bluuebunny/crossref_metadata_2025_split huggingface dataset:
МУЛЬТИОМНЫЙ ПОДХОД ИЗУЧЕНИЕ КЛЕТОЧНОГО ОТВЕТА BACTEROIDES FRAGILIS К МЕРОПЕНЕМУ
Authors: Баянбек Д.С. , Бекбаева A. , Ауганова Д.Н. , Тарлыков П.В. , Кожахметова С.С. , Жолдыбаева Е.В. 
Published: September 2024

На основе исследования ВОЗ, по глобальному росту устойчивости к карбапенемам и бета-лактамам среди изолятов Bacteroides fragilis, показали, что частота резистентности обычно колеблется от 1% до 5% в зависимости от географического расположения.
В данном исследовании был проанализирован клинический изолят Bacteroides fragilis BFR_KZ01 (wMEM), полученный от пациентов с интраабдоминальными заболеваниями, а также субкультуры, выращенные с использованием меропенема (MEM2, MEM8) и без антибиотика (rMEM2, rMEM8). Основная цель исследования заключалась в изучении транскриптома и протеома указанных бактерий с целью выявления связей между их генами и механизмами резистентности.
Бактериальный изолят был выращен в сердечно-мозговом бульоне при 37°C в анаэробных условиях в течение 48 часов. Субкультуры бактерии проходили культивацию в средах с меропенемом и без него с интервалом в 48 часов в течение 8 дней.
Чувствительность к меропенему оценили с помощью полосок M.I.C. Evaluator™. Использовали коммерческий набор RNeasy mini kit для извлечения общей РНК из жидких культур B. fragilis. Секвенирование РНК, ориентированное на конкретные области, проводилось на платформе DNBSEQ. Белки B. fragilis были извлечены и разделены с использованием метода додецилсульфата натрия-полиакриламидного гель-электрофореза (SDS-PAGE). Элюированные пептиды были анализированы с использованием метода жидкостной хроматографии-тандемной масс-спектрометрии (LC-MS/MS). Протеомные данные анализировали с использованием программы Mascot 2.6.1. Для кластерного анализа использовали онлайн базу данных для аннотации, визуализации и интегрированных открытий (DAVID).
Субингибирующая концентрация меропенема составила (SIC) 0,5 мкг/мл. Картирование референсного генома позволило выявить 2 477 экспрессированных генов среди всех образцов B. fragilis BFR KZ01. Десять генов с дифференциальной экспрессией были обнаружены как общие между группами сравнения под воздействием антибиотиков и после удаления меропенема (wMEM против MEM2 и MEM2 против rMEM8), однако значимых обогащенных терминов генной онтологии не выявлено. Кластер обогащения, связанный с оксидоредуктазой W-0560, дифференциально экспрессируемых генов после удаления антибиотика, был выявлен как значимый. С использованием LC-MS/MS было идентифицировано 859 белков B. fragilis. Три белка были увеличены в обогащенной категории сворачивания белков: 3-оксоацил-[ацил-карриер-белок] редуктаза, субъединица биотин-карбоксилазы ацетил-КоА карбоксилазы и бета-кетоацил-АЦП синтаза III. Белки-шапероны включают пептидил-пролил-цис-транс-изомеразы FKBP-типа (участвующие в цис-транс-изомеризации пролиловых пептидных связей) и GroES (ко-шаперон, функционирующий вместе с GroEL).
Полученные результаты углубляют наше понимание ответа B. fragilis на меропенем, особенно в контексте бета-лактамазы SIC, и способствуют более глубокому анализу стратегий выживания бактерий в условиях стресса.
Microbial production of 5-
epi
-jinkoheremol, a plant-derived antifungal sesquiterpene
Authors: Wang Guoli , Wu Zhenke , Li Mingkai , Liang Xiqin , Wen Yiwei , Zheng Qiusheng , Li Defang , An Tianyue 
Published: September 2024

ABSTRACT

Synthetic biology using microbial chassis is emerging as a powerful tool for the production of natural chemicals. In the present study, we constructed a microbial platform for the high-level production of a sesquiterpene from
Catharanthus roseus
, 5-
epi
-jinkoheremol, which exhibits strong fungicidal activity. First, the mevalonate and sterol biosynthesis pathways were optimized in engineered yeast to increase the metabolic flux toward the biosynthesis of the precursor farnesyl pyrophosphate. Then, the transcription factor Hac1- and m
6
A writer Ime4-based metabolic engineering strategies were implemented in yeast to increase 5-
epi
-jinkoheremol production further. Next, protein engineering was performed to improve the catalytic activity and enhance the stability of the 5-
epi
-jinkoheremol synthase TPS18, resulting in the variant TPS18
I21P/T414S
, with the most improved properties. Finally, the titer of 5-
epi
-jinkoheremol was elevated to 875.25 mg/L in a carbon source-optimized medium in shake flask cultivation. To the best of our knowledge, this is the first study to construct an efficient microbial cell factory for the sustainable production of this antifungal sesquiterpene.

IMPORTANCE

Biofungicides represent a new and sustainable tool for the control of crop fungal diseases. However, hindered by the high cost of biofungicide production, their use is not as popular as expected. Synthetic biology using microbial chassis is emerging as a powerful tool for the production of natural chemicals. We previously identified a promising sesquiterpenoid biofungicide, 5-
epi
-jinkoheremol. Here, we constructed a microbial platform for the high-level production of this chemical. The metabolic engineering of the terpene biosynthetic pathway was firstly employed to increase the metabolic flux toward 5-
epi
-jinkoheremol production. However, the limited catalytic activity of the key enzyme, TPS18, restricted the further yield of 5-
epi
-jinkoheremol. By using protein engineering, we improved its catalytic efficiency, and combined with the optimization of regulation factors, the highest production of 5-
epi
-jinkoheremol was achieved. Our work was useful for the larger-scale efficient production of this antifungal sesquiterpene.
Conjugation of anti-HIV gp41 monoclonal antibody to a drug capable of targeting resting lymphocytes produces an effective cytotoxic anti-HIV immunoconjugate
Authors: Pincus Seth H. , Cole Frances M. , Ober Kelli , Tokmina-Lukaszewska Monika , Marcotte Tamera , Kovacs Ernest W. , Zhu Tong , Khasanov Alisher , Copié Valérie , Peters Tami 
Published: September 2024

ABSTRACT

HIV-infected cells persisting in the face of suppressive antiretroviral therapy are the barrier to curing infection. Cytotoxic immunoconjugates targeted to HIV antigens on the cell surface may clear these cells. We showed efficacy in mouse and macaque models using immunotoxins, but immunogenicity blunted the effect. As an alternative, we propose antibody drug conjugates (ADCs), as used in cancer immunotherapy. In cancer, the target is a dividing cell, whereas it may not be in HIV. We screened cytotoxic drugs on human primary cells and cell lines. An anthracycline derivative, PNU-159682 (PNU), was highly cytotoxic to both proliferating and resting cells. Human anti-gp41 mAb 7B2 was conjugated to ricin A chain or PNU. The conjugates were tested
in vitro
for cytotoxic efficacy and anti-viral effect, and
in vivo
for tolerability. The specificity of killing for both conjugates was demonstrated on Env+ and Env− cells. The toxin conjugate was more potent and killed more rapidly, but 7B2–PNU was effective at levels achievable in patients. The ricin conjugate was well tolerated in mice; 7B2–PNU was toxic when administered intraperitoneally but was tolerated intravenously. We have produced an ADC with potential to target the persistent HIV reservoir in both dividing and non-dividing cells while avoiding immunogenicity. Cytotoxic anti-HIV immunoconjugates may have greatest utility as part of an “activate and purge” regimen, involving viral activation in the reservoir. This is a unique comparison of an immunotoxin and ADC targeted by the same antibody and tested in the same systems.

IMPORTANCE
HIV infection can be controlled with anti-retroviral therapy, but it cannot be cured. Despite years of therapy that suppresses HIV, patients again become viremic shortly after discontinuing treatment. A long-lived population of memory T cells retain the genes encoding HIV, and these cells secrete infectious HIV when no longer suppressed by therapy. This is the persistent reservoir of HIV infection. The therapies described here use anti-HIV antibodies conjugated to poisons to kill the cells in this reservoir. These poisons may be of several types, including protein toxins (immunotoxins) or anti-cancer drugs (antibody drug conjugates, ADCs). We have previously shown that an anti-HIV immunotoxin had therapeutic effects in animal models, but it elicited an anti-drug immune response. Here, we have prepared an anti-HIV ADC, which would be less likely to provoke an immune response, and show its potential for use in eliminating the persistent reservoir of HIV infection.
Comparison of two digital alignment systems for toric intraocular lens implantation
Authors: Zeilinger Johannes , Schlatter Andreas , Ruiss Manuel , Bayer Natascha , Kronschläger Martin , Findl Oliver 
Published: September 2024

PurposeTo compare the two most used digital alignment systems regarding precision, repeatability and loss of track.Methods15 eyes of 15 patients older than 21 years with cataracts were included in this prospective study. The two systems were intraoperatively superimposed and recorded, and the alignment of the two displayed alignment axes was analysed regarding precision, repeatability and loss of track.ResultsThere was a significant difference in precision and repeatability between the two digital alignment systems regarding the projected alignment axis. The deviation from the actual target axis was significantly different, with a mean of 0.34°±0.75° for the Zeiss system and 1.60°±1.08° for the Alcon system (p=0.03, n=14). The within-subject SD was significantly lower with 0.21° for the Zeiss system and 0.34° for the Alcon system (p=0.03, n=14).ConclusionsThe Zeiss Callisto system showed a significantly lower deviation from the target axis, higher stability with eye movements and less need for microscope illumination than the Alcon system. Both systems showed high precision when compared with manual marking methods.Trial registration numberNCT05220683.
Impacts of Job Demands on Turnover Intention Among Registered Nurses in Hong Kong Public Hospitals: Exploring the Mediating Role of Burnout and Moderating Effect of Pay Level Satisfaction
Authors: Wong Ka Po , Zhang Bohan , Xie Yao Jie , Wong Frances Kam Yuet , Lai Claudia Kam Yuk , Chen Shu-Cheng , Qin Jing 
Published: September 2024

Background: High turnover rates and burnout are prevalent issues among registered nurses in public hospitals in Hong Kong. Pay level satisfaction is one of the crucial factors influencing organisational and professional turnover intention. Understanding whether pay level satisfaction can mitigate the negative impact of burnout on turnover intention can provide insights into the role of financial rewards in employee retention.Objective: This study aims to evaluate the relationship between job demands and turnover intention among registered nurses in Hong Kong public hospitals. Additionally, it seeks to examine the mediating role of burnout and explore the potential moderating effect of pay level satisfaction on the relationship between burnout and turnover intention.Methods: The study was a cross‐sectional online survey of public hospital staff in Hong Kong. A total of 502 registered nurses who had worked at their employing facility for at least 6 months participated in this cross‐sectional survey. Study variables included work overload, job stress, work–family conflict, family–work conflict, conflict with other nurses, burnout, pay level satisfaction and turnover intention. The collected data were analysed using bivariate Pearson correlation analysis and mediated moderation analysis with the PROCESS macro in SPSS 28.0.Results: Burnout mediated the relationship between job demands, including work overload, job stress, work–family conflict, family–work conflict and conflicts with nurses, and organisational and professional turnover intention. Pay level satisfaction did not exert a moderating influence on the relationship between job demands and turnover intention through burnout mediating this relationship.Conclusions: The importance of addressing job stress and burnout to mitigate turnover intention and promote nurse retention is underscored. Contrary to expectations, pay level satisfaction did not buffer the negative impact of job demands on turnover intentions via burnout. This suggests that compensation alone may not be sufficient to offset the detrimental effects of high job demands and burnout on nurses’ intention to leave their jobs or the profession. Further research is warranted to explore potential moderators that may influence the relationship between job demands and turnover intention.
Supplementary Table S13 from Comprehensive analysis of tumor microenvironment reveals prognostic ceRNA network related to immune infiltration in sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas. , Zhao Qi 
Published: September 2024

<p>Supplementary Table S13. Univariate and multivariable Cox regression analysis of nodes involved in the prognostics related ceRNA network.</p>
Emerging Tumor-Agnostic Molecular Targets
Authors: Bhamidipati Dedipya , Schram Alison M. 
Published: September 2024

Abstract
Advances in tumor molecular profiling have uncovered shared genomic and proteomic alterations across tumor types that can be exploited therapeutically. A biomarker-driven, disease-agnostic approach to oncology drug development can maximize the reach of novel therapeutics. To date, eight drug–biomarker pairs have been approved for the treatment of patients with advanced solid tumors with specific molecular profiles. Emerging biomarkers with the potential for clinical actionability across tumor types include gene fusions involving NRG1, FGFR1/2/3, BRAF, and ALK and mutations in TP53 Y220C, KRAS G12C, FGFR2/3, and BRAF non-V600 (class II). We explore the growing evidence for clinical actionability of these biomarkers in patients with advanced solid tumors.
Tracing the Roots of Islamophobia in Recent Indian Films
Authors: Das Suchismita , Pal Satanik 
Published: September 2024

Abstract
This article analyses the recent rise of Islamophobic films in India. While it may seem that social media has led to a rise in Hindu nationalism and Islamophobia in the recent past, it is crucial to recognize that this narrative is incomplete. The rise of Islamophobia in the country can be traced back to the 20th century freedom struggle where a counter-narrative to Gandhian concepts of communal harmony can be found in the writings of various leaders, artists and activists. Social media has allowed for a re-proliferation of those strands of thought in recent times through the platforms such as Youtube, which has led to the success of movies like The Kashmir Files or The Kerala Story.
Texas Water Observatory: A Distributed Network for Monitoring Water, Energy, and Carbon Cycles under Variable Climate and Land Use on Gulf Coast Plains
Authors: Mohanty Binayak P. , Mbabazi Deanroy , Miller Gretchen , Moore Georgianne , Everett Mark , Rajan Nithya , Morgan Cristine L. S. , Gaur Nandita , Sehgal Vinit , Sedaghatdoost Amir , Hong Minki , Kathuria Dhruva , Deshpande Ajinkya , Singh Siddharth , Martin J. Michael , Calabrese Salvatore , Mishra Debasish , Singh Rishabh , Chun Beomseok , Souza Rodolfo , Knappett Peter S. K. , Smith Douglas R. , Jones Curtis 
Published: September 2024

Abstract
In the Gulf Coastal Plains of Texas, a state-of-the-art distributed network of field observatories, known as the Texas Water Observatory (TWO), is developed to better understand the water, energy, and carbon cycles across the critical zone (encompassing aquifers, soils, plants, and atmosphere) at different spatiotemporal scales. Using more than 300 advanced real-time/near-real-time sensors, this observatory monitors high-frequency water, energy, and carbon storage and fluxes in the Brazos River corridor, which are critical for coupled hydrologic, biogeochemical, and land–atmosphere process understanding in the region. TWO provides a regional resource for better understanding and/or managing agriculture, water resources, ecosystems, biodiversity, disasters, health, energy, and weather/climate. TWO infrastructure spans common land uses in this region, including traditional/aspirational cultivated agriculture, rangelands, native prairie, bottomland hardwood forest, and coastal wetlands. Sites represent landforms from low-relief erosional uplands to depositional lowlands across climatic and geologic gradients of central Texas. We present the overarching vision of TWO and describe site design, instrumentation specifications, data collection, and quality control protocols. We also provide a comparison of water, energy, and carbon budget across sites, including evapotranspiration, carbon fluxes, radiation budget, weather, profile soil moisture and soil temperature, soil hydraulic properties, hydrogeophysical surveys, groundwater levels, and groundwater quality reported at TWO primary sites for 2018–20 (with certain data gaps). In conjunction with various Earth-observing remote sensing and legacy databases, TWO provides a master testbed to evaluate process-driven or data-driven critical zone science, leading to improved natural resource management and decision support at different spatiotemporal scales.

Significance Statement
We provide the vision, design setup, and data acquisition of a state-of-the-art network of field observatories across the Gulf Coastal Plains of Texas. This observatory provides a wealth of measurements of the water, energy, and carbon fluxes, thereby providing a critical testbed for improving the understanding of terrestrial hydrological, biogeochemical, and atmospheric processes across diverse land-use and climate conditions.
Abyssal Slope Currents
Authors: Capó Esther , McWilliams James C. , Gula Jonathan , Molemaker M. Jeroen , Damien Pierre , Schubert René 
Published: September 2024

Abstract
Realistic computational simulations in different oceanic basins reveal prevalent prograde mean flows (in the direction of topographic Rossby wave propagation along isobaths; aka topostrophy) on topographic slopes in the deep ocean, consistent with the barotropic theory of eddy-driven mean flows. Attention is focused on the western Mediterranean Sea with strong currents and steep topography. These prograde mean currents induce an opposing bottom drag stress and thus a turbulent boundary layer mean flow in the downhill direction, evidenced by a near-bottom negative mean vertical velocity. The slope-normal profile of diapycnal buoyancy mixing results in downslope mean advection near the bottom (a tendency to locally increase the mean buoyancy) and upslope buoyancy mixing (a tendency to decrease buoyancy) with associated buoyancy fluxes across the mean isopycnal surfaces (diapycnal downwelling). In the upper part of the boundary layer and nearby interior, the diapycnal turbulent buoyancy flux divergence reverses sign (diapycnal upwelling), with upward Eulerian mean buoyancy advection across isopycnal surfaces. These near-slope tendencies abate with further distance from the boundary. An along-isobath mean momentum balance shows an advective acceleration and a bottom-drag retardation of the prograde flow. The eddy buoyancy advection is significant near the slope, and the associated eddy potential energy conversion is negative, consistent with mean vertical shear flow generation for the eddies. This cross-isobath flow structure differs from previous proposals, and a new one-dimensional model is constructed for a topostrophic, stratified, slope bottom boundary layer. The broader issue of the return pathways of the global thermohaline circulation remains open, but the abyssal slope region is likely to play a dominant role.
Modelling wound area in studies of wound healing interventions
Authors: Watson Samuel I. , Gkini Eleni , Bishop Jon , Scandrett Katie , Napit Indra , Lilford Richard J. 
Published: September 2024

Abstract
Background
Experimental studies of wound healing often use survival analysis and time to event outcomes or differences in wound area at a specific time point. However, these methods do not use a potentially large number of observations made over the course of a trial and may be inefficient. A model-based approach can leverage all trial data, but there is little guidance on appropriate models and functional forms to describe wound healing.

Methods
We derive a general statistical model and review a wide range of plausible mathematical models to describe wound healing. We identify a range of possible derived estimands and their derivation from the models. Using data from a trial of an intervention to promote ulcer healing in patients affected by leprosy that included three measurement methods repeated across the course of the study, we compare the goodness-of-fit of the models using a range of methods and estimate treatment effects and healing rate functions with the best-fitting models.

Results
Overall, we included 5,581 ulcer measurements of 1,578 unique images from 130 patients. We examined the performance of a range of models. The square root, log square root, and log quadratic models were the best fitting models across all outcome measurement methods. The estimated treatment effects magnitude and sign varied by time post-randomisation, model type, and outcome type, but across all models there was little evidence of effectiveness. The estimated effects were significantly more precise than non-parametric alternatives. For example, estimated differences from the three outcome measurements at 42-days post-randomisation were − 0.01 cm2 (-0.77, 0.74), -0.44 cm2 (-1.64, 0.76), and 0.11 cm2 (-0.87, 1.08) using a non-parametric method versus − 0.03 cm2 (-0.14, 0.06), 0.06 cm2 (-0.05, 0.17), and 0.03 cm2 (-0.07, 0.17) using a square-root model.

Conclusions
Model-based analyses can dramatically improve the precision of estimates but care must be taken to carefully compare and select the best fitting models. The (log) square-root model is strongly recommended reflecting advice from a century ago.