity, lack of comprehensive discussion of lessons, less interaction among peers/classmates, rare opportunity to enhance speaking skills, and absence of feedback mechanism. It was also found that students’ coping mechanisms include relocating to places known to have a greater internet access, disregarding public distractions, studying independently, reserving battery, and asking support from peers.
The Potential Role of the Artificial Intelligence in Combating Climate Change and Natural Resources Management: Political, Legal and Ethical Challenges
Authors: Lozo Olena , Onishchenko Oleksii
Published: October 2021

The aim of the article is to study the role of artificial intelligence (AI) in solving current issues of climate change, environmental protection and natural resources management. The advantages and threats of using AI for the development of political and legal parameters for ensuring the safe and effective implementation of technological system, as well as ensuring sustainable control over its functioning and development trends, are analyzed. The relevance of the topic is substantiated by the fact that the legislative basis in this area is at the early stage of formation, while the scale of the impact of AI on all the aspects of social life may be impossible to accurately foresee. A special attention is paid to the analysis of the legal regulation of these issues in the context of European Union and Ukraine. The present work is one of the few that addresses three issues: climate change, the growing influence of artificial intelligence, and the possibility of legal regulation of the use of AI to solve urgent environmental problems without threatening the fundamental human rights and freedoms.
The Nexus between Illicit Drug Trafficking and Terror: The PKK as an Example of Hybrid Transnational Threat
Authors: KARAMAN Haydar
Published: October 2021

All terrorist groups need finance to operate. It is a means for certain groups to accomplish their objectives; for others, it is the aims itself per se. Terrorist groups are therefore involved in different levels of organized crime. One of them is illicit drug trafficking, which has a nexus with organized crime and terrorist groups. This study aims to demonstrate a better understanding of the Kurdistan Workers' Party's (PKK) evolution into an organized criminal organization and its funding sources. From this point of view, the PKK is classified as a narco-terrorist organization with strong financial motives in this paper. As it will be analyzed on paper, its financial motivations frequently have weighed in the same level as its political motivation. It began to act as a hybrid organization through transnational offences, and it has steadily strengthened its criminal capabilities. Its members retain their deceptive political rhetoric to perform their illegal operations more easily. The organization can also be defined as a hybrid transnational organized crime group by UN standards, given the severity of its crimes and its criminal network spanning the Middle East, Turkey, and Europe.
Factors affecting the outcome of the usage of high-flow nasal cannula on severe or critically ill COVID-19 patients: a multicentric study from a developing nation
Authors: Das Moumita , Das Shuva , Bhuiyan AFM T , Nath Sudipta Deb , Biswas Rajdeep , Gupta Jitu D , Ball Anjan , Alam Mohammad J , Karim Md H , Nath Ranjan K , Saha Ayan
Published: October 2021

In resource-constrained settings, High-Flow Nasal Cannula (HFNC) can reduce the burden on mechanical ventilation in COVID-19 induced Acute Hypoxemic Respiratory Failure (AHRF). The aim was to observe the factors those might affect the outcome of the usage of HFNC on severe/critically ill COVID-19 patients. This is a multicentric prospective observational study. We observed rRT-PCR positive severe/critically ill ICU patients requiring HFNC for more than six hours. Statistical analysis was done to correlate between factors and outcome. Weaning from HFNC was successful in 47.5% of patients. The death rate was higher in ≥ 50 years older (56.50%), and patients with asthma (60.57%), COPD (60.00%), and CKD (68.42%). Fever (91.67%), cough (72.5%), and dyspnea (67.5%) were the most common symptoms. Mortality rates were higher for patients with raised blood sugar, creatinine levels. Severely systemic inflammatory response was seen very high for the expired patients. On HFNC, percent saturation of oxygen (SpO2) and partial pressure of oxygen (PaO2) progression was significantly high for the surviving patients requiring less inspired fraction of oxygen (FiO2%). The survival rate was higher for the patients using both HFNC and non-rebreather mask (NRM) concomitantly. While after HFNC- SpO2% and FiO2% were significantly related with outcome of the HFNC only treated patients, duration of hospital stay and on HFNC- FiO2% affected the HFNC + NRM treated patients’ outcome. HFNC could save more lives of critically ill AHRF patients who otherwise might need invasive or noninvasive ventilation. Some biochemical tests were observed to have association with the prognosis of the disease though HFNC was given to all. Survival benefit of dual HFNC and NRM therapy needs future study.
Asian J. Med. Biol. Res. 2021, 7 (3), 260-272
PENERAPAN ALGORITMA NAIVE BAYES UNTUK ANALISIS SENTIMEN REVIEW DATA TWITTER BMKG NASIONAL
Authors: Darwis Dedi , Siskawati Nery , Abidin Zaenal
Published: October 2021

Pertumbuhan twitter terus meningkat setiap waktu, sehingga hal tersebut dimanfaatkan para pengguna twitter untuk menyampaikan informasi berupa kritik maupun saran kepada pelayanan yang diberikan BMKG Nasional dengan lebih mudah. Metode yang digunakan dalam penelitian ini adalah klasifikasi data adalah Naïve Bayes Classifier (NBC). Sistem yang dikembangkan dengan menggunakan  data internal yang diambil dari internet/twitter untuk proses penentuan kalimat termasuk opini positif, netral atau negatif. Penentuan tersebut digolongkan sebagai proses pengklasifikasian. Serta menggunakan Application Python 3.74. Hasil Penelitian ini masuk kedalam fined grained sentiment analysis yaitu analisis pada suatu kalimat komentar. Data tersebut akan diproses menggunakan text mining, kemudian dilanjutkan dengan mengklasifikasikan tweet ke dalam tiga kelas, yaitu positif, negatif, dan netral. Klasifikasi ini menggunakan algoritma naive bayes. Klasifikasi dapat memberikan kemudahan bagi pengguna untuk melihat opini positif, negatif, dan netral. Hasil uji akurasi pada metode naive bayes untuk klasifikasi yaitu 69.97%.
Analisa Komponen ITSM Pada E-learning Perguruan Tinggi Di Kota Palembang Menggunakan ITIL V.3
Authors: Hastini Safta , Cholil Widya
Published: October 2021

E-learning merupakan peralihan proses pembelajaran dari tatap muka langsung di dalam kelas menjadi pembelajaran berbasis digital. Dalam bidang pendidikan, e-learning sebagai kemajuan teknologi informasi telah dimanfaatan sebagai sarana pembelajaran di perguruan tinggi karena dirasakan mampu meningkatkan kegiatan akademik khususnya perguruan tinggi agar menjadi lebih efektif dan efisien. Ketergantungan terhadap TI semakin meningkat untuk mencapai tujuan organisasi perguruan tinggi tersebut. Salah satu tujuan itu adalah menjadi perguruan tinggi bertaraf internasional dan maju dalam ilmu pengetahuan dan teknologi (IPTEK). Dimana perguruan tinggi yang telah memanfaatkan TI dengan baik akan menjadi perguruan tinggi yang lebih diminati oleh masyarakat. Hal ini disebabkan perguruan tinggi telah memanfaatkan TI dalam proses pembelajaran. Oleh karena itu, untuk mendukung penerapannya e-learning perguruan tinggi harus memadai bukan hanya dari aplikasi e-learning maupun user, akan tetapi  proses layanan-layanan berbasis TI pada e-learning perlu diatur dan didukung dengan manajemen layanan TI yang baik agar penerapan e-learning bisa berjalan sesuai dengan yang diharapkan perguruan tinggi. Information Technology Service Management (ITSM) merupakan suatu metode yang sistematis dalam melakukan pengelolaan terhadap layanan TI dengan kerangka kerja IT Infrastructure Library Versi 3 (ITIL v.3) yang terdiri dari 5 proses yaitu service strategy, service design, service transition, service operation dan continual service improvement. ITIL v.3 melakukan perbaikan kualitas layanan TI dan pengukuran secara berkelanjutan terhadap perkembangan layanan TI yang disampaikan kepada pengguna maupun pelanggan, sehingga perguruan tinggi bisa menilai sejauhmana pengelolaan terhadap layanan TI pada e-learning sebagai sarana pembelajaran. Perguruan tinggi yang diteliti adalah perguruan tinggi swasta yang ada di kota Palembang, yaitu Universitas X, Universitas Y dan Universitas Z. Metodologi pengumpulan data menggunakan kuisioner. Selanjutnya data yang didapat dari hasil kuesioner di analisa untuk mengetahui kondisi sistem yang sedang berjalan. Berdasarkan hasil rata-rata penilaian terhadap proses ITIL v.3 nilai maturity level masing-masing perguruan tinggi yang diteliti menghasilkan nilai maturity level 3 (defined). Defined artinya proses-proses yang direncanakan dan sudah dilaksanakan secara rutin dan didokumentasikan dengan standar tertentu.
Pengembangan Sistem Informasi Keberadaan Dosen Menggunakan Model Prototype
Authors: Wahyuni Evi Dwi
Published: October 2021

Masalah yang dihadapi di jurusan Informatika Universitas Muhammadiyah Malang, mahasiswa sering kali menanyakan keberadaan dosen kepada staff administrasi sebelum dilihat diruangannya. Hal ini cukup menyita waktu dan mengganggu pekerjaan. Penelitian terdahulu telah dilakukan untuk mengatasi permasalahan tersebut dan hanya sampai pada perancangan prototype. Tetapi, prototype yang telah dibuat, sudah pernah ada sistem serupa yang diterapkan di jurusan namun tidak berjalan lancar karena tidak semua dosen mau untuk menginputkan data ke sistem. penelitian ini memberikan solusi agar sistem yang dibuat dapat diterima dan sesuai dengan apa yang dibutuhkan pengguna. Penelitian ini telah berhasil menerapkan metode pengembangan prototype untuk pengembangan sistem informasi keberadaan dosen. Dengan tahapan pengembangan dimulai dari inisialisasi, perancangan prototype, production, evaluasi pengguna dan pengujian. Pengujian sistem terhadap 11 poin kebutuhan fungsional juga telah berhasil dilakukan, diperoleh hasil yang baik sebesar 100%.
Model Machine Learning untuk Klasifikasi Keluarga Sejahtera Study Kasus : Kecamatan Kota Palembang
Authors: Ninditama Ilsa Palingga
Published: October 2021

Pemerintah Indonesia telah berkomitmen untuk memperkuat program keluarga berencana terintegrasi melalui 4 (empat) pendekatan pilar program, yaitu Program Keluarga Berencana (KB), Keluarga Sejahtera (KS), Kesehatan Reproduksi (KR) dan Pemberdayaan Keluarga (PK) bagi seluruh penduduk Indonesia.. Pada artikel ini penulis membahas pilar Keluarga Sejahtera dan telah mengumpulkan data penduduk di Kota Palembang yang terdaftar sebagai Keluarga Sejahtera. Menggunakan metode Data mining atau data science yang terdiri dari kombinasi statistic, matematika dan kecerdasan buatan dengan k-NN dan Naïve bayes sebagai algorthim untuk mengolah data. Data fokus pada rentang tahun 2015 hingga 2020 dengan 10.187 record, penulis menggunakan Rapidminer sebagai alat untuk menganalisis data dari tahap preprocessing, data pelatihan dan mengklasifikasikan variabel menggunakan k-NN dan Naïve bayes untuk membuat model dan menentukan kriteria yang akan membantu BKKBN dalam menentukan keluarga sejahtera guna mempermudah penyuluh lapangan KB dalam melaksanakan konseling KB. . Dari hasil analisis data didapatkan bahwa penggunaan naïve bayes 93,99% lebih akurat dibandingkan k-NN dengan akurasi 87,28%. Berdasarkan hasil tersebut, dapat disimpulkan bahwa klasifikasi keluarga sejahtera telah mencapai tujuan visi Pemerintah.
The Use of Apostrophes in Theses of English Students at the University of Bengkulu
Authors: Arimbi Rilda Apriananda , Zahrida Zahrida , Kurniawan Ildi
Published: October 2021

The purposes of this study were to find out the functions of apostrophes used in the students’ theses and to identify the quality of students’ understanding in using apostrophes. The objects of this research were 40 theses of 2015 English students who graduated in 2019. The instruments of this research were documents and a table checklist that were used to find out the functions and errors of apostrophes in introduction, results and discussion chapters. The data were analyzed by using descriptive quantitative method. The results showed that there were five functions of apostrophes including plural possession (65.9%), singular possession (29.1%), contraction (3.9%), separate possession (0.6%), and joint possession (0.5%). In addition, there were four types of errors consisting of possession words without apostrophes (57.1%), apostrophes in the wrong places (37.8%), plural nouns with apostrophes and the letter s (3.8%), and contractions without apostrophes (1.3%). From the calculation, the percentage of all errors was 25% which indicated that the quality of the students’ understanding of the use of apostrophes was at a “high” level. It can be concluded that the students already understands the use of apostrophes well.
Short and Long Haul Pilots Rosters, Stress, Sleep Problems, Fatigue, Mental Health, and Well-Being
Authors: Venus Marion , Holtforth Martin grosse
Published: October 2021

OBJECTIVE: This research was conducted to compare short haul (SH) and long haul (LH) pilots regarding sleep restrictions and fatigue risks on flight duty, stress, sleep problems, fatigue severity, well-being, and mental health. METHOD: There were 406 international
SH and LH pilots who completed the cross-sectional online survey. Pilots sleep restrictions and fatigue-risk profiles (e.g., time pressure, late arrivals, minimum rest), sleep problems, fatigue severity, well-being, and symptoms of depression, anxiety, and common mental disorders (CMD) were
measured and compared for SH and LH pilots. RESULTS: Although SH and LH pilots were scheduled for only 51.465.4% of the legally allowed duty and flight hours, 44.8% of SH pilots reported severe fatigue (FSS 4 to 4.9), and an additional 31.7% high fatigue (FSS 5), compared with 34.7%
and 37.3% LH pilots. Considerable sleep problems in 8 nights/mo were reported by 24.6% SH vs. 23.5% LH pilots. Positive depression screenings were reported by 18.1% SH and 19.3% LH pilots. Positive anxiety screenings were reported by 9.6% SH and 5% LH pilots. Of all investigated pilots, 20%
reported significant symptoms of depression or anxiety, and 7.23% had positive depression and anxiety screenings. LH pilots reported significantly better well-being than SH pilots. CONCLUSIONS: Our results show that even far less duty and flight hours than legally allowed according
to flight time limitations lead to high levels of fatigue, sleep problems, and significant mental health issues among pilots. SH pilots were even more affected than LH pilots. Pilots fatigue should be considered an immediate threat to aviation safety and pilots fitness to fly by promoting
fatigue and burnout. Venus M, grosse Holtforth M. Short and long haul pilots rosters, stress, sleep problems, fatigue, mental health, and well-being. Aerosp Med Hum Perform. 2021; 92(10):786-797.
Exercise Effects on Neck Function Among F-15E Aircrew
Authors: Lee Maximilian S. , Briggs Robert , Scheirer Vanessa , Kearby Gregory , Young Brian A.
Published: October 2021

BACKGROUND: Neck pain (NP) is common among high performance aircrew, yet evidence remains insufficient to guide examination, treatment, and prevention. The purpose of this randomized pilot study was to collect baseline data for neck function for F-15E aircrew and determine efficacy
and feasibility of two separate exercise protocols in measuring short-term outcomes of subjective and objective neck function in order to inform future study design. METHODS: Randomized to either progressive (PRO) or general (GEN) exercise groups were 41 F-15E aircrew. Data collection
occurred at baseline, 3 wk, and 3 mo. RESULTS: At baseline, 39% of the subjects reported current NP, 79.5% reported a history of NP attributed to flying, 12.8% reported being removed from flying duties due to NP, and 10% reported receiving medical care for NP. PRO and GEN group
randomization showed similar baseline assessment data. Blinding was successful and exercise logs showed 31.6% compliance with prescribed exercise regimens. There were small but statistically significant increases in neck range of motion in both groups over the course of the study. Aircrew
with current NP had significantly higher F-15E flight hours. DISCUSSION: This study supports the high prevalence of NP in aircrew, yet low frequency of seeking care for NP. Future studies to assess NP prevention and treatment in aircrew require an integrated approach that includes
operational exercise policy and long-term data collection in flying units with dedicated resources for assessment and analysis. Lee MS, Briggs R, Scheirer V, Kearby G, Young BA. Exercise effects on neck function among F-15E aircrew. Aerosp Med Hum Perform. 2021; 92(10):815-824.
Indirect Measurements of Acceleration Atelectasis and the Role of Inspired Oxygen Concentrations
Authors: Pollock Ross D. , Gates Sonny D. , Radcliffe Jeremy J. , Stevenson Alec T.
Published: October 2021

BACKGROUND: A growing number of symptom reports suggestive of acceleration atelectasis in fast jet aircrew have raised the question as to whether traditional guidelines on inspired gas composition remain valid. The aim of this study was to assess the effects of inspired O2
concentration on the development of acceleration atelectasis when wearing modern anti-G garments.METHODS: There were 14 nonaircrew subjects who completed 5 centrifuge exposures to +5 Gz lasting 90 s. During exposures subjects breathed a gas mixture containing 21, 35,
45, 60, or 75% O2. To assess the extent of atelectasis post-Gz, forced inspiratory vital capacity (FIVC), regional FIVC (EITFIVC), shunt, respiratory resistance, reactance, and compliance and peripheral O2 saturation during a hypoxic exposure were
measured.RESULTS: Compared with baseline, FIVC was not statistically significantly altered. EITFIVC was 14.4% lower after the 75% O2 exposure only with a greater symptom reporting with higher FIO2 in some individuals. A significantly greater
shunt (3>6%) followed the 60 and 75% O2 exposures. O2 concentration during Gz had no effect on respiratory resistance, reactance, compliance, or hypoxemia.DISCUSSION: There is evidence of mild acceleration atelectasis present when breathing 60%
O2, particularly in susceptible individuals, with 75% O2 causing more obvious physiological compromise. An inspired oxygen concentration of <60% will prevent the majority of individuals from developing acceleration atelectasis.Pollock RD, Gates SD, Radcliffe
JJ, Stevenson AT. Indirect measurements of acceleration atelectasis and the role of inspired oxygen concentrations. Aerosp Med Hum Perform. 2021; 92(10):780-785.
Cerebral Oxygenation Responses to Aerobatic Flight
Authors: Fresnel Eléonore , Dray Gérard , Pla Simon , Jean Pierre , Belda Guilhem , Perrey Stéphane
Published: October 2021

BACKGROUND: Aerobatic pilots must withstand high and sudden acceleration forces (Gz) up to ±10 Gz. The physiological consequences of such a succession of high and abrupt positive and negative Gz on the human body over time remain mostly unknown. This case report emphasizes changes in physiological factors such as cerebral oxygenation and heart rate dynamics collected in real aerobatic flights. CASE REPORT: A 37-yr-old man, experienced in aerobatic flying, voluntarily took part in this study. During two flight runs (15-20 min), the pilot performed aerobatic maneuvers with multiple high (±10 Gz) positive and negative accelerations. During the flights he wore a Polar heart rate sensor while cerebral oxygenation was measured continuously over his prefrontal cortex via near-infrared spectroscopy (NIRS). NIRS allows for measurement of the relative concentration changes of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb), making it possible to determine cerebral oxygenation and hemodynamic status. DISCUSSION: The continuous in-flight monitoring of O2Hb and HHb revealed the large effects of successive positive and negative Gz exposures on cerebral hemodynamics alterations. The results showed a significant and positive correlation between changes in Gz exposures and O2Hb concentration. This case report highlights that NIRS provides some valuable and sensitive indicators for the monitoring of cerebral hemodynamics during aerobatic flights exposed to multiple and high acceleration forces. To our knowledge, this first study quantifying cerebral oxygenation changes in aerobatics opens the way for the assessment of individual physiological responses and tolerance in pilots to repeated high Gz during real flights. Fresnel E, Dray G, Pla S, Jean P, Belda G, Perrey S. Cerebral oxygenation responses to aerobatic flight. Aerosp Med Hum Perform. 2021; 92(10):838-842.
Heterozygous Familial Hyperlipidemia in a Fighter Pilot
Authors: Gatzke Lori C.
Published: October 2021

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disease characterized by elevated low-density lipoprotein cholesterol (LDL-C) that increases risk for clinically significant atherosclerotic cardiovascular disease (ASCVD). This common (1:220)
disease is present within the fighter pilot community and hesitation to treat this condition at younger ages results in a higher risk for coronary artery disease (CAD), the presence of which can be catastrophic for flying safety. CASE REPORT: A 40-yr-old asymptomatic F-15 pilot
presented with persistently elevated LDL-C levels > 190 mg dL1 and a significant family history of CAD. Coronary artery calcium, CT angiography, and finally, invasive angiography were used to further stratify him as having mild CAD. Initiation of statin therapy significantly
lowered his LDL and subsequent risk for disease progression, allowing him to return to flying. DISCUSSION: Early recognition and treatment of HeFH is imperative for lowering the risk of ASCVD. Often the medical community supporting flyers is hesitant to diagnose or treat this condition,
due to nonrecognition, the young age of presentation, or reluctance to potentially ground a flyer. By intervening earlier, rather than waiting, aviators can remain on flying status longer with lower risk to themselves and their aircrew. Gatzke LC. Heterozygous familial hyperlipidemia
in a fighter pilot. Aerosp Med Hum Perform. 2021; 92(10):835-837.
Layer-by-Layer Fabrication of Hydrogel Microsystems for Controlled Drug Delivery From Untethered Microrobots
Authors: Bernasconi Roberto , Pizzetti Fabio , Rossetti Arianna , Butler Brendan , Levi Marinella , Pané Salvador , Rossi Filippo , Magagnin Luca
Published: October 2021

Targeted drug delivery from untethered microrobots is a topic of major interest in current biomedical research. The possibility to load smart materials able to administer active principles on remotelyin vivoguidable microdevices constitutes one of the most attractive opportunities to overcome the drawbacks of classical untargeted delivery methodologies. Hydrogels, in particular, are ideal candidates as drug-carrying materials due to their biocompatibility, low cost, and ease of manufacturing. On the other hand, these polymers suffer from poor control over release rate and overall released amount. Starting from these premises, the present article demonstrates the possibility to tune the release of hydrogels applied on magnetically steerable microrobots by fabricating microsystemsvialayer-by-layer self-assembly. By doing this, the diffusion of chemicals from the hydrogel layers to the external environment can be optimized and the phenomenon of burst release can be strongly limited. The microrobotic platforms employed to transport the hydrogel active material are fabricated by employing 3D printing in combination with wet metallization and present a gold layer on their surface to enhance biocompatibility. The maneuverability of microdevices coated with both thin and thick multilayers is investigated, individuating optimized parameters for efficient actuation.
Seismic Design and Performances of Frame Structures Connected to a Strongback System and Equipped with Different Configurations of Supplemental Viscous Dampers
Authors: Palermo Michele , Laghi Vittoria , Gasparini Giada , Silvestri Stefano , Trombetti Tomaso
Published: October 2021

The paper investigates the dynamic behavior of structural systems obtained by connecting a moment-resisting frame structure with a vertical rigid truss pinned at the base, known in literature as “strongback,” and equipped with added fluid-viscous dampers. The strongback, designed in order to remain in the elastic field under strong seismic ground motion, acts as a mast by imposing to the structure a linear lateral deformed shape. By regularizing the lateral drift profile of the structure, the strongback limits undesired effects such as weak-storey mechanisms, damage concentration and residual drifts. In addition, when supplemental dampers are inserted in the structure, a considerable amount of energy can be dissipated, thus reducing the peak seismic response. The aim of the work is twofold: i) to provide analytical formulations for the preliminary design of added dampers based on the Generalized Single Degree Of Freedom (GSDOF) concept, and ii) to evaluate the increase in energy dissipation capabilities for selected dampers configurations thanks to the presence of the strongback. The formulas are developed for different configurations of added viscous dampers: dampers inserted within the frame between all or selected consecutive storeys (inter-storey placement) and dampers located at the base of the strongback to realize a rigid “dissipative tower.” The effectiveness of the dampers configurations is evaluated through dynamic time-history analyses.
Advances in Unhealthy Nutrition and Circadian Dysregulation in Pathophysiology of NAFLD
Authors: Guo Xin , Zheng Juan , Zhang Shixiu , Jiang Xiaofan , Chen Ting , Yu Jiayu , Wang Shu'e , Ma Xiaomin , Wu Chaodong
Published: October 2021

Unhealthy diets and lifestyle result in various metabolic conditions including metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Much evidence indicates that disruption of circadian rhythms contributes to the development and progression of excessive hepatic fat deposition and inflammation, as well as liver fibrosis, a key characteristic of non-steatohepatitis (NASH) or the advanced form of NAFLD. In this review, we emphasize the importance of nutrition as a critical factor in the regulation of circadian clock in the liver. We also focus on the roles of the rhythms of nutrient intake and the composition of diets in the regulation of circadian clocks in the context of controlling hepatic glucose and fat metabolism. We then summarize the effects of unhealthy nutrition and circadian dysregulation on the development of hepatic steatosis and inflammation. A better understanding of how the interplay among nutrition, circadian rhythms, and dysregulated metabolism result in hepatic steatosis and inflammation can help develop improved preventive and/or therapeutic strategies for managing NAFLD.
Siglec-15 Is an Immune Suppressor and Potential Target for Immunotherapy in the Pre-Metastatic Lymph Node of Colorectal Cancer
Authors: Du Hang , Tang Jingling , Li Xiaoyun , Wang Xinjun , Wu Liyun , Zhang Ruyi , Hu Pingsheng , Yang Yuan
Published: October 2021

Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients. In this study, a total of 38 pairs of SNs and NSNs were collected, in which 26 pairs of non-metastatic lymph nodes were subjected to RNA-seq and bioinformatics analysis for the gene expression profiles. There were 16 differentially expressed genes between SNs and NSNs being identified, including 9 upregulated and 7 downregulated genes in SN. Gene Ontology (GO) classification analysis revealed that the differentially expressed genes were mainly involved in leukocyte differentiation, chemokine secretion, and immune system regulation. In the meantime, gene set enrichment analysis (GSEA) showed that immune-related signaling pathways, such as transforming growth factor beta (TGF-β) signaling and tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, were enriched in NSN, while cell proliferation–related signaling pathways were enriched in SN, including MYC signaling and G2M checkpoint signaling. We further identified SIGLEC15 as a top upregulated gene in SN. However, RNAscope assay showed that SIGLEC15 was not largely co-expressed with M2 macrophage marker CD163. We then selected eight pairs of lymph nodes for further cytological studies. Flow cytometry analysis revealed that Siglec-15 was expressed on all myeloid cell subsets. The relative expression of SEGLEC15 (SN/NSN) was correlated with the microsatellite instability (MSI) status in colorectal cancer patients. Further studies found that small interfering ribonucleic acid (siRNA)-mediated silencing of SLGLEC15 can enhance the anti-tumor function of T cells, as indicated by cytokine release analysis. In conclusion, we presented here a first report on the gene expression profiling of the pre-metastatic lymph node in colorectal cancer. The findings in this study suggest that SIGLEC15 plays an important role in SN immunosuppression. SEGLEC15 silencing could be a therapeutic strategy for restoring T cell function in tumor SNs.
Detection of Atherosclerosis by Small RNA-Sequencing Analysis of Extracellular Vesicle Enriched Serum Samples
Authors: Hildebrandt Alex , Kirchner Benedikt , Meidert Agnes S. , Brandes Florian , Lindemann Anja , Doose Gero , Doege Alexander , Weidenhagen Rolf , Reithmair Marlene , Schelling Gustav , Pfaffl Michael W.
Published: October 2021

Atherosclerosis can occur throughout the arterial vascular system and lead to various diseases. Early diagnosis of atherosclerotic processes and of individual disease patterns would be more likely to be successful if targeted therapies were available. For this, it is important to find reliable biomarkers that are easily accessible and with little inconvenience for patients. There are many cell culture, animal model or tissue studies that found biomarkers at the microRNA (miRNA) and mRNA level describing atherosclerotic processes. However, little is known about their potential as circulating and liquid biopsy markers in patients. In this study, we examined serum-derived miRNA – profiles from 129 patients and 28 volunteers to identify potential biomarkers. The patients had four different atherosclerotic manifestations: abdominal aneurysm (n = 35), coronary heart disease (n = 34), carotid artery stenosis (n = 24) and peripheral arterial disease (n = 36). The samples were processed with an extracellular vesicle enrichment protocol, total-RNA extraction and small RNA-sequencing were performed. A differential expression analysis was performed bioinformatically to find potentially regulated miRNA biomarkers. Resulting miRNA candidates served as a starting point for an overrepresentation analysis in which relevant target mRNAs were identified. The Gene Ontology database revealed relevant biological functions in relation to atherosclerotic processes. In patients, expression of specific miRNAs changed significantly compared to healthy volunteers; 27 differentially expressed miRNAs were identified. We were able to detect a group-specific miRNA fingerprint: miR-122-5p, miR-2110 and miR-483-5p for abdominal aortic aneurysm, miR-370-3p and miR-409-3p for coronary heart disease, miR-335-3p, miR-381-3p, miR493-5p and miR654-3p for carotid artery stenosis, miR-199a-5p, miR-215-5p, miR-3168, miR-582-3p and miR-769-5p for peripheral arterial disease. The results of the study show that some of the identified miRNAs have already been associated with atherosclerosis in previous studies. Overrepresentation analysis on this data detected biological processes that are clearly relevant for atherosclerosis, its development and progression showing the potential of these miRNAs as biomarker candidates. In a next step, the relevance of these findings on the mRNA level is to be investigated and substantiated.
Identification of an Immune-Related LncRNA Signature in Gastric Cancer to Predict Survival and Response to Immune Checkpoint Inhibitors
Authors: Ding Zuoyou , Li Ran , Han Jun , Sun Diya , Shen Lei , Wu Guohao
Published: October 2021

Immune microenvironment in gastric cancer is closely associated with patient’s prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of immune responses. In this study, we aimed to construct a prognostic model based on immune-related lncRNAs (IRLs) to predict the overall survival and response to immune checkpoint inhibitors (ICIs) of gastric cancer (GC) patients. The IRL signature was constructed through a bioinformatics method, and its predictive capability was validated. A stratification analysis indicates that the IRL signature can distinguish different risk patients. A nomogram based on the IRL and other clinical variables efficiently predicted the overall survival of GC patients. The landscape of tumor microenvironment and mutation status partially explain this signature’s predictive capability. We found the level of cancer-associated fibroblasts, endothelial cells, M2 macrophages, and stroma cells was high in the high-risk group, while the number of CD8+ T cells and T follicular helper cells was high in the low-risk group. Immunophenoscore (IPS) is validated for ICI response, and the IRL signature low-risk group received higher IPS, representing a more immunogenic phenotype that was more inclined to respond to ICIs. In addition, we found RNF144A-AS1 was highly expressed in GC patients and promoted the proliferation, migration, and invasive capacity of GC cells. We concluded that the IRL signature represents a novel useful model for evaluating GC survival outcomes and could be implemented to optimize the selection of patients to receive ICI treatment.
Prognostic and Immunological Role of Key Genes of Ferroptosis in Pan-Cancer
Authors: Shi Zhi-Zhou , Tao Hao , Fan Ze-Wen , Song Sheng-Jie , Bai Jie
Published: October 2021

Solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and apoptosis inducing factor mitochondria associated 2 (AIFM2) are the key regulators in ferroptosis. However, the expression patterns and prognostic roles of these genes in pan-cancer are still largely unclear. The expression patterns and prognostic roles of SLC7A11, GPX4, and AIFM2 and the relationships between the expression levels of these genes and immune infiltration levels in pan-cancer were analyzed by using TIMER, gene expression profiling interactive analysis (GEPIA), Oncomine, and Kaplan–Meier databases. Our results showed that both SLC7A11 and GPX4 were overexpressed in colorectal cancer, and SLC7A11 was overexpressed in lung cancer. High levels of SLC7A11 and AIFM2 were significantly linked with the shortened disease-free survival and overall survival (OS) in adrenocortical carcinoma (ACC), respectively. And high expression of SLC7A11, GPX4, and AIFM2 were significantly correlated with the shortened OS of acute myeloid leukemia patients. In esophageal carcinoma (ESCA), GPX4 expression was significantly associated with the infiltration of macrophage and myeloid dendritic cell, and AIFM2 expression was significantly associated with the infiltration of CD4+ T cell. Importantly, GPX4 expression was positively correlated with the expression levels of monocyte markers (CD14 and CD115) and M2 macrophage markers (VSIG4 and MS4A4A) both in ESCA and in head and neck squamous cell carcinoma (HNSC). In summary, SLC7A11, GPX4, and AIFM2 are dysregulated in many types of cancers, and are candidate prognostic biomarkers for many types of cancers, and can be used to evaluate the infiltration of immune cells in tumor tissues.
Targeted Inhibition of Fibroblast Growth Factor Receptor 1-GLI Through AZD4547 and GANT61 Modulates Breast Cancer Progression
Authors: Riaz Syeda Kiran , Khan Walizeb , Wang Fen , Khaliq Tanwir , Malik Amber , Razia Eisha Tir , Khan Jahangir Sarwar , Haque Shafiul , Hashem Anwar M. , Alkhayyat Shadi S. , Azhar Najiah Esam , Harakeh Steve , Ansari Mohammad Javed , Haq Farhan , Malik Muhammad Faraz Arshad
Published: October 2021

The underlying mechanism of fibroblast growth factor receptor 1 (FGFR1) mediated carcinogenesis is still not fully understood. For instance, FGFR1 upregulation leads to endocrine therapy resistance in breast cancer patients. The current study aimed to identify FGFR1-linked genes to devise improved therapeutic strategies. RNA-seq and microarray expression data of 1,425 breast cancer patients from two independent cohorts were downloaded for the analysis. Gene Set Enrichment Analysis (GSEA) was performed to identify differentially expressed pathways associated with FGFR1 expression. Validation was done using 150 fresh tumor biopsy samples of breast cancer patients. The clinical relevance of mRNA and protein expression of FGFR1 and its associated genes were also evaluated in mouse embryonic fibroblasts (MEFs) and breast cancer cell line (MDA-MB-231). Furthermore, MDA-MB-231 cell line was treated with AZD4547 and GANT61 to identify the probable role of FGFR1 and its associated genes on cells motility and invasion. According to GSEA results, SHH pathway genes were significantly upregulated in FGFR1 patients in both discovery cohorts of breast cancer. Statistical analyses using both discovery cohorts and 150 fresh biopsy samples revealed strong association of FGFR1 and GLI1, a member of SHH pathway. The increase in the expression of these molecules was associated with poor prognosis, lymph node involvement, late stage, and metastasis. Combined exposures to AZD4547 (FGFR1 inhibitor) and GANT61 (GLI1 inhibitor) significantly reduced cell proliferation, cell motility, and invasion, suggesting molecular crosstalk in breast cancer progression and metastasis. A strong positive feedback mechanism between FGFR1–GLI1 axis was observed, which significantly increased cell proliferation and metastasis. Targeting FGFR1–GLI1 simultaneously will significantly improve the prognosis of breast cancer in patients.
Telomere Signaling and Maintenance Pathways in Spermatozoa of Infertile Men Treated With Antioxidants: An in silico Approach Using Bioinformatic Analysis
Authors: Panner Selvam Manesh Kumar , Baskaran Saradha , Sikka Suresh C.
Published: October 2021

Telomere shortening is considered as a marker of cellular senescence and it is regulated by various signaling pathways. Sperm telomere appears to play important role in its longevity and function. Antioxidant intake has been known to prevent the shortening of telomere. In the management of male infertility, antioxidants are commonly used to counterbalance the seminal oxidative stress. It is important to understand how antioxidants treatment may modulate telomere signaling in sperm. In the current study, we have identified 377 sperm proteins regulated by antioxidants based on data mining of published literature. Bioinformatic analysis revealed involvement of 399 upstream regulators and 806 master regulators associated with differentially expressed sperm proteins. Furthermore, upstream regulator analysis indicated activation of kinases (EGFR and MAPK3) and transcription factors (CCNE1, H2AX, MYC, RB1, and TP53). Hence, it is evident that antioxidant supplementation activates molecules associated with telomere function in sperm. The outcome of this in silico study suggests that antioxidant therapy has beneficial effects on certain transcription factors and kinases associated with sperm telomere maintenance and associated signaling pathways that may play an important role in the management of male factor infertility.
Noble Metal-Free Hierarchical ZrY Zeolite Efficient for Hydrogenation of Biomass-Derived Levulinic Acid
Authors: Hu Di , Xu Hong , Wu Zuotong , Zhang Man , Zhao Zhiyue , Wang Yuchen , Yan Kai
Published: October 2021

Developing a low-cost and robust catalyst for efficient transformation of biomass-derived platform chemicals plays a crucial role in the synthesis of future transportation fuels. Herein, a post-synthetic strategy was employed to develop a noble metal-free and robust ZrY zeolite catalyst, which is efficient for the hydrogenation of biomass-derived levulinic acid (LA) into biofuel γ-valerolactone (GVL), whereas over 95% yield of GVL was achieved in 10 h at 220°C. The effects of acidic properties from ZrY catalysts and various reaction parameters on the catalytic performance were then discussed in detail. Subsequently, different characterization tools were used to compare the difference and relationship of structure activity between the fresh and spent ZrY catalysts. It was found that acidity and the metal–support interaction were important for the direct synthesis of GVL. This work provides a guideline to design a noble metal-free catalyst for high-value utilization of biomass-derived sources.
Developing, Modifying, and Validating a TaqMan Real-Time PCR Technique for Accurate Identification of Leishmania Parasites Causing Most Leishmaniasis in Iran
Authors: Fotouhi-Ardakani Reza , Ghafari Seyedeh Maryam , Ready Paul Donald , Parvizi Parviz
Published: October 2021

Many laboratory methods are used to diagnose leishmaniasis because it is characterized by varied symptoms and caused by different Leishmania species. A quantitative real-time PCR method based on a TaqMan probe was developed and modified for accurate identification of human cutaneous leishmaniasis (caused by Leishmania major or Leishmania tropica) from endemic areas of Iran. Two gene regions of amino acid permease 3 (AAP3) and cytochrome oxidase II (COII) were considered. Six new sets of species-specific primers and probes were designed. A total of 123 samples were examined and employed to evaluate and validate real-time PCR. According to parasitic load of the genesig®Leishmania Advanced Standard Kit, a serial dilution of purified plasmid (2–2×107 copies/reaction) was prepared under the same conditions for both genes. Specific primers and probes were able to detect three and six parasite copies in AAP3 and COII genes, respectively, and were able to detect three copies of parasites for L. major and L. tropica. The sensitivities of the reference kit and our method were 98.7 and 98.1%, respectively, and specificity was 100% for detecting parasite genomes in all assays. Designed primers and probes performed well in terms of efficiency and regression coefficient. For AAP3 and COII genes, respectively, the linear log range was 7 and the correlation coefficient (R2) was 0.749 and 0.996 for the reference kit using the standard generated curve and 0.98 and 0.96 with serial dilutions of parasite DNA. This research detected L. major and L. tropica definitely and opens the horizon for the other scientists in the multiplex reactions in designing and optimization of the conditions in silico and in vivo.
Association Between Waist Circumference and the Prevalence of (Pre) Hypertension Among 27,894 US Adults
Authors: Sun Jin-Yu , Hua Yang , Zou Hua-Yi-Yang , Qu Qiang , Yuan Yue , Sun Guo-Zhen , Sun Wei , Kong Xiang-Qing
Published: October 2021

Aims: This study aimed to investigate the association between waist circumference and the prevalence of (pre) hypertension.

Methods: Cross-sectional data from the 2007–2018 National Health and Nutrition Examination Survey were analyzed. The historical trend of abdominal obesity was assessed by the Cochran–Armitage trend test. After preprocessed by the multiple imputation strategy, we used generalized additive models to assess the association of waist circumference with systolic/diastolic blood pressure and performed correlation analysis by the Spearman correlation coefficient. Moreover, we used multivariable logistic regression (non-adjusted, minimally adjusted, and fully adjusted models), restricted cubic spline, and sensitivity analysis to investigate the association between waist circumference and (pre) hypertension.

Results: A total of 27,894 participants were included in this study. In the fully adjusted model, waist circumference was positively associated with (pre) hypertension with odds ratios (95% confidence intervals) of 1.28 (1.18–1.40) in the young group and 1.23 (1.15–1.33) in the old group. Restricted cubic spline showed a higher prevalence of (pre) hypertension with the increase of waist circumference. In the subgroup analysis, waist circumference showed a robust trend across all BMI categories with odds ratios (95% confidence intervals) of 3.33 (1.29–8.85), 1.35 (1.17–1.57), 1.27 (1.13–1.41), and 1.09 (1.01–1.17) in underweight, normal weight, overweight, and obese individuals, respectively.

Conclusion: This study highlighted waist circumference as a significant biomarker to evaluate the risk of (pre) hypertension. Our results supported the measure of waist circumference regardless of BMI when evaluating the cardiometabolic risk related to fat distribution.