bluuebunny/crossref_metadata_2025 huggingface dataset:
METHODS OF COUNTERING INTELLIGENCE USING SMALL-SIZED UNMANNED AERIAL VEHICLES
Authors: Ignatenko Nikita V. , Polikanin Alexey N.
Published: October 2021

Small-sized aircrafts are increasingly used for espionage or intelligence. This is due to their small size, which gives them the advantage of being unnoticed. Easily carried in a backpack or bag, they can be launched almost anywhere in the world. Drones easily provide the collection of useful information with the help of technical means installed on them, it can be both cameras that have high resolution, and directional microphones that collect the recording of confidential information for tens of meters from the object of intelligence. All this poses a threat to the inhabitants of all countries of the world. In this article, a study is conducted on possible methods for detecting small-sized aircrafts, general effectiveness of these methods is evaluated, and it’s concluded that passive radar is a promising method of countering and detecting unmanned aerial vehicles.
The Complete Proof of the Riemann Hypothesis
Authors: Vega Frank
Published: October 2021

Robin criterion states that the Riemann Hypothesis is true if and only if the inequality $\sigma(n) < e^{\gamma } \times n \times \log \log n$ holds for all $n > 5040$, where $\sigma(n)$ is the sum-of-divisors function and $\gamma \approx 0.57721$ is the Euler-Mascheroni constant. We show there is a contradiction just assuming the possible smallest counterexample $n > 5040$ of the Robin inequality. In this way, we prove that the Robin inequality is true for all $n > 5040$ and thus, the Riemann Hypothesis is true.
Труды Маргианской археологической экспедиции. Том 8. Исследования Гонур-депе в 2015–2019 годах
Authors: Артемьев Владимир Иванович , Бендезу-Сармиенто Хулио ,   La Délégation archéologique française en Afghanistan — DAFA, Бисциони Рафаэль , Саидмурод Бобомуллоев , Вахдати Али Акбар , Виноградова Наталья Матвеевна , Вртанесян Гарегин Суренович , Грушин Сергей Петрович , Гутков Александр Иванович , Дубова Надежда Анатольевна ,   Институт этнологии и антропологии им. Н.Н. Миклухо-Маклая РАН, Кордоба Зоило Хоакин Мария , Куфтерин Владимир Владимирович , Мамедов Мухаммед Аннаевич , Палагута Илья Владимирович , Сатаев Роберт Мидхатович , Семененко Александр Андреевич , Фрибус Алексей Викторович , Рябова Татьяна Николаевна , Чёрная Мария Петровна
Published: October 2021

Данный выпуск Трудов включает значительный мемориальный раздел, посвященный ушедшим из жизни коллегам, основателям данной серии и друзьям Маргианской экспедиции — П.М. Кожину, М.Ф. Косареву и О. Леконту. Публикуется ряд неизвестных ранее работ П.М. Кожина. Приводится информация о раскопках 2015–¬2019 гг. на Гонуре и в музеях Туркменистана, дается архитектурный анализ ряда сооружений Гонура и описываются особенности технологии изготовления керамики, а также анализируются остеологические данные. Публикуются результаты изучения могильников в Восточном Иране и на территории Пенджикентского района Таджикистана, а также сведения о распространении разных форм мечей на территории Древнего Востока и долины р. Инд. Завершает книгу раздел о гордости Туркменистана – ахалтекинских скакунах. Издание предназначено для археологов, антропологов и историков архитектуры. This issue of Transaction includes a large memorial section dedicated to the deceased colleagues, founders of this series and friends of the Margiana expedition – Pavel M. Kozhin, Michael F. Kosarev and Olivier Lecomte. A number of previously unknown works by Pavel M. Kozhin is publishing. Information on excavations in 2015–2019 is provided at Gonur and in museums of Turkmenistan, an architectural analysis of a number of structures of Gonur is given and the features of the technology of pottery making as well as osteological data are described. The results of the study of burial grounds in Eastern Iran and on the territory of the Pendjikent region of Tajikistan are published as well as information about the distribution of different forms of swords on the territory of the Ancient East and the valley of the river Indus. A section about the pride of Turkmenistan - Akhal-Teke horses ends the book . The issue is intended for archaeologists, anthropologists and historians of architecture.
Screening of Potent Phytochemical Inhibitors Against SARS-CoV-2 Main Protease: An Integrative Computational Approach
Authors: Mahmud Shafi , Hasan Md. Robiul , Biswas Suvro , Paul Gobindo Kumar , Afrose Shamima , Mita Mohsana Akter , Sultana Shimu Mst. Sharmin , Promi Maria Meha , Hani Umme , Rahamathulla Mohamed , Khan Md. Arif , Zaman Shahriar , Uddin Md. Salah , Rahmatullah Mohammed , Jahan Rownak , Alqahtani Ali M. , Saleh Md. Abu , Emran Talha Bin
Published: October 2021

Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine because it is well-conserved and plays a vital role in viral replication. Mpro inhibition can stop the replication, transcription as well as recombination of SARS-CoV-2 after the infection and thus can halt the formation of virus particles, making Mpro a viable therapeutic target. Here, we constructed a phytochemical dataset based on a rigorous literature review and explored the probability that various phytochemicals will bind with the main protease using a molecular docking approach. The top three hit compounds, medicagol, faradiol, and flavanthrin, had binding scores of −8.3, −8.6, and −8.8 kcal/mol, respectively, in the docking analysis. These three compounds bind to the active groove, consisting of His41, Cys45, Met165, Met49, Gln189, Thr24, and Thr190, resulting in main protease inhibition. Moreover, the multiple descriptors from the molecular dynamics simulation, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond analysis, confirmed the stable nature of the docked complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed a lack of toxicity or carcinogenicity for the screened compounds. Our computational analysis may contribute toward the design of an effective drug against the main protease of SARS-CoV-2.
Pannexin 1 Regulates Skeletal Muscle Regeneration by Promoting Bleb-Based Myoblast Migration and Fusion Through a Novel Lipid Based Signaling Mechanism
Authors: Suarez-Berumen Katia , Collins-Hooper Henry , Gromova Anastasia , Meech Robyn , Sacco Alessandra , Dash Phil R. , Mitchell Robert , Shestopalov Valery I. , Woolley Thomas E. , Vaiyapuri Sakthivel , Patel Ketan , Makarenkova Helen P.
Published: October 2021

Adult skeletal muscle has robust regenerative capabilities due to the presence of a resident stem cell population called satellite cells. Muscle injury leads to these normally quiescent cells becoming molecularly and metabolically activated and embarking on a program of proliferation, migration, differentiation, and fusion culminating in the repair of damaged tissue. These processes are highly coordinated by paracrine signaling events that drive cytoskeletal rearrangement and cell-cell communication. Pannexins are a family of transmembrane channel proteins that mediate paracrine signaling by ATP release. It is known that Pannexin1 (Panx1) is expressed in skeletal muscle, however, the role of Panx1 during skeletal muscle development and regeneration remains poorly understood. Here we show that Panx1 is expressed on the surface of myoblasts and its expression is rapidly increased upon induction of differentiation and thatPanx1–/–mice exhibit impaired muscle regeneration after injury.Panx1–/–myoblasts activate the myogenic differentiation program normally, but display marked deficits in migration and fusion. Mechanistically, we show that Panx1 activates P2 class purinergic receptors, which in turn mediate a lipid signaling cascade in myoblasts. This signaling induces bleb-driven amoeboid movement that in turn supports myoblast migration and fusion. Finally, we show that Panx1 is involved in the regulation of cell-matrix interaction through the induction of ADAMTS (Disintegrin-like and Metalloprotease domain with Thrombospondin-type 5) proteins that help remodel the extracellular matrix. These studies reveal a novel role for lipid-based signaling pathways activated by Panx1 in the coordination of myoblast activities essential for skeletal muscle regeneration.
Prognostic Significance of Preprocedural N-Terminal Pro-B-Type Natriuretic Peptide Assessment in Diabetic Patients With Multivessel Coronary Disease Undergoing Revascularization
Authors: Wang Le , Cong Hong-liang , Zhang Jing-xia , Hu Yue-cheng , Li Xi-ming , Zhang Ying-yi , Wang Lin , Yang Hua , Ren Li-bin , Qi Wei , Liu Chun-wei
Published: October 2021

Background and Aims: The N-terminal pro-B-type natriuretic peptide (NT-proBNP) may predict adverse cardiovascular outcomes in patients with diabetes. However, its prognostic value in patients with multivessel disease (MVD) undergoing coronary revascularization remains unclear. This study aimed to evaluate the prognostic significance of preprocedural NT-proBNP levels in diabetic patients with MVD undergoing coronary revascularization.

Methods: A total of 886 consecutive diabetic patients with MVD who underwent coronary revascularization were enrolled in this study. Patients were divided into quartiles according to their pre-procedural NT-proBNP levels. Kaplan-Meier curves and Cox regression analyses were performed to evaluate the risk of cardiovascular events, including all-cause death, cardiovascular death, myocardial infarction (MI), stroke, and major adverse cardiovascular events (MACE), according to the NT-proBNP quartiles.

Results: During a median follow-up period of 4.2 years, 111 patients died (with 82 being caused by cardiovascular disease), 133 had MI, 55 suffered from stroke, and 250 experienced MACE. Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of all-cause death, cardiovascular death, MI, and MACE (log-rank test, P < 0.001, respectively). Multivariate Cox regression analysis revealed that NT-proBNP level was an independent predictor of adverse outcomes, including all-cause death (HR, 1.968; 95% CI, 1.377–2.812; P < 0.001), cardiovascular death (HR, 1.940; 95% CI, 1.278–2.945; P = 0.002), MI (HR, 1.722; 95% CI, 1.247–2.380; P = 0.001), and MACE (HR, 1.356; 95% CI, 1.066–1.725; P = 0.013). The role of NT-proBNP in predicting adverse outcomes was similar in patients with stable angina pectoris and acute coronary syndrome. Moreover, preprocedural NT-proBNP alone discriminated against the SYNTAX II score for predicting all-cause death [area under the curve (AUC), 0.662 vs. 0.626, P = 0.269], cardiovascular death (AUC, 0.680 vs. 0.622, P = 0.130), MI (AUC, 0.641 vs. 0.579, P = 0.050), and MACE (AUC, 0.593 vs. 0.559, P = 0.171). The addition of NT-proBNP to the SYNTAX II score showed a significant net reclassification improvement, integrated discrimination improvement, and improved C-statistic (all P < 0.05).

Conclusion: NT-proBNP levels were an independent prognostic marker for adverse outcomes in diabetic patients with MVD undergoing coronary revascularization, suggesting that preprocedural NT-proBNP measurement might help in the risk stratification of high-risk patients.
Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy
Authors: Gao Lu , Guo Sen , Long Rui , Xiao Lili , Yao Rui , Zheng Xiaolin , Zhang Yanzhou , Wang Xiaofang
Published: October 2021

Lysosomal-associated protein transmembrane 5 (LAPTM5) is mainly expressed in immune cells and has been reported to regulate inflammation, apoptosis and autophagy. Although LAPTM5 is expressed in the heart, whether LAPTM5 plays a role in regulating cardiac function remains unknown. Here, we show that the expression of LAPTM5 is dramatically decreased in murine hypertrophic hearts and isolated hypertrophic cardiomyocytes. In this study, we investigated the role of LAPTM5 in pathological cardiac hypertrophy and its possible mechanism. Our results show that LAPTM5 gene deletion significantly exacerbates cardiac remodeling, which can be demonstrated by reduced myocardial hypertrophy, fibrosis, ventricular dilation and preserved ejection function, whereas the opposite phenotype was observed in LAPTM5 overexpression mice. In line with the in vivo results, knockdown of LAPTM5 exaggerated angiotensin II-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes, whereas overexpression of LAPTM5 protected against angiotensin II-induced cardiomyocyte hypertrophy in vitro. Mechanistically, LAPTM5 directly bound to Rac1 and further inhibited MEK-ERK1/2 signaling, which ultimately regulated the development of cardiac hypertrophy. In addition, the antihypertrophic effect of LAPTM5 was largely blocked by constitutively active mutant Rac1 (G12V). In conclusion, our results suggest that LAPTM5 is involved in pathological cardiac hypertrophy and that targeting LAPTM5 has great therapeutic potential in the treatment of pathological cardiac hypertrophy.
Case Report: Abnormal ECG and Pantalgia in a Patient With Guillain–Barré Syndrome
Authors: Cao Xiangqi , Tang Manyun , Liu Hui , Yue Xin , Luo Guogang , Yan Yang
Published: October 2021

Background: Guillain–Barré syndrome (GBS) is an acute immune-mediated disorder in the peripheral nervous system (PNS) characterized by symmetrical limb weakness, sensory disturbances, and clinically absent or decreased reflexes. Pantalgia and dysautonomia, including cardiovascular abnormalities, are common findings in the spectrum of GBS. It is usually challenging to distinguish GBS-related electrocardiogram (ECG) abnormities and chest pain from acute coronary syndrome (ACS) in patients with GBS due to the similar clinical symptom and ECG characteristics. Here, we present a case of GBS complicating ACS.

Case Summary: A 37-year-old woman with a 2-month history of GBS presented to the emergency department due to pantalgia. The ECG showed a pattern of transitional T-wave inversion in the leads I, aVL, and V2 through V4 and shortly returned to normal, which appeared several times in a short time, but lab testing was unremarkable. Then, a further coronary computed tomography angiography (CTA) revealed the presence of critical stenosis of the left anterior descending artery, leading to the diagnosis of ACS. During the follow-up, she suffered from a non-ST-elevation myocardial infarction and accepted revascularization of the left anterior descending artery in the second week after discharge.

Conclusion: Guillain–Barré syndrome could accompany chest pain and abnormalities on ECG. Meanwhile, it is essential to bear in mind that “GBS-related ECG abnormalities and chest pain” is a diagnosis of exclusion that can only be considered after excluding coronary artery disease, especially when concomitant chest pain, despite being a common presentation of pantalgia, occurs.
Deep-Water Syn-rift Stratigraphy as Archives of Early-Mid Pleistocene Palaeoenvironmental Signals and Controls on Sediment Delivery
Authors: Cullen Timothy M. , Collier Richard E. Ll. , Hodgson David M. , Gawthorpe Robert L. , Kouli Katerina , Maffione Marco , Kranis Haralambos , Eliassen Gauti T.
Published: October 2021

The timing and character of coarse siliciclastic sediment delivered to deep-water environments in active rift basins is governed by the complicated interactions of tectonics, climate, eustasy, hinterland geology, and shelf process regime. The stratigraphic archives of deep-water syn-rift basin-fills provide records of palaeoenvironmental changes (e.g. climate and vegetation) in onshore catchments, particularly where they are connected by narrow shelves. However, a chronostratigraphically constrained record of climatic fluctuations and process responses in the hinterland source area recorded in deep-water deposits is rare. Here, we integrate a fully cored research borehole with outcrop exposures of deep-water syn-rift stratigraphy to reconstruct palaeoenvironmental change within the stratigraphy of the West Xylokastro Fault Block in the Corinth Rift, Greece. We used palaeomagnetic and palynological analyses from borehole core samples to develop a chronostratigraphic and palaeoenvironmental model, which we compare to global records of Early-Mid Pleistocene climate and eustatic change. This framework allows establishment of a chronostratigraphic and palaeoenvironmental context to stratigraphic variability encountered in outcrop and in the borehole. Our results show that the ∼240 m thick studied succession was deposited from ∼1.1 to 0.6 Ma across the Early-to Mid-Pleistocene transition. During the Early Pleistocene, obliquity-paced climatic variability is largely coherent with vegetation changes of forest coverage within catchments on the southern margin of the Corinth Rift. Large magnitude, eccentricity-paced cyclicity dominant after the Mid-Pleistocene Transition can alter sediment supply from onshore catchments during the warming stages of severe interglacials where expansion of forest cover may trap sediment within catchments. Conglomeratic grade sediment delivery to the deep-water is enhanced during glacial periods, interpreted to reflect sparse forest cover and large winter storms, and during semi-arid, grassland-dominated interglacial highstands during severe interglacials. Base-level rise during minor interglacials is easily outpaced by high sediment supply and is seldom represented stratigraphically. The study demonstrates the value of integrated palynological and sedimentological studies, whilst applying a conservative approach to interpretation when dealing with sparse palynological records from proximal deep-water stratigraphy. The case study provides conceptual models where climatic and vegetation changes can begin to be incorporated as a key control on sediment flux from onshore drainage basins to deep-water syn-rift successions.
Localized Enhancement of Infrared Radiation Temperature of Rock Compressively Sheared to Fracturing Sliding: Features and Significance
Authors: Liu Xiangxin , Wu Lixin , Zhang Yanbo , Mao Wenfei
Published: October 2021

Previous experiments indicated that infrared radiation temperature (IRT) was applied in monitoring rock stress or rock mass fracturing, and abnormal IRT phenomena preceding rock failure or tectonic earthquakes were frequently reported. However, the characteristics of IRT changing with rock fracturing and frictional sliding are not clear, which leaves much uncertainties of location and pattern identification of stress-produced IRT. In this study, we investigated carefully the localized IRT enhancement of rock compressively sheared to fracturing and sliding (named as CSFS) with marble and granite specimens. Infrared thermogram and visible photos were synchronously observed in the process of rock CSFS experiment. We revealed that localized IRT enhancement was determined by local stress locking, sheared fracturing, and frictional sliding, and the relations between the Kcv of IRT and the shear force are almost linear in wave length 3.7–4.8 μm. In the process of rock CSFS, the detected ΔIRT which resulted from thermoelastic effect is 0.418 K, while the detected ΔIRT resulted from friction effect reaches up to 10.372 K, which is about 25 times to the former. This study is of potential values for infrared detection of rock mass failure in engineering scale and satellite remote sensing of the seismogenic process in the regional scale.
Investigation on the Influences of STEAM-Based Curriculum on Scientific Creativity of Elementary School Students
Authors: Tran Ngoc-Huy , Huang Chin-Fei , Hsiao Kuo-Hung , Lin Kuan-Li , Hung Jeng-Fung
Published: October 2021

Up until now, there have been several different viewpoints on creativity in general and creativity in the science field in particular. Furthermore, STEAM (science, technology, engineering, arts, and mathematics) education is increasingly successful and widespread around the world; however, few studies on its impact on scientific creativity exist. As a result, research on the influence of STEAM-based curriculum on students’ scientific creativity is critical. Elementary school students were chosen to be investigated in this research, and the main topic of the STEAM-based curriculum was about a house-shaped money-saving tube with the concept of lock science, which was developed and created by the authors’ team. This research produced two phases of courses: Lock Science Courses (2 weeks) and STEAM-based courses (2 weeks). In this study, sixty-six elementary students from two separate courses were divided into two groups: control and experimental. This research used a counterbalanced design. The control group took Lock Science Courses first and then STEAM-based courses, while the experimental group did the opposite. As a pretest and posttest, students in both groups were asked to complete the “scientific creativity test” (Cronbach’s α, 0.87). The findings of the paired t-test study indicate that both the control and experimental groups have shown significant improvement in their scientific creativity. However, only the fluency and flexibility components of scientific creativity (consisting of fluency, flexibility, and originality) showed considerable development, whereas the originality component remained unchanged. This research also found that after engaging in a STEAM-based curriculum, there was no substantial difference in scientific creativity between males and females. Further discussion is provided.
Association of Anthropometric Indices With the Development of Diabetes Among Hypertensive Patients in China: A Cohort Study
Authors: Liu Yingshan , Liu Xiaocong , Zhang Shuting , Zhu Qibo , Fu Xiaoying , Chen Hongmei , Guan Haixia , Xia Yinghua , He Qun , Kuang Jian
Published: October 2021

Background

Patients with comorbidity of hypertension and diabetes are associated with higher morbidity and mortality of cardiovascular disease than those with hypertension or diabetes alone. The present study aimed to identify anthropometric risk factors for diabetes among hypertensive patients who were included in a retrospective cohort study.

Methods

Hypertensive adults without diabetes were recruited in China. Demographic, clinical, biochemical, and anthropometric indices were collected at baseline and during the follow-up. Anthropometric measures included BMI, waist circumference, waist-to-height ratio (WHtR), and waist-to-hip ratio, and several novel indices. To estimate the effect of baseline and dynamic changes of each anthropometric index on risk of new-onset diabetes (defined as self-reported physician-diagnosed diabetes and/or use of hypoglycemic medication, or new-onset FPG≥7.0 mmol/L during follow-up), Cox regression models were used.

Results

A total of 3852 hypertensive patients were studied, of whom 1167 developed diabetes during follow-up. Multivariate Cox regression analyses showed that there was a graded increased risk of incident diabetes with successively increasing anthropometric indices mentioned above (all P<0.05). Regardless of the baseline general obesity status, elevated WHtR was both related to higher risk of diabetes; the HRs (95%CI) of baseline BMI<24 kg/m2 & WHtR≥0.5 group and BMI≥24 kg/m2 & WHtR≥0.5 group were 1.34 (1.05, 1.72), 1.85 (1.48, 2.31), respectively. Moreover, the dynamic changes of WHtR could sensitively reflect diabetes risk. Diabetes risk significantly increased when patients with baseline WHtR<0.5 progressed to WHtR≥0.5 during the follow-up (HR=1.63; 95%CI, 1.11, 2.40). There was also a decreasing trend towards the risk of incident diabetes when baseline abnormal WHtR reversed to normal at follow-up (HR=1.93; 95%CI, 1.36, 2.72) compared with those whose WHtR remained abnormal at follow-up (HR=2.04; 95%CI, 1.54, 2.71).

Conclusions

Central obesity is an independent and modifiable risk factor for the development of diabetes among hypertensive patients. Measuring indices of central obesity in addition to BMI in clinics could provide incremental benefits in the discrimination of diabetes among Chinese hypertensive patients. Dynamic changes of WHtR could sensitively reflect changes in the risk of diabetes. Therefore, long-term monitoring of hypertensive patients using non-invasive anthropometric measures and timely lifestyle intervention could effectively reduce the development of diabetes.
Bothersome Flies: How Free-Ranging Horses Reduce Harm While Maintaining Nutrition
Authors: Rubenstein Daniel I. , Feinstein Lisa H.
Published: October 2021

The horses of Shackleford Banks, NC, United States are harassed by many species of biting flies. Apart from being a nuisance, their bites can lead to blood loss and transmit disease. As a result, these horses tend to avoid areas where fly abundances are high. Like other free-ranging horse populations, environmental factors such as low wind speeds and high temperatures increase fly loads per horse. Similarly, coat color matters since darker horses attract more flies than lighter ones, especially on hot sunny days. Many horse populations reduce per capita fly loads by living in large groups or by bunching tightly together. Shackleford horses do so, too, but also use wind speed differences among habitats to modulate fly numbers. By adopting a systematic pattern of moving between habitats such that they only visit a habitat when wind speed is high enough to keep fly harassment to a tolerable level, they can avoid being bitten while continuing to forage. Typically, they begin the day foraging on the salt marshes where fly abundance is inherently low and are lowered further by faint early morning breezes. Later in the morning, horses move to grassy patches (swales) when increasing wind speed reduces fly landings there to levels found on the marshes. Later still, when wind speeds peak, horses begin foraging among the sand dunes. At this point wind speeds are high enough so that horses using any habitat will be minimally harassed by flies, thus enabling them to freely choose where to feed based on which habitat meets particular dietary needs for protein, energy and nutrients on any particular day. Hence, Shackleford horses follow the breeze to solve a challenging dilemma of maintaining a high nutritional plane without succumbing to fly harassment. Other free-ranging horses populations appear to have a more limited “either-or” choice of “bite or be bitten,” thus limiting their decision-making options.
Low Pollinator Sharing Between Coexisting Native and Non-native Plant Pairs: The Effect of Corolla Length and Flower Abundance
Authors: Abdallah Mohamad , Hervías-Parejo Sandra , Traveset Anna
Published: October 2021

Understanding the mechanisms by which non-native plants can attract pollinators in their new geographical zones is important because such species infiltrate native communities and can disrupt native ecological interactions. Despite the large number of studies assessing how invasive plants impact plant–pollinator interactions, the specific comparison of pollination interactions between native and non-native plant pairs has received much less attention. Here we focused on four coexisting co-flowering pairs of common native and non-native species, both with abundant flowers but different floral traits, and asked: (1) to what extent native and non-native plants share pollinator species, and whether the non-native plants attract a different set of pollinators, (2) whether the most shared pollinators are the most frequent floral visitors and the most generalized in their interactions, and (3) how much of the variation in the diversity and frequency of pollinator species between native and non-native plant species can be explained by floral trait dissimilarity and flower abundance. Direct pollinator observations revealed that the plant pairs shared a low fraction (0–33%) of insect species, i.e., non-native plants tended to acquire a different set of pollinators than their native counterparts. The most shared pollinators in each plant pair were the most common but not the most generalized species, and non-native species attracted both generalized and specialized pollinators. Corolla length at opening and flower abundance showed to be important in determining the differences in flower visitation rate between natives and non-natives. Our findings support the general pattern that non-native species have no barriers at the pollination stage to integrate into native communities and that they may attract a different assemblage of pollinators relative to those that visit native plants with which they coexist.
Multiplexed Microsphere-Based Flow Cytometric Assay to Assess Strain Transcending Antibodies to Plasmodium vivax Duffy Binding Protein II Reveals an Efficient Tool to Identify Binding-Inhibitory Antibody Responders
Authors: Alves Jéssica R. S. , de Araújo Fernanda F. , Pires Camilla V. , Teixeira-Carvalho Andréa , Lima Barbara A. S. , Torres Letícia M. , Ntumngia Francis B. , Adams John H. , Kano Flora S. , Carvalho Luzia H.
Published: October 2021

Malaria remains a major public health problem worldwide, and Plasmodium vivax is the most widely distributed malaria parasite. Naturally acquired binding inhibitory antibodies (BIAbs) to region II of the Duffy binding protein (DBPII), a P. vivax ligand that is critical for reticulocyte invasion, are associated with a reduced risk of clinical malaria. Owing to methodological issues in evaluating antibodies that inhibit the DBPII–DARC interaction, a limited number of studies have investigated DBPII BIAbs in P. vivax-exposed populations. Based on the assumption that individuals with a consistent BIAb response are characterized by strain-transcending immune responses, we hypothesized that detecting broadly reactive DBPII antibodies would indicate the presence of BIAb response. By taking advantage of an engineered DBPII immunogen targeting conserved DBPII neutralizing epitopes (DEKnull-2), we standardized a multiplex flow cytometry-based serological assay to detect broadly neutralizing IgG antibodies. For this study, a standard in vitro cytoadherence assay with COS-7 cells expressing DBPII was used to test for DBPII BIAb response in long-term P. vivax-exposed Amazonian individuals. Taken together, the results demonstrate that this DBPII-based multiplex assay facilitates identifying DBPII BIAb carriers. Of relevance, the ability of the multiplex assay to identify BIAb responders was highly accurate when the positivity for all antigens was considered. In conclusion, the standardized DBPII-based flow cytometric assay confirmed that DBPII-BIAb activity was associated with the breadth rather than the magnitude of anti-DBPII antibodies. Altogether, our results suggest that multiplex detection of broadly DBPII-reactive antibodies facilitates preliminary screening of BIAb responders.
Unsatisfied Reporting Quality of Clinical Trials Evaluating Immune Checkpoint Inhibitor Therapy in Cancer
Authors: Chen Chen , Zhou Yixin , Zhang Xuanye , Wang Yuhong , He Li-na , Lin Zuan , Chen Tao , Jiang Yongluo , Hong Shaodong , Zhang Li
Published: October 2021

Background

More and more immune-oncology trials have been conducted for treating various cancers, yet it is unclear what the reporting quality of immune-oncology trials is,and characteristics associated with higher reporting quality.

Objective

This study aims to evaluate the reporting quality of immune-oncology trials.

Methods

The PubMed and Cochrane library were searched to identify all English publications of clinical trials assessing immunotherapy for cancer. Reporting quality of immune-oncology trials was evaluated by a quality score with 11 points derived from the Trial Reporting in Immuno-Oncology (TRIO) statement, which contained two parts: an efficacy score of 6 points and toxicity score of 5 point. Linear regression was used to identify characteristics associated with higher scores.

Results

Of the 10,169 studies screened, 298 immune-oncology trial reports were enrolled. The mean quality score, efficacy score, and toxicity score were 6.46, 3.61, and 2.85, respectively. The most common well-reported items were response evaluation criteria (96.0%) and toxicity grade (98.7%), followed by Kaplan-Meier survival analyses (80.5%). Treatment details beyond progression (12.8%) and toxicity onset time and duration (7.7%) were poorly reported. Multivariate regression revealed that higher impact factor (IF) (IF >20 vs. IF <5, p < 0.001), specific tumor type (p = 0.018 for lung, p = 0.021 for urinary system, vs. pan cancer), and a certain kind of immune checkpoint blocking agent (p < 0.001 for anti-PD-1 or multiagents, vs. anti-CTLA-4) were independent predictors of higher-quality score. Similar independent predictive characteristics were revealed for high-efficacy score. Only IF >20 had a significant high-toxicity score (p < 0.001).

Conclusion

Immune-oncology trial reports presented an unsatisfied quality score, especially in the reporting of treatment details beyond progression and toxicity onset time and duration. High IF journals have better reporting quality. Future improvement of trial reporting was warranted to the benefit-risk assessment of immunotherapy.
Blood Transcriptomes of Anti-SARS-CoV-2 Antibody-Positive Healthy Individuals Who Experienced Asymptomatic Versus Clinical Infection
Authors: Sfikakis Petros P. , Verrou Kleio-Maria , Ampatziadis-Michailidis Giannis , Tsitsilonis Ourania , Paraskevis Dimitrios , Kastritis Efstathios , Lianidou Evi , Moutsatsou Paraskevi , Terpos Evangelos , Trougakos Ioannis , Chini Vasiliki , Manoloukos Menelaos , Moulos Panagiotis , Pavlopoulos Georgios A. , Kollias George , Hatzis Pantelis , Dimopoulos Meletios A.
Published: October 2021

The reasons behind the clinical variability of SARS-CoV-2 infection, ranging from asymptomatic infection to lethal disease, are still unclear. We performed genome-wide transcriptional whole-blood RNA sequencing, bioinformatics analysis and PCR validation to test the hypothesis that immune response-related gene signatures reflecting baseline may differ between healthy individuals, with an equally robust antibody response, who experienced an entirely asymptomatic (n=17) versus clinical SARS-CoV-2 infection (n=15) in the past months (mean of 14 weeks). Among 12.789 protein-coding genes analysed, we identified six and nine genes with significantly decreased or increased expression, respectively, in those with prior asymptomatic infection relatively to those with clinical infection. All six genes with decreased expression (IFIT3, IFI44L, RSAD2, FOLR3, PI3, ALOX15), are involved in innate immune response while the first two are interferon-induced proteins. Among genes with increased expression six are involved in immune response (GZMH, CLEC1B, CLEC12A), viral mRNA translation (GCAT), energy metabolism (CACNA2D2) and oxidative stress response (ENC1). Notably, 8/15 differentially expressed genes are regulated by interferons. Our results suggest that subtle differences at baseline expression of innate immunity-related genes may be associated with an asymptomatic disease course in SARS-CoV-2 infection. Whether a certain gene signature predicts, or not, those who will develop a more efficient immune response upon exposure to SARS-CoV-2, with implications for prioritization for vaccination, warrant further study.
Regulatory T Cells: Regulation of Identity and Function
Authors: Grover Payal , Goel Peeyush N. , Greene Mark I.
Published: October 2021

T regulatory cells suppress a variety of immune responses to self-antigens and play a role in peripheral tolerance maintenance by limiting autoimmune disorders, and other pathological immune responses such as limiting immune reactivity to oncoprotein encoded antigens. Forkhead box P3 (FOXP3) expression is required for Treg stability and affects functional activity. Mutations in the master regulator FOXP3 and related components have been linked to autoimmune diseases in humans, such as IPEX, and a scurfy-like phenotype in mice. Several lines of evidence indicate that Treg use a variety of immunosuppressive mechanisms to limit an immune response by targeting effector cells, including secretion of immunoregulatory cytokines, granzyme/perforin-mediated cell cytolysis, metabolic perturbation, directing the maturation and function of antigen-presenting cells (APC) and secretion of extracellular vesicles for the development of immunological tolerance. In this review, several regulatory mechanisms have been highlighted and discussed.
suPAR, a Circulating Kidney Disease Factor
Authors: Wei Changli , Spear Ryan , Hahm Eunsil , Reiser Jochen
Published: October 2021

Urokinase plasminogen activator receptor (uPAR) is a multifaceted, GPI-anchored three-domain protein. Release of the receptor results in variable levels of soluble uPAR (suPAR) in the blood circulation. suPAR levels have been linked to many disease states. In this mini-review, we discuss suPAR as a key circulating molecule mediating kidney disease with a particular focus on differently spliced isoforms.
Opportunities and Challenges for Machine Learning in Rare Diseases
Authors: Decherchi Sergio , Pedrini Elena , Mordenti Marina , Cavalli Andrea , Sangiorgi Luca
Published: October 2021

Rare diseases (RDs) are complicated health conditions that are difficult to be managed at several levels. The scarcity of available data chiefly determines an intricate scenario even for experts and specialized clinicians, which in turn leads to the so called “diagnostic odyssey” for the patient. This situation calls for innovative solutions to support the decision processviaquantitative and automated tools. Machine learning brings to the stage a wealth of powerful inference methods; however, matching the health conditions with advanced statistical techniques raises methodological, technological, and even ethical issues. In this contribution, we critically point to the specificities of the dialog of rare diseases with machine learning techniques concentrating on the key steps and challenges that may hamper or create actionable knowledge and value for the patient together with some on-field methodological suggestions and considerations.
Textual Inference Comprehension in Mild Cognitive Impairment: The Influence of Semantic Processing and Verbal Episodic Memory
Authors: Maziero Maria Paula , Belan Ariella Fornachari Ribeiro , Camargo Marina von Zuben de Arruda , Silagi Marcela Lima , Forlenza Orestes Vicente , Radanovic Marcia
Published: October 2021

Language complaints, especially in complex tasks, may occur in mild cognitive impairment (MCI). Various language measures have been studied as cognitive predictors of MCI conversion to Alzheimer's type dementia. Understanding textual inferences is considered a high-demanding task that recruits multiple cognitive functions and, therefore, could be sensitive to detect decline in the early stages of MCI. Thus, we aimed to compare the performance of subjects with MCI to healthy elderly in a textual inference comprehension task and to determine the best predictors of performance in this ability considering one verbal episodic memory and two semantic tasks. We studied 99 individuals divided into three groups: (1) 23 individuals with amnestic mild cognitive impairment (aMCI), (2) 42 individuals with non-amnestic mild cognitive impairment (naMCI), (3), and (4) 34 cognitively healthy individuals for the control group (CG). A reduced version of The Implicit Management Test was used to assess different types of inferential reasoning in text reading. MCI patients performed poorer than healthy elderly, and there were no differences between MCI subgroups (amnestic and non-amnestic). The best predictors for inference-making were verbal memory in the aMCI and semantic tasks in the naMCI group. The results confirmed that the failure to understand textual inferences can be present in MCI and showed that different cognitive skills like semantic knowledge and verbal episodic memory are necessary for inference-making.
Are TREK Channels Temperature Sensors?
Authors: Rueda-Ruzafa Lola , Herrera-Pérez Salvador , Campos-Ríos Ana , Lamas J. A.
Published: October 2021

Internal human body normal temperature fluctuates between 36.5 and 37.5°C and it is generally measured in the oral cavity. Interestingly, most electrophysiological studies on the functioning of ion channels and their role in neuronal behavior are carried out at room temperature, which usually oscillates between 22 and 24°C, even when thermosensitive channels are studied. We very often forget that if the core of the body reached that temperature, the probability of death from cardiorespiratory arrest would be extremely high. Does this mean that we are studying ion channels in dying neurons? Thousands of electrophysiological experiments carried out at these low temperatures suggest that most neurons tolerate this aggression quite well, at least for the duration of the experiments. This also seems to happen with ion channels, although studies at different temperatures indicate large changes in both, neuron and channel behavior. It is known that many chemical, physical and therefore physiological processes, depend to a great extent on body temperature. Temperature clearly affects the kinetics of numerous events such as chemical reactions or conformational changes in proteins but, what if these proteins constitute ion channels and these channels are specifically designed to detect changes in temperature? In this review, we discuss the importance of the potassium channels of the TREK subfamily, belonging to the recently discovered family of two-pore domain channels, in the transduction of thermal sensitivity in different cell types.
Epidemiological and Clinical Characteristics of Sporadic Creutzfeldt–Jakob Disease: A Retrospective Study in Eastern China
Authors: Feng Shuo , Zhao Xinjing , Zhou Xueying , Ye Xiang , Yu Xiaolin , Jiang Wei , Deng Yu , Zhou Shengnian , Ma Lin , Shan Peiyan , Zhou Guoyu
Published: October 2021

Objective: We aimed to characterize the epidemiological and clinical characteristics of sporadic Creutzfeldt–Jakob disease (sCJD) in eastern China in this retrospective study.

Methods: This study enrolled 67 patients with sCJD hospitalized in a grade-A tertiary hospital in eastern China from January 2010 to January 2020. Demographic data, clinical symptoms, brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid (CSF) 14-3-3 protein test, polymerase chain reaction (PCR), and DNA sequence determination of genes were collected and analyzed.

Results: There were 62 patients with probable sCJD and 5 patients with possible sCJD. Male (28 cases) to female (39 cases) ratio was 1:1.39. Mean age at disease onset was 64.42 ± 9.00 years (range: 29–88 years), and mean survival time was 9.39 ± 12.58 months (range: 1–60 months for patients who received the follow-ups). The most common onset symptoms were dementia (49.25%), movement disorder (44.78%), and visual disturbance (22.39%), while the most frequent clinical manifestations were language disorders (74.63%), ataxia (70.15%), and myoclonus (70.15%). The positive rates of brain MRI abnormalities, 14-3-3 protein in CSF, and periodic sharp wave complexes (PSWCs) on EEG were 84.90, 68.00, and 46.03%, respectively. The 14-3-3 protein positive (p = 0.033) and PSWCs on EEG (p = 0.020) acted as the favorable and unfavorable factor for over 1 year of survival time, respectively.

Conclusions: There were some differences in epidemiological and clinical characteristics among patients in China and those of other countries. The prognosis and its influencing factors were relatively unexplored in China. The mean survival time of Chinese patients was longer than that of Caucasian patients but shorter than that of Japanese patients. The 14-3-3 protein in CSF and PSWCs on EEG were both closely related to the survival time. It is necessary to promote autopsy or biopsy to better understand sCJD in China.
The Grouping-Induced Numerosity Illusion Is Attention-Dependent
Authors: Pomè Antonella , Caponi Camilla , Burr David C.
Published: October 2021

Perceptual grouping and visual attention are two mechanisms that help to segregate visual input into meaningful objects. Here we report how perceptual grouping, which affects perceived numerosity, is reduced when visual attention is engaged in a concurrent visual task. We asked participants to judge the numerosity of clouds of dot-pairs connected by thin lines, known to cause underestimation of numerosity, while simultaneously performing a color conjunction task. Diverting attention to the concomitant visual distractor significantly reduced the grouping-induced numerosity biases. Moreover, while the magnitude of the illusion under free viewing covaried strongly with AQ-defined autistic traits, under conditions of divided attention the relationship was much reduced. These results suggest that divided attention modulates the perceptual grouping of elements by connectedness and that it is independent of the perceptual style of participants.
Improved Visual Recognition Memory Model Based on Grid Cells for Face Recognition
Authors: Liu Jie , Xu Wenqiang , Li Xiumin , Zheng Xiao
Published: October 2021

Traditional facial recognition methods depend on a large number of training samples due to the massive turning of synaptic weights for low-level feature extractions. In prior work, a brain-inspired model of visual recognition memory suggested that grid cells encode translation saccadic eye movement vectors between salient stimulus features. With a small training set for each recognition type, the relative positions among the selected features for each image were represented using grid and feature label cells in Hebbian learning. However, this model is suitable only for the recognition of familiar faces, objects, and scenes. The model's performance for a given face with unfamiliar facial expressions was unsatisfactory. In this study, an improved computational model via grid cells for facial recognition was proposed. Here, the initial hypothesis about stimulus identity was obtained using the histograms of oriented gradients (HOG) algorithm. The HOG descriptors effectively captured the sample edge or gradient structure features. Thus, most test samples were successfully recognized within three saccades. Moreover, the probability of a false hypothesis and the average fixations for successful recognition were reduced. Compared with other neural network models, such as convolutional neural networks and deep belief networks, the proposed method shows the best performance with only one training sample for each face. Moreover, it is robust against image occlusion and size variance or scaling. Our results may give insight for efficient recognition with small training samples based on neural networks.