bluuebunny/crossref_metadata_2025 huggingface dataset:
BREAST CANCER IN WESTERN KAZAKHSTAN: INCIDENCE, MORTALITY AND FACTORS ASSOCIATED WITH SURVIVAL
Authors: Aitmagambetova Marzhan A. , Bekmukhambetov Yerbol Zh. , Smagulova Gaziza A. , Tulyayeva Anar B. , Koyshybaev Arip K. , Grjibovski Andrey M.
Published: August 2021

Background: Breast cancer is the most common cancer among women. Incidence of and mortality from breast cancer varies considerably between countries. The evidence from Kazakhstan, however, is almost non-existent in international peer-reviewed literature. Aim: To study incidence of and mortality from breast cancer in Western Kazakhstan and assesse selected determinants of survival among breast cancer patients. Methods: A registry-based historical cohort study. Data on all primary cases of breast cancer in the Aktobe region in 2014-2018 and their follow-up data were obtained from the regional cancer registry. Standardized incidence and mortality data were calculated using Segi world reference population. One- and five-years survival was calculated using actuarial analysis. Factors associated with survival were assessed using multivariable Cox regression. Crude and adjusted hazard ratios (HR) were calculated with 9 5 % confidence intervals (CI). Results: From 2014 to 2018, 891 new cases and 251 deaths from breast cancer were registered in the Aktobe region. Standardized incidence of breast cancer increased from 40.8 to 44.6 per 100,000 while standardized mortality decreased from 12.4 to 8.8 per 100,000 during the study period. Only 16.4 % of cases were diagnosed at stage I, while 21.6 % of cancer cases were detected at stage III or IV. One- and five-year survival estimates based on the registry data was 94.5 % (95 % CI: 92.5-96.5) and 90.2 % (95 % CI: 88.2-92.2), respectively. Patients with stage III (HR = 7.4, 95 % CI: 1.7-31.6) and stage IV (HR = 29.7, 95 % CI: 6.7-131.8) had shorter survival than patients with stage I. Conclusions: Both incidence and mortality of breast cancer in Western Kazakhstan are lower than in most European countries. The incidence has been gradually increasing while no clear pattern on mortality was observed. Surprisingly high level of five-year survival in the study area requires further investigation. The results should be interpreted with caution assuming valid data on cancer-specific mortality and non-differential reporting of deaths across the studied characteristics.
Comparación de la performance de dos catalizadores sólidos a base de Na y Ce soportados sobre SBA-15 para la producción de biodiesel mediante catálisis heterogénea alcalina
Authors: Sánchez Faba Edgar Maximiliano , Stobbia Daniel , Ferrero Gabriel Orlando , Eimer Griselda Alejandra
Published: August 2021

En este trabajo se presenta la comparación de la actividad de dos catalizadores sólidos mesoporosos (uno unimetálico y otro bimetálico) con propiedades básicas para la producción de biodiesel mediante catálisis heterogénea. Inicialmente, los catalizadores se sintetizaron por impregnación húmeda del soporte SBA-15 con sodio y cerio (10Na/SBA-15 y 5Na/20Ce/SBA-15). Luego se realizó la caracterización fisicoquímica y textural de estos materiales para estudiar tanto su estructura como sus propiedades básicas. Los materiales se emplearon en la transesterificación de aceite de girasol con metanol absoluto. Si bien el catalizador unimetálico produjo un alto contenido de ésteres metílicos en el primer ciclo, al reutilizarlo, los contenidos fueron disminuyendo, dando cuenta de la existencia de lixiviado de las especies activas. Por su parte, el catalizador bimetálico mostró una mayor estabilidad, consiguiéndose contenidos de FAME por sobre el 85% p/p en cuatro ciclos de reutilización.
Materiales de dióxido de titanio como fotocatalizadores activos en la remoción de ibuprofeno de matrices acuosas, a partir de tecnologías ambientalmente amigables
Authors: Ochoa Rodríguez Pablo Alejandro , Vaschetto Eliana Gabriela , Brunetti Verónica , Sueldo Occello Valeria Noemí , Casuscelli Sandra Graciela , Elías Verónica Rita , Eimer Griselda Alejandra
Published: August 2021

Se sintetizaron nanopartículas de dióxido de titanio mesoporosas autodopadas con carbono empleando un método de síntesis amigable con el medio. Los materiales fueron caracterizados con distintas técnicas, entre ellas estudios de profundidad de los sólidos mediante XPS. Éstos, permitieron dilucidar avances sobre la naturaleza de las especies de carbono responsables de la fotosensibilidad de los materiales, pudiendo distinguir entre el carbono superficial y el carbono que forma parte de la matriz de titania. Se estudió el efecto de la calcinación en términos de la respuesta de los sólidos a luz visible LED, para degradar ibuprofeno (IBU) en soluciones acuosas. La mayor degradación se alcanzó empleando el fotocatalizador autodopado con carbono y tratado a 200 °C. Se propuso que la generación de nuevos estados electrónicos, responsables de reducir la banda prohibida del TiO2, debido a la presencia de carbono en distintos sitios en la red, es la responsable de este comportamiento.
Test-Retest Differences of the Speech Discrimination Score in Patients with Hearing Loss
Authors: Lim Taehun , Oh Joo Hyung , Hwang Junho , Joo Joon Bum , Cho Ju Eun , Kim Jong Yang
Published: August 2021

Background and Objectives The diagnosis of hearing impairment is based on repeated audiometry, including pure tone audiometry (PTA), speech reception threshold test (SRT), and speech discrimination test (SDT). SDT results particularly show a wide discrepancy upon repeated testing, while malingering is suspected when having more than 12% difference between 3 individual SDT results. Therefore, in this study, we compared the proportion of malingering found in repeated SDT with that found in other audiometric tests and analyzed the characteristics of malingering group in order to reevaluate the current criteria of defining malingering.Subjects and Method We retrospectively assessed the audiometry results of 113 patients (226 ears) with hearing impairment. Each ear was divided into a malingering group and a true hearing loss group. The proportion of ears corresponding to each malingering criterion was compared using a chi-square test. An independent sample t-test was performed to identify the differences between the characteristics between the two groups.Results The number of ears that met the malingering criteria were 19 (8.41%) in PTA, 15 (6.64%) in SRT, and 75 (33.19%) in SDT. There was a significant difference in the proportion of malingering between the 3 hearing test modalities (p<0.001). There was no significant difference in auditory brainstem response, mean age and sex distribution between the malingering group and the true hearing loss group.Conclusion When conducting repeated SDT, there is a risk of misdiagnosing an actual hearing loss patient as a malingering patient under the current malingering criteria. Therefore, the current criteria on SDT requires reevaluation.
Critical Legal issues in the Nigerian Gas to Power Contractual Arrangements
Authors: Aladeitan Olanrewaju , Anaghara-Uzor Obiageli Phina
Published: August 2021

The natural gas and power sectors are pivotal sectors of the Nigerian economy with reflective effect on its gross domestic product. The Federal Government in its gas revolution agenda is taking giant strides to reposition the sector to more adequately harness its abundant natural gas resources and ensure availability of natural gas to the domestic market with the gas supply to the power sector being regulated to build base load volumes to ensure stable electricity supply to its citizens. The synergic connection of the gas and power sectors can only validly exist upon legitimate contractual arrangements such as the gas sale and purchase agreement, the gas transport agreement and the gas sale aggregation agreement which is unique to Nigerian domestic gas industry. Out of these arrangements flow pertinent legal issues which define clearly the relations between the parties. This paper therefore throws more light on some of these salient issues which arise pursuant to the respective agreements. It is hoped that this discourse would guide and further facilitate a deeper understanding of these critical terms.
Studi Fenomenologi Pengalaman Ibu dengan HIV/AIDS dalam Mengasuh Anak
Authors: Rahmawati Dewi , Ernawati Eka
Published: August 2021

Masalah yang ditimbulkan akibat penyakit HIV/AIDS dapat berdampak terhadap kehidupan ibu dengan HIV/AIDS dan berpengaruh terhadap kehidupan mengasuh anak. Kompleksitas pengaruh penyakit HIV/AIDS membantu ibu merubah pola asuh dalam merawat diri, anak dan keluarganya. Tujuan penelitian ini untuk mengetahui pengalaman ibu dengan HIV/AIDS dalam mengasuh anak. Desain penelitian menggunakan kualitatif dengan pendekatan fenomenologi. Hasil penelitian mendapatkan tiga tema yaitu: perubahan psikologis ibu dengan status HIV, harapan terhadap orang tersayang, dan pemilihan pola asuh dominan oleh ODHA kepada anaknya. Dampak penyakit HIV masih menimbulkan respon psikologis ibu dalam menerima kondisi sakit, yang berdampak terhadap pemilihan pola asuh yang dominan antara otoriter dan permisif. Kompleksnya permasalahan yang ditimbulkan akibat HIV/AIDS membutuhkan sistem layanan kesehatan terintegrasi lintas sektoral dengan departemen agama, pendidikan, dan sosial. Perlunya peningkatan layanan konselor di rumah sakit dan departemen agama untuk mengembangkan program atau topik konseling pranikah bagi pasangan yang akan menikah. Perlunya menyiapkan atau memperkaya tema bimbingan pranikah terutama resiko keluarga HIV ataupun penyakit menular lainnya. Departemen pendidikan sebaiknya mengadakan sosialisasi mengenai pendekatan dan pencegahan HIV bagi siswa sekolah. Departemen sosial perlu memastikan ketersedian fasilitas untuk layanan kesehatan sosial yang bisa menampung anak dengan HIV atau anak terdampak HIV.
RANCANG BANGUN MESIN KONVERSI SAMPAH PLASTIK KAPASITAS 3 KG MENJADI BAHAN BAKAR MINYAK
Authors: Maulana Ikhsan , Saputra Indra Wahyu
Published: August 2021

Sampah plastik merupakan masalah serius yang belum terselesaikan di Indonesia, jika tidak ditanggulangi dengan serius akan mengakibatkan kerusakan lingkungan yang semakin parah. Oleh karena itu harus dilakukan proses recycling sampah plastik. Penelitian ini menggunakan metode pirolisis untuk mengubah plastik menjadi bahan bakar. Jenis plastik yang digunakan adalah PET (polyethylene Terephthalate). Pembuatan alat terdiri dari kompor, ruang pemanasan, ruang pembakaran, kondensor dan ruang filter asap pembakaran. Penelitian ini melakukan proses pembuatan komponen pada alat dengan tahap-tahap sesuai teori perancangan. metode pada alat ini melakukan proses pirolisis, dimana uap hasil pemanasan plastik dimanfaatkan dengan cara didinginkan sehingga merubah fase uap menjadi fase cair atau biasa disebut kondensasi.  Pengujian yang dilakukan pada alat menggunakan 3 kg sampah plastik PET dengan menghitung berapa banyak bahan bakar oli bekas yang di butuhkan dan berapa bahan bakar minyak yang dihasilkan saat alat dioperasikan dalam jangka waktu 60 menit. Dari hasil pengujian didapatkan bakan bakar oli bekas yang dibutuhkan sebanyak ± 140 mL liter dan hasil bahan bakar minyak sebanyak ± 140 mL liter dalam jangka waktu 60 menit.
RANCANG BANGUN ALAT SANDBLASTING SEBAGAI PEMBERSIH KOTORAN PADA PERMUKAAN LOGAM
Authors: Pambudi Faisal Arif , Naubnome Viktor , Fauzi Najmudin
Published: August 2021

Sandblasting adalah salah satu dari cara pembersihan permukaan terutama logam supaya kotoran seperti  karat, oli, dan cat yang terdapat pada permukaan logam dapat dibersihkan. Proses sandblasting dilakukan dengan menembakan bahan abrasive dengan tekanan udara tinggi kepermukaan logam sehingga kotoran yang menempel akan terkikis dan rontok. Tujuan dari penelitian ini adalah untuk merancang dan membuat sebuah alat sandblasting dengan biaya yang terjangkau untuk industri manufaktur kecil menengah. Metode yang digunakan dalam penelitian ini dibagi berberapa tahap. Tahap pertama adalah mendesain alat dengan aplikasi gambar teknik serta menentukan alat dan bahan yang diperlukan. Tahap ini juga akan menentukan kenyamanan dan keamanan bagi operator yang mengoperasikan alat sandblasting ini. Tahap kedua adalah merakit alat yang sesuai dengan desain gambar dan alat serta bahan. Tahap terakhir adalah uji coba alat sandblasting dengan menggunakan spesimen plat baja karbon rendah SS400 yang berkarat. Semua tahapan tersebut dilakukan di Laboratorium Teknik Universitas Singaperbangsa Karawang.
PENGARUH JENIS BAHAN BAKAR GASOLIN TERHADAP PRESTASI, PEMBAKARAN, GETARAN, KEBISINGAN, DAN EMISI GAS BUANG PADA MESIN TYPE TV-1
Authors: Putra Andi Erwin Eka , Aziz Nasruddin
Published: August 2021

The growth of vehicles in Indonesia is dominated by motorcycles. The current compression ratio of the motorcycle is above 9 : 1. Types of gasoline on the market have octane number of 88, 90, 92. The purpose of this study is to analyze engine and combustion performance, noise and vibration, and emissions from gasoline type with a compression ratio of 10 : 1. This study was used engine with 1 cylinder and 4 strokes, sound level meter to measure noise, VibexpertII with acceleration mode for vibration measurement, AGS-688 for exhaust emission test. The test results showed that the break power of all fuels tends to be constant and the smallest SFC is an octane number of 92 (ON 92). The combustion performance of ON 92 also tends to be stable, but noise and vibration of ON 92 are higher. CO and HC emissions of all fuel tend to be constant.
ANALISA KEKUATAN MEKANIS SAMBUNGAN LAS KAMPUH V TUNGGAL DAN V GANDA PADA BAJA KARBON RENDAH DENGAN PROSES PENGELASAN SMAW
Authors: Sudarsono Sudarsono , Hidayat Hidayat , Aminur Aminur , Pranoto Sarwo , Aksar Prinob
Published: August 2021

Welding is one of the methods widely used in the joining of metals for structural elements. One of the factors that influence the strength of welded metals is types of welding joints. Suitability of the type of welding joint with geometries of base metals is required to obtain welded metal products with optimum properties. In this study an attempt is made to investigate mechanical properties of welded metals with two different types of joints (single-V and double-V) using the shielded metal arc welding (SMAW) process. Low carbon steel with bevel angle of 60° was used in this study. Welding process was performed using current of 70 A with a constant welding speed. The flexural properties and uniaxial tensile properties are studied by three-point bending test and uniaxial tensile test respectively. Test results show that the tensile strength and the bending strength of single-V specimens is 521.64 N/mm2 and 525.11 N/mm2 respectively. In addition, the tensile strength and the bending strength of double-V specimens is 517.33 N/mm2 and  504.24 N/mm2 respectively
Natural cybernetics and mathematical history: the principle of least choice in history
Authors: Penchev Vasil
Published: August 2021

The paper follows the track of a previous paper “Natural cybernetics of time” in relation to history in a research of the ways to become mathematical regardless of being a descriptive humanitarian science with investigating unique events and thus rejecting any repeatability. The pathway of classical experimental science to be mathematized gradually and smoothly by more and more relevant mathematical models seems to be inapplicable. Anyway quantum mechanics suggests another pathway for mathematization; considering the historical reality as dual or “complementary” to its model. Particularly, a fundamental law of mathematical history, the law of least choice of the real historical pathway is deducible from the same approach. Its counterpart in physics is the well-known and confirmed law of least action as far as the quantity of action corresponds equivocally to the quantity of information or that of number elementary historical choices.
Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer
Authors: Li Kuo , Zhang Youjiu , Wang Xiaomei , Zhu Ran , Ma Changsheng , Hu Rui
Published: August 2021

Purpose: In this study, we independently synthesised and labelled a novel bidentate bifunctional chelating agent, 177Lu-3,4-HOPO-Cetuximab, that achieved tight binding between targeting and radioactivity, and evaluated its targeted killing ability of cells in vitro and in vivo.

Method: 3,4-HOPO was successfully synthesised through a series of chemical steps using malt phenol as the raw material, which was then coupled with Cetuximab labelled with 177Lu. 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab was tested for its cell viability and cell-binding rate after different times and at different doses by CCK-8 and cell-binding experiments. 177Lu-3,4-HOPO-Cetuximab (~500 μCi) and 177Lu-DOTA-Cetuximab (~500 μCi) were injected into the tail vein of a subcutaneous metastasis mouse model of triple-negative breast cancer with a single injection, and tumour volume growth and body weight changes were regularly monitored for 20 days. The radioactivity distribution in nude mice was analysed after sacrifice, and the treated and untreated tumour tissues were analysed by HE staining.

Result: The cell viability of 177Lu-3,4-HOPO-Cetuximab declined exponentially after treatment for 48 h at 50 Bq/mL to 500 kBq/mL, respectively; the cell activity was slowed down from 8 to 96 h at a dose of 500 kBq; while the binding rate of 4T1 cells in 177Lu-3,4-HOPO-Cetuximab from 1 to 24 h, respectively, increased logarithmically, which was similar with 177Lu-DOTA-Cetuximab. After 20 days of treatment, the body weight of nude mice with 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were hardly changed, while the body weight with physiological saline decreased significantly. The tumour inhibition rate of the 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were (37.03 ± 11.16)% and (38.7 ± 5.1)%; HE staining showed that tumour cells were affected by the action of 177Lu causing necrosis.

Conclusion: The experiments showed that 177Lu-3,4-HOPO-Cetuximab has a certain targeted therapeutic ability for triple-negative breast cancer, and it is expected to become a potential targeted nuclear medicine treatment for triple-negative breast cancer.
Current Trends and Research Topics Regarding Intestinal Organoids: An Overview Based on Bibliometrics
Authors: Zhang Meng-Meng , Yang Ke-Lu , Cui Yan-Cheng , Zhou Yu-Shi , Zhang Hao-Ran , Wang Quan , Ye Ying-Jiang , Wang Shan , Jiang Ke-Wei
Published: August 2021

Currently, research on intestinal diseases is mainly based on animal models and cell lines in monolayers. However, these models have drawbacks that limit scientific advances in this field. Three-dimensional (3D) culture systems named organoids are emerging as a reliable research tool for recapitulating the human intestinal epithelium and represent a unique platform for patient-specific drug testing. Intestinal organoids (IOs) are crypt–villus structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs) and have the potential to serve as a platform for individualized medicine and research. However, this emerging field has not been bibliometric summarized to date. Here, we performed a bibliometric analysis of the Web of Science Core Collection (WoSCC) database to evaluate 5,379 publications concerning the use of organoids; the studies were divided into four clusters associated with the current situation and future directions for the application of IOs. Based on the results of our bibliometric analysis of IO applications, we systematically summarized the latest advances and analyzed the limitations and prospects.
Gas Chromatography-Tandem Mass Spectrometry Method for the Selective Detection of Glycols and Glycerol in the Liquids and Aerosols of E-Cigarette, or Vaping, Products
Authors: Pérez José J. , Watson Clifford H. , Blount Benjamin C. , Valentín-Blasini Liza
Published: August 2021

The long-term health effects of using e-cigarette, or vaping, products (EVPs; also known as e-cigarettes, electronic nicotine delivery systems, and vape pens) remain largely unknown. The inhalation of excipients, such as propylene glycol (PG) and glycerin (GLY), may have long-term health effects. In addition to the direct health effects of PG and GLY, glycerin-containing products can be contaminated with toxic ethylene glycol (EG) and diethylene glycol (DEG). To assess this issue, we developed a simple, versatile, high-throughput isotope dilution gas chromatography-tandem mass spectrometry method for quantifying these common excipients and contaminants. The method is applicable to both the liquid contents and machine-generated aerosols of EVPs. Our rigorous method validation demonstrates that the new method is specific, precise, accurate, and rugged/robust. The calibration range is linear from 0.1–7 mg for the excipients and 2.5–1,000 µg for the contaminants. These ranges encompass expected excipients levels in EVP e-liquids and their machine-generated aerosols and the relevant maximum residue safety limit of 1 mg/g, or 0.1% (w/w), for the contaminants. The calculated limits of detection for PG, GLY, EG, and DEG were determined as 0.0109 mg, 0.0132 mg, 0.250 µg, and 0.100 µg, respectively. The method was applied to the aerosol emissions analysis of 141 EVPs associated with the 2019 lung injury outbreak, and found typical levels of PG (120.28–689.35 mg/g of aerosol) and GLY (116.83–845.96 mg/g of aerosol) in all nicotine-containing products; PG (81.58–491.92 mg/g of aerosol) and GLY (303.86–823.47 mg/g of aerosol) in 13% of cannabidiol (CBD) products; PG (74.02–220.18 mg/g of aerosol) and GLY (596.43–859.81 mg/g of aerosol) in products with neither nicotine nor CBD; and none detected in tetrahydrocannabinol (THC) products. No products contained glycol contaminants above the recommended maximum residue safety limit.
Loss of Function of Scavenger Receptor SCAV-5 Protects C. elegans Against Pathogenic Bacteria
Authors: Luo Aixiao , Jing Huiru , Yuan Lei , Wang Yanzhe , Xiao Hui , Zheng Qian
Published: August 2021

Scavenger receptors play a critical role in innate immunity by acting as the pattern-recognition receptors. There are six class B scavenger receptors homologs in C. elegans. However, it remains unclear whether they are required for host defense against bacterial pathogens. Here, we show that, of the six SCAV proteins, only loss of function scav-5 protect C. elegans against pathogenic bacteria S. typhimurium SL1344 and P. aeruginosa PA14 by different mechanism. scav-5 mutants are resistant to S. typhimurium SL1344 due to dietary restriction. While scav-5 acts upstream of or in parallel to tir-1 in conserved PMK-1 p38 MAPK pathway to upregulate the innate immune response to defend worms against P. aeruginosa PA14. This is the first demonstration of a role for SCAV-5 in host defense against pathogenic bacteria. Our results provide an important basis for further elucidating the underlying molecular mechanism by which scav-5 regulates innate immune responses.
Lessons Learned for Pathogenesis, Immunology, and Disease of Erythrocytic Parasites: Plasmodium and Babesia
Authors: Djokic Vitomir , Rocha Sandra C. , Parveen Nikhat
Published: August 2021

Malaria caused by Plasmodium species and transmitted by Anopheles mosquitoes affects large human populations, while Ixodes ticks transmit Babesia species and cause babesiosis. Babesiosis in animals has been known as an economic drain, and human disease has also emerged as a serious healthcare problem in the last 20–30 years. There is limited literature available regarding pathogenesis, immunity, and disease caused by Babesia spp. with their genomes sequenced only in the last decade. Therefore, using previous studies on Plasmodium as the foundation, we have compared similarities and differences in the pathogenesis of Babesia and host immune responses. Sexual life cycles of these two hemoparasites in their respective vectors are quite similar. An adult Anopheles female can take blood meal several times in its life such that it can both acquire and transmit Plasmodia to hosts. Since each tick stage takes blood meal only once, transstadial horizontal transmission from larva to nymph or nymph to adult is essential for the release of Babesia into the host. The initiation of the asexual cycle of these parasites is different because Plasmodium sporozoites need to infect hepatocytes before egressed merozoites can infect erythrocytes, while Babesia sporozoites are known to enter the erythrocytic cycle directly. Plasmodium metabolism, as determined by its two- to threefold larger genome than different Babesia, is more complex. Plasmodium replication occurs in parasitophorous vacuole (PV) within the host cells, and a relatively large number of merozoites are released from each infected RBC after schizogony. The Babesia erythrocytic cycle lacks both PV and schizogony. Cytoadherence that allows the sequestration of Plasmodia, primarily P. falciparum in different organs facilitated by prominent adhesins, has not been documented for Babesia yet. Inflammatory immune responses contribute to the severity of malaria and babesiosis. Antibodies appear to play only a minor role in the resolution of these diseases; however, cellular and innate immunity are critical for the clearance of both pathogens. Inflammatory immune responses affect the severity of both diseases. Macrophages facilitate the resolution of both infections and also offer cross-protection against related protozoa. Although the immunosuppression of adaptive immune responses by these parasites does not seem to affect their own clearance, it significantly exacerbates diseases caused by coinfecting bacteria during coinfections.
The Tick Microbiota Dysbiosis Promote Tick-Borne Pathogen Transstadial Transmission in a Babesia microti–Infected Mouse Model
Authors: Wei Nana , Cao Jie , Zhang Houshuang , Zhou Yongzhi , Zhou Jinlin
Published: August 2021

Ticks are obligate hematophagous ectoparasites. They are important vectors for many pathogens, of both medical and veterinary importance. Antibiotic residues in animal food are known, but very little is known about the effects of antibiotic residues in animals on the microbiome diversity of ticks and tick-borne pathogen transmission. We used a Haemaphysalis longicornis–infested mouse model to evaluate the effect of antibiotic usage on tick microbiome. Nymphal ticks were fed on an antibiotic cocktail-treated or water control mice. Adult ticks molted from nymphs fed on the antibiotic cocktail-treated mouse had a dysbiosed microbiota. Nymphal ticks were also fed on a B. microti–infected mice that had been treated with antibiotic cocktail or water. We found that the B. microti infection in adult ticks with a dysbiosed microbiota (44.7%) was increased compared with the control adult ticks (24.2%) by using qPCR targeting 18S rRNA gene. This may increase the risk of tick-borne pathogens (TBPs) transmission from adult ticks to a vertebrate host. These results show that an antibiotic-treated mouse can induce tick microbiota dysbiosis. Antibiotic treatment of B. microti-infected mouse poses the possibility of increasing transstadial transmission of B. microti from the nymph to the adult H. longicornis. These findings suggest that B. microti transmission may be exacerbated in high antibiotic usage areas.
Elevated Plasma Fibrinogen Is Associated With Excessive Inflammation and Disease Severity in COVID-19 Patients
Authors: Sui Jingrui , Noubouossie Denis F. , Gandotra Sheetal , Cao Liyun
Published: August 2021

Background

The coronavirus disease-19 (COVID-19) is characterized with intense inflammatory response, cardiac involvement, and coagulopathy. Fibrinogen, as a biomarker for inflammation, cardiovascular disease, and coagulation, has not been fully investigated yet. The aim of this study was to assess the clinical application of fibrinogen in COVID-19 patients.

Methods

We retrospectively analyzed the demographic and laboratory characteristics of 119 COVID-19 patients in the University of Alabama of Birmingham Medical Center. Correlations of fibrinogen on admission with intensive care unit (ICU) admission, disease severity, and laboratory parameters were analyzed.

Results

Among the 119 COVID-19 patients, 77.3% (92/119) had severe disease, and 59.5% (71/119) patients were admitted to the ICU. Elevated fibrinogen was detected in 67.2% (80/119) of the patients. Fibrinogen levels were significantly associated with inflammatory markers and disease severity, but not with cardiac injury biomarker high sensitivity troponin I. Patients with severe disease had increased fibrinogen levels upon admission compared to patients with non-severe disease (P = 0.001). Fibrinogen level at 528.0 mg/dl was the optimal cutoff to predict disease severity, with a sensitivity and specificity of 66.7% and 70.3% (area undty -60er the curve [AUC] 0.72, P = 0.0006).

Conclusions

Fibrinogen is commonly elevated in COVID-19 patients, especially in those with severe disease. Elevated fibrinogen correlates with excessive inflammation, disease severity, and ICU admission in COVID-19 patients.
Pandemic Communication: Information Seeking, Evaluation, and Self-Protective Behaviors in Vietnam and the Republic of Korea
Authors: Diers-Lawson Audra , Johnson Sophie , Clayton Teela , Kimoto Riko , Tran Bach Xuan , Nguyen Long Hoang , Park Kisoo
Published: August 2021

Saliou (Eur J Epidemiol, 1994, 10 (4), 515–517) argued that pandemics are special kinds of crises and requires the public health sector to focus on: 1) reducing uncertainty, 2) rumor mitigation, and 3) ensuring the public reduces their risk of contracting the disease. With this as a backdrop, the central aim of this research is to better understand the connections between public information seeking, evaluation, and self-protective behaviors in the COVID-19 pandemic and focuses on a comparison between the Republic of Korea and Vietnam to provide insights into the influence of the individual, institutional, and information factors influencing people’s experience with COVID-19. Thus, there are two major contributions of this study. First, it provides a cross-theory evaluation of the factors that contribute to information seeking, evaluation, and self-protective behaviors. Second, the study identifies potentially critical differences in information seeking, evaluation, and self-protective behaviors based on acute disease reproduction in countries with a successful pandemic suppression history. Findings suggest that in countries where there are high levels of trust and satisfaction even small changes in the infection rates lead to different information seeking and self-protective behaviors.
Autonomous Cooperative Control for Hybrid AC/DC Microgrids Considering Multi-Energy Complementarity
Authors: Zhou Dan , Chen Shangren , Wang Hanyun , Guan Minyuan , Zhou Lihua , Wu Jian , Hu Yaojie
Published: August 2021

Multi-energy hybrid AC/DC microgrids (MGs), considering ice storage systems (ISSs), can promote the flexible integration and efficient utilization of distributed generators (DGs) and energy storage systems (ESSs), provide a reliable power supply for local loads, and achieve multi-energy complementarity and energy savings at the same time. An autonomous cooperative control of multi-energy MGs is proposed in this paper, which can realize the following targets: 1) In the energy storage period, ice storage systems and energy storage systems can absorb energy in accordance with their rated capacity. 2) In the energy releasing period, ice storage systems are first put into operation, and the rest of the equivalent cooling loads and electrical loads are shared by the energy storage systems according to their rated capacity ratio. Besides, the complete system small signal model is constructed, which can be used to analyze the features and characteristics of the system and guide the optimal design of the control parameters. Finally, the effectiveness of the proposed control is corroborated by several case studies conducted in PSCAD/EMTDC.
Risk Analysis of Voltage Violation With PHEV Inter-Area Mobile Charging Strategy Under Gas Station Networks Attacked
Authors: Li Xue , Zhang Zhourong , Du Dajun
Published: August 2021

To reduce the risk of voltage violation after gas station networks (GSNs) are attacked, this study investigates an inter-area mobile charging strategy of plug-in hybrid electric vehicles (PHEVs) to decrease the charging load by taking full advantage of charging resources. First, considering the location of the charging station, the waiting time, and the charging fee, an inter-area mobile charging strategy of PHEVs is proposed, and a mobile charging model of PHEVs among regions is established to relieve the charging pressure. Second, the risk index is developed to analyze the risk of voltage violation in terms of the results of probabilistic load flow (PLF). Finally, the proposed strategy is tested on a modified coastal active power distribution network, and simulation results show that the charging load of PHEVs is dispersed among regions and the risk of voltage over-limit can be reduced.
On the Cost-Effective Design of Agglomeration Bonus Schemes for the Conservation of Multiple Competing Species
Authors: Drechsler Martin
Published: August 2021

An important mechanism of species co-existence in spatially structured landscapes is the competition-colonisation trade-off which states that co-existence of competing species is possible if, all other things equal, the better competitor is the worse coloniser. The effectiveness of this trade-off for the facilitation of co-existence, however, is likely to depend on the spatial arrangement of the habitat, because too strong agglomeration of the habitat may overly benefit the strong competitor (being the poor disperser), implying extinction of the inferiour competitor, while too much dispersion of the habitat may drive the superiour competitor (being the inferiour coloniser) to extinction. In working landscapes, biodiversity conservation is often induced through conservation payments that offset the forgone profits incurred by the conservation measure. To control the spatial arrangement of conservation measures and habitats in a conservation payment scheme, the agglomeration bonus has been proposed to provide financial incentives for allocating conservation measures in the vicinity of other sites with conservation measures. This paper presents a generic spatially explicit ecological-economic simulation model to explore the ability of the agglomeration bonus to cost-effectively conserve multiple competing species that differ by their competition strengths, their colonisation rates and their dispersal ranges. The interacting effects of the agglomeration bonus and different species traits and their trade-offs on the species richness in the model landscape are analysed. Recommendations for the biodiversity-maximising design of agglomeration bonus schemes are derived.
A de novo GRIN1 Variant Associated With Myoclonus and Developmental Delay: From Molecular Mechanism to Rescue Pharmacology
Authors: Zhang Jin , Tang Weiting , Bhatia Nidhi K. , Xu Yuchen , Paudyal Nabina , Liu Ding , Kim Sukhan , Song Rui , XiangWei Wenshu , Shaulsky Gil , Myers Scott J. , Dobyns William , Jayaraman Vasanthi , Traynelis Stephen F. , Yuan Hongjie , Bozarth Xiuhua
Published: August 2021

N-Methyl-D-aspartate receptors (NMDARs) are highly expressed in brain and play important roles in neurodevelopment and various neuropathologic conditions. Here, we describe a new phenotype in an individual associated with a novelde novodeleterious variant inGRIN1(c.1595C>A, p.Pro532His). The clinical phenotype is characterized with developmental encephalopathy, striking stimulus-sensitive myoclonus, and frontal lobe and frontal white matter hypoplasia, with no apparent seizures detected. NMDARs that contained the P532H within the glycine-binding domain of GluN1 with either the GluN2A or GluN2B subunits were evaluated for changes in their pharmacological and biophysical properties, which surprisingly revealed only modest changes in glycine potency but a significant decrease in glutamate potency, an increase in sensitivity to endogenous zinc inhibition, a decrease in response to maximally effective concentrations of agonists, a shortened synaptic-like response time course, a decreased channel open probability, and a reduced receptor cell surface expression. Molecule dynamics simulations suggested that the variant can lead to additional interactions across the dimer interface in the agonist-binding domains, resulting in a more open GluN2 agonist-binding domain cleft, which was also confirmed by single-molecule fluorescence resonance energy transfer measurements. Based on the functional deficits identified, several positive modulators were evaluated to explore potential rescue pharmacology.
Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican
Authors: Hernández-Doño Susana , Jakez-Ocampo Juan , Márquez-García José Eduardo , Ruiz Daniela , Acuña-Alonzo Víctor , Lima Guadalupe , Llorente Luis , Tovar-Méndez Víctor Hugo , García-Silva Rafael , Granados Julio , Zúñiga Joaquín , Vargas-Alarcón Gilberto
Published: August 2021

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes’ frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A∗29:02∼C∗16:01∼B∗44:03∼DRB1∗07:01∼DQB1∗02:02, pC = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations.
Search for Selection Signatures Related to Trypanosomosis Tolerance in African Goats
Authors: Serranito Bruno , Taurisson-Mouret Dominique , Harkat Sahraoui , Laoun Abbas , Ouchene-Khelifi Nadjet-Amina , Pompanon François , Benjelloun Badr , Cecchi Giuliano , Thevenon Sophie , Lenstra Johannes A. , Da Silva Anne
Published: August 2021

Livestock is heavily affected by trypanosomosis in Africa. Through strong selective pressure, several African indigenous breeds of cattle and small ruminants have acquired varying degrees of tolerance against this disease. In this study, we combined LFMM and PCAdapt for analyzing two datasets of goats from West-Central Africa and East Africa, respectively, both comprising breeds with different assumed levels of trypanotolerance. The objectives were (i) to identify molecular signatures of selection related to trypanotolerance; and (ii) to guide an optimal sampling for subsequent studies. From 33 identified signatures, 18 had been detected previously in the literature as being mainly associated with climatic adaptations. The most plausible signatures of trypanotolerance indicate the genes DIS3L2, COPS7B, PD5A, UBE2K, and UBR1. The last gene is of particular interest since previous literature has already identified E3-ubiquitin ligases as playing a decisive role in the immune response. For following-up on these findings, the West-Central African area appears particularly relevant because of (i) a clear parasitic load gradient related to a humidity gradient, and (ii) still restricted admixture levels between goat breeds. This study illustrates the importance of protecting local breeds, which have retained unique allelic combinations conferring their remarkable adaptations.
Nociceptive Sensory Neurons Mediate Inflammation Induced by Bacillus Anthracis Edema Toxin
Authors: Yang Nicole J. , Neel Dylan V. , Deng Liwen , Heyang Michelle , Kennedy-Curran Angela , Tong Victoria S. , Park Jin Mo , Chiu Isaac M.
Published: August 2021

Bacterial products are able to act on nociceptive neurons during pathogenic infection. Neurogenic inflammation is an active part of pain signaling and has recently been shown to impact host-pathogen defense. Bacillus anthracis Edema Toxin (ET) produces striking edema in peripheral tissues, but the cellular mechanisms involved in tissue swelling are not completely understood. Here, we find that nociceptive neurons play a role in ET-induced edema and inflammation in mice. Subcutaneous footpad infection of B. anthracis Sterne caused ET-dependent local mechanical allodynia, paw swelling and body weight gain. Subcutaneous administration of ET induced paw swelling and vascular leakage, the early phases of which were attenuated in the absence of Trpv1+ or Nav1.8+ nociceptive neurons. Nociceptive neurons express the anthrax toxin receptor ANTXR2, but this did not mediate ET-induced edema. ET induced local cytokine expression and neutrophil recruitment, which were dependent in part on Trpv1+ nociceptive neurons. Ablation of Trpv1+ or Nav1.8+ nociceptive neurons also attenuated early increases in paw swelling and body weight gain during live B. anthracis infection. Our findings indicate that nociceptive neurons play an active role in inflammation caused by B. anthracis and Edema Toxin to potentially influence bacterial pathogenesis.
Case Report: Abscopal Effect of Microwave Ablation in a Patient With Advanced Squamous NSCLC and Resistance to Immunotherapy
Authors: Shao Chuchu , Yang Menghang , Pan Yingying , Xie Dacheng , Chen Bin , Ren Shengxiang , Zhou Caicun
Published: August 2021

Currently, immunotherapy has been a backbone in the treatment of advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, only a small proportion of NSCLC patients respond to immune checkpoint inhibitors, and majority of patients with initial response will develop acquired resistance at 5 years, which usually manifests as oligo-progression or oligo-metastases. Evidence from multiple clinical trials indicates that local consolidative therapies could improve the prognosis of oligometastatic NSCLC patients. Herein, we reported a case of advanced squamous lung cancer which showed a durable abscopal effect from microwave ablation after acquired resistance of immunotherapy.
Protease-Activation of Fc-Masked Therapeutic Antibodies to Alleviate Off-Tumor Cytotoxicity
Authors: Elter Adrian , Yanakieva Desislava , Fiebig David , Hallstein Kerstin , Becker Stefan , Betz Ulrich , Kolmar Harald
Published: August 2021

The interaction of the Fc region of therapeutic antibodies and antibody-drug conjugates with Fcγ receptors (FcγRs) can lead to unpredictable and severe side effects. Over the last decades several strategies have been developed to overcome this drawback, including extensive Fc- and glycoengineering and antibody isotype switching. However, these approaches result in permanently Fc-silenced antibody derivates which partially or completely lack antibody-mediated effector functions. Nevertheless, for a majority of antibody-based drugs, Fc-mediated effector functions, like antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP) as well as complement-dependent cytotoxicity (CDC), represent the most substantial modes of action. We argued that a new strategy combining the beneficial properties of Fc-silencing and controlled activation of effector functions can pave the way to potent antibody therapeutics, reducing the FcγRs-mediated off-target toxicity. We present a novel Fc-tamed antibody format, where the FcγR-binding sites of antibodies are blocked by anti-isotypic masking units, hindering the association of FcγR and complement component 1 (c1q) to the Fc domain. The masking units were genetically fused to trastuzumab, including a protease-addressable peptide-liker. Our Fc-tamed antibodies demonstrated completely abolished interaction to soluble high-affinity Fcγ-Receptor I and c1q. In reporter cell-based ADCC assays, our Fc-tamed antibodies exhibited a 2,700 to 7,100-fold reduction in activation, compared to trastuzumab. Upon demasking by a tumor-associated protease, the Fc-activated antibodies demonstrated restored FcγR-binding, c1q-binding and the ability to induce potent ADCC activation. Furthermore, cell killing assays using donor-derived NK cells were performed to validate the functionality of the Fc-tamed antibody variants. To our knowledge, this approach represents the first non-permanently Fc-silenced antibody, which can be re-activated by a tumor-associated protease, eventually extending the field of novel antibody formats.
Poliovirus Vaccination Induces a Humoral Immune Response That Cross Reacts With SARS-CoV-2
Authors: Comunale Brittany A. , Engineer Lilly , Jiang Yong , Andrews John C. , Liu Qianna , Ji Lyuqing , Yurkovich James T. , Comunale Roderick A. , Xie Qiyi
Published: August 2021

Background: Millions have been exposed to SARS-CoV-2, but the severity of resultant infections has varied among adults and children, with adults presenting more serious symptomatic cases. Children may possess an immunity that adults lack, possibly from childhood vaccinations. This retrospective study suggests immunization against the poliovirus may provide an immunity to SARS-CoV-2.

Methods: Publicly available data were analyzed for possible correlations between national median ages and epidemiological outbreak patterns across 100 countries. Sera from 204 adults and children, who were immunized with the poliovirus vaccine, were analyzed using an enzyme-linked immunosorbent assay. The effects of polio-immune serum on SARS-CoV-2-induced cytopathology in cell culture were then evaluated.

Results: Analyses of median population age demonstrated a positive correlation between median age and SARS-CoV-2 prevalence and death rates. Countries with effective poliovirus immunization protocols and younger populations have fewer and less pathogenic cases of COVID-19. Antibodies to poliovirus and SARS-CoV-2 were found in pediatric sera and in sera from adults recently immunized with polio. Sera from polio-immunized individuals inhibited SARS-CoV-2 infection of Vero cell cultures. These results suggest the anti-D3-pol-antibody, induced by poliovirus vaccination, may provide a similar degree of protection from SARS-CoV-2 to adults as to children.

Conclusions: Poliovirus vaccination induces an adaptive humoral immune response. Antibodies created by poliovirus vaccination bind the RNA-dependent RNA polymerase (RdRp) protein of both poliovirus and SARS-CoV-2, thereby preventing SARS-CoV-2 infection. These findings suggest proteins other than “spike” proteins may be suitable targets for immunity and vaccine development.