bluuebunny/crossref_metadata_2025 huggingface dataset:
ПРИМЕНЕНИЕ ЛЮМИНЕСЦЕНТНО-МИКРОСКОПИЧЕСКОГО И ИММУНОФЕРМЕНТНОГО МЕТОДОВ ИССЛЕДОВАНИЯ НЕТОЗА ПРИ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ У ДЕТЕЙ (ДОКЛАД ПОДГОТОВЛЕН ПРИ ПОДДЕРЖКЕ ГРАНТА РОССИЙСКОГО НАУЧНОГО ФОНДА № 23-25-10043)
Authors: Новиков Д.Г. , Индутный А.В. , Золотов А.Н. , Мордык А.В.
Published: September 2024

Нетоз – вид программируемой клеточной смерти нейтрофильных лейкоцитов, сопровождающейся выбросом нейтрофильных внеклеточных ловушек (НВЛ) и играющий значительную роль в механизмах развитии многих инфекционных заболеваний, в том числе туберкулеза. При этом, несмотря на имеющиеся особенности развития туберкулезной инфекции в детском возрасте, процесс образования НВЛ практически не изучен в этой возрастной группе.
Для исследования нетоза была предложена запатентованная коллективом авторов методика оценки НВЛ, полученных при воздействии неспецифического антигенного стимулятора – культуры микроорганизмов Lactobacillus reutri, L. acidophilius, L. rhamnosis и Bifidumbacterium longum на нейтрофильные лейкоциты, выделенные из перифирической венозной крови на градиенте плотности раствора фиколла-верографина. Вне- и внутриклеточную ДНК визуализировали при помощи    интеркалирующего красителя йодида пропидия, нейтрофильные лейкоциты – при помощи моноклональных антител к CD15, меченных флуоресцентным красителем FITC. 
При сравнительном исследовании, проведенном с помощью данной методики у взрослых и детей (4-7 лет), больных туберкулезом было выявлено, что у детей нейтрофилы при воздействии неспецифического антигенного стимулятора интенсивнее, чем у взрослых, формировали нитевидные НВЛ (p=0,0131). При этом было обнаружено, что преимущественно нитевидные НВЛ формировались и у здоровых детей из группы контроля, но в меньшем количестве, чем у детей у диагностированным первичным туберкулёзным комплексом (p=0,0046). Напротив, нейтрофилы взрослых с инфильтративной или очаговой формой туберкулеза чаще формировали облаковидные НВЛ (p=0,0000).
Также было обнаружено, что в группе с латентной туберкулезной инфекцией нетозобразующая способность нейтрофилов была выше в сравнении с контрольной группой.  У данной группы детей также чаще наблюдались нитевидные НВЛ (p=0,0297).
Цитруллинированный гистон Н3 (citH3) – продукт посттрансляционной модификации белков, имеющей место в том числе в процессе нетоза. Уровни citH3 оценивали  в периферической крови с помощью тест-системы «Citrullinated Histone H3 (Clone 11D3) ELISA Kit» (Cayman Chemical Company, США). Была выявлена сильная корреляционная взаимосвязь между концентрацией citH3 и формированием нитевидных НВЛ (r=0,86; p=0,0137).
Таким образом, обе рассматриваемые методики могут использоваться для исследования туберкулезной инфекции у детей, показывая достаточно высокую степень сходимости результатов.
CYTOSKELETON DYNAMICS AND SPATIAL ORGANIZATION DURING EPITHELIAL-TO-MESENCHYMAL TRANSITION
Authors: Nurmagambetova A. , Mustyatsa V. , Saidova A. , Vorobjev I.
Published: September 2024

Epithelial-to-mesenchymal transition (EMT) is a crucial process that occurs during normal development, such as embryogenesis and organ formation. If it is inappropriately activated, it can lead to pathological processes like metastasis. Although EMT is well studied at the morphological and transcriptome level, cytoskeleton changes during this process are less understood. In our work we aimed to describe the morphological changes that occurred in MCF-7, A-549 and HaCaT cells after EMT, analyze microtubule dynamics, spatial distribution and its contribution to cell motility, identify changes in actin filament organization and study focal adhesion turnover in the cells after EMT.
We hypothesized that the dynamics of microtubules in cells undergoing EMT might change. Cells undergoing EMT were expected to have more dynamic microtubules. Also, cells undergoing EMT are expected to adhere more efficiently to diverse substrates, and therefore spread and move more easily. Focal contacts in cells undergoing EMT were expected to be more pronounced and dynamic than in cells that not undergoing EMT.
The research methods used in the study included inducing EMT in modified MCF-7 cells through an inserted inducible Tet-on system and stimulation of EMT in A-549 and HaCaT cells using TGF-β. The cells were observed using bright field microscopy, and immunofluorescence analysis was conducted to visualize microtubules and actin filaments. Transfection with EB-3–RFP protein was done to describe and measure microtubule dynamics, while transduction with Talin-RFP and transient transfection with Ptag-RFP-vinculin was done to visualize focal adhesions. Time-lapse fluorescent microscopy was used to record films, and the Fiji Image J program was used to analyze the data. All statistical analysis was performed using GraphPad Prism (Dotmatics, USA), and a nonparametric Mann-Whitney U test or parametric t-test with Welch correction. The actin filament measurements were completed using Matlab scripts.
The major research findings: In all three-cell models after EMT, cell morphology changed. Cells increased in size. MCF-7 and HaCaT became spread out, while A-549 became elongated. Some of the cells lost cell-cell contacts. All three cell models after EMT had alterations in microtubule organization and dynamics. MCF-7 and HaCaT cells showed more frequently individual MTs at cell edges, while A-549 had less covered nucleus by MTs after EMT. Microtubule dynamics (growth velocity) increased, and the length of microtubule growth tracks became longer. The average angle of MT growth trajectories to cell radius decreased. Actin fibers rearranged into more pronounced stress fibers after EMT. Alterations in the focal adhesion behaviors were different in three models used. These results indicate that cytoskeletal changes during EMT mainly include increased microtubule dynamics.
ПЕРСПЕКТИВНОЕ НАПРАВЛЕНИЕ ДЛЯ НПЦТ В РАМКАХ РАЗВИТИЯ КЛЕТОЧНЫХ ТЕХНОЛОГИЙ
Authors: Оспанова М. Е. , Абдрахманова С.А. , Ахаева М.А. , Жалмагамбетова С.Д.
Published: September 2024

Одним из перспективных клинических направлений является применение МСК в рамках тандемной трансплантации с гемопоэтическими стволовыми клетками (ГСК) при онкогематологических заболеваниях и ряде аутоиммунных заболеваний, а также использование МСК в лечении рефрактерных форм реакции трансплантат против хозяина, развившейся после аллогенной трансплантации ГСК.
Применение МСК в лечебных целях требует проведения культивирования и накопления клеточной массы in vitro в достаточном количестве для клинического применения.
Внедрить технологию заготовки МСК, выделенных из костного мозга аллогенных доноров.
В качестве материала для получения сыворотки АВ (IV) группы крови по системе АВ0 была использована кровь доноров группы АВ (IV), допущенных к донации в рамках национальных требований к донорам крови.
Для экспериментального выделения и культивирования МСК был взят костный мозг от двух аллогеных взрослых доноров путем миелоэксфузии из тазовых костей. Мононуклеарная фракция была выделена на градиенте плотности. Для приготовления полной питательной среды исползовались среда альфа-МЕМ, растворы глютамина, антибиотика-антимикотика. АВ-сыворотка добавлялась в объеме, составляющем 10% от объема приготовляемой питательной среды.
Клетки культивировали в течение 7-14 суток в СО2-инкубаторе при температуре +37℃ и влажности до 95%, с 5% содержанием СО2. Количество клеток и жизнеспособности оценивали в камере Горяева. Иммунофенотипирование клеточного продукта проводили методом проточной цитофлоуметрии.
В ходе наблюдения за ростом клеток отмечалась достаточно активное увеличение конфлюэнтности до 85-92%, один пассаж занимал срок от 4 до 14 дней в зависимости от посевной концентрации, которая составляла от 3000 до 8500 клеток на кв.см. Количество МСК увеличилось относительно первоначально внесенных клеток в пределах от 1,1 до 3,5 раз. В ходе эксперимента проводились процедуры заморозки клеточного продукта с последующими размораживанием и культивирование. При однократном замораживании потери клеток составили до 52%, но при последующем культивировании в течение 7 дней количество клеток увеличилось в 7,2-7,9 раз. При повторном замораживании замораживании потери клеток составили до 68% и уже при последующем культивировании в течение 7 дней количество клеток увеличилось в 1,55 раз.
При микроскопии выявлено, что клетки имели вид вытянутых веретенообразных клеток фибробластоподобной формы, характерной для МСК. Жизнеспособность клеток составляла 92-96 %.
При иммунотипировании конечного клеточного продукта обнаружение маркеров CD90+ CD105+ CD73+, присутствующих на мембранах МСК, составило 98,3%.
АВ-сыворотка в составе полной питательной среды для наращивания МСК поддерживает пролиферативный потенциал и обеспечивает сохранение морфологии клеток и может быть использована для эффективного культивирования МСК человека и разработки клеточных препаратов на их основе, пригодных для безопасного клинического применения. Повторные заморозки негативно влияют на пролиферативный потенциал клеток.
Essential Improvements in Fat Percentage and Cardiometabolic Fitness After a Residential Stay for Socially Vulnerable Children—With and Without the “11 for Health” Concept
Authors: Møller Trine K. , Krustrup Peter , Brønd Jan C. , Geiker Nina R.W. , Larsen Malte N.
Published: September 2024

The Danish Christmas Seal Homes offer a 10-week residential stay for socially vulnerable children. We aimed to examine the effects on body composition and cardiometabolic fitness variables of the standard program (SG) and whether substituting physical activity sessions with sessions from a football-based health education program is beneficial for the participants (“11 for Health”; SG+). Three hundred and nine children participated in SG (12.4 [1.6] y) and 305 in SG+ (12.4 [1.4] y). Fat percentage was lowered by 6% for females (from 37% to 31%) and 8% for males (from 36% to 28%), with no between-group differences. We observed improvements in systolic and diastolic blood pressure (3 and 5 mm Hg, respectively), resting heart rate (10 beats/min), aerobic fitness, jump performance, and relative muscle mass with no between-group differences. Furthermore, there were between-group differences in insulin levels for females (1.7 pmol/L; 95% CI, 0.3 to 3.0) and postural balance for males (1.0 s; 95% CI, 0.0 to 2.0), both in favor of SG+, and covered distance in the Andersen test for females (26 m; 95% CI, 3 to 49) in favor of SG. In conclusion, a 10-week stay at the Danish Christmas Seal Home resulted in clinically relevant improvement in fat percentage and cardiometabolic fitness in socially vulnerable children, regardless of the program type.
Minimal-gain-printed silicon nanolaser
Authors: Park Byoung Jun , Kim Min-Woo , Park Kyong-Tae , Kim Hwi-Min , You Byeong Uk , Yu Aran , Kim Jin Tae , No You-Shin , Kim Myung-Ki
Published: September 2024

While there have been notable advancements in Si-based optical integration, achieving compact and efficient continuous-wave (CW) III-V semiconductor nanolasers on Si at room temperature remains a substantial challenge. This study presents an innovative approach: the on-demand minimal-gain-printed Si nanolaser. By using a carefully designed minimal III-V optical gain structure and a precise on-demand gain-printing technique, we achieve lasing operation with superior spectral stability under pulsed conditions and observe a strong signature of CW operation at room temperature. These achievements are attributed to addressing both fundamental and technological issues, including carrier diffusion, absorption loss, and inefficient thermal dissipation, through minimal-gain printing in the nanolaser. Moreover, our demonstration of the laser-on-waveguide structure emphasizes the integration benefits of this on-demand gain-printed Si nanolaser, highlighting its potential significance in the fields of Si photonics and photonic integrated circuits.
Hybrid nanoparticle–mediated simultaneous ROS scavenging and STING activation improve the antitumor immunity of in situ vaccines
Authors: Li Jianing , Wu Tianze , Wang Weidong , Gong Yimin , Lu Mingzhu , Zhang Mengmeng , Lu Wanyue , Zhou Yaming , Yang Yannan
Published: September 2024

In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle–based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond–bridged organosilica nanoparticles, followed by coating with a Mn
2+
-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn
2+
and SN38 comediated signaling and simultaneously scavenge preexisting H
2
O
2
in the TME and Mn
2+
-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.
Two-dimensional silk
Authors: Shi Chenyang , Zorman Marlo , Zhao Xiao , Salmeron Miquel B. , Pfaendtner Jim , Liu Xiang Yang , Zhang Shuai , De Yoreo James J.
Published: September 2024

Despite the promise of silk-based devices, the inherent disorder of native silk limits performance. Here, we report highly ordered two-dimensional silk fibroin (SF) films grown epitaxially on van der Waals (vdW) substrates. Using atomic force microscopy, nano–Fourier transform infrared spectroscopy, and molecular dynamics, we show that the films consist of lamellae of SF molecules that exhibit the same secondary structure as the nanocrystallites of native silk. Increasing the SF concentration results in multilayers that grow either by direct assembly of SF molecules into the lamellae or, at high concentrations, along a two-step pathway beginning with a disordered monolayer that then crystallizes. Scanning Kelvin probe measurements show that these films substantially alter the surface potential; thus, they provide a platform for silk-based electronics on vdW solids.
Spatial dissociation between recognition and navigation in the primate hippocampus
Authors: Xu Xiao , Du Kechen , Mao Dun
Published: September 2024

The primate hippocampus, crucial for both episodic memory and spatial navigation, remains an enigma regarding whether these functions share the same neural substrates. We investigated how identical hippocampal neurons in macaque monkeys dynamically shifted their representations between tasks. In a recognition memory task, a notable fraction of hippocampal neurons showed that rate modulation strongly correlated with recognition performance. During free navigation in an open arena, spatial view, rather than position, predominantly influenced the spatial selectivity of hippocampal neurons. Neurons selective for recognition memory displayed minimal spatial tuning, while spatially tuned neurons exhibited limited memory-related activity. These neural correlates of recognition memory and space were more pronounced in the anterior and posterior portions of the hippocampus, respectively. These opposing gradients extended further into the anterior and posterior neocortices. Overall, our findings suggest the presence of orthogonal long-axis gradients between recognition memory and spatial navigation in the hippocampal-neocortical networks of macaque monkeys.
Development of miRNA-based PROTACs targeting Lin28 for breast cancer therapy
Authors: Xu Jianfei , Zhao Xiaoran , Liang Xingxing , Guo Dongyang , Wang Jing , Wang Qian , Tang Xinjing
Published: September 2024

Lin28, a highly conserved carcinogenic protein, plays an important role in the generation of cancer stem cells, contributing to the unfavorable prognosis of cancer patients. This RNA binding protein specifically binds to pri/pre-microRNA (miRNA) lethal-7 (let-7), impeding its miRNA maturation. The reduced expression of tumor suppressor miRNA let-7 fosters development and progression-related traits such as proliferation, invasion, metastasis, and drug resistance. We report a series of miRNA-based Lin28A-miRNA proteolysis-targeting chimeras (Lin28A-miRNA-PROTACs) designed to efficiently degrade Lin28A through a ubiquitin-proteasome–dependent mechanism, resulting in up-regulation of mature let-7 family. The augmented levels of matured let-7 miRNAs further exert inhibitory effects on cancer cell proliferation and migration, and increase its sensitivity to chemotherapy. In a mouse ectopic tumor model, Lin28A-miRNA-PROTAC demonstrates a substantial efficacy in inhibiting tumor growth. When combined with tamoxifen, the tumors exhibit gradual regression. This study displays an effective miRNA-based PROTACs to degrade Lin28A and inhibit tumor growth, providing a promising therapeutic avenue for cancer treatment with miRNA-based therapy.
Mechanochemically accelerated deconstruction of chemically recyclable plastics
Authors: Hua Mutian , Peng Zhengxing , Guha Rishabh D. , Ruan Xiaoxu , Ng Ka Chon , Demarteau Jeremy , Haber Shira , Fricke Sophia N. , Reimer Jeffrey A. , Salmeron Miquel B. , Persson Kristin A. , Wang Cheng , Helms Brett A.
Published: September 2024

Plastics redesign for circularity has primarily focused on monomer chemistries enabling faster deconstruction rates concomitant with high monomer yields. Yet, during deconstruction, polymer chains interact with their reaction medium, which remains underexplored in polymer reactivity. Here, we show that, when plastics are deconstructed in reaction media that promote swelling, initial rates are accelerated by over sixfold beyond those in small-molecule analogs. This unexpected acceleration is primarily tied to mechanochemical activation of strained polymer chains; however, changes in the activity of water under polymer confinement and bond activation in solvent-separated ion pairs are also important. Together, deconstruction times can be shortened by seven times by codesigning plastics and their deconstruction processes.
A deep intronic splice–altering
AIRE
variant causes APECED syndrome through antisense oligonucleotide-targetable pseudoexon inclusion
Authors: Ochoa Sebastian , Hsu Amy P. , Oler Andrew J. , Kumar Dhaneshwar , Chauss Daniel , van Hamburg Jan Piet , van Laar Gustaaf G. , Oikonomou Vasileios , Ganesan Sundar , Ferré Elise M. N. , Schmitt Monica M. , DiMaggio Tom , Barber Princess , Constantine Gregory M. , Rosen Lindsey B. , Auwaerter Paul G. , Gandhi Bhumika , Miller Jennifer L. , Eisenberg Rachel , Rubinstein Arye , Schussler Edith , Balliu Erjola , Shashi Vandana , Neth Olaf , Olbrich Peter , Le Kim My , Mamia Nanni , Laakso Saila , Nevalainen Pasi I. , Grönholm Juha , Seppänen Mikko R. J. , Boon Louis , Uzel Gulbu , Franco Luis M. , Heller Theo , Winer Karen K. , Ghosh Rajarshi , Seifert Bryce A. , Walkiewicz Magdalena , Notarangelo Luigi D. , Zhou Qing , Askentijevich Ivona , Gahl William , Dalgard Cliffton L. , Perera Lalith , Afzali Behdad , Tas Sander W. , Holland Steven M. , Lionakis Michail S.
Published: September 2024

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a life-threatening monogenic autoimmune disorder primarily caused by biallelic deleterious variants in the autoimmune regulator (
AIRE
) gene. We prospectively evaluated 104 patients with clinically diagnosed APECED syndrome and identified 17 patients (16%) from 14 kindreds lacking biallelic
AIRE
variants in exons or flanking intronic regions; 15 had Puerto Rican ancestry. Through whole-genome sequencing, we identified a deep intronic
AIRE
variant (c.1504-818 G>A) cosegregating with the disease in all 17 patients. We developed a culture system of
AIRE
-expressing primary patient monocyte-derived dendric cells and demonstrated that c.1504-818 G>A creates a cryptic splice site and activates inclusion of a 109–base pair frame-shifting pseudoexon. We also found low-level
AIRE
expression in patient-derived lymphoblastoid cell lines (LCLs) and confirmed pseudoexon inclusion in independent extrathymic
AIRE
–expressing cell lines. Through protein modeling and transcriptomic analyses of
AIRE
-transfected human embryonic kidney 293 and thymic epithelial cell 4D6 cells, we showed that this variant alters the carboxyl terminus of the AIRE protein, abrogating its function. Last, we developed an antisense oligonucleotide (ASO) that reversed pseudoexon inclusion and restored the normal
AIRE
transcript sequence in LCLs. Thus, our findings revealed c.1504-818 G>A as a founder APECED-causing
AIRE
variant in the Puerto Rican population and uncovered pseudoexon inclusion as an ASO-reversible genetic mechanism underlying APECED.
Preschool-age children maintain a distinct memory CD4
+
T cell and memory B cell response after SARS-CoV-2 infection
Authors: Manfroi Benoît , Cuc Bui Thi , Sokal Aurélien , Vandenberghe Alexis , Temmam Sarah , Attia Mikaël , El Behi Mohamed , Camaglia Francesco , Nguyen Ngan Thu , Pohar Jelka , Salem-Wehbe Layale , Pottez-Jouatte Valentine , Borzakian Sibyline , Elenga Narcisse , Galeotti Caroline , Morelle Guillaume , de truchis de Lays Camille , Semeraro Michaela , Romain Anne-Sophie , Aubart Mélodie , Ouldali Naim , Mahuteau-Betzer Florence , Beauvineau Claire , Amouyal Elsa , Berthaud Romain , Crétolle Célia , Arnould Marc Duval , Faye Albert , Lorrot Mathie , Benoist Grégoire , Briand Nelly , Courbebaisse Marie , Martin Roland , Van Endert Peter , Hulot Jean-Sébastien , Blanchard Anne , Tartour Eric , Leite-de-Moraes Maria , Lezmi Guillaume , Ménager Mickael , Luka Marine , Reynaud Claude-Agnès , Weill Jean-Claude , Languille Laetitia , Michel Marc , Chappert Pascal , Mora Thierry , Walczak Aleksandra M. , Eloit Marc , Bacher Petra , Scheffold Alexander , Mahévas Matthieu , Sermet-Gaudelus Isabelle , Fillatreau Simon
Published: September 2024

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–reactive CD3
+
CD4
+
CD154
+
T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4
+
T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4
+
T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2–reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.
Perfusion imaging metrics after acute traumatic spinal cord injury are associated with injury severity in rats and humans
Authors: Khaing Zin Z. , Leyendecker Jannik , Harmon Jennifer N. , Sivakanthan Sananthan , Cates Lindsay N. , Hyde Jeffrey E. , Krueger Melissa , Glenny Robb W. , Bruce Matthew , Hofstetter Christoph P.
Published: September 2024

Traumatic spinal cord injury (tSCI) causes an immediate loss of neurological function, and the prediction of recovery is difficult in the acute phase. In this study, we used contrast-enhanced ultrasound imaging to quantify intraspinal vascular disruption acutely after tSCI. In a rodent thoracic tSCI model, contrast-enhanced ultrasound revealed a perfusion area deficit that was positively correlated with injury severity and negatively correlated with hindlimb locomotor function at 8 weeks after injury. The spinal perfusion index was calculated by normalizing the contrast inflow at the injury center to the contrast inflow in the injury periphery. The spinal perfusion index decreased with increasing injury severity and positively correlated with hindlimb locomotor function at 8 weeks after injury. The feasibility of intraoperative contrast-enhanced ultrasound imaging was further tested in a cohort of 27 patients with acute tSCI of varying severity and including both motor-complete and motor-incomplete tSCIs. Both the perfusion area deficit and spinal perfusion index were different between motor-complete and motor-incomplete patients. Moreover, the perfusion area deficit and spinal perfusion index correlated with the injury severity at intake and exhibited a correlation with extent of functional recovery at 6 months. Our data suggest that intraoperative contrast-enhanced, ultrasound-derived metrics are correlated with injury severity and chronic functional outcome after tSCI. Larger clinical studies are required to better assess the reliability of the proposed contrast-enhanced ultrasound biomarkers and their prognostic capacity.
Offline data processing system of the BESIII experiment
Authors: Zou Jiaheng , Li Weidong , Ma Qiumei , You Zhengyun , Sun Shengsen , Deng Ziyan , Ji Xiaobin , Zhemchugov Alexy , Fang Wenxing , Fu Chengdong , He Kanglin , Huang Xingtao , Lin Tao , Liu Chunxiu , Liu Huaimin , Mao Zepu , Qiu Jinfa , Sun Yongzhao , Wen Shuopin , Wu Linghui , Wang Liangliang , Yuan Ye , Zhang Yao , Zhang Xiaomei , Zhao Guang
Published: September 2024

The BESIII experiment has been operating since 2009 and has received several upgrades, to study the $$\tau $$
τ
-charm physics utilizing the BEPCII accelerator. The BEPCII is a double-ring multi-bunch collider with a luminosity of $$1 \times 10^{33} \, {\text {cm}}^{-2} \, {\text {s}}^{-1}$$

1
×

10
33

cm

-
2

s

-
1

optimized at a center-of-mass (cms) energy of $$2 \times 1.89$$

2
×
1.89

GeV. The rich physics topics, long lifetime and the large volume of data present challenges to offline data processing. This paper describes the design and implementation of the offline software system to meet the requirements and challenges of BESIII, including offline software architecture, geometry management, database management, event data model and tag-based analysis.
Investigating $$D^0$$ meson production in p-Pb collisions at 5.02 TeV with a multi-phase transport model
Authors: Zhang Chao , Zheng Liang , Shi Shusu , Lin Zi-Wei
Published: September 2024

We study the production of $$D^0$$

D
0

meson in p+p and p-Pb collisions using the improved AMPT model considering both coalescence and independent fragmentation of charm quarks after the Cronin broadening is included. After a detailed discussion of the improvements implemented in the AMPT model for heavy quark production, we show that the modified AMPT model can provide a good description of $$D^0$$

D
0

meson spectra in p-Pb collisions, the $$Q_{\textrm{pPb}}$$

Q
pPb

data at different centralities and $$R_{\textrm{pPb}}$$

R
pPb

data in both mid- and forward (backward) rapidities. We also studied the effects of nuclear shadowing and parton cascade on the rapidity dependence of $$D^{0}$$

D
0

meson production and $$R_{\textrm{pPb}}$$

R
pPb

. Our results indicate that using the same strength of the Cronin effect (i.e $$\delta $$
δ
value) as that obtained from the mid-rapidity data leads to a considerable overestimation of the $$D^0$$

D
0

meson spectra and $$R_{\textrm{pPb}}$$

R
pPb

data at high $$p_{\textrm{T}}$$

p
T

in the backward rapidity. As a result, the $$\delta $$
δ
is determined via a $$\chi ^2$$

χ
2

fitting of the $$R_{\textrm{pPb}}$$

R
pPb

data across various rapidities. This work lays the foundation for a better understanding of cold-nuclear-matter (CNM) effects in relativistic heavy-ion collisions.
Hybrid ANFIS‐PI‐Based Robust Control of Wind Turbine Power Generation System
Authors: Ishaque Muhammad , Laghari Javed Ahmed , Bhayo Muhammad Akram , Chandio Sadullah , Mahariq Ibrahim
Published: September 2024

This paper introduces a novel hybrid controller designed for a wind turbine power generation system (WTPGS) that utilizes a permanent magnet synchronous generator (PMSG). This hybrid controller combines the adaptability of an adaptive neuro‐fuzzy inference system (ANFIS) with the simplicity of a proportional‐integral (PI) controller. The PI controllers are traditionally used for stability and noise handling. ANFIS adds adaptability, making it more suitable to cope with the variable nature of wind energy. The primary objective of this hybrid strategy is to augment the overall control performance and reliability of PMSG‐based WTPGS when encountered with continuous variable wind conditions. However, implementing the PI controller alone with the WTPGS often suffers from high overshoot and sluggish response in nonlinear systems like WTPGS. In contrast, ANFIS controllers offer superior performance to PI and other artificial intelligence controllers but are still susceptible to noise issues. In this paper, the proposed WTPGS system is designed in MATLAB/Simulink software where a hybrid controller (ANFIS‐PI) is implemented in the machine‐side converter (MSC) and grid‐side converter (GSC) of a variable speed PMSG‐based wind turbine to enhance its performance subjected to wind variations. The hybrid controller is implemented in such a way that the ANFIS controller is implemented in the outer layers while the PI controller is applied in the inner layers of both MSC and GSC. The simulation results for this hybrid controller in the MSC outperform those of the conventional PI controller. They demonstrate minimal overshooting and settling time, maintaining consistent stability even when subjected to various test signals at different intervals. Similarly, the GSC also surpasses conventional PI controllers, achieving a significant 6.4% reduction in maximum overshoot and a decrease of 4.36 seconds in settling time. This highlights its strong suitability for wind turbine applications.
Effects of Integrated Application of Vermicompost and Inorganic Fertilizers on Selected Soil Characteristics and Productivity of Wheat (Triticum aestivum L.) and Faba Bean (Vicia faba L.) in Dire and Legedadi Watersheds of Ethiopia
Authors: Habtamu Meseret , Elias Eyasu , Soromessa Teshome , Argaw Mekuria
Published: September 2024

The adoption of integrated soil fertility management (ISFM) practices can improve soil quality and sustainably increase crop yield while slowing down the rate of ongoing degradation. This research assessed the effects of selected ISFM practices on soil properties at the Dire and Legedadi watersheds, central highlands of Ethiopia, in the 2021 and 2022 cropping seasons. Eight treatments were selected (sole wheat, sole faba bean, 100% recommended NPS + urea fertilizers, 100% recommended vermicompost (VC), wheat with half dose both NPS + urea and VC, wheat and faba bean intercropping with half dose both NPS + urea and VC, wheat and faba bean intercropping with half‐dose NPS + urea fertilizers, and wheat and faba bean intercropping with 50% VC). The treatments were studied on farmers’ fields using a randomized complete block design with three replications. Analysis of variance showed that soil samples collected from each plot indicated significant differences in soil organic carbon (SOC), total nitrogen (TN), available phosphorus (Pav), exchangeable bases (Ca2+, Na+, and Kexc), and cation exchange capacity (CEC). Soil pH and moisture showed improvement in combined fertilizers application compared to the preplanting soil sample. A combined application of VC and NPS + urea fertilizers significantly (p < 0.05) increased SOC, Pav, K+, Na+, and CEC compared to the control. A combined application of VC and NPS + urea fertilizers improved the soil quality. The highest TN contents of 0.36% at the Dire site and 0.30% at the Legedadi site were obtained with the full dose VC treatment. Additionally, this treatment resulted in the greatest water‐holding capacity and soil carbon stock at both sites. Similarly, the wheat‐faba bean intercropped plots showed a significant (p < 0.05) effect on the soil carbon stock and sequestration over the control in both study sites. Based on the results of the current study, it can be concluded that the combined application of a half dose of each VC and NPS + urea fertilizers improved most soil physicochemical properties at both sites. This suggests that using a combination of VC and NPS + urea fertilizers can help farmers reduce their inorganic fertilizer needs by 50%.
Effect of Zinc Supplementation on Body Composition of Duchenne Muscular Dystrophy Patients: A Quasi‐Experimental Study
Authors: Cunha Thais A. , Vermeulen-Serpa Karina M. , Grilo Evellyn C. , Dourado-Júnior Mário E. T. , Bezerra Breno G. P. , Torres Núbia R. S. M. , Lopes Márcia M. G. D. , Leite-Lais Lucia , Brandão-Neto José , Vale Sancha H. L.
Published: September 2024

Background. The study hypothesized that zinc supplementation would increase or preserve lean body mass in Duchenne muscular dystrophy (DMD) patients. Therefore, we aimed to evaluate the body composition of DMD patients before and after zinc supplementation. Materials and Methods. The study is a clinical trial comprising 21 boys diagnosed with DMD. Dietary intake parameters were evaluated before zinc supplementation. Serum zinc levels, anthropometry, and body composition were measured in three moments, four months apart. The patients received 5, 10, or 15 mg of zinc bis‐glycine supplementation according to age as an oral solution daily for four months. The sample was distributed into two groups according to serum zinc status: zinc deficiency (G1) or adequate zinc (G2). Results. There was a significant difference in lean body mass between the groups: zinc deficiency (G1) or adequate zinc (G2), at three times (p = 0.041, 0.016, and 0.009, respectively). After oral zinc supplementation, serum zinc levels were not different between groups. We did not observe differences when associating the parameters between times and groups. Conclusion. Zinc supplementation was able to maintain lean body mass and fat mass in patients with DMD with previous deficiencies. Therefore, it is necessary to have a prior screening of serum zinc levels to observe changes after supplementation.
Functionalized Bioadsorbent Application on Methylene Blue Removal From Wastewater—A Review
Authors: Mougnol Jean B. Batchamen , Rathilal Sudesh
Published: September 2024

There are many pollutants present in wastewater that require urgent remediation. Methylene blue (MB) has become the most undesirable pollutant. Various industries such as petroleum, pharmaceuticals, textiles and households have been responsible for releasing MB into the environment. Its toxicity and acute health implications for animals and humans have suggested several technological applications for its removal. Biological methods using plant‐based wastes have been identified to be the most effective material for removing MB and other dye pollutants. Previous research studies have employed biological adsorbents to eliminate MB and were reviewed. The purpose of the study was to determine the removal efficiency gap of MB using biological wastes. In this present review, various biological wastes and their functionalization were explored. The study proved that chemically modified bioadsorbents were favourable in removing MB. Its ability to produce secondary pollutants from chemical agents has made it undesirable. Several factors such as pH, dosage of catalyst, contact time and temperature have also been reviewed to influence biosorption. The best data representations to describe the biosorption of MB were the Langmuir and pseudo‐second‐order models.
Unmet Need for Modern Contraceptive Methods Among Displaced Married Women in Their Reproductive Years in Bishan Guracha Town, West Arsi Zone, Oromia Region, Ethiopia
Authors: Million Sisay , Gebru Zeleke , Hassen Sultan , Tesfaye Selamnesh
Published: September 2024

Background: Refugees and conflict‐affected areas are often unreached by national strategies and programs. As a result, high unmet needs are more likely because of their social interruption with their traditional information sources, support, protection, and lack of income which limits refugees’ ability to make a free choice that would allow them to plan and space the number of children they desire. Information on the unmet needs of internally displaced persons (IDPs) women is scarce. This study is aimed at assessing the magnitude of the unmet need for modern contraceptive methods and associated factors among IDPs currently married reproductive‐age women.

Methods: A community‐based cross‐sectional study was conducted among 393 internally displaced women currently married reproductive‐age women using a simple random sampling method using a structured, pretested, and interview‐administered questionnaire. A logistic regression model was used to identify associated factors. Statistically significant variables at p value < 0.25 in the bivariate analysis were entered into multivariable analysis, and statistical significance was declared at p value ≤ 0.05.

Results: About 160 (40.7%) (95% CI: 35.94%–45.67%) of women had an unmet need for modern contraceptive methods, 139 (35.4%) for spacing, and 21 (5.3%) for limiting. Less than 18 years of age at first marriage, lack of access to modern contraception, lack of discussion with healthcare providers, and travel time of 30 min or more to obtain family planning were found to be risk factors for unmet contraceptive needs. The risk of unmet need for modern contraceptives was high among women who were married at age of less than 18 years of age in comparison with women who were married at 18 and above (AOR = 1.559; 95%CI = 1.019–2.385). Unmet needs were higher among participants who had no adequate availability of modern contraceptive methods than those who had adequate availability of modern contraceptive methods (AOR = 1.738; 95%CI = 1.125–2.684). Similarly, the odds of unmet needs were 1.673 times higher among participants who did not discuss FP with healthcare providers than those who discussed FP with healthcare providers (AOR = 1.673; 95%CI = 1.085–2.581). Moreover, the odds of unmet needs were 1.551 times higher among participants who traveled 30 min and above to access family planning services as compared to those respondents who traveled below 30 min (AOR = 1.551; 95%CI = 1.002–2.401).

Conclusion and Recommendations: The magnitude of the unmet need for modern contraceptive methods was higher than both the Ethiopian national and Oromia regional state total unmet need for the general population. Governmental and nongovernmental organizations should increase their efforts to reduce this high magnitude of unmet needs by emphasizing those factors that have a great contribution to unmet needs.
Supp methods and figure legends from A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans
Authors: Gorgoń Szymon , Billing Ola , Eriksson Anna U. , Hemmingsson Oskar
Published: September 2024

Supplementary methods and figure legends
Figure S4 from A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans
Authors: Gorgoń Szymon , Billing Ola , Eriksson Anna U. , Hemmingsson Oskar
Published: September 2024

Automated scoring of larvae in the ST65 strain.
Figure S2 from A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans
Authors: Gorgoń Szymon , Billing Ola , Eriksson Anna U. , Hemmingsson Oskar
Published: September 2024

Z-factors for automated scoring protocols in the ST65 strain.
Figure S1 from A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans
Authors: Gorgoń Szymon , Billing Ola , Eriksson Anna U. , Hemmingsson Oskar
Published: September 2024

Manual scoring of vulval induction in the ST65 strain.
Figure 6 from A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans
Authors: Gorgoń Szymon , Billing Ola , Eriksson Anna U. , Hemmingsson Oskar
Published: September 2024

Blinded screen identification of MAPK/ERK pathway inhibitors. A, Violin plot showing the vulvae/adult score distribution of screened compounds after applying exclusion criteria. B, Hit validation of 1° hits. The plot shows the mean values for duplicate experiments. C, Violin plot showing percent adults with the Muv phenotype after treatment with validated 1° hits in lin-1(e1777) mutants. Compound names after unmasking are indicated in B and C.
Figure 5 from A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans
Authors: Gorgoń Szymon , Billing Ola , Eriksson Anna U. , Hemmingsson Oskar
Published: September 2024

In silico scoring pipelines. A,In silico scoring of fluorescent foci using MetaXpress and CellProfiler software. From left, brightfield images, GFP images, and the concomitant detection mask that shows each detected feature in different colors (scale bars, 1 mm). Enlarged panels to the right show examples of what each program scores as adult pharynges, larval pharynges, and vulvae (scale bars, 100 μm). B–D, Boxplots showing scoring of the number of vulvae per adult worm after 10 μmol/L drug exposure. Boxes represent minimum to maximum distributions of three independent experiments with a line at the median from (B) manual scoring, (C) MetaXpress, and (D) CellProfiler pipelines. E, Violin plot comparing the number of reported vulvae per adult at 10 μmol/L drug exposure from MetaXpress, CellProfiler, and manual scoring protocols. F and G, Regression analysis of the number of reported vulvae per adult at 10 μmol/L drug exposure using (F) MetaXpress vs. manual scoring pipelines and (G) CellProfiler vs. manual scoring pipelines.
Table S3 from Estrogen Receptor Blockade Potentiates Immunotherapy for Liver Metastases by Altering the Liver Immunosuppressive Microenvironment
Authors: Benslimane Yasmine , Amalfi Kevin , Lapin Sara , Perrino Stephanie , Brodt Pnina
Published: September 2024

qPCR primer sequences.
Figure S5 from Estrogen Receptor Blockade Potentiates Immunotherapy for Liver Metastases by Altering the Liver Immunosuppressive Microenvironment
Authors: Benslimane Yasmine , Amalfi Kevin , Lapin Sara , Perrino Stephanie , Brodt Pnina
Published: September 2024

Macrophages analyses. Shown in (a) are the M1:M2 macrophages ratio analysis results using additional CD38 marker (n=3-4) and (b) TNF-alpha for M1-like macrophages characterization, and the use of the additional OVX+E2 experimental group which shows a reverse trend upon estrogen supplementation compared to the OVX group (n=3-4). Shown in (c) are the macrophages flow cytometry analysis results in FC1199 pancreatic liver metastasis model at Day 12 post-tumor injection (n=4).
Figure S4 from Estrogen Receptor Blockade Potentiates Immunotherapy for Liver Metastases by Altering the Liver Immunosuppressive Microenvironment
Authors: Benslimane Yasmine , Amalfi Kevin , Lapin Sara , Perrino Stephanie , Brodt Pnina
Published: September 2024

Lymphocytes flow cytometry analyses in FC1199 tumor model. Shown are the lymphocytes flow cytometry analysis of lymphocytes in FC1199 pancreatic liver metastasis model at Day 8 post-tumor injection in SHAM-control, OVX, and OVX + E2 mice (n=4).
Figure S1 from Estrogen Receptor Blockade Potentiates Immunotherapy for Liver Metastases by Altering the Liver Immunosuppressive Microenvironment
Authors: Benslimane Yasmine , Amalfi Kevin , Lapin Sara , Perrino Stephanie , Brodt Pnina
Published: September 2024

NK cells cytotoxicity is not significantly different between estrogen-depleted and estrogen-competent mice. NK cells were sorted based on CD3 (PE) and NK1.1 (APC), and MC-38 were pre-incubated with the Incucyte Cytotox Green Dye (Excitation Max 491 nm, Emission Max 509 nm). The NK cells and MC-38 cells were co-cultured at a ratio of 5:1 for up to 30h. Shown in the figure is quantification of dead (green) MC-38 cells normalized to time 0h (n=3).
Data from A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans
Authors: Gorgoń Szymon , Billing Ola , Eriksson Anna U. , Hemmingsson Oskar
Published: September 2024

Abstract
Oncogenic signaling through the MAPK/ERK pathway drives tumor progression in many cancers. Although targeted MAPK/ERK pathway inhibitors improve survival in selected patients, most tumors are resistant. New drugs could be identified in small-animal models that, unlike in vitro models, can address oral uptake, compound bioavailability, and toxicity. This requires pharmacologic conformity between human and model MAPK/ERK pathways and available phenotypic assays. In this study, we test if the conserved MAPK/ERK pathway in Caenorhabditis elegans could serve as a model for pharmacological inhibition and develop in vivo pipelines for high-throughput compound screens. Using fluorescence-based image analysis of vulva development as a readout for MAPK/ERK activity, we obtained excellent assay Z-scores for the MEK inhibitors trametinib (Z = 0.95), mirdametinib (Z = 0.93), and AZD8330 (Z = 0.87), as well as the ERK inhibitor temuterkib (Z = 0.86). The throughput was 800 wells per hour, with an average seed density of 25.5 animals per well. Readouts included drug efficacy, toxicity, and pathway specificity, which was tested against pathway activating upstream (lin-15)- and downstream (lin-1) mutants. To validate the model in a high-throughput setting, we screened a blinded library of 433 anticancer compounds and identified four MEK inhibitors among seven positive hits. Our results highlight a high degree of pharmacological conformity between C. elegans and human MAPK/ERK pathways, and the presented high-throughput pipeline may discover and characterize novel inhibitors in vivo.
Significance:
Many tumors depend on MAPK/ERK signaling to sustain growth, avoid cell death, and metastasize. We show that specific and clinically relevant MAPK/ERK signaling inhibitors can be discovered in vivo with a high-throughput screening pipeline in small animals.
“Nem todo evangélico é conservador”: religião e política entre evangélicos de esquerda no Brasil
Authors: Ribeiro Wallace Cabral
Published: September 2024

The evangelical field is a very heterogeneous religious segment and there is no single way of being evangelical and expressing that faith. Within this segment, there is a dispute between the various actors in their political, theological and identity dimensions about what it is to be a Christian, what it is to be evangelical and how they and the church should politically position themselves in the face of human dramas. This article aims to produce a socio-anthropological analysis of the articulation between religion and politics around evangelicals located in the field of the political left. For this, we will focus on the performance of some agents (leadership, collectives, groups and organizations) directly involved in the clashes of the aforementioned issues. We will analyze the speeches, actions, conflicts, as well as symbolic aspects involved. To achieve the defined objectives, we will carry out a bibliographic survey, documental survey, interviews and field visits.