bluuebunny/crossref_metadata_2025 huggingface dataset:
Hranice Československej republiky optikou Versaillského mierového systému
Authors:   Univerzita Pavla Jozefa Šafárika v Košiciach, Kováčová Dominika , Pištejová Lucia , Vaňa Ivan
Published: June 2024

Predkladaná monografia sa venuje povojnovému usporiadaniu vzťahov a mierovým rokovaniam súvisiacim s ustálením hraníc novovytvorenej Československej republiky. Práca sa podrobnejšie venuje rokovacím procesom súvisiacim s prípravou a podpisom Versaillskej a Saint-Germainskej mierovej zmluvy. Obdobne podrobne následne rozoberá peripetie súvisiace s tvorbou Trianonskej mierovej zmluvy pojednávajúcej o hranici s Maďarskom a jej následným vytýčením v teréne. V neposlednom rade práca zachytáva ustálenie medzinárodných vzťahov Československa s Poľskom a ich spoločnú hranicu s osobitným zameraním na arbitrážne riešenie v otázke územia Oravy a Spiša.
Note for the P versus NP Problem (II)
Authors: Vega Frank
Published: June 2024

One of the biggest unsolved mysteries in computer science is the P versus NP problem. It asks a simple question: can every problem whose solution can be quickly verified be solved just as quickly (Here, "quickly" means in polynomial time)? While the question itself was hinted at in a 1955 letter from John Nash, a formalization of the problem is credited to Stephen Cook and Leonid Levin. Despite decades of effort, no one has been able to definitively answer it. Closely related is the concept of NP-completeness. If even one NP-complete problem can be solved efficiently (in polynomial time), then it implies P equals NP. This work proposes that a specific NP-complete problem, ONE-IN-THREE 3SAT, can be solved efficiently. In this way, we prove that P is equal to NP.
(Yet another) way to prove the Pythagoras’ theorem
Authors: Kumar K S Ajay
Published: June 2024

This article attempts a new way of proving the Pythagoras’ theorem. For centuries, people have used diverse tools such as combinatorics, calculus, geometry, algebra and trigonometry to come up with hundreds of different ways to prove the theorem. Here, I use some geometry, trigonometry and algebra to prove the theorem. There are few proofs using trigonometry.
Note for the Riemann Hypothesis
Authors: Vega Frank
Published: June 2024

Let $\Psi(n) = n \cdot \prod_{q \mid n} \left(1 + \frac{1}{q} \right)$ denote the Dedekind $\Psi$ function where $q \mid n$ means the prime $q$ divides $n$. Define, for $n \geq 3$; the ratio $R(n) = \frac{\Psi(n)}{n \cdot \log \log n}$ where $\log$ is the natural logarithm. Let $N_{n} = 2 \cdot \ldots \cdot q_{n}$ be the primorial of order $n$. A trustworthy proof for the Riemann hypothesis has been considered as the Holy Grail of Mathematics by several authors. The Riemann hypothesis is a conjecture that the Riemann zeta function has its zeros only at the negative even integers and complex numbers with real part $\frac{1}{2}$. There are several statements equivalent to the famous Riemann hypothesis. We show if the inequality $R(N_{n+1}) < R(N_{n})$ holds for $n$ big enough, then the Riemann hypothesis is true. In this note, we prove that $R(N_{n+1}) < R(N_{n})$ always holds for $n$ big enough.
Innovative Approach in Digital Forensics: ShortcutBased Speech Recognition, Sentiment Analysis and Body Language Evaluation
Authors: Siyez Özgecan
Published: June 2024

In the field of digital forensics, the analysis of audio and video recordings plays a critical role. Traditional methods require manual examination of these recordings, which is time-consuming and prone to errors. In this paper, we introduce an innovative method that performs multi-faceted analyses such as speech-to-text conversion, sentiment analysis, and body language evaluation using user-defined shortcut keys. This method, termed "Shortcut-Based Speech Recognition, Sentiment Analysis, and Body Language Evaluation," significantly enhances forensic analysis processes by speeding up and increasing the accuracy of evidence analysis. This new method leverages speech recognition technology to convert audio recordings into text, conducts sentiment analysis on the text, and performs body language evaluation from video recordings. Users can execute these analyses using their chosen shortcut keys and save the results to a log file. This enables forensic experts to examine digital evidence more efficiently and effectively. Our innovative approach contributes to digital forensic investigations by providing accuracy and speed in identifying critical information. The user-defined shortcut keys simplify and accelerate the analysis process, aiding researchers and forensic experts in achieving faster and more accurate results. Furthermore, the method's multi-analysis capabilities offer a comprehensive approach to evidence evaluation, facilitating stronger evidence presentations in court.
Фетиши Aklama Kpakpewo народа адан: традиция и интерпретация / Fetishes Aklama Kpakpewo of the Adan People: Tradition and Interpretation
Authors: Медушевский Н.А.
Published: June 2024

Статья представляет исследование традиции создания фетишей Aklama kpakpewo («маленькие резные идолы») народа адан. Адан (адангме, адангбе) проживают на территории современных Ганы и Того. Их традиционной религией является культ вуду, в рамках которого сформирована сложная сакральная система, включающая несколько уровней иерархии божеств, духов, мистических существ азиза, духов предков и амулетов магического свойства. Все эти элементы имеют физическое выражение в виде фетишей, наиболее типичными среди которых являются фигуры Aklama kpakpewo. Фигуры просты в исполнении, но чрезвычайно разнообразны, что вызывает сложности в их интерпретации. Автор предпринимает попытку реализовать комплексный анализ данного типа фетишей исходя из материалов, собранных антропологами и этнографами, начиная с конца ХIX в. В работе применяется эмпирический подход, который основан на изучении большой совокупности фигур фетишей, находящихся в музеях, частных собраниях, а также в личной коллекции автора.
This article studies the tradition of creating Aklama kpakpewo fetishes of the Adan people, who are a part of the large Ewe ethnic group and live in modern Ghana and Togo. The traditional religion of this society is the Vodun cult, with a complex sacred system formed within it, which includes several levels of hierarchy of deities, spirits, mystical creatures of Aziz, ancestral spirits and amulets of magical properties. All these elements have a physical expression in the form of fetishes, the most typical of which are the Aklama kpakpewo figures. These figures are simple, but extremely diverse, which makes them difficult to interpret. In this paper, the author attempts a comprehensive analysis of this type of fetish based on materials collected by anthropologists and ethnographers starting from the end of the 19th century. The work uses historiographical analysis and an empirical approach. The latter is based on the author's study of a large collection of fetish figures located in museums, private collections, as well as in the author's personal collection.
Обряды и традиции детского цикла у каракалпаков в условиях глобализации / Children-focused Family Life Cycle Traditions among Karakalpaks in the Context of Globalization
Authors: Турекеев К.Ж.
Published: June 2024

На современном этапе процессы глобализации, охватившие практически все части земного шара, оказывают влияние на повседневную жизнь, культуру и обычаи каждого народа. Данное воздействие затрагивает и сферу семейных обрядов, включая ритуалы и традиции детского цикла. Изучая обряды, связанные с рождением и воспитанием детей, мы можем наблюдать, как под влиянием модернизации общества у каракалпаков укореняются новые обряды и обычаи. Результаты полевых исследований показывают, что традиционные обряды претерпевают трансформации, адаптируясь к сегодняшним условиям. Особенно ярко инновации проявляются в таких обрядах, как «Гендер пати» (Gender Party), проводимом во время беременности, церемонии наречения имени с популяризацией новых имен, обряд «тусаў кесиў», превратившийся в празднование «годика» с одноименным названием и другие. Исследование показывает, что на эти изменения влияют СМИ, особенно телевидение, процессы ассимиляции и интеграции различных культур, а также интернет-пространство, ставшее неотъемлемой частью жизни жителей республики.
At the present stage, the processes of globalization have an impact on the daily life, culture and customs of every nation. This impact affects the sphere of family rituals, including rituals and traditions of the children's cycle. Studying the rituals related to the birth and upbringing of children, we can observe how new rituals and customs are taking root among Karakalpaks under the influence of modernization. The results of field research show that traditional rituals undergo transformations, adapting to new conditions. Innovations are especially evident in such rituals as the Gender Party held during pregnancy, naming ceremonies with new names gaining popularity, the " Tusau Keser" ritual, which turned into the celebration of the "year" with the same name, and others. The study shows that these changes are influenced by the media, especially television, the processes of assimilation and integration of different cultures, as well as the Internet space, which has become an integral part of life in the republic.
Судьба прогнозов на основе концепта этнорасовых групп / The Fate of Forecasts Based on the Concept of Ethnoracial Groups
Authors: Тишков В.А.
Published: June 2024

В статье дается оценка книги В. И. Козлова об иммиграции и этнорасовых проблемах в Британии (1987) и анализируется сделанный им на период 1980-х годов прогноз развития ситуации. Автор сопоставляет перспективный сценарий 35-летней давности с современными реалиями и отмечает, что миграция и политика мультикультурализма привели к радикальным переменам в национальной и этнической идентификациях жителей страны. На примере Англии и Уэльса по итогам переписи 2011 и 2021 гг. анализируются сложные идентичности и перемены в пользу общебританской идентификации, особенно т.н. цветного населения страны, доля которого и роль в жизни Великобритании заметно выросли, вызывая реакцию английского национализма, но не отрицая вариант национального единения на основе культурно сложной британской идентичности. Высказаны идеи относительно изучения феномена культурного разнообразия и обновленного понимания этничности.
The paper reviews V. I. Kozlov’s book on immigration and ethnic-racial problems in Great Britain (1987) and evaluates his forecast going back to the 1980s on the future evolution of the migration situation. The author compares the 35 years ago scenario with the nowadays realities and concludes that mass migration and the policy of multiculturalism have caused radical changes in the national and ethnic identities of the British population. On a basis of England and Wales 2011 and 2021 censuses he analyses multiply identities and changes in favor of Britishness identity versus Englishness, especially among the country's non-white population, whose role in this country’s life has grown greatly, causing a reaction of English nationalism, but not hindering the scenario of nation-building based on a culturally inclusive pan- British identity. The article includes elaborations on super- diversity debates and on how contemporary census practices destroy narrow understanding of ethnicity as culturally homogeneous groupings.
The whole transcriptome analysis using FFPE and fresh tissue samples identifies the molecular fingerprint of osteosarcoma
Authors: Poudel Bal Hari , Koks Sulev
Published: June 2024

Osteosarcoma is a form of bone cancer that predominantly impacts osteoblasts, the cells responsible for creating fresh bone tissue. Typical indications include bone pain, inflammation, sensitivity, mobility constraints, and fractures. Utilising imaging techniques such as X-rays, MRI scans, and CT scans can provide insights into the size and location of the tumour. Additionally, a biopsy is employed to confirm the diagnosis. Analysing genes with distinct expression patterns unique to osteosarcoma can be valuable for early detection and the development of effective treatment approaches. In this research, we comprehensively examined the entire transcriptome and pinpointed genes with altered expression profiles specific to osteosarcoma. The study mainly aimed to identify the molecular fingerprint of osteosarcoma. In this study, we processed 90 FFPE samples from PathWest with an almost equal number of osteosarcoma and healthy tissues. RNA was extracted from Paraffin-embedded tissue; RNA was sequenced, the sequencing data was analysed, and gene expression was compared to the healthy samples of the same patients. Differentially expressed genes in osteosarcoma-derived samples were identified, and the functions of those genes were explored. This result was combined with our previous studies based on FFPE and fresh samples to perform a meta-analysis. We identified 1,500 identical differentially expressed genes in PathWest osteosarcoma samples compared to normal tissue samples of the same patients. Meta-analysis with combined fresh tissue samples identified 530 differentially expressed genes. IFITM5, MMP13, PANX3, and MAGEA6 were some of the most overexpressed genes in osteosarcoma samples, while SLC4A1, HBA1, HBB, AQP7 genes were some of the top downregulated genes. Through the meta-analysis, 530 differentially expressed genes were identified to be identical among FFPE (105 FFPE samples) and 36 fresh bone samples. Deconvolution analysis with single-cell RNAseq data confirmed the presence of specific cell clusters in FFPE samples. We propose these 530 DEGs as a molecular fingerprint of osteosarcoma.
Towards an effective approach for composition of model transformations
Authors: Abdelmalek Hamza , Khriss Ismaïl , Jakimi Abdeslam
Published: June 2024

Model Driven Engineering (MDE) adoption in the industry suffers from many technical and non-technical problems. One of the significant technical problems lies in the difficulty of building complex transformations from the composition of small and reusable transformations. Another problem resides in developing transformations from scratch in case they are missing. In this paper, we present an approach to how to handle these issues. The approach allows composing reusable transformations to build more complex ones by providing a catalog of prebuilt transformations targeting common architectures, frameworks, and design patterns. To give guidance and simplify the task of developing new transformations, we describe a platform description model of an entire system or a part of it in two views: a UML profile and a set of transformations. We also present three transformation types, each of which handles different abstraction design concerns. Generic transformations are small and reusable to build complex transformations, system-independent transformations are reusable and implement high-level design decisions, and system-specific transformations are not reusable and implement all design decisions needed for a given system. The approach is implemented as a plugin for a UML modeling tool and validated by developing a system that simulates the behavior of a gas station through model transformations built from the composition of reusable transformations.
Transition of dome formation to sudden explosive eruptions at Popocatépetl, Mexico: magnetic indicators
Authors: Martin-Del-Pozzo Ana Lillian , Santos Morales César Alberto
Published: June 2024

Transitions from effusive to explosive activity can increase hazards making it crucial to define early indicators such as changes in the magnetic signals. After more than 80 cycles of crater-dome extrusion and destruction from 1996 on, Popocatépetl volcano (Mexico) experienced changes in its behavior from March 15 to 18 July 2019, when no lava domes were observed. Some of the domes behaved as contained lava flows within the crater floor (pancakes) while others were more irregular-shaped. Activity decreased considerably over this 2019 interval except for the unexpected explosions in March and June, that produced ash plumes reaching up to 14,000 m a.s.l. In order to investigate the causes of the transition from effusive to explosive behavior in March and June, we analyzed the time series from the magnetic monitoring network at Popocatépetl volcano between October 2018 and December 2019. The raw signals were analyzed by weighted differences (WD) based on the elimination of non-local changes from the total intensity values of the geomagnetic field and the discrete-time continuous wavelet transform was used to evaluate the local variations of energy within the time series. The high energy periods (linked to negative magnetic anomalies) are induced by magma ascent associated with movement within the conduit. They indicate that the sudden explosions were due to the ascent of several magma batches that were slowed during ascent and were not able to reach the surface. Changes in the rheology of the lava are linked to the influx of several batches of magma with different compositions as well as to compaction by gas loss when ascending andesitic magma pushed out overlying more viscous degassed magma clearing the conduit, which can explain why these sudden explosions were more energetic. Several geophysical data sets as well as tephra compositions were integrated to support this conclusion. The correlated multiparameters also confirm that geomagnetic volcano monitoring has been essential in understanding the processes that drive the observed changes in eruptive behavior. We present new evidence for the detection of transient events produced by magma ascent and changes in the feeding system of Popocatépetl volcano with wavelet analysis. Detailed vulcanomagnetic processing, especially when it is correlated with other monitoring parameters, provides information on ascending magma and several conduit processes that would otherwise be camouflaged. Ascending batches may precede an eruption but they can also ascend in several pulses indicating how dome growth occurs.
Experimental and numerical studies on CO2 injectivity in low permeability oil reservoirs
Authors: Meng Fankun , Cao Lin , Zhou Yuhui , Liu Botao , Wen Chengyue , Liu Jia
Published: June 2024

Introduction: Contrary to the traditional recognition that CO2 has large injectivity (the ratio of CO2 injection volume to pressure drop) in low permeability oil reservoirs to keep the formation pressure at a high level, the CO2 injection rate usually cannot attain the set value. It is essential to study the factors that influence CO2 injectivity and propose the optimal strategies to improve the CO2 injectivity.

Methods: Therefore, in this study, several core samples collected from low permeability oil reservoirs are used to experimentally investigate the influences of CO2 injection rate, formation permeability, pressure and water saturation on CO2 injectivity, and the corresponding pressure drop, oil and gas production are examined. To determine the primary factor that influences the CO2 injectivity, orthogonal experimental design (ODE) and numerical simulations are utilized. In addition, to improve CO2 injectivity, the techniques of mini-fracturing and radial perforation are presented, and the threshold values for these two parameters are determined.

Result and discussion: The results demonstrate that according to the magnitude of the extent that influences CO2 injectivity, the rank for the above factors is CO2 injection rate, reservoir pressure, formation water saturation and permeability. The oil recovery is mainly influenced by CO2 injection rate and formation permeability, and the influences of reservoir pressure and water saturation on oil recovery are smaller. The threshold values for radial perforation and fracture half-length are 25 m and 50m, respectively, which can provide some guidance for the strategies that should be taken to improve the CO2 injectivity and recover more oil from low permeability oil reservoirs.
Endoplasmic reticulum stress in pancreatic β-cell dysfunctionality and diabetes mellitus: a promising target for generation of functional hPSC-derived β-cells in vitro
Authors: Diane Abdoulaye , Allouch Asma , Mu-U-Min Razik Bin Abdul , Al-Siddiqi Heba Hussain
Published: June 2024

Diabetes mellitus (DM), is a chronic disorder characterized by impaired glucose homeostasis that results from the loss or dysfunction of pancreatic β-cells leading to type 1 diabetes (T1DM) and type 2 diabetes (T2DM), respectively. Pancreatic β-cells rely to a great degree on their endoplasmic reticulum (ER) to overcome the increased secretary need for insulin biosynthesis and secretion in response to nutrient demand to maintain glucose homeostasis in the body. As a result, β-cells are potentially under ER stress following nutrient levels rise in the circulation for a proper pro-insulin folding mediated by the unfolded protein response (UPR), underscoring the importance of this process to maintain ER homeostasis for normal β-cell function. However, excessive or prolonged increased influx of nascent proinsulin into the ER lumen can exceed the ER capacity leading to pancreatic β-cells ER stress and subsequently to β-cell dysfunction. In mammalian cells, such as β-cells, the ER stress response is primarily regulated by three canonical ER-resident transmembrane proteins: ATF6, IRE1, and PERK/PEK. Each of these proteins generates a transcription factor (ATF4, XBP1s, and ATF6, respectively), which in turn activates the transcription of ER stress-inducible genes. An increasing number of evidence suggests that unresolved or dysregulated ER stress signaling pathways play a pivotal role in β-cell failure leading to insulin secretion defect and diabetes. In this article we first highlight and summarize recent insights on the role of ER stress and its associated signaling mechanisms on β-cell function and diabetes and second how the ER stress pathways could be targeted in vitro during direct differentiation protocols for generation of hPSC-derived pancreatic β-cells to faithfully phenocopy all features of bona fide human β-cells for diabetes therapy or drug screening.
Association of random glucose to albumin ratio with post-contrast acute kidney injury and clinical outcomes in patients with ST-elevation myocardial infarction
Authors: Lai Ping , Gu Xiaoyan , Lin Xuhui , He Yu , Dai Yining , Duan Chongyang , Liu Yuanhui , He Wenfei
Published: June 2024

Purpose

Both glucose and albumin are associated with chronic inflammation, which plays a vital role in post-contrast acute kidney injury (PC-AKI). To explore the relationship between random glucose to albumin ratio (RAR) and the incidence of PC-AKI after percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).

Patients and methods

STEMI patients who underwent PCI were consecutively enrolled from January, 01, 2010 to February, 28, 2020. All patients were categorized into T1, T2, and T3 groups, respectively, based on RAR value (RAR < 3.377; 3.377 ≤ RAR ≤ 4.579; RAR > 4.579). The primary outcome was the incidence of PC-AKI, and the incidence of major adverse clinical events (MACE) was the second endpoint. The association between RAR and PC-AKI was assessed by multivariable logistic regression analysis.

Results

A total of 2,924 patients with STEMI undergoing PCI were finally included. The incidence of PC-AKI increased with the increasing tertile of RAR (3.2% vs 4.8% vs 10.6%, P<0.001). Multivariable regression analysis demonstrated that RAR (as a continuous variable) was associated with the incidence of PC-AKI (adjusted odds ratio (OR) =1.10, 95% confidence interval (CI) =1.04 - 1.16, P<0.001) and in-hospital MACE (OR=1.07, 95% CI=1.02 - 1.14, P=0.012); RAR, as a categorical variable, was significantly associated with PC-AKI (T3 vs. T1, OR=1.70, 95% CI=1.08 - 2.67, P=0.021) and in-hospital MACE (T3 vs. T1, OR=1.63, 95% CI=1.02 - 2.60, P=0.041) in multivariable regression analyses. Receiver operating characteristic curve analysis showed that RAR exhibited a predictive value for PC-AKI (area under the curve (AUC)=0.666, 95% CI=0.625 - 0.708), and in-hospital MACE (AUC= 0.662, 95% CI =0.619 - 0.706).

Conclusions

The high value of RAR was significantly associated with the increasing risk of PC-AKI and in-hospital MACE after PCI in STEMI patients, and RAR offers a good predictive value for those outcomes.
Characteristics of water and heat change during the freezing-thawing process at an alpine steppe in seasonally frozen ground of the Northern Tibetan plateau
Authors: Chen Jiuyun , Yan Yan , Liu Yanling
Published: June 2024

Introduction: Permafrost and seasonally frozen soil are widely distributed on the Qinghai–Tibetan Plateau, and the freezing–thawing cycle can lead to frequent phase changes in soil water, which can have important impacts on ecosystems.

Methods: To understand the process of soil freezing-thawing and to lay the foundation for grassland ecosystems to cope with complex climate change, this study analyzed and investigated the hydrothermal data of Xainza Station on the Northern Tibet from November 2019 to October 2021.

Results and Discussion: The results showed that the fluctuation of soil temperature showed a cyclical variation similar to a sine (cosine) curve; the deep soil temperature change was not as drastic as that of the shallow soil, and the shallow soil had the largest monthly mean temperature in September and the smallest monthly mean temperature in January. The soil water content curve was U-shaped; with increased soil depth, the maximum and minimum values of soil water content had a certain lag compared to that of the shallow soil. The daily freezing-thawing of the soil lasted 179 and 198 days and the freezing-thawing process can be roughly divided into the initial freezing period (November), the stable freezing period (December–early February), the early ablation period (mid-February to March), and the later ablation period (March–end of April), except for the latter period when the average temperature of the soil increased with the increase in depth. The trend of water content change with depth at all stages of freezing-thawing was consistent, and negative soil temperature was one of the key factors affecting soil moisture. This study is important for further understanding of hydrothermal coupling and the mechanism of the soil freezing-thawing process.
Mendelian randomization and Bayesian model averaging of autoimmune diseases and Long COVID
Authors: Feng Jieni , Chen Jiankun , Li Xiaoya , Ren Xiaolei , Chen Junxu , Li Zuming , Wu Yuan , Zhang Zhongde , Yang Rongyuan , Li Jiqiang , Lu Yue , Liu Yuntao
Published: June 2024

Background

Following COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated.

Methods

Summary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn’s disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA).

Results

The evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00–1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01–1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03–1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD.

Conclusion

This MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.
Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia
Authors: Lickliter Jason , Yang Xin , Guo Jiawang , Pan Wubin , Wei Zheng
Published: June 2024

Background

Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR1. In this first-in-human study, icanbelimod was investigated in healthy men in Australia.

Methods

Participants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort.

Results

Icanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (Tmax 4–7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to non-serious TEAEs. Up-titration attenuated heart rate reductions.

Conclusion

Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts.

Clinical trial registration

ClinicalTrials.gov, identifier NCT02280434.b
Functional integration design and aerodynamic characterization of a hexacopter agricultural unmanned aerial vehicle based on its appearance
Authors: Liu Zhe
Published: June 2024

Introduction: As an advanced agricultural technology equipment, the functional integration design and appearance aerodynamic characteristics of hexacopter agricultural UAV are significant for improving the efficiency of agricultural production.

Methods: Firstly, the study carried out the functional integration design of the hexacopter agricultural UAV, and completed the matching analysis and selection of the relevant components of the power system. Then, the numerical simulation method of computational fluid dynamics was used to analyze the aerodynamic characteristics of the UAV. Finally, the role of different propeller pitch on important parameters such as lift and range time of the UAV was verified.

Results and discussion: The results showed that in the XY section of the UAV, namely, the surface parallel to the flight direction, the areas with high streamline velocity were mainly concentrated at the intersection of the airflow with the landing gear and the motor. The streamlines in the front of the UAV were tightly and neatly distributed, while those in the rear were sparser. The motor force efficiencies of the UAVs with different propeller pitches ranged from 7.05 to 7.25 g/w. At a flight speed of 5 m/s, the motor force effect of the UAV with a pitch of 260 mm reached 7.25 g/w, which was the highest value among all models. Meanwhile, it had the longest endurance time of 19.14 min, indicating the best performance. The results suggested that it not only promoted the modernization of agricultural UAVs but also effectively enhanced the efficiency of agricultural production.
Embolization coils in treating postoperative bronchopleural fistula: a systematic review
Authors: Luo Xiaojuan , Zhan Ke , Bai Yang
Published: June 2024

Objective

This study aims to comprehensively evaluate embolization coils in treating postoperative bronchopleural fistula (BPF).

Methods

A systematic review based on PubMed, Embase, and The Cochrane Library studies was conducted. All cases receiving embolization coils in treating postoperative BPF were included. The primary outcome was the efficacy of embolization coils in achieving closure of postoperative BPF.

Results

20 patients from 9 studies were included in this systematic review. A median number of 3 (range: 1–10) embolization coils with sealants obtained a complete closure rate of 80% in patients with postoperative BPF with sizes ranging from 2 to 3.1 mm. Three patients with BPF over 3 mm and one with multiple organ failure failed this treatment. Two cases of coil migration were reported without causing respiratory failure or fistula recurrence.

Conclusion

Embolization coils might be considered a safe and effective bronchoscopic treatment for small postoperative BPF of less than 3 mm in size. More extensive and rigorous studies are needed to further evaluate and confirm the optimal use of embolization coils in the context of an alternative to surgical repair.
The advances in adjuvant therapy for tuberculosis with immunoregulatory compounds
Authors: Mi Jie , Wu Xueqiong , Liang Jianqin
Published: June 2024

Tuberculosis (TB) is a chronic bacterial disease, as well as a complex immune disease. The occurrence, development, and prognosis of TB are not only related to the pathogenicity of Mycobacterium tuberculosis (Mtb), but also related to the patient’s own immune state. The research and development of immunotherapy drugs can effectively regulate the body’s anti-TB immune responses, inhibit or eliminate Mtb, alleviate pathological damage, and facilitate rehabilitation. This paper reviews the research progress of immunotherapeutic compounds for TB, including immunoregulatory compounds and repurposing drugs, and points out the existing problems and future research directions, which lays the foundation for studying new agents for host-directed therapies of TB.
Budding and explosive membrane vesicle production by hypervesiculating Escherichia coli strain ΔrodZ
Authors: Ojima Yoshihiro , Toda Kaho , Sawabe Tomomi , Kumazoe Yuki , Tahara Yuhei O. , Miyata Makoto , Azuma Masayuki
Published: June 2024

Escherichia coli produces extracellular vesicles called outer membrane vesicles. In this study, we investigated the mechanism underlying the hypervesiculation of deletion mutant ΔrodZ of E. coli. RodZ forms supramolecular complexes with actin protein MreB and peptidoglycan (PG) synthase, and plays an important role in determining the cell shape. Because mreB is an essential gene, an expression-repressed strain (mreBR3) was constructed using CRISPRi, in which the expression of mreB decreased to 20% of that in the wild-type (WT) strain. In shaken-flask culture, the ΔrodZ strain produced >50 times more vesicles than the WT strain. The mreB-repressed strain mreBR3 showed eightfold higher vesicle production than the WT. ΔrodZ and mreBR3 cells were observed using quick-freeze replica electron microscopy. As reported in previous studies, ΔrodZ cells were spherical (WT cells are rod-shaped). Some ΔrodZ cells (around 7% in total) had aberrant surface structures, such as budding vesicles and dented surfaces, or curved patterns on the surface. Holes in the PG layer and an increased cell volume were observed for ΔrodZ and mreBR3 cells compared with the WT. In conditions of osmotic support using sucrose, the OD660 value of the ΔrodZ strain increased significantly, and vesicle production decreased drastically, compared with those in the absence of sucrose. This study first clarified that vesicle production by the E. coli ΔrodZ strain is promoted by surface budding and a burst of cells that became osmotically sensitive because of their incomplete PG structure.
Multiplex detection and identification of viral, bacterial, and protozoan pathogens in human blood and plasma using an expanded high-density resequencing microarray platform
Authors: Kourout Moussa , Espich Scott , Fisher Carolyn , Tiper Irina , Purkayastha Anjan , Smith Sean , Santana-Quintero Luis , Duncan Robert
Published: June 2024

Introduction: Nucleic acid tests for blood donor screening have improved the safety of the blood supply; however, increasing numbers of emerging pathogen tests are burdensome. Multiplex testing platforms are a potential solution.

Methods: The Blood Borne Pathogen Resequencing Microarray Expanded (BBP-RMAv.2) can perform multiplex detection and identification of 80 viruses, bacteria and parasites. This study evaluated pathogen detection in human blood or plasma. Samples spiked with selected pathogens, each with one of 6 viruses, 2 bacteria and 5 protozoans were tested on this platform. The nucleic acids were extracted, amplified using multiplexed sets of primers, and hybridized to a microarray. The reported sequences were aligned to a database to identify the pathogen. To directly compare the microarray to an emerging molecular approach, the amplified nucleic acids were also submitted to nanopore next generation sequencing (NGS).

Results: The BBP-RMAv.2 detected viral pathogens at a concentration as low as 100 copies/ml and a range of concentrations from 1,000 to 100,000 copies/ml for all the spiked pathogens. Coded specimens were identified correctly demonstrating the effectiveness of the platform. The nanopore sequencing correctly identified most samples and the results of the two platforms were compared.

Discussion: These results indicated that the BBP-RMAv.2 could be employed for multiplex detection with potential for use in blood safety or disease diagnosis. The NGS was nearly as effective at identifying pathogens in blood and performed better than BBP-RMAv.2 at identifying pathogen-negative samples.
Dietary patterns and the risk of tuberculosis-drug-induced liver injury: a cohort study
Authors: Wang Jinyu , Zhou Yarui , Zhao Cong , Xiong Ke , Liu Yufeng , Zhao Shanliang , Ma Aiguo
Published: June 2024

Background and purpose

Nutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury.

Methods

This cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA).

Results

The CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40–0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35–0.64)] in the multivariate logistic model. A positive association between “Organ meat, poultry, and vegetable oil” dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42–6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09–3.05)] was observed.

Conclusion

In conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the “Organ meat, poultry, and vegetable oil” dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.
Case report: Splenic inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS): a trial of immunotherapy and review of the literature
Authors: Resnick K. A. , Monroe C. , Siddiqi I. , Tam E.
Published: June 2024

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare malignancy with fewer than 150 cases in the literature. IPT-like FDCS follows an indolent course with most cases definitively managed with surgical resection. We present a case of IPT-like FDCS with multiple recurrences with a trial of immunotherapy. The patient initially presented with splenic involvement requiring splenectomy, subsequently recurring in the liver requiring hepatic resections. Afterwards, there was recurrence with pelvic/small bowel involvement for which treatment was trialed with ipilimumab and nivolumab. The patient progressed despite dual immune checkpoint inhibitor therapy requiring a small bowel resection. To date, this is the first case of immunotherapy use in IPT-like FDCS. Therefore, more evidence is needed to support additional treatments in recurrent IPT-like FDCS after resection.
Gaussian filter facilitated deep learning-based architecture for accurate and efficient liver tumor segmentation for radiation therapy
Authors: Lin Hongyu , Zhao Min , Zhu Lingling , Pei Xi , Wu Haotian , Zhang Lian , Li Ying
Published: June 2024

Purpose

Addressing the challenges of unclear tumor boundaries and the confusion between cysts and tumors in liver tumor segmentation, this study aims to develop an auto-segmentation method utilizing Gaussian filter with the nnUNet architecture to effectively distinguish between tumors and cysts, enhancing the accuracy of liver tumor auto-segmentation.

Methods

Firstly, 130 cases of liver tumorsegmentation challenge 2017 (LiTS2017) were used for training and validating nnU-Net-based auto-segmentation model. Then, 14 cases of 3D-IRCADb dataset and 25 liver cancer cases retrospectively collected in our hospital were used for testing. The dice similarity coefficient (DSC) was used to evaluate the accuracy of auto-segmentation model by comparing with manual contours.

Results

The nnU-Net achieved an average DSC value of 0.86 for validation set (20 LiTS cases) and 0.82 for public testing set (14 3D-IRCADb cases). For clinical testing set, the standalone nnU-Net model achieved an average DSC value of 0.75, which increased to 0.81 after post-processing with the Gaussian filter (P<0.05), demonstrating its effectiveness in mitigating the influence of liver cysts on liver tumor segmentation.

Conclusion

Experiments show that Gaussian filter is beneficial to improve the accuracy of liver tumor segmentation in clinic.
Systematic studies on the kinetic process of 20(S)-protopanaxadiol in rats and dogs: absorption, distribution, metabolism and excretion
Authors: Li Pengfei , Zhang Min , Chen Meng , Liu Guangxu , Meng Linghui , Zhang Dan
Published: June 2024

Background and Objective

Ginseng has been regarded as a precious medicinal herb with miraculous effects in Eastern culture. The primary chemical constituents of ginseng are saponins, and the physiological activities of ginsenosides determine their edible and medicinal value. The aim of this study is to comprehensively and systematically investigate the kinetic processes of 20(S)—protopanaxadiol (PPD) in rats and dogs, in order to promote the rational combination of ginseng as a drug and dietary ingredient.

Methods

PPD was administered, and drug concentration in different biological samples were detected by liquid chromatography tandem mass spectrometry (LC/MS/MS) and radioactive tracer methods. Pharmacokinetic parameters such as absorption, bioavailability, tissue distribution, plasma protein binding rate, excretion rate, and cumulative excretion were calculated, along with inference of major metabolites.

Results

This study systematically investigated the absorption, distribution, metabolism, excretion (ADME) of PPD in rats and dogs for the first time. The bioavailabilities of PPD were relatively low, with oral absorption nearly complete, and the majority underwent first-pass metabolism. PPD had a high plasma protein binding rate and was relatively evenly distributed in the body. Following oral administration, PPD underwent extensive metabolism, potentially involving one structural transformation and three hydroxylation reactions. The metabolites were primarily excreted through feces and urine, indicating the presence of enterohepatic circulation. The pharmacokinetic processes of PPD following intravenous administration aligned well with a three-compartment model. In contrast, after gastric administration, it fitted better with a two-compartment model, conforming to linear pharmacokinetics and proportional elimination. There were evident interspecies differences between rats and dogs regarding PPD, but individual variations of this drug were minimal within the same species.

Conclusion

This study systematically studied the kinetic process of PPD in rats and also investigated the kinetic characteristics of PPD in dogs for the first time. These findings lay the foundation for further research on the dietary nutrition and pharmacological effects of PPD.
Large field-of-view pine wilt disease tree detection based on improved YOLO v4 model with UAV images
Authors: Zhang Zhenbang , Han Chongyang , Wang Xinrong , Li Haoxin , Li Jie , Zeng Jinbin , Sun Si , Wu Weibin
Published: June 2024

Introduction

Pine wilt disease spreads rapidly, leading to the death of a large number of pine trees. Exploring the corresponding prevention and control measures for different stages of pine wilt disease is of great significance for its prevention and control.

Methods

To address the issue of rapid detection of pine wilt in a large field of view, we used a drone to collect multiple sets of diseased tree samples at different times of the year, which made the model trained by deep learning more generalizable. This research improved the YOLO v4(You Only Look Once version 4) network for detecting pine wilt disease, and the channel attention mechanism module was used to improve the learning ability of the neural network.

Results

The ablation experiment found that adding the attention mechanism SENet module combined with the self-designed feature enhancement module based on the feature pyramid had the best improvement effect, and the mAP of the improved model was 79.91%.

Discussion

Comparing the improved YOLO v4 model with SSD, Faster RCNN, YOLO v3, and YOLO v5, it was found that the mAP of the improved YOLO v4 model was significantly higher than the other four models, which provided an efficient solution for intelligent diagnosis of pine wood nematode disease. The improved YOLO v4 model enables precise location and identification of pine wilt trees under changing light conditions. Deployment of the model on a UAV enables large-scale detection of pine wilt disease and helps to solve the challenges of rapid detection and prevention of pine wilt disease.