bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and Characterization of Cross-Reactive Human Monoclonal Antibodies that Potently Neutralize Australian Bat Lyssavirus Variants and Other Phylogroup 1 Lyssaviruses
Authors: Weir Dawn , Coggins Si'Ana , Vu Bang , Coertse Jessica , Yan Lianying , Smith Ina , Laing Eric , Markotter Wanda , Broder Christopher , Schaefer Brian
Published: February 2021

Australian bat lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid bats (ABLVp) and the yellow-bellied sheath-tailed bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections consists of wound cleansing, ad-ministration of the rabies vaccine and injection of rabies immunoglobulin (RIG) proximal to the wound. Despite the efficacy of PEP, the inaccessibility of human RIG (HRIG) in the developing world and the high immunogenicity of equine RIG (ERIG) has led to consideration of human monoclonal antibodies (hmAbs) as a passive immunization option that offers enhanced safety and specificity. Using a recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (G) protein of ABLVs and phage display, we identified two hmAbs, A6 and F11, which completely neutralize ABLVs/ABLVp, and RABV at concentrations ranging from 0.19-3.12 µg/mL and 0.39-6.25 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the lyssavirus G protein, ef-fectively neutralizing phylogroup 1 lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse lyssaviruses. These results suggest A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 lyssavirus infections.
Inactivation of Human Coronavirus by Fathhome’s Dry Sanitizer Device: Rapid and Eco-friendly Ozone-based Disinfection of SARS-CoV-2
Authors: Uppal Timsy , Khazaieli Amir , Snijders Antoine , Verma Subhash C.
Published: February 2021

The pandemic history of pathogenic SARS-CoV-2 associated COVID-19 infection began in December 2019, with its emergence in Wuhan, China. Pertaining to its high transmissibility and wide host adaptability, this new and unique human coronavirus spread across the planet affecting almost every country, inflicting 91 million people and causing 1.9 million deaths (as of January 17th, 2021). Limited or negligible pre-existing immunity to multiple SARS-CoV-2 variants has resulted in severe morbidity and mortality worldwide, as well as a record-breaking surge in the use of medical-surgical supplies and personal protective equipments. In response to the global need for effective sterilization techniques, this study evaluated the virucidal efficacy of FATHHOME’s self-contained, ozone-based dry-sanitizing device, by dose and time response assessment. We tested inactivation of human coronavirus, HCoV-OC43, a close genetic model of SARS-CoV-2, on porous (N95 filtering facepiece respirator/FFR) and nonporous (glass) surfaces. We started our assays with 20 ppm of ozone for 10 min exposure, which was able to effectively reduce, 99.8% and 99.9% of virus from glass and N95 FFR surfaces, respectively. Importantly, the virus was completely inactivated, below the detection limit (over 6-log10 reduction) with 25 ppm ozone for 15 mins on both tested surfaces. As expected, a higher ozone concentration (50 ppm) resulted in faster inactivation of HCoV-OC43 with 100% inactivation in 10 mins from both the surfaces, with no residual ozone present after completion of the 5-minute post exposure recapture cycle and no measurable increase in ambient ozone levels. These results confirmed that FATHHOME’s device may provide a safe and viable solution for rapid decontamination of SARS-CoV-2- from worn items, frequently touched items, and PPE including N95 FFRs, face shields and other personal items.
Metabolite Structure Assignment of Seized Products Containing Cathinone Derivatives through High Resolution Analytical Techniques
Authors: Gonçalves João , Alves Vera  L. , Aguiar Joselin , Caldeira Maria , Teixeira Helena , Câmara José S.
Published: February 2021

The innovation of the new psychoactive substances (NPS) market requires the rapid identification of new substances that can be a risk to public health, in order to reduce the damage due to their use. Twelve seized products suspected to contain illicit substances were analyzed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), gas chromatography coupled to mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). Synthetic cathinones (SCat) were found in all products, either as a single component or in mixtures. Infrared spectra of all products were consistent with the molecular structure of SCat, showing an intense absorption band at 1700–1674 cm‐1, corresponding to the carbonyl stretching, a medium/strong peak at 1605-1580 cm-1, indicating stretching vibrations in the aromatic ring (C=C) and bands with relative low intensity at frequencies near 2700–2400 cm-1, corresponding to an amine salt. It was possible to identify a total of eight cathinone derivatives by GC-MS and NMR analysis: 4’-methyl-α-pyrrolidinohexanophenone (MPHP), α-pyrrolidinohexanophenone (α-PHP), 3-fluoromethcathinone (3-FMC), methedrone, methylone, buphedrone, N-ethylcathinone, and pentedrone. Among the adulterants found in these samples, caffeine was the most frequently detected substance, followed by ethylphenidate. These results highlight the prevalence of SCat in seized materials of the Portuguese market. Reference standards are usually required for confirmation, but when reference materials are not available, the combination of complementary techniques is fundamental for a rapid and an unequivocal identification of such substances.
PERBANDINGAN SIKLUS HIDUP PRODUK DOTA 2 DAN CS:GO BERDASARKAN STRATEGI EVENT MARKETING
Authors: Junianta Reynaldi Dwi , Sanaji Sanaji
Published: February 2021

The purpose of this research is to get the Product Life Cycleâ€™s phase from Dota 2 and CS:GO based on Polli and Cook model and to know the difference of impact of Marketing Event Dota 2 and CS:GO strategy on Product Life Cycle Dota 2 and CS:GO.

The method of this research is qualitative. The data used are secondary data collected through documents on the internet. The data processed by the Polli and Cook formulas to produce the Product Life Cycle stages and data on Event Marketing both games are collected and compared each criteria.

The results show that product life cycle both online games can be proved by Polli and Cook model. At each stage the two games have different strategies. Dota 2 Product Life Cycle stages are: 1) the introduction phase starts and ends in July 2012; 2) the growth stage starts in July 2012 and ends in November 2012; 3) the maturity phase starts in December 2012 until now. CS:GO Product Life Cycle stages are: 1) introduction phase starts and ends in August 2012; 2) the growth stage starts in August 2012 and ends in January 2014; 3) the maturity stage starts in February 2014 until now.
PENGARUH MOTIVASI KERJA DAN KOMITMEN ORGANISASI PADA KINERJA KARYAWAN PT X
Authors: Dewi Susita  , Widya Parimita  , Sofiana Setyawati
Published: February 2021

Tujuan penelitian ini adalah: Untuk mengetahui 1) Deskripsi motivasi kerja, komitmen organisasi, dan kinerja karyawan PT X. 2) Pengaruh motivasi kerja terhadap kinerja karyawan PT X, 3) Pengaruh komitmen organisasi terhadap kinerja karyawan PT X. Penelitian ini dilakukan terhadap 106 karyawan PT X. Teknik pengumpulan data menggunakan metode survei dengan menyebarkan kuesioner kepada para responden. Kemudian data diproses menggunakan aplikasi SPSS versi 22. Penelitian ini menggunakan teknik analisis deskriptif dan eksplanatori. Hasil regresi menunjukan bahwa terdapat pengaruh positif dan signifikan antara motivasi kerja terhadap kinerja karyawan, dan juga antara komitmen organisasi terhadap kinerja karyawan.
PENGARUH FAKTOR MIKROEKONOMI DAN FAKTOR MAKROEKONOMI TERHADAP PROFITABILITAS PERUSAHAAN (STUDI KASUS: PT PERKEBUNAN NUSANTARA V)
Authors: Hendramiko  , Noer Azam Achsani  , Hendro Sasongko
Published: February 2021

Penelitian ini bertujuan untuk menganalisis pengaruh faktor mikroekonomi dan faktor makroekonomi terhadap Gross Operating Profit (GOP), dengan studi kasus pada PT Perkebunan Nusantara V. Data-data penelitian berasal dari laporan keuangan PTPN V yang dimuat dalam Laporan Manajemen bulanan dan Laporan Tahunan (Annual Report) periode tahun 2012-2017 (time series). Teknik pengolahan data dalam penelitian ini menggunakan model Vector Autoregression (VAR) dengan data 72 bulan, yaitu mulai bulan Januari 2012 sampai dengan bulan Desember 2017. Teknik analisis data yang digunakan untuk menjawab pertanyaan penelitian tentang pengaruh faktor mikroekonomi dan faktor makroekonomi terhadap Gross Operating Profit (GOP) PTPN V. Hasil FEVD menunjukkan variabel penelitian yang berpengaruh terhadap GOP adalah GOP bulan sebelumnya sebesar 65,55%, faktor makroekonomi sebesar 21,38%, dan faktor makroekonomi sebesar 13,07%. Berdasarkan hasil penelitian ini, manajemen PTPN V diharapkan dapat mempertahankan kestabilan tingkat profitabilitasnya setiap bulannya untuk mempertahankan kelangsungan bisnis di masa yang akan datang.
SURVEI INDEKS KEPUASAN MASYARAKAT (IKM) PENGGUNA JASALAYANAN KESEHATAN BPJS DI RS HASAN SADIKIN BANDUNG
Authors: Mohamad Rizan
Published: February 2021

Tujuan penelitian ini adalah: 1. Menilai indeks kepuasan pelanggan pengguna jasa kesehatan BPJS di RS Hasan Sadikin Bandung. Unit analisis adalah pengguna jasa pelayanan kesehatan BPJS yang berobat rawat jalan di poliklinik RS Hasan Sadikin Bandung. Hasil analisis deskriptif menunjukan; (1). Indeks Kepuasan Publik (IKM) pelanggan jasa pelayanan BPJS kesehatan di RS Hasan Sadikin Bandung sebesar 3,56988 dengan kriteria Sangat Baik. Hasil analisis dari masing-masing parameter IKM dapat terlihat sebagai berikut; (1). Prosedur pelayanan Baik dengan skor 3,00; (2) Persyaratan pelayanan Sangat Baik dengan skor 3,67; (3) Kejelasan petugas pelayanan Sangat Baik dengan skor 3,67; (4) Kedisiplinan petugas pelayanan Sangat Baik dengan skor 3,80; (5) Tanggung jawab petugas pelayanan Sangat Baik dengan skor 3,73; (6) Kemampuan petugas pelayanan Sangat Baik dengan skor 3,60; (7) Kecepatan pelayanan Baik dengan skor 3,00; (8) Keadilan mendapatkan pelayanan Sangat Baik dengan skor 3,67; (9) Kesopanan dan keramahan petugas Sangat Baik dengan skor 3,60; (10) Kewajaran biaya pelayanan Sangat Baik dengan skor 3,60; (11) Kepastian biaya pelayanan Sangat Baik dengan skor 3,80; (12) Kepastian jadwal pelayanan Sangat Baik dengan skor 3,80; (13) Kenyamanan lingkungan Sangat Baik dengan skor 3,67; dan (14) Keamanan pelayanan Sangat Baik dengan skor 3,67. Dengan demikian didapat nilai indeks sebesar 3,56988, selanjutnya nilai IKM setelah dikonversi (Nilai Indeks x Nilai Dasar), yaitu; 3,56988 x 25 = 89,247.
PENGARUH LITERASI KEUANGAN DAN ANTESEDENNYA TERHADAP TOLERANSI RISIKO DENGAN MODERASI FAKTOR DEMOGRAFI PADA PEKERJA MUDA DI INDONESIA
Authors: Permanasari Fitriani Marfuah , Harya Kuncara  , Ari Warokka
Published: February 2021

Penelitian ini bertujuan untuk melihat pengaruh literasi keuangan dan antesedennya terhadap toleransi risiko dengan moderasi faktor demografi pada pekerja muda di Indonesia. Anteseden dalam penelitian ini menggunakan Pendidikan Keuangan, Pengetahuan Keuangan, Sikap Keuangan dan Perilaku Keuangan. Penelitian dimoderasi oleh faktor demografi yaitu jenis kelamin dan status pernikahan. Penelitian dilakukan terhadap 580 pekerja muda di Indonesia khususnya di JABODETABEK melalui survey online (google-form). Metode penelitian yang digunakan dalam penelitian ini menggunakan pendekatan kuantitatif menggunakan teknik SEM (Structural Equation Modeling), untuk menguji efek moderasi peneliti menggunakan Multigrup Analysis. Penelitian ini menghasilkan bahwa literasi keuangan dan anteseden memiliki pengaruh positif pada toleransi risiko, sedangkan faktor demografi seperti jenis kelamin dan status pernikahan masing-masing memiliki pengaruh pada toleransi risiko.
Efficacy of vafidemstat in experimental autoimmune encephalomyelitis highlights the KDM1A/RCOR1/HDAC epigenetic axis in multiple sclerosis
Authors: Cavalcanti Fernando , Gonzalez-Rey Elena , Delgado Mario , Mestre Leyre , Guaza Carmen , Lufino Michele MP , Xaus Jordi , Mascaró Cristina , Lunardi Serena , Sacilotto Natalia , Dessanti Paola , Rotllant David , Navarro Xavier , Herrando-Grabulosa Mireia , Buesa Carlos , Maes Tamara
Published: February 2021

Background Vafidemstat (ORY-2001) is a clinical stage inhibitor of the Lysine Specific Demethylase KDM1A in development for treatment of neurodegenerative and psychiatric diseases. KDM1A demethylates H3K4me1/2 and together with the histone deacetylases HDAC1/2, it forms part of co-repressor complexes recruited by zinc finger factors to control transcription. The exact role of KDM1A in neuroinflammation remained to be explored. Methods Compounds were administered p.o. gavage to mice with MOG35-55 induced experimental autoimmune encephalomyelitis or mice infected with Theiler’s murine encephalomyelitis virus. Immune cell infiltration was analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by ELISA. Genome wide gene expression in spinal cord and brain were analyzed by two-color microarray analysis and qRT-PCR. Results ORY-2001 improved the clinical score in mouse experimental autoimmune encephalomyelitis and in mice infected with the Theiler’s murine encephalomyelitis virus. The compound reduced lymphocyte egress and infiltration of immune cells in the spinal cord and prevented demyelination. ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the induction of the inflammatory gene expression signature in the central nervous system more potently. Gene expression changes and axonal protection in animals, and protection against glutamate excitoxicity in spinal cord explants support that ORY-2001 has neuroprotective qualities. Conclusions ORY-2001 exerts therapeutic activity in two mouse models of multiple sclerosis. The anti-inflammatory properties of ORY-2001 are being tested in a Phase IIa clinical trial in patients with relapse remitting and secondary progressive multiple sclerosis, and in severely ill COVID-19 patients at risk for acute respiratory distress syndrome.
Chronic Effects of Different Intensities of Interval Training on Hemodynamic, Autonomic and Cardiorespiratory Variables of Physically Active Elderly People
Authors: Sant'Ana Leandro , Vianna Jeferson , Ribeiro Aline , Reis Natália , Silva João Guilherme , Campos Yuri , Monteiro Estevão , Brown Amanda , Novaes Jefferson , Scartoni Fabiana , Machado Sérgio , Budde Henning
Published: February 2021

Background

Interval training is an important strategy for promoting physiological adaptations. Therefore, this study aimed to verify the chronic effects of interval training (TI) with different intensities on hemodynamic, autonomic and cardiorespiratory variables of physically active elderly people.
Methods

Twenty-four physically active older men (age: 68.8 ± 6.8 years, body mass: 74.4 ± 18.1 kg, height: 170 ± 8 m, body mass index: 25.1 ± 2.2 kg / m²) participated in the study. Participants were randomized into three experimental groups: training group A (TGA, n = 8), training group B (TGB, n = 8), and control group (GC, n = 8). TGA and TGB groups performed 32 training sessions separated by a 48-hour interval. TGA showed 4-min with intensity relative to 55 to 60% of the HRmax and 1-min at 70 to 75% of the HRmax. TGB training group performed the same protocol but performed 4-min at 45 to 50% HRmax and 1-min at 60 to 65% HRmax. Both training groups performed each series for six times, totaling 30-min per session. The evaluations were carried out in the pre (baseline) moments after the 16th and 32nd intervention sessions. GC only carried out assessments. Hemodynamic variables (HRR, SBP, DBP, MBP, and DP), autonomic (HRV indices, in the time and frequency domain), and cardiorespiratory (VO2max estimated) variables were evaluated.
Results

There were no statistically significant differences in comparisons between protocols and moments (p > 0.05). However, the size of the effect and the percentage delta indicated clinical results with relevant magnitudes between protocols and moments, indicating favorable responses to the IT intervention in hemodynamic, autonomic, and cardiorespiratory variables.
Conclusion

IT can be an essential strategy in the prescription of training for conditional improvement of variables of cardioprotective function in physically active and healthy older people. However, other studies are suggested to establish the efficiency of this method for cardiovascular and cardiorespiratory variables in the elderly.
The Path to Implementation of A Clinical Laboratory System in A Developing Country
Authors: Lucien Mentor Ali Ber , Sakandé Jean , Masetti Chloé , Cicéron Micheline , Adrien Paul , Kouanda Seni , Canarie Michael F. , Maki Gina , Kaljee Linda M. , Kilgore Paul E. , Parke Dana M. , Joseph Gerard A. , Lafosse Elsie , Buteau Josiane , Stanislas Magalie , Dely Patrick , Zervos Marcus J. , Boncy Jacques
Published: February 2021

Background An effective laboratory system is an essential component of a public health system caring for patients with communicable and non-communicable diseases. Unfortunately, in developing countries this system is often sub-optimal, which negatively impacts health care. This paper describes the current situation of the clinical laboratory sector in Haiti and highlights challenges that exist in Haiti and other developing countries as they try to establish a clinical laboratory system. Method A cross-sectional survey was conducted in 30 laboratories across Haiti from January 19 to February 4, 2016. The laboratories surveyed were public or mixed public-private sector facilities belonging to different levels of the healthcare hierarchy. Labs were visited and directors of the health care institutions, lab managers, and members of their teams were interviewed and National Public Health Laboratory documents and information about the legal framework of the laboratory system was reviewed. Results The National Laboratory of Public Health is the reference lab for the national lab network and plays a key role in epidemiologic surveillance. Investigators felt that that the general conditions in the nation’s labs (83%) are good, but numerous deficiencies are identified. Electricity is often limited and 86% of facilities have mixed energy system. Bacterial cultures and susceptibilities are not performed. Most of the lab technologists (88.2%) have received only 2 two-year training certificates, while only the remainder (11.8%) had completed three-year programs training. Few continuing education opportunities are available. Equipment repair is available in more facilities (83%) than routine maintenance (63%) and is complicated by the diversity of brands employed. A total of 93% of the labs participate in the quality control program run by the National Lab. Conclusion The establishment of an effective national laboratory system requires coordination and input from many areas, including regulation of the sector, training of the technicians, sound infrastructure (including a stable supply of electricity) and dependable communications. Achieving this in developing countries will only be possible if different actors, national and international, coordinate their efforts.
Regional cerebral blood flow decline can predict atrophy in Alzheimer’s disease spectrum
Authors: Nabizadeh Fardin , Rostami Mohammad Reza , Balabandian Mohammad
Published: February 2021

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by symptoms such as dementia, personality changes, and executive dysfunction. Brain atrophy and structural changes based on the MRI play an important role as a valid biomarker of AD and can support the clinical diagnosis of AD. The decline in the regional cerebral blood flow (rCBF) is believed to be among the first changes in Alzheimer’s continuum. The reason for this reduction in cerebral blood flow is not fully understood yet. Previous studies revealed the association between amyloid-beta and rCBF pattern and suggested that reduced rCBF is an early consequence of neural death and is prior to the considerable grey matter loss. In this study we investigated the association between rCBF and brain structural changes in three different groups of subjects consisted of control (CN), MCI, and AD groups. Our findings revealed a significant correlation between rCBF and structural changes including cortical volume, subcortical volume, surface area, and thickness in all groups after adjusting for age, sex, and APOE genotyping status. As our investigation, cerebral blood flow as measured by ASL-MRI might independent from Aβ and tau accumulation predict future structural changes and causes neurodegeneration in relation to AD development.
Matrix Metalloproteinases Neutralizing Agents: A Possible Treatment Modality for Oral Lichen Planus (Preliminary Study)
Authors: Elsabagh Hossam , Gaweesh Yasmine , Ghonima Jaylane
Published: February 2021

Background: Oral lichen planus is one of the most prevalent oral diseases. Matrix metalloproteinases have been implicated in its pathogenesis thus this study was executed to evaluate the effectiveness of matrix metalloproteinases neutralizing agents in the treatment of oral lichen planus. Methods: Patients were assigned to either control group who received topical corticosteroids and antifungal treatment, or test group who received matrix metalloproteinases neutralizing spray. All patients were evaluated for disease severity and pain at baseline, 1 week, and 4 weeks after treatment. Results: The mean pain score in test and control groups was 9.00 (0.89), and 9.33 (0.82), respectively, at baseline while it was 2.33 (1.75) and 2.83 (1.72) at 4th week follow up. The mean disease severity score was 4.33 (0.52) for test group and 4.50 (0.55) for control group at baseline and decreased to 1.83 (0.75) and 2.17 (0.98) at 4th week follow up. Despite the better results seen in test group on the expense of control group, no statistically significant differences could be detected between groups at any timepoint. Conclusion: The use of matrix metalloproteinases neutralizing agents might be an equally effective sole treatment for erosive oral lichen planus compared to the conventional treatment, without the risk of secondary candidiasis. Trial registration: The study was registered retrospectively at ClinicalTrials.gov (NCT04336488), date (07/04/2020)
Characteristics, Comorbidities, and Outcomes among Patients admitted with COVID-19 in Sheikh Khalifa Medical City: A Retrospective Study
Authors: Qadi Lara Al , Abdelwahab Moustafa , Jawabreh Mohammad Al , Sulaiman Hanan , Blooki Mariam Al
Published: February 2021

Background: Many studies were published to describe the clinical characteristics of COVID-19, however there is still lack of knowledge and it’s time to take stock of the war against coronavirus disease 2019 (COVID-19) pandemic before we hit another million in a matter of days. Simply Identifying COVID-19 features will help in mapping the disease and guiding pandemic management. A retrospective review, retrospective study was initiated in SKMC to describe the demographic data, clinical characteristics, and outcomes of COVID-19 cases who were hospitalized during that period. Methods: Confirmed positive COVID-19 sample patients from April 1st 2020 to May 31st 2020 in Sheikh Khalifa Medical City. Clinical characteristics, Demographic data, incubation periods, laboratory findings, and patient outcomes data retrieved from 336 cases in the electronic medical chart (SALAMTAK). Results: The median age was 44 years and 83.9% (n = 282) of the patients were men. The patients with diabetes mellitus being the most common risk factor (25.0%), followed by hypertension (22.9%) and Age ≥60 were (13.4%). Total 36 patients (10.7%) were asymptomatic. The most common symptoms were upper respiratory tract symptoms, manifested as dry cough (70.2%), and followed by fever (54.2%), shortness of breath (43.5%), headache (25.9%) and sore throat (25.3%). Less common symptoms were diarrhea (16.7%) chest pain (14.6%). The maximum length of stay is 32 days. The minimum length of stay in [ICU/HDU] was 1 day and the maximum was 21 days. Conclusion: In this retrospective study, fever and cough were common symptoms. Special attention should be given to patients with risk factors especially patients with one risk factor such as diabetic patients, patients with hypertension and older patients over 60 years as they are the most highly prevalent in this case series. Disease was affecting males and D-dimer was significantly elevated in deceased patients.
Preference of Proteomonas Sulcata Anion Channelrhodopsin for Nitrate Revealed Using a pH Electrode Method
Authors: Kikuchi Chihiro , Kurane Hina , Watanabe Takuma , Demura Makoto , Kikukawa Takashi , Tsukamoto Takashi
Published: February 2021

Ion channel proteins are physiologically important molecules in living organisms. Their molecular functions have been investigated using electrophysiological methods, which enable quantitative, precise and advanced measurements and thus require complex instruments and experienced operators. For simpler and easier measurements, we measured the anion transport activity of light-gated anion channelrhodopsins (ACRs) using a pH electrode method, which has already been established for ion pump rhodopsins. Using that method, we successfully measured the anion transport activity and its dependence on the wavelength of light, i.e. its action spectra, and on the anion species, i.e. its selectivity or preference, of several ACRs expressed in yeast cells. In addition, we identified the strong anion transport activity and the preference for NO3- of an ACR from a marine cryptophyte algae Proteomonas sulcata, named PsuACR_353. Such a preference was discovered for the first time in microbial pump- or channel-type rhodopsins. Nitrate is one of the most stable forms of nitrogen and is used as a nitrogen source by most organisms including plants. Therefore, PsuACR_353 may play a role in NO3- transport and might take part in NO3--related cellular functions in nature. Measurements of a mutant protein revealed that a Thr residue in the 3rd transmembrane helix, which corresponds to Cys102 in GtACR1, contributed to the preference for NO3-. These findings will be helpful to understand the mechanisms of anion transport, selectivity and preference of PsuACR_353.
Molecular Alterations in Basal Cell Carcinoma Subtypes
Authors: Nardo Lucia Di , Pellegrini Cristina , Stefani Alessandro Di , Ricci Francesco , Fossati Barbara , Regno Laura Del , Carbone Carmine , Piro Geny , Corbo Vincenzo , Delfino Pietro , Summa Simona De , Maturo Maria Giovanna , Rocco Tea , Tortora Giampaolo , Fargnoli Maria Concetta , Peris Ketty
Published: February 2021

A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour.We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.9% and 45.6% of BCCs, respectively. A high mutation rate was also detected in CSMD1 (63.2%), NOTCH1 (43.8%) and DPP10 (35.1%), and frequent non-coding mutations were identified in TERT (57.9%) and DPH3 promoter (49.1%). CSMD1 mutations significantly co-occurred with TP53 changes (p=0.002). A significant association was observed between the superficial type of BCC and PTCH1 (p=0.017) and NOTCH1 (p=0.018) mutations. In addition, PTCH1 mutations were significantly associated with intermittent sun exposure (p=0.046) and the occurrence of single lesions (p=0.021), while NOTCH1 mutations were more frequent in BCCs located on the trunk compared to the head/neck and extremities (p=0.001).In conclusion, we provide further insights into the molecular alterations underlying the tumorigenic mechanism of superficial and nodular BCCs with a view towards novel rationale-based therapeutic strategies.
3D Reconstruction of Coronary Artery Stents From Optical Coherence Tomography: Experimental Validation and Clinical Feasibility
Authors: Wu Wei , A. Khan Behram , Sharzehee Mohammadali , Zhao Shijia , Samant Saurabhi , Watanabe Yusuke , Murasato Yoshinobu , Mickley Timothy , Bicek Andrew , Bliss Richard , Burzotta Francesco , Samady Habib , Brilakis Emmanouil S. , Dangas George , Louvard Yves , Stankovic Goran , Dubini Gabriele , Migliavacca Francesco , Kassab Ghassan S. , Edelman Elazer R. , Chiastra Claudio , Chatzizisis Yiannis S.
Published: February 2021

The structural morphology of stents (e.g. expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment in coronary arteries are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically correct 3D reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents by OCT and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility and ability to perform CFD studies. Our method has the following steps: 3D lumen reconstruction by OCT and angiography, stent strut segmentation on OCT images, packaging, rotation and straightening of the segmented struts, and planar unrolling of the segmented struts, planar stent wireframe reconstruction, rolling back of the planar stent wireframe to the 3D reconstructed lumen, and stent volume reconstruction. We tested the accuracy and reproducibility of our method in stented patient-specific silicone models using micro computed tomography and stereoscopy as reference. The clinical feasibility and CFD studies were performed in clinically stented coronary bifurcations. Our experimental and clinical studies showed that our proposed algorithm can reproduce the complex stent configuration in space with high precision and reproducibility. Furthermore, our studies showed that the algorithm is feasible in clinical cases with stents deployed in diseased, bifurcated coronary arteries, enabling CFD studies to assess the hemodynamic environment. Notably, the high accuracy of our algorithm was consistent across different stent designs and diameters. Our method coupled with patient-specific CFD studies can facilitate stenting optimization, training in stenting techniques, and stent research and development.
Sustainability in Quality Improvement (SusQI): Challenges and Strategies for Translating Undergraduate Learning Into Clinical Practice
Authors: Marsden Oliver , Clery Philippa , Smith Stuart d'Arch , Leedham-Green Kathleen
Published: February 2021

Background

The healthcare sector is a major contributor to climate change and there are international calls to mitigate environmental degradation through more sustainable forms of clinical care. The UK healthcare sector has committed to net zero carbon by 2040 and sustainable healthcare is a nationally mandated outcome for all UK graduating doctors who must demonstrate their ability to address social, economic and environmental challenges. Bristol Medical School piloted successful Sustainability in Quality Improvement (SusQI) teaching, but identified challenges translating classroom learning into clinical practice. This paper aims to identify and address those challenges.
Methods

We conducted five focus groups that identified and iteratively explored barriers and facilitators to practice among medical students, comparing a range of experiences to generate a conceptual framework. We then combined our findings with behaviour change theory to generate educational recommendations.
Results

Students that applied their learning to the clinical workplace were internally motivated and self-determined but needed time and opportunity to complete projects. Other students were cautious of disrupting established hierarchies and practices or frustrated by institutional inertia. These barriers impacted on their confidence in suggesting or achieving change. A minority saw sustainable healthcare as beyond their professional role.
Conclusions

We present a series of theoretically informed recommendations. These include wider curricular engagement with concepts of sustainable clinical practice; supportive workplace enablement strategies such as workplace champions and co-creation of improvement goals; and time and headspace for students to engage through structured opportunities for credit-bearing project work.
Identification of Core Gene Biomarkers in Patients With Hypertrophic Cardiomyopathy
Authors: Yang Xiaomeng , Jiang Hong
Published: February 2021

Objective：Hypertrophic cardiomyopathy (HCM) is a kind of common hereditary myocardial disease. However, there is still a lack of detailed research in the specific mechanism of HCM. In the present study, gene microarray data were used for bioinformatics analysis to explore differentially expressed genes (DEGs) and signaling pathways between HCM patients and normal control, which would provide suggestion for the prevention and treatment for the further study of HCM.Methods: Gene microarray data of HCM patients and normal control were obtained from the Gene Expression Omnibus (GEO) database affiliated to National Center for Biotechnology Information (NCBI). Gene microarray data of 15 HCM patients and 10 normal people were respectively included. We compared the number of DEGs between the two groups, performed gene ontology (GO) enrichment analysis, kyoto encyclopedia of genes and genomes (KEGG) analysis, construct a protein-protein interaction (PPI) network based on the DEGs detected above.Results: A total of 501 DEGs were selected through analysis, among which 275 were up-regulated and 226 were down-regulated. The DEGs are mainly concentrated in ribosomes, myocardial contractions and various signaling pathways. The down-regulated cellular components and molecular functions of HCM patients were mainly associated with ribosome-related components, and PPI network also found that the DEGs were mainly derived from the ribosome family. Upregulated pathways were mainly enriched in Hippo signaling pathway, PI3K-Akt signaling pathway, AMPK signaling pathway, and adrenergic signaling in cardiomyocytes.Conclusion: By analyzing the DEGs between HCM and normal patients, differentially expressed genes, cellular components and biological processes were found. By exploring the specific mechanism of these DEGs and intervening HCM through various medical procedures, useful suggestions can be provided for targeted prevention, precise treatment and outcome improvement of HCM patients.
Association of Sarcopenic Obesity and Body Composition With Metabolically Unhealthy Overweight/Obese Phenotypes Among Iranian Women: A Cross-Sectional Study
Authors: Jibril Aliyu Tijani , Mirzababaei Atieh , Shiraseb Farideh , Rasaei Niloufar , Mirzaei Khadijeh
Published: February 2021

Objectives

Obesity is a major risk factor for metabolic syndrome, with its prevalence has increased over the past decade. Major changes in body composition with aging have a significant effect on many clinical outcomes. Sarcopenic obesity consists of both the presence of abnormal adipose tissue with a deficit of muscle mass.
Results

Of the 241 subjects in this study (average age 35.32 years), 176 (73.03%) were classified as MUO phenotype. Based on this study, the prevalence of sarcopenic obesity was 7.88%. We found that high fat-free mass was more strongly and significantly associated with MUO phenotype. Furthermore, we found that individuals with high fat-free mass and high skeletal muscle mass had a significantly low prevalence of MUO phenotype. A significant positive correlation between metabolic phenotypes and sarcopenic obesity was also observed after all potential covariates were adjusted for. These results of this study suggest that increased adiposity and decreased skeletal muscle mass are associated with unfavorable metabolic traits among overweight and obese Iranian women. SO was also found to be associated with a greater risk of developing MUO phenotype.
Age-Dependent Occurrence and Progression of White Matter Hyperintensities in Patients With Systemic Lupus Erythematosus
Authors: Sano Eri , Ishida Shimon , Takeuchi Tohru , Nakaya Yoshifumi , Arawaka Shigeki
Published: February 2021

To elucidate the process of white matter hyperintensities (WMH) deterioration in SLE, we here report the occurrence of WMH on brain magnetic resonance imaging (MRI) by age group and the WMH deterioration rate in patients with SLE. Age-adjusted ratios of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) in the SLE group (n = 142) were higher than those in the control group (n = 216, p = 0.003 and p < 0.0001, respectively). The difference was remarkable in middle-aged patients (≥40 and <60 years) (p < 0.0001 for PVH and DWMH). In middle-aged patients with SLE, WMH were associated with factors related to atherosclerosis, including hypertension (OR, 4.0; 95% CI, 1.1–15.8 for PVH and OR, 4.5; 95% CI, 1.1–18.5 for DWMH) and dyslipidemia (OR, 22.2; 95% CI, 1.6–300.5 for PVH). In Kaplan–Meier analysis, the overall rate of one grade WMH deterioration on the Fazekas scale was 8.2% per year after a 15-year follow-up (<60 years, n = 68). WMH in middle-aged patients declined more rapidly than younger patients. Our study reveals that middle-aged patients with SLE pose a risk for developing WMH because of atherosclerotic changes and also can have progressively worsening WMH.
Enhance Smooth Muscle Cells Apoptosis Associated With Pulmonary Arterial Remodeling in Dogs Affected With Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease
Authors: Sakarin Siriwan , Rungsipipat Anudep , Surachetpong Sirilak Disatian
Published: February 2021

Background: Degenerative mitral valve disease (DMVD) is the most common cause of pulmonary hypertension (PH) in dogs. Medial thickening of the pulmonary artery is a major histopathological change in PH. A decrease in apoptosis of pulmonary arterial smooth muscle cells (SMCs) may be the cause of medial thickening. This study aimed to demonstrate the expression of apoptosis molecules in the pulmonary artery of dogs affected with PH secondary to DMVD (DMVD+PH) compared to DMVD without PH (DMVD) and healthy dogs (control). Lung samples were collected from three groups including control (n=5), DMVD (n=7) and DMVD+PH (n=7) groups. Masson trichrome and apoptotic proteins including Bax, Bcl2 and caspase-3 and -8, were stained. Results: The medial thickness in the DMVD and DMVD+PH groups was greater than in the control group and it was greatest in the DMVD+PH group. Bax, Bcl2 and caspase-3 and -8 were expressed mainly in the medial layer of the pulmonary artery. The percentages of Bax and caspase-3 and -8 positive cells were higher in the DMVD group compared to the DMVD+PH group, whereas the percentage of Bcl2-positive cells was increased in the DMVD and DMVD+PH groups. These findings suggested that apoptosis of pulmonary arterial SMCs occurred mainly in the DMVD group and decreased dramatically in the DMVD+PH group. Conclusions: An increase in the medial thickness in dogs affected with PH secondary to DMVD may occur due to a decrease in apoptosis of pulmonary arterial SMCs.
The Effect of Comorbidities on Glycemic Control Among Colombian Adults With Diabetes Mellitus: a Longitudinal Approach With Real-world Data
Authors: Urina-Jassir Manuel , Herrera-Parra Lina Johana , Vargas Juliana Alexandra Hernández , Valbuena-García Ana María , Acuña-Merchán Lizbeth , Urina-Triana Miguel
Published: February 2021

Background: Achieving an optimal glycemic control has been described to reduce the incidence of diabetes mellitus (DM) related complications. The association between comorbidities and glycemic control remains unclear. Our aim is to evaluate the effect of comorbidities on glycemic control in people with DM.Methods: A retrospective longitudinal study on data from the National Registry of Chronic Kidney Disease from 2014 to 2019 in Colombia. The outcome was poor glycemic control (PGC = HbA1c ≥7.0%). The association between each comorbidity (hypertension (HTN), chronic kidney disease (CKD) or obesity) and PGC was evaluated through multivariate mixed effects logistic regression models. The measures of effect were odds ratios (OR) and their 95% confidence intervals (CI). We also evaluated statistical interaction between each comorbidity and ethnicity. Results: From 969,531 people at baseline, 85% had at least one comorbidity; they were older and mostly female. In people with DM and CKD, the odds of having a PGC were 78% (OR: 1.78, CI 95%: 1.55-2.05) higher than those without CKD. Same pattern was observed in obese for whom the odds were 52% (OR: 1.52, CI 95%: 1.31-1.75) higher than in non-obese. Non-significant association was found between HTN and PGC. The association of interest was statistically modified by ethnicity (afro descendant). Conclusions: Prevalence of comorbidities was high in adults with DM. Patients with concomitant CKD or obesity had significantly higher odds of having a PGC.
Performance Evaluation of the Serological Test and Dynamic Changes of Anti-2019-nCoV Antibodies Among COVID‐19 Patients
Authors: Chen Lifeng , Chen Jun , Ren Yi , Du Ronghui , Li Na , Xiang Hao
Published: February 2021

BackgroundSerological tests for anti-2019-nCoV antibodies have been developed, however, validation with clinical samples was insufficient and mixed. MethodsA total of 197 patients with COVID-19 hospitalized in the Wuhan Pulmonary Hospital and 114 healthy people were enrolled in this study. The IgM/IgG was measured by chemiluminescence detection kit and the performance of IgM/IgG was assessed through diagnostic test. A smooth spline function was used to fit a possible dynamic changes of antibody content.ResultsThe sensitivity and specificity to diagnose COVID-19 were 96.95% and 92.98% for IgG, and 65.99% and 98.25% for IgM, respectively. The period with the highest IgM positive rate (93.75%) was 11 to 13 days after the onset, while the IgG positive rate was almost 100% in the patients whose serum was collected 7 days after onset. Small differences were found in IgM content among mild/regular, severe and critical patients. IgG content in critical patients were highest in the 2-week post-symptom onset group, while the IgG in the severe patients were highest in the 15-28 days and more than 28 days post-symptom onset.ConclusionsSerological testing performed well in the diagnosis for COVID-19, and the positive rate and variance of IgG are higher than those of IgM.
Relation of Hypertension With Migraine and Chronic Daily Headache in Population of Rafsanjan Cohort Study
Authors: Mohammadi Movahedeh , Ayoobi Fatemeh , Khalili Parvin , Soltani Narjes , Vecchia Carlo La , Vakilian Alireza
Published: February 2021

Background: Headache has a variety of types, such as Migraine and chronic daily headache (CDH) in its primary form. There is a positive correlation between these two types of headaches and hypertension (HTN), but in some works this correlation has been reported negatively. Therefore, we planned to study HTN-Migraine as well as HTN-CDH correlation in our population.Methods: A sample of Rafsanjan population (10000 individuals) entered the cohort study, as a part of the prospective epidemiological research studies in IrAN (PERSIAN). In this population, we compared the frequency of HTN categories in cases with Migraine and CDH with a normal population (without Migraine).Results: Out of 9990 participants (46.6% males and 53.4% females) about 29% had Migraine and 7.5 % had CDH.HTN was found in 24.27% of Migraine and 31.98% of CDH cases. HTN was also found to be associated with Migraine and CDH in the crude model. Two Categories of HTN (Long controlled and uncontrolled) were not associated with Migraine. On the other hand, CDH showed associations with all the HTN categories. Moreover, in a model, which included all variables and confounders, Migraine and CDH had association with HTN without any considerable changes.Conclusion: Our study showed that there is strong HTN-Migraine as well as HTN-CDH correlations in the studied population.
Effects of Prophylactic Antibiotic Administration and Antibiotic Timing on Culture Results and Clinical Outcomes of Pediatric Musculoskeletal Infection: A Protocol for A Randomized, Controlled, Clinical Trial
Authors: Xia Yongjie , Deng Chao , Zhou Yibiao , Wu Dechao , Liu Zhiyong , Xie Liangfu , E Bing , Han Jingming , You Chao
Published: February 2021

Background: Musculoskeletal infection (MSI) is a common cause of morbidity among the pediatric population. Some clinicians recommend withholding prophylactic antibiotics until culture collection with an aim to improve the culture sensitivity. However, a recent retrospective study reported that prophylactic antibiotic administration did not affect culture sensitivities in either disseminated or local MSI in pediatric population, which is surprising. Therefore, the aim of this study is to investigate the effects of prophylactic antibiotic administration and the timing of antibiotic administration on culture sensitivity and clinical outcomes of pediatric MSI.Methods: A randomized, controlled, clinical trial will be carried out. Individuals aged 0 to 18 years with a diagnosis of MSI will be screened and evaluated at the Shenzhen Children’s Hospital. The participants will be randomly allocated into four groups, and they will receive the antibiotic treatment at different time points, that is, 1 week, 3 days, 1 day prior to culture collection and 1 day after culture collection, respectively. The primary outcome will be culture sensitivity. In addition, the disease-related markers including white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate, vital signs as well as the length of hospital stay will be measured or recorded accordingly. Using chi-squared tests, the rates of positive cultures will be compared between different groups. Statistical comparisons between the different patient groups regarding the confounding and outcome variables will be conducted using independent t-tests, Mann-Whitney U tests, chi-squared tests and Fisher’s exact tests as appropriate with the significance level set to 5% (P<0.05).Discussion: The results of this study would provide some evidence for the clinical management of pediatric MSIs with regards to the application of prophylactic antibiotics.Trial registration: Chinese Clinical Trial Registry, ChiCTR2100041631. Registered at 1 January 2021, http://www.chictr.org.cn/hvshowproject.aspx?id=69850.