bluuebunny/crossref_metadata_2025 huggingface dataset:
Four months of rifampicin monotherapy for latent tuberculosis infection in children
Authors: Oh Chi Eun , Menzies Dick
Published: October 2021

Diagnosing and treating latent tuberculosis infection (LTBI) is an important part of efforts to combat tuberculosis (TB). The Korean guidelines for TB published in 2020 recommend 2 LTBI regimens for children and adolescents: 9 months of daily isoniazid (9H) and 3 months of daily isoniazid plus rifampicin. Isoniazid for 6–12 months has been used to effectively treat LTBI in children for over 50 years. However, a long treatment period results in poor patient compliance. This review summarizes pediatric data on the treatment completion rate, safety, and efficacy of 4 months of daily rifampicin (4R) and evaluates the pharmacokinetics and pharmacodynamics of rifampicin in children. The 4R regimen has a higher treatment completion rate than the 9H regimen and equivalent safety in children. The efficacy of preventing TB is also consistent with that of 9H when summarizing reports published to date. A shorter treatment period could increase patient compliance and, therefore, prevent TB in more patients. By using an effective, safe, and highly compliant regimen for the treatment of children with LTBI, we would become one step closer to our goal of eradicating TB.
Effect of Alloying Elements and Microstructure on the Dynamic Strain Aging Behavior of 1.25Cr-0.5Mo and 2.25Cr-1Mo Steels
Authors: Lee Yo Seob , Lee Ho Jung , Lee Jong Hyeon
Published: October 2021

The effect of alloying elements and microstructure on the dynamic strain aging (DSA) behavior of 1.25Cr-0.5Mo (P11, ASTM 335Gr.P11) and 2.25Cr-1Mo (P22, ASTM 335Gr.P22) steels was investigated. For both steels, different cooling conditions such as air-cooling (AC) and oil-quenching (OQ) were applied. Tensile tests were conducted in the temperature range of 20-450 ℃ and a strain rate in the range of 6 × 10-5- 6 × 10-3 s-1 for the steels with different cooling conditions. The P11AC steel showed serration behavior over a wider temperature range and exhibited higher ultimate tensile strength (UTS) than for the P22AC steel. This is attributed to the effects of alloying elements (Cr, Mo and Si) due to dissolved C, and the ferrite fraction on mechanical behavior. Meanwhile, the P11AC and P11OQ steels also showed different behaviors for DSA starting temperature, DSA temperature range, and serration type. The AC condition showed higher UTS from the interaction solid solution hardening (ISSH) effect due to substitutional Cr, Mo, and interstitial C elements. The calculated activation energy value (Q) for the P11 steel was around 94-103 kJ/mol-1, similar to that of ferritic steels, and it was higher for the P22 steel, with a Q value of 233 kJ/mol-1 from the ISSH effect.
Unregistered industrial design: protection in the European Union and the problem of trolling in Ukraine
Authors: Kapitsa Yurii
Published: October 2021

Kapitsa Y. Unregistered industrial design: protection in the European Union and the problem of trolling in Ukraine. The article considers a new provisions concerning unregistered industrial design (hereinafter — UD), introduced by the Law of Ukraine № 815-IX of 21.07.2020.There is an incomplete reflection in the Association Agreement between the EU and Ukraine and in the adopted Law of the provisions of Council Regulation (EC) No 6/2002 on Community designs, in particular the lack of implementation of Art. 85 (2) of the Regulation concerning the conditions under which courts consider UD to be valid; and the rulings of the Court of Justice that the right holder must provide evidence that the UD was copied by a third party, Case C-345/13 etc.This may result in trolling in Ukraine with the use of UD to prohibit the use of known products or products created independently, bypassing trademarks.It is actual to:• provide amendments to the Law of Ukraine «On protection of rights to industrial designs» concerning the provisions of Art. 85 (2) of Regulation № 6/2002 and the case law of the Court of Justice;• extend the competence of the Appeals Chamber to cases concerning the recognition of UD as invalid;• amend the Law as well Art. 139, 140 of the Code of Civil Procedure of Ukraine and Art. 151, 153 of the Economic and Procedural Code of Ukraine regarding the provisions of Art. 50 TRIPS which stipulates that judicial authorities shall have the authority to require the applicant to provide any reasonably available evidence in order to satisfy themselves with a sufficient degree of certainty that the applicant is the right holder and that the applicant’s right is being infringed or that such infringement is imminent.There is a danger of partial approximation not to the whole EU acquis governing the protection of relevant IP rights which may result in the difficulty of applying implemented provisions of EU acts and developing national case law which could contradict EU case law.Key words: unregistered industrial design, protection of intellectual property rights, approximation of legislation, trolling
Alarm warning dan rem otomatis berbasis detak jantung pada olahraga bersepeda
Authors: Saputra Yogi Dwi , Safitri Hari Kurnia
Published: October 2021

Jantung merupakan organ vital pada tubuh manusia. Oleh karena itu, penting dalam memelihara kesehatan jantung. Salah satunya melalui pelatihan berbasis detak jantung, yaitu menjaga detak jantung dalam kisaran yang ditetapkan. Salah satu pengaplikasiannya adalah olahraga bersepeda, namun tidak jarang pesepeda melebihi target maksimal saat bersepeda, sehingga hal tersebut menyalahi aturan dalam pelatihan. Prinsip kerja alat ini adalah mengaktifkan alarm warning jika detak jantung pengguna melebihi target maksimal saat latihan dan mengaktifkan rem otomatis ketika pengguna menghiraukan alarm warning. Target latihan diperoleh dari perhitungan umur, maximal heart rate (MHR), Rest Heart Rate (RHR), dan riwayat latihan. Penelitian ini menggunakan grove heart rate sensor sebagai sensor detak jantung dengan mikrokontroler Arduino MEGA. Proses pengambilan maupun penyimpanan data pada database dilakukan oleh NodeMCU.  Motor DC 12V digunakan sebagai penarik rem dengan driver motor sebagai pengatur arah dan putaran motor. Berdasarkan hasil pengujian diperoleh bahwa data detak jantung peserta latihan tersimpan dalam database sistem, alarm warning  bekerja(buzzer on) jika detak jantung  peserta diatas 135 bpm, dan  rem otomatis bekerja pada saat detak jantung peserta latihan diatas 135 bpm dengan berubahnya panjang tali rem dari 15 cm menjadi 12 cm.

The heart is a vital organ in the human body. Therefore, it is important in maintaining heart health. One of them is through heart rate-based training, which is keeping the heart rate within a specified range. One of its applications is cycling, but it is not uncommon for cyclists to exceed the maximum target when cycling, so that this violates the rules in training. The working principle of this tool is to activate an alarm warning if the user's heart rate exceeds the maximum target during training and activate the automatic brake when the user ignores the alarm warning. Training targets are obtained from the calculation of age, maximal heart rate (MHR), Rest Heart Rate (RHR), and training history. This study uses a grove heart rate sensor as a heart rate sensor with an Arduino MEGA microcontroller. The process of retrieving and storing data in the database is carried out by NodeMCU. DC 12V motor is used as a brake puller with the motor driver to control the direction and rotation of the motor.  Base on the test result, it is found that the participant’s heart rate data is stored in the database system, the alarm warning work (buzzer on)if the participant’s herat rate is above 135 bpm, and the brakes automatically work when the participant’s herat rate is above 135 bpm by changing the length of the brake rope from 15cm to 12 cm.
BIG DATA СЕБЯ: ФЕСТИВАЛЬ БИОХАКИНГА В МОСКВЕ
Authors: СОКОЛОВА Елена Константиновна
Published: October 2021

В сентябре 2019 года в Москве прошел первый фестиваль биохакинга1 «Rocket Science Fest». Концепция мероприятия построена вокруг идеи сбора данных о себе с целью улучшения качества жизни – как сформулировали организаторы «Big data себя»: «Доктор Хаус утверждал, что все врут. И это отчасти правда, ведь все мы до сих пор описываем своё самочувствие словами, надеясь, что доктор поймёт и поможет. Зачем надеяться, когда можно знать точно?!» 2. Елена Соколова встретилась с со-организатором фестиваля и руководителем PRT Lab Артемом Давыдовым. Они обсудили идею и опыт проведения фестиваля, а также отношение россиян к своему здоровью в контексте технологий, исследование которого было осуществлено совместными усилиями канала «Rocket Science» и портала «The-Challenger.ru».
ФИЛОСОФСКИЕ ПРОБЛЕМЫ БИОЛОГИИ И МЕДИЦИНЫ: ФЕНОМЕН БИОРАЦИОНАЛЬНОСТИ
Authors: Аверкина Елена Ивановна
Published: October 2021

В тексте представлены основное содержание и итоги работы 13-й научно-практической конференции «Философские проблемы биологии и медицины: феномен биорациональности», прошедшей в Москве 23–24 октября 2019 года.
COVID-19: вторая волна
Authors: Харитонова Валентина Ивановна
Published: October 2021

В статье рассматривается период «второй волны» пандемии (преимущественное в России). Обращается внимание на основные события и реакцию на них как со стороны административных и законодательных органов, так и общества. Выделяются важнейшие проблемы, возникшие в связи с попытками остановить пандемию, в частности вакцины и вакцинация. Кратко характеризуются основные направления и специфика полевой и научно-исследовательской деятельности медицинских антропологов и иных специалистов, работающих вместе с ними в едином интердисциплинарном поле.
МОДЕЛИ ПРОФЕССИОНАЛИЗАЦИИ ВРАЧЕЙ-СТОМАТОЛОГОВ
Authors: Лелюхин Сергей Викторович , Бахова Жанна Хадисовна
Published: October 2021

Статья посвящена выявлению моделей профессионализации врачей-стоматологов, обучающихся в интернатуре и/или ординатуре. Авторами было проведено нарративное интервью, выполнен контент-анализ интервью журналистского расследования сайта «МБХ медиа» и публикаций в сообществе стоматологов «Аккредитация стоматологов» в социальной сети «вКонтакте». В первой, идеальной модели профессионализации, объективация культурного капитала в форме академической квалификации происходит в результате обучения стоматологов в образовательных организациях, которые придерживаются высоких стандартов – как в учебной программе, так и в преподавательском составе. Вторая модель профессионализации, конформистская, характерна для тех, кто обучается номинально, постигает профессиональные знания, умения и навыки на работе, никак не связанной с интернатурой и/или ординатурой. Третья, имитационная модель, фактически не приводит к профессионализации врача-стоматолога, хотя он и приобретает культурный капитал, имеет доступ к профессиональной деятельности в виде диплома об окончании интернатуры и/или ординатуры. В образовательной организации они никому не были нужны, к самостоятельной работе они не готовы. Если они стремятся стать профессионалами по факту, а не номинально, то после учёбы они вынуждены искать работу, где будут старшие врачи, способные на наставничество.
ШКОЛА МЕДИЦИНСКОЙ АНТРОПОЛОГИИ И БИОЭТИКИ – ОНЛАЙН
Authors: Харитонова Валентина Ивановна
Published: October 2021

Автор рассматривает особенности работы международной Школы медицинской антропологии и биоэтики, впервые проведенной для студентов МГМСУ им. А.И. Евдокимова в онлайн-режиме. Занятия были организованы во время пандемии, когда все преподавание в университете осуществлялось с помощью онлайн-трансляций. Характеризуются предложенные студентам лекции и интерактивные семинары, экскурсионные показы. Оценивается степень заинтересованности слушателей в предложенной им дополнительной подготовке гуманитарного профиля.
МИЛОСЕРДИЕ ВЫШЕ СПРАВЕДЛИВОСТИ
Authors: Носенко-Штейн Елена Эдуардовна
Published: October 2021

Это интервью было проведено в июле 2020 г., основным его фокусом была деятельность еврейских благотворительных организаций, направленная на разнообразную поддержку пожилых людей и людей с ограниченными возможностями здоровья в современной России. Е.Э. Носенко-Штейн, многие годы занимавшаяся проблемами современного российского еврейства, а также вопросами адаптации людей с инвалидностью, беседовала с А.Е. Кирносом – врачом, поэтом и директором еврейской благотворительной организации «Яд Эзра / Рука помощи». Эта организация, возникшая во время перестройки, оказывает разнообразную помощь евреям, а также неевреям – жертвам нацизма и пожилым людям, нуждающимся в медицинском уходе и разнообразной помощи и психологической поддержке. А.Е. Кирнос рассказал о своей жизни, приходе в эту благотворительную организацию и основных принципах еврейской благотворительности.
ПАНДЕМИЯ COVID-19 КАК РЕЗУЛЬТАТ ПОЛИТИКИ «ОТКРЫТОГО МИРА» И «ПЛАНЕТАРНОГО ТУРИЗМА»
Authors: Чекурова Наталья Эрнстовна
Published: October 2021

В статье с позиций путешественника и участника событий описывается введение массовых ограничений в начале пандемии COVID-19 в Индии и Латвии, а также реакция населения на них. Автор прослеживает негативное экологическое влияние бурно развивающейся туристической отрасли, связанных с ней процессов глобализации и технизации. Пандемия COVID-19 рассматривается как следствие нарушения баланса между человеческой деятельностью и природой. Подобные глобальные риски, касающиеся всего человечества, возникают в связи с характерными для современности видами активности, в том числе – добровольными нелинейными миграциями туристов.
Effects of Narrow-Windrow Burning on Weed Dynamics in Soybean in Louisiana
Authors: Patterson Katie M. , Schwartz-Lazaro Lauren M. , LaBiche Gabrielle , Stephenson Daniel O.
Published: October 2021

The soil seedbank allows for long-term persistence of weed species in agricultural fields. Some weed species can persist in the soil seedbank for extended periods. Restricting inputs into the weed seedbank has a large impact on future population density and influences management practices of these weeds in soybean production systems. Harvest weed seed control (HWSC) tactics incorporate mechanical and cultural management strategies to target weed seeds present at harvest. A 3-year trial was initiated to determine if continual use of the HWSC method, narrow windrow burning, selects for earlier seed set and shattering in Louisiana soybean. No shifts in weed populations or shattering time were observed. However, there was a significant reduction in weed density and the weed seed present in the soil seedbank when HWSC and robust herbicide programs were used in combination. Therefore, utilizing multiple effective weed management strategies is imperative in reducing the soil seedbank.
Salmonella Diversity Along the Farm-to-Fork Continuum of Pastured Poultry Flocks in the Southeastern United States
Authors: Rothrock Michael J. , Guard Jean Y. , Oladeinde Adelumola
Published: October 2021

Greater consumer demand for all natural, antibiotic-free poultry products has led to an increase in pastured poultry operations. Given the increased level of environmental interaction, and the potential increase in exposure to foodborne pathogens, a greater understanding of the prevalence and diversity of Salmonella populations inherent within pastured poultry flocks. To achieve this, 42 pastured poultry flocks from 11 farms were sampled using a farm-to-fork strategy and Salmonella was isolated and characterized through pre-harvest (feces, soil) to post-harvest (ceca, whole carcass rinse) to the final product (whole carcass rinse) the consumer would purchase. Salmonella was isolated from 353 of a total of 2,305 samples, representing an overall prevalence of 18.1%. By far the most prevalent serotype was Kentucky (72.7% of all isolates), with <16% of all Salmonella representing a top serotype of concern for human health according to the CDC. Even though these flocks were raised antibiotic-free, Salmonella isolates exhibited resistances to a variety of antibiotics, with the two most common resistances being toward tetracycline and streptomycin (68.8 and 64.4% of all isolates, respectively); however, almost 98% of the multidrug resistant isolates were serotype Kentucky. Salmonella prevalence and diversity (both in terms of serotypes and antibiotic resistance profiles) were related more to the farm location than to the type of sample from which the Salmonella was isolated from along the farm-to-fork continuum. Based on these data, while Salmonella prevalence was similar to that from conventional poultry operations, serotypes of lesser concern to human health (Kentucky, Indiana) tended to fill the ecological niche for Salmonella species throughout the farm-to-fork continuum in these pastured poultry flocks. The diversity of these Salmonella populations tended to be farm specific, indicating the need for more tailored intervention strategies to continue to enhance the safety of these products.
Effects Induced by Osteophytes on the Strain Distribution in the Vertebral Body Under Different Loading Configurations
Authors: Marras Daniele , Palanca Marco , Cristofolini Luca
Published: October 2021

The mechanical consequences of osteophytes are not completely clear. We aimed to understand whether and how the presence of an osteophyte perturbs strain distribution in the neighboring bone. The scope of this study was to evaluate the mechanical behavior induced by the osteophytes using full-field surface strain analysis in different loading configurations. Eight thoracolumbar segments, containing a vertebra with an osteophyte and an adjacent vertebra without an osteophyte (control), were harvested from six human spines. The position and size of the osteophytes were evaluated using clinical computed tomography imaging. The spine segments were biomechanically tested in the elastic regime in different loading configurations while the strains over the frontal and lateral surface of vertebral bodies were measured using digital image correlation. The strain fields in the vertebrae with and without osteophytes were compared. The correlation between osteophyte size and strain alteration was explored. The strain fields measured in the vertebrae with osteophytes were different from the control ones. In pure compression, we observed a mild trend between the size of the osteophyte and the strain distribution (R2 = 0.32, p = 0.15). A slightly stronger trend was found for bending (R2 = 0.44, p = 0.075). This study suggests that the osteophytes visibly perturb the strain field in the nearby vertebral area. However, the effect on the surrounding bone is not consistent. Indeed, in some cases the osteophyte shielded the neighboring bone, and in other cases, the osteophyte increased the strains.
Local Dynamics of the Hydration Water and Poly(Methyl Methacrylate) Chains in PMMA Networks
Authors: Fujii Yoshihisa , Tominaga Taiki , Murakami Daiki , Tanaka Masaru , Seto Hideki
Published: October 2021

The dynamic behavior of water molecules and polymer chains in a hydrated poly(methyl methacrylate) (PMMA) matrix containing a small amount of water molecules was investigated. Water molecules have been widely recognized as plasticizers for activating the segmental motion of polymer chains owing to their ability to reduce the glass transition temperature. In this study, combined with judicious hydrogen/deuterium labeling, we conducted quasi-elastic neutron scattering (QENS) experiments on PMMA for its dry and hydrated states. Our results clearly indicate that the dynamics of hydrated polymer chains are accelerated, and that individual water molecules are slower than bulk water. It is therefore suggested that the hydration water affects the local motion of PMMA and activates the local relaxation process known as restricted rotation, which is widely accepted to be generally insensitive to changes in the microenvironment.
What Does Time-Dependent Fluorescence Shift (TDFS) in Biomembranes (and Proteins) Report on?
Authors: Scollo Federica , Evci Hüseyin , Amaro Mariana , Jurkiewicz Piotr , Sykora Jan , Hof Martin
Published: October 2021

The organization of biomolecules and bioassemblies is highly governed by the nature and extent of their interactions with water. These interactions are of high intricacy and a broad range of methods based on various principles have been introduced to characterize them. As these methods view the hydration phenomena differently (e.g., in terms of time and length scales), a detailed insight in each particular technique is to promote the overall understanding of the stunning “hydration world.” In this prospective mini-review we therefore critically examine time-dependent fluorescence shift (TDFS)—an experimental method with a high potential for studying the hydration in the biological systems. We demonstrate that TDFS is very useful especially for phospholipid bilayers for mapping the interfacial region formed by the hydrated lipid headgroups. TDFS, when properly applied, reports on the degree of hydration and mobility of the hydrated phospholipid segments in the close vicinity of the fluorophore embedded in the bilayer. Here, the interpretation of the recorded TDFS parameters are thoroughly discussed, also in the context of the findings obtained by other experimental techniques addressing the hydration phenomena (e.g., molecular dynamics simulations, NMR spectroscopy, scattering techniques, etc.). The differences in the interpretations of TDFS outputs between phospholipid biomembranes and proteins are also addressed. Additionally, prerequisites for the successful TDFS application are presented (i.e., the proper choice of fluorescence dye for TDFS studies, and TDFS instrumentation). Finally, the effects of ions and oxidized phospholipids on the bilayer organization and headgroup packing viewed from TDFS perspective are presented as application examples.
A Nanofiber Mat With Dual Bioactive Components and a Biomimetic Matrix Structure for Improving Osteogenesis Effect
Authors: Han Yadi , Shen Xiaofeng , Chen Sihao , Wang Xiuhui , Du Juan , Zhu Tonghe
Published: October 2021

The challenge of effectively regenerating bone tissue through tissue engineering technology is that most tissue engineering scaffolds cannot imitate the three-dimensional structure and function of the natural extracellular matrix. Herein, we have prepared the poly(L-lactic acid)–based dual bioactive component reinforced nanofiber mats which were named as poly(L-lactic acid)/bovine serum albumin/nanohydroxyapatite (PLLA/BSA/nHAp) with dual bioactive components by combining homogeneous blending and electrospinning technology. The results showed that these nanofiber mats had sufficient mechanical properties and a porous structure suitable for cell growth and migration. Furthermore, the results of cell experiments in vitro showed that PLLA/BSA/nHAp composite nanofiber mat could preferably stimulate the proliferation of mouse osteoblastic cells (MC3T3 cells) compared with pure PLLA nanofiber mats. Based on these results, the scaffolds developed in this study are considered to have a great potential to be adhibited as bone repair materials.
Glycoproteomic Characterization of FUT8 Knock-Out CHO Cells Reveals Roles of FUT8 in the Glycosylation
Authors: Yang Ganglong , Wang Qiong , Chen Lijun , Betenbaugh Michael J. , Zhang Hui
Published: October 2021

The α1,6-fucosyltransferase (encoded by FUT8 gene) is the key enzyme transferring fucose to the innermost GlcNAc residue on an N-glycan through an α-1,6 linkage in the mammalian cells. The presence of core fucose on antibody Fc region can inhibit antibody-dependent cellular cytotoxicity (ADCC) and reduce antibody therapeutic efficiency in vivo. Chinese hamster ovary (CHO) cells are the predominant production platform in biopharmaceutical manufacturing. Therefore, the generation of FUT8 knock-out (FUT8KO) CHO cell line is favorable and can be applied to produce completely non-fucosylated antibodies. The characterization of monoclonal antibodies as well as host cell glycoprotein impurities are required for quality control purposes under regulation rules. To understand the role of FUT8 in the glycosylation of CHO cells, we generated a FUT8 knock-out CHO cell line and performed a large-scale glycoproteomics to characterize the FUT8KO and wild-type (WT) CHO cells. The glycopeptides were enriched by hydrophilic chromatography and fractionated 25 fractions by bRPLC followed by analysis using high-resolution liquid chromatography mass spectrometry (LC-MS). A total of 7,127 unique N-linked glycosite-containing intact glycopeptides (IGPs), 928 glycosites, and 442 glycoproteins were identified from FUT8KO and WT CHO cells. Moreover, 28.62% in 442 identified glycoproteins and 26.69% in 928 identified glycosites were significantly changed in the FUT8KO CHO compared to wild-type CHO cells. The relative abundance of all the three N-glycan types (high-mannose, hybrid, and complex) was determined in FUT8KO comparing to wild-type CHO cells. Furthermore, a decrease in fucosylation content was observed in FUT8KO cells, in which core-fucosylated glycans almost disappeared as an effect of FUT8 gene knockout. Meantime, a total of 51 glycosylation-related enzymes were also quantified in these two cell types and 16 of them were significantly altered in the FUT8KO cells, in which sialyltransferases and glucosyltransferases were sharply decreased. These glycoproteomic results revealed that the knock-out of FUT8 not only influenced the core-fucosylation of proteins but also altered other glycosylation synthesis processes and changed the relative abundance of protein glycosylation.
Modified Embedded-Atom Interatomic Potential Parameters of the Ti–Cr Binary and Ti–Cr–N Ternary Systems
Authors: Ding Shoubing , Li Yue , Luo Yiying , Wu Zhimin , Wang Xinqiang
Published: October 2021

The second nearest-neighbor modified embedded-atom method (2NN MEAM) potential parameters of the Ti–Cr binary and Ti–Cr–N ternary systems are optimized in accordance with the 2NN MEAM method. The novel constructed potential parameters can well reproduce the multiple fundamental physical characteristics of binary and ternary systems and reasonably agree with the first-principles calculation or experimental data. Thus, the newly constructed 2NN MEAM potential parameters can be used for atomic simulations to determine the underlying principle of the hardness enhancement of TiN/CrN multilayered coatings.
EhVps23: A Component of ESCRT-I That Participates in Vesicular Trafficking and Phagocytosis of Entamoeba histolytica
Authors: Galindo Ausencio , Javier-Reyna Rosario , García-Rivera Guillermina , Bañuelos Cecilia , Montaño Sarita , Ortega-Lopez Jaime , Chávez-Munguía Bibiana , Salazar-Villatoro Lizbeth , Orozco Esther
Published: October 2021

The endosomal sorting complex required for transport (ESCRT) is formed by ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III complexes, and accessory proteins. It conducts vesicular trafficking in eukaryotes through the formation of vesicles and membrane fission and fusion events. The trophozoites of Entamoeba histolytica, the protozoan responsible for human amoebiasis, presents an active membrane movement in basal state that increases during phagocytosis and tissue invasion. ESCRT-III complex has a pivotal role during these events, but ESCRT-0, ESCRT-I and ESCRT-II have been poorly studied. Here, we unveiled the E. histolytica ESCRT-I complex and its implication in vesicular trafficking and phagocytosis, as well as the molecular relationships with other phagocytosis-involved molecules. We found a gene encoding for a putative EhVps23 protein with the ubiquitin-binding and Vps23 core domains. In basal state, it was in the plasma membrane, cytoplasmic vesicles and multivesicular bodies, whereas during phagocytosis it was extensively ubiquitinated and detected in phagosomes and connected vesicles. Docking analysis, immunoprecipitation assays and microscopy studies evidenced its interaction with EhUbiquitin, EhADH, EhVps32 proteins, and the lysobisphosphatidic acid phospholipid. The knocking down of the Ehvps23 gene resulted in lower rates of phagocytosis. Our results disclosed the concert of finely regulated molecules and vesicular structures participating in vesicular trafficking-related events with a pivotal role of EhVps23.
Role of Runx2 in Calcific Aortic Valve Disease in Mouse Models
Authors: Dharmarajan Subramanian , Speer Mei Y. , Pierce Kate , Lally Jake , Leaf Elizabeth M. , Lin Mu-En , Scatena Marta , Giachelli Cecilia M.
Published: October 2021

Background: Calcific aortic valve disease is common in the aging population and is characterized by the histological changes of the aortic valves including extracellular matrix remodeling, osteochondrogenic differentiation, and calcification. Combined, these changes lead to aortic sclerosis, aortic stenosis (AS), and eventually to heart failure. Runt-related transcription factor 2 (Runx2) is a transcription factor highly expressed in the calcified aortic valves. However, its definitive role in the progression of calcific aortic valve disease (CAVD) has not been determined. In this study, we utilized constitutive and transient conditional knockout mouse models to assess the molecular, histological, and functional changes in the aortic valve due to Runx2 depletion.

Methods: Lineage tracing studies were performed to determine the provenance of the cells giving rise to Runx2+ osteochondrogenic cells in the aortic valves of LDLr−/− mice. Hyperlipidemic mice with a constitutive or temporal depletion of Runx2 in the activated valvular interstitial cells (aVICs) and sinus wall cells were further investigated. Following feeding with a diabetogenic diet, the mice were examined for changes in gene expression, blood flow dynamics, calcification, and histology.

Results: The aVICs and sinus wall cells gave rise to Runx2+ osteochondrogenic cells in diseased mouse aortic valves. The conditional depletion of Runx2 in the SM22α+ aVICs and sinus wall cells led to the decreased osteochondrogenic gene expression in diabetic LDLr−/− mice. The transient conditional depletion of Runx2 in the aVICs and sinus wall cells of LDLr−/−ApoB100 CAVD mice early in disease led to a significant reduction in the aortic peak velocity, mean velocity, and mean gradient, suggesting the causal role of Runx2 on the progression of AS. Finally, the leaflet hinge and sinus wall calcification were significantly decreased in the aortic valve following the conditional and temporal Runx2 depletion, but no significant effect on the valve cusp calcification or thickness was observed.

Conclusions: In the aortic valve disease, Runx2 was expressed early and was required for the osteochondrogenic differentiation of the aVICs and sinus wall cells. The transient depletion of Runx2 in the aVICs and sinus wall cells in a mouse model of CAVD with a high prevalence of hemodynamic valve dysfunction led to an improved aortic valve function. Our studies also suggest that leaflet hinge and sinus wall calcification, even in the absence of significant leaflet cusp calcification, may be sufficient to cause significant valve dysfunctions in mice.
Association of Increased Remnant Cholesterol and the Risk of Coronary Artery Disease: A Retrospective Study
Authors: Kexin Wang , Yaodong Ding , Wen Gao , Rui Wang , Jiaxin Yang , Xiaoli Liu , Hua Shen , Hailong Ge
Published: October 2021

Background and Aims: Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy in coronary artery disease (CAD). But some patients with the normal levels of LDL-C still suffer from CAD progression and malignant outcomes (e.g., major adverse cardiovascular events [MACEs]), and the mechanism is unclear. The previous prospective studies demonstrated that the remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) were capable to predict the risk of CAD. This study evaluated the association between RC and non-HDL-C with the risk of CAD.

Methods: In our study, 12,563 patients were enrolled. We categorized patients into four concordance/discordance groups according to the median of RC, LDL-C, and non-HDL-C. Then, we performed a propensity score matching (PSM) strategy. The unadjusted and adjusted multivariate logistic regression models were used to evaluate the relationship between the lipid concentrations.

Results: In this study, 8,658 (68.9%) patients were male with a median age of 61 (54 and 67) years. The multivariate logistic regression showed the odds ratio (OR) of RC was 1.952 (CI = 1.276–2.988, p = 0.002). The OR of the low RC/high LDL-C group was 0.626 (CI = 0.504–0.778, p < 0.001) and the OR of the low RC/high non-HDL-C group was 0.574 (CI = 0.462–0.714, p < 0.001). The p-values for interaction between the RC and hypertension, diabetes were both < 0.001.

Conclusion: Our study showed a significant association between the RC and CAD. The level of RC was more capable to reflect the risk of CAD than LDL-C and non-HDL-C. There was an interaction relationship between RC and age, gender, hypertension, diabetes, in CAD. But we did not find whether there was a relationship between the non-HDL-C and CAD.
Machine Learning Algorithms to Detect Sex in Myocardial Perfusion Imaging
Authors: Souza Filho Erito Marques de , Fernandes Fernando de Amorim , Portela Maria Gabriela Ribeiro , Newlands Pedro Heliodoro , Carvalho Lucas Nunes Dalbonio de , Santos Tadeu Francisco dos , Santos Alair Augusto Sarmet M. D. dos , Mesquita Evandro Tinoco , Seixas Flávio Luiz , Mesquita Claudio Tinoco , Gismondi Ronaldo Altenburg
Published: October 2021

Myocardial perfusion imaging (MPI) is an essential tool used to diagnose and manage patients with suspected or known coronary artery disease. Additionally, the General Data Protection Regulation (GDPR) represents a milestone about individuals' data security concerns. On the other hand, Machine Learning (ML) has had several applications in the most diverse knowledge areas. It is conceived as a technology with huge potential to revolutionize health care. In this context, we developed ML models to evaluate their ability to distinguish an individual's sex from MPI assessment. We used 260 polar maps (140 men/120 women) to train ML algorithms from a database of patients referred to a university hospital for clinically indicated MPI from January 2016 to December 2018. We tested 07 different ML models, namely, Classification and Regression Tree (CART), Naive Bayes (NB), K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Adaptive Boosting (AB), Random Forests (RF) and, Gradient Boosting (GB). We used a cross-validation strategy. Our work demonstrated that ML algorithms could perform well in assessing the sex of patients undergoing myocardial scintigraphy exams. All the models had accuracy greater than 82%. However, only SVM achieved 90%. KNN, RF, AB, GB had, respectively, 88, 86, 85, 83%. Accuracy standard deviation was lower in KNN, AB, and RF (0.06). SVM and RF had had the best area under the receiver operating characteristic curve (0.93), followed by GB (0.92), KNN (0.91), AB, and NB (0.9). SVM and AB achieved the best precision. Our results bring some challenges regarding the autonomy of patients who wish to keep sex information confidential and certainly add greater complexity to the debate about what data should be considered sensitive to the light of the GDPR.
Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications
Authors: Xia Xiao-dan , Peng Zhong-sheng , Gu Hong-mei , Wang Maggie , Wang Gui-qing , Zhang Da-wei
Published: October 2021

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptor (LDLR) and plays a central role in regulating plasma levels of LDL cholesterol levels, lipoprotein(a) and triglyceride-rich lipoproteins, increasing the risk of cardiovascular disease. Additionally, PCSK9 promotes degradation of major histocompatibility protein class I and reduces intratumoral infiltration of cytotoxic T cells. Inhibition of PCSK9 increases expression of LDLR, thereby reducing plasma levels of lipoproteins and the risk of cardiovascular disease. PCSK9 inhibition also increases cell surface levels of major histocompatibility protein class I in cancer cells and suppresses tumor growth. Therefore, PCSK9 plays a vital role in the pathogenesis of cardiovascular disease and cancer, the top two causes of morbidity and mortality worldwide. Monoclonal anti-PCSK9 antibody-based therapy is currently the only available treatment that can effectively reduce plasma LDL-C levels and suppress tumor growth. However, high expenses limit their widespread use. PCSK9 promotes lysosomal degradation of its substrates, but the detailed molecular mechanism by which PCSK9 promotes degradation of its substrates is not completely understood, impeding the development of more cost-effective alternative strategies to inhibit PCSK9. Here, we review our current understanding of PCSK9 and focus on the regulation of its expression and functions.
Improvements in High-Density Lipoprotein Quantity and Quality Contribute to the Cardiovascular Benefits by Anti-tumor Necrosis Factor Therapies in Rheumatoid Arthritis: A Systemic Review and Meta-Analysis
Authors: Luo Yonghong , Ren Xiaolei , Weng Shuwei , Yan Chunhui , Mao Qiaoxia , Peng Daoquan
Published: October 2021

Objective: Inflammation plays important role in atherosclerotic cardiovascular diseases (CVDs), but the interaction between the inflammation and lipid profile is largely unrevealed in humans. Patients with rheumatoid arthritis (RA) suffer from a higher risk of CVDs. Decreased total cholesterol (TC) and high-density lipoprotein (HDL) were prevalent in patients with RA. Anti-tumor necrosis factor (TNF) therapies relieve disease activity and decrease CVDs risk in RA, but their comprehensive effects on the lipid profile are unclear. This study aims to investigate the changes in blood lipid profile along time in the patients with RA accepting anti-TNF therapies by meta-analysis.

Methods: The MEDLINE, the Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible literature. Data of lipids were classified into short-, mid-, and long-term according to treatment duration. Meta-analyses were performed to compare the lipid levels before and after treatments.

Results: A total of 44 records and 3,935 patients were included in the meta-analyses. Anti-TNF therapies were associated with significant increase in TC [mean difference (MD): +0.14, +0.23, and +0.26 mmol/l, respectively] and HDL (MD): +0.11, +0.12, and +0.11 mmol/l, respectively) in the short-, mid-, and long-term; anti-TNF therapies were associated with increased low-density lipoprotein (LDL) (MD: +0.06 mmol/l) and apolipoprotein A1 (ApoA1) (MD: +0.07 g/l) in the short-term, but not in the mid-term and long-term; triglyceride (TG) and apolipoprotein B (ApoB) do not change significantly in all the periods; proatherosclerotic indexes (TC/HDL, ApoB/ApoA1, and LDL/HDL) tend to decrease in the short- and mid-term, but return to baseline in the long-term after TNF inhibition.

Conclusion: Anti-TNF therapies were related to a long-term raised HDL level, which, together with evidence of improved HDL function, may contribute partially to the decreased CVDs risk by TNF inhibition.
Thyroxine Supplementation in Pregnant Women After Thyroidectomy for Thyroid Cancer and Neonatal Birth Weight
Authors: Ding Zheng , Guo Fei , Zhou Yulai , Huang Xiaoyi , Liu Zhiwei , Fan Jianxia
Published: October 2021

Patients are often supplemented with a sufficient dose of thyroxine after thyroidectomy for thyroid cancer. However, the influence of thyroxine supplementation on fetal growth in pregnant women after thyroidectomy for thyroid cancer remains unclear. The aim of this study was to investigate the effect of thyroxine supplementation on neonatal birth weight. This cohort study included 49,896 pregnant women (278 patients with a history of thyroidectomy for thyroid cancer and 39,363 control cases after exclusion). Thyroid parameters were examined in pregnant women and their newborns. The associations between maternal thyroid function and neonatal birth weight and small for gestational age were studied using regression analyses. In the levothyroxine supplementation group, free thyroxine (FT4) levels were significantly higher in both early pregnancy (P < 0.001) and late pregnancy (P < 0.001) groups than in the control group. Furthermore, levels of neonatal thyroid stimulating hormone (P = 0.032) and birth weight (P = 0.043) were significantly lower than those in the control group. We also observed a significant inverse association between maternal FT4 levels in early pregnancy and neonatal birth weight (P=0.028), especially in male newborns (P=0.036). In summary, after thyroidectomy for thyroid cancer, a sufficient dose of thyroxine supplementation in early pregnancy is significantly associated with reduced birth weight and may need to be monitored.
Bacterioplankton Richness and Composition in a Seasonal Urban River
Authors: Xiao Zufei , Li Gang , Zhao Yi , Xiao Keqing , Chen Qinglin , Bao Peng , Tang Jianfeng , Ruan Tian , Zama Eric Fru , Xu Yaoyang
Published: October 2021

Urbanization and seasonality strongly influence the bacterial composition of the soil. However, aquatic environments such as rivers are understudied owing to their high dynamics and therefore rules relating to more static habitats such as lentic or terrestrial environments may be limited. Here, we compared the spatiotemporal patterns of bacterioplankton communities in the Zhangxi river along a gradient of urbanization using 16S ribosomal DNA identification. The alpha and beta diversity of bacterioplankton showed no significant response to watershed urbanization. A significant difference in predicted functional profiles of the bacterioplankton community was also revealed between the wet and dry seasons. The bacterioplankton community assembly was driven by both deterministic and stochastic processes. Stochasticity was one of the most vital processes affecting the bacterioplankton communities in both wet and dry seasons, explaining over 50% variation in the community by the null model analysis. Bacterioplankton co-occurrence patterns in the river changed with the seasons. More notably, the composition of bacterioplankton communities was inconsistent with alternations of the spatial distance offering meaningful implications for interactions between zero-radius operational taxonomic units and the dynamics of the bacterioplankton communities in surface water. In summary, we found clear patterns of seasonal variations in the bacterioplankton community structures.
Biomass Production Assessment in a Protected Area of Dry Tropical forest Ecosystem of India: A Field to Satellite Observation Approach
Authors: Thakur Tarun K. , Patel Digvesh K. , Thakur Anita , Kumar Anirudh , Bijalwan Arvind , Bhat Jahangeer A. , Kumar Amit , Dobriyal M. J. , Kumar Munesh , Kumar Amit
Published: October 2021

In recent decades, degradation and loss of the world’s forest ecosystems have been key contributors to biodiversity loss and future climate change. This article analyzes plant diversity, biomass, carbon sequestration potential (CSP), and the net primary productivity (NPP) of four vegetation types viz., Dense mixed forest (DMF); Open mixed forest (OMF); Teak plantation (TP), and Sal mixed forest (SMF) in the dry tropical forest ecosystem of central India through remote sensing techniques together with physical ground observations during 2013–2018. The total C storage in trees varied from 16.02 to 47.15 Mg ha−1 in studied vegetation types with the highest in DMF and lowest in OMF. The total C storage in stem wood, branches, and foliage falls in the range of 52.93–78.30%, 9.49–22.99%, and 3.31–12.89% respectively. The total standing biomass varied from 83.77 to 111.21 Mg ha−1 and these variations are due to different vegetation types, with the highest in DMF followed by TP, SMF while the lowest was estimated in OMF. The net primary productivity (NPP) [aboveground (AG) + belowground (BG)] varied from 7.61 to 9.94 Mg ha−1 yr−1 with mean values of 8.74 Mg ha−1 yr−1 where AG shares a maximum contribution of 77.66%. The total biomass production was distributed from 64.09 to 82.91% in AG and 17.08–35.91% in BG components. The present study outlines that the studied forest ecosystem has the substantial potential of carbon sequestration and a great possibility of mitigating local and global climate change.
Nexus Between COVID-19 Infections, Exchange Rates, Stock Market Return, and Temperature in G7 Countries: Novel Insights From Partial and Multiple Wavelet Coherence
Authors: Singh Sanjeet , Bansal Pooja , Bhardwaj Nav , Agrawal Anirudh
Published: October 2021

This study attempts to analyze the time-varying pattern between the exchange rates, stock market return, temperature, and number of confirmed COVID-19 cases in G7 countries caused by the COVID-19 pandemic. We have implemented our analysis using wavelet coherence and partial wavelet coherence (PWC) on independent variables from January 4, 2021 to July 31, 2021. This paper contributes to the earlier work on the same subject by employing wavelet coherence to analyze the effect of the sudden upsurge of the COVID-19 pandemic on exchange rates, stock market returns, and temperature to sustain and improve previous results regarding correlation analysis between the above-mentioned variables. We arrived at the following results: 1) temperature levels and confirmed COVID-19 cases are cyclical indicating daily temperatures have a material bearing on propagating the novel coronavirus in G7 nations; 2) noteworthy correlations at truncated frequencies show that a material long-term impact has been observed on exchange rates and stock market returns of G7 and confirmed COVID-19 cases; 3) accounting for impact of temperature and equity market returns, a more robust co-movement is observed between the exchange rate returns of the respective nations and the surge in COVID-19 cases; and 4) accounting for the influence of temperature and exchange rate returns and the increase in the confirmed number of coronavirus-infected cases and equity returns, co-movements are more pronounced. Besides academic contributions, this paper offers insight for policymakers and investment managers alike in their attempt to navigate the impediments created by the coronavirus in their already arduous task of shaping the economy and predicting stock market patterns.
Evaluation of Seasonal Heat Stress on Transcriptomic Profiles and Global DNA Methylation of Bovine Oocytes
Authors: Diaz Fabian A , Gutierrez-Castillo Emilio J , Foster Brittany A , Hardin Paige T , Bondioli Kenneth R , Jiang Zongliang
Published: October 2021

Heat stress affects oocyte developmental competence and is a major cause of reduced fertility in heat stressed cattle. Negative effects of heat stress on the oocyte have been observed at morphological, biochemical and developmental levels. However, the mechanisms by which heat stress affects the oocyte at the transcriptional and epigenetic levels remain to be further elucidated. Here we aimed to investigate the effect of heat stress on oocyte quality, transcriptomic profiles and DNA methylation of oocytes collected through the transition from spring to summer under Louisiana conditions. Summer season resulted in a lower number of high quality oocytes obtained compared to the spring season. There was no difference in in vitro maturation rates of oocytes collected during spring as compared to summer. RNA sequencing analysis showed that a total of 211 and 92 genes were differentially expressed as a result of heat stress in GV and MII oocytes, respectively. Five common genes (E2F8, GATAD2B, BHLHE41, FBXO44, and RAB39B) were significantly affected by heat in both GV and MII oocytes. A number of pathways were also influenced by heat stress including glucocorticoid biosynthesis, apoptosis signaling, and HIPPO signaling in GV oocytes, and Oct4 pluripotency, Wnt/beta-catenin signaling, and melatonin degradation I in MII oocytes. In addition, fluorescent immunocytochemistry analysis showed no difference in global levels of DNA methylation and DNA hydroxymethylation at either the GV or MII stage between spring and summer oocytes. The results of this study contribute to a better understanding of the effect of heat stress on the molecular mechanisms altered in bovine oocytes.