bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term culture promotes changes to growth, gene expression, and metabolism in CHO cells that are independent of production stability
Authors: Torres Mauro , Betts Zeynep , Scholey Rachel , Elvin Mark , Place Svetlana , Hayes Andrew , Dickson Alan J. 
Published: April 2023

AbstractPhenotypic stability of Chinese hamster ovary (CHO) cells over long term culture (LTC) presents one of the most pressing challenges in the development of therapeutic protein manufacturing processess. However, our current understanding of the consequences of LTC on recombinant (r−) CHO cell lines is still limited, particularly as clonally‐derived cell lines present distinct production stability phenotypes. This study evaluated changes of culture performance, global gene expression, and cell metabolism of two clonally‐derived CHO cell lines with a stable or unstable phenotype during the LTC (early [EP] vs. late [LP] culture passages). Our findings indicated that LTC altered the behavior of CHO cells in culture, in terms of growth, overall gene expression, and cell metabolism. Regardless whether cells were categorized as stable or unstable in terms of r‐protein production, CHO cells at LP presented an earlier decline in cell viability and loss of any observable stationary phase. These changes were parallelled by the upregulation of genes involved in cell proliferation and survival pathways (i.e., MAPK/ERK, PI3K‐Akt). Stable and unstable CHO cell lines both showed increased consumption of glucose and amino acids at LP, with a parallel accumulation of greater amounts of lactate and TCA cycle intermediates. In terms of production stability, we found that decreased r‐protein production in the unstable cell line directly correlated to the loss in r‐gene copy number and r‐mRNA expression. Our data revealed that LTC produced ubiquitious effects on CHO cell phenotypes, changes that were rooted in alterations in cell transcriptome and metabolome. Overall, we found that CHO cells adapted their cellular function to proliferation and survival during the LTC, some of these changes may well have limited effects on overall yield or specific productivity of the desired r‐product, but they may be critical toward the capacity of cells to handle r‐proteins with specific molecular features.
Triboelectric nanogenerators and piezoelectric nanogenerators for preventing and treating heart diseases
Authors: Zhao Luming , Wong Siew Yee , Sim Jia Yu , Zhou Jin , Li Xu , Wang Changyong 
Published: April 2023

AbstractHeart diseases pose a serious threat to human health, and their incidence has been increasing in recent years. In past decades, many strategies have been developed to decrease the mortality and morbidity of heart diseases, among them, strategies involving cardiac electronic devices (CEDs) have been effective in treating and preventing heart diseases. To allow the CEDs to work continuously without the need to replace batteries and to meet the requirements of convenience and comfort in the process of use, nanogenerator (NG)‐based CEDs were proposed, widely studied, continuously optimized in recent years owing to their advantages of small dimensions, self‐powering ability, and good biocompatibility. In this review, recent improvements of NG‐based CEDs of two typical types (i.e., triboelectric nanogenerator [TENG] and piezoelectric nanogenerator [PENG]) and their structures and functions are summarized and discussed. The demands, remaining challenges, and future development trends of NG‐based CEDs are also discussed.
Optical coherence tomography in patients with Wilson's disease
Authors: Ning Wei‐Qin , Lyu Chun‐Xiao , Diao Sheng‐Peng , Huang Ye‐Qing , Liu Ai‐Qun , Yu Qing‐Yun , Peng Zhong‐Xing , Hong Ming‐Fan , Zhou Zhi‐Hua 
Published: April 2023

AbstractBackgroundMorphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD.MethodsA total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM–IPL).ResultsCompared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 μm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 μm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 μm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 μm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients.ConclusionOur results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.
Small‐Molecule Modulation of Protein Lipidation: From Chemical Probes to Therapeutics
Authors: Wang Zhen , Ying Jiafu , Zhang Xuanpu , Miao Chen , Xiao Yu , Zou Jie , Chen Baoen 
Published: April 2023

AbstractProtein lipidation is a widespread modification that regulates protein subcellular localization, structure and function. Dysregulation of protein lipidation has been implicated in various human diseases, including neurological disorders, infectious diseases and cancers. Thus lipid‐modifying enzymes and their substrate proteins are emerging as attractive drug targets. The development of small‐molecule modulators of protein lipidation has remarkably impacted our understanding of lipid‐modification biology and potential therapeutics. In this review, we summarize recent progress in small‐molecule targeting of protein lipidation and highlight therapeutic opportunities.
Where is the Macrocycle? Comment on “Simultaneous Organic and Inorganic Host‐Guest Chemistry within Pillararene‐Protein Cage Frameworks.”
Authors: Crowley Peter B. 
Published: April 2023

AbstractKostiainen and co‐workers claim to have prepared crystals of ferritin by “electrostatically bridging” the protein with a cationic pillar[5]arene. Questions remain regarding the contribution of the pillar[5]arene to protein assembly and the putative role as a molecular glue.
Platelet‐to‐lymphocyte ratio a potential prognosticator in acute myocardial infarction: A prospective longitudinal study
Authors: Wang Hongling , Li Li , Ma Yi 
Published: April 2023

AbstractBackgroundThe ratio of platelets to lymphocytes (PLR) can serve as a potential biomarker for predicting the prognosis of individuals with acute myocardial infarction (AMI).AimThe purpose of the research was to evaluate the in‐hospital outcomes of AMI patients and the predictive significance of PLR on major adverse cardiac events (MACE).MethodsA total of 799 AMI patients who had successful primary PCI within 12 h of the onset of chest pain were separated into low PLR (n = 511) and high PLR (n = 288) groups using a PLR cutoff value of 178. At admission, total white blood cell, neutrophil, lymphocyte, and platelet counts were assessed.ResultsIn patients with a high PLR group with PLR > 178, the incidence of MACE: heart rupture, acute heart failure, total adverse events, and mortality due to all events was considerably greater. In an analysis of the receiver operating characteristic curve, a high PLR > 178 accurately predicted adverse outcomes (73% specificity and 65% sensitivity). Age, hypertension, and PLR were found as independent predictors of adverse outcomes by multiple logistic regression.ConclusionsAMI patients with high PLR had poor hospital outcomes. These findings recommend PLR as an independent risk factor for hospital‐acquired complications, suggesting that inflammation and prothrombotic state may contribute to the poor prognosis of high PLR patients.
Prospective evaluation of the tolerability and efficacy of niraparib dosing based on baseline body weight and platelet count: Results from the PRIMA/ENGOT‐OV26/GOG‐3012 trial
Authors: Mirza Mansoor R. , González‐Martín Antonio , Graybill Whitney S. , O’Malley David M. , Gaba Lydia , Stephanie Yap Oi Wah , Guerra Eva M. , Rose Peter G. , Baurain Jean‐François , Ghamande Sharad A. , Denys Hannelore , Prendergast Emily , Pisano Carmela , Follana Philippe , Baumann Klaus , Calvert Paula M. , Korach Jacob , Li Yong , Malinowska Izabela A. , Gupta Divya , Monk Bradley J. 
Published: April 2023

AbstractBackgroundThe PRIMA/ENGOT‐OV26/GOG‐3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first‐line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.MethodsIn the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first‐line platinum‐based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg once daily. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg once daily in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg once daily in all other patients. Efficacy and safety outcomes were assessed by starting dose.ResultsOverall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46–0.76] vs. ISD HR, 0.69 [95% CI, 0.48–0.98]) and the homologous recombination–deficient (FSD HR, 0.44 [95% CI, 0.30–0.64] vs. ISD HR, 0.39 [95% CI, 0.22–0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment‐emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD.ConclusionsIn PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen.
Maximizing sampling efficiency to detect differences in fish community composition using environmental DNA metabarcoding in subarctic fjords
Authors: Guri Gledis , Westgaard Jon‐Ivar , Yoccoz Nigel , Wangensteen Owen S. , Præbel Kim , Ray Jessica Louise , Kelly Ryan P. , Shelton Andrew Olaf , Hanebrekke Tanja , Johansen Torild 
Published: April 2023

AbstractEnvironmental DNA (eDNA) has gained popularity as a tool for ecosystem biomonitoring and biodiversity assessment. Although much progress has been made regarding laboratory and fieldwork protocols, the issue of sampling efficiency requires further investigation, particularly in three‐dimensional marine systems. This study focuses on fish community composition in marine ecosystems and aims to analyze the efficiency of sampling design given the sampling effort for distinguishing between different communities. We sampled three fjords in Northern Norway, taking samples along fjord transects and at three different depths, and amplified a fragment of the mitochondrial 12S rRNA gene of bony fishes using the MiFish primers. We evaluated the effect of (i) the number of sampling stations, (ii) samples' spatial distribution, and (iii) the data treatment approach (presence/absence versus semiquantitative) for maximizing the efficiency of eDNA metabarcoding sampling when inferring differences of fish community compositions between fjords. We found that the manner of data treatment strongly affected the minimum number of sampling stations required to detect differences among communities; because the semiquantitative approach retained some information about abundance of the underlying reads, it was the most efficient. Furthermore, we found little‐to‐no difference of fish communities in samples from intermediate depths when comparing vertical fish communities. Lastly, we found that the differences between fish communities at the surface were the highest across the horizontal distance and overall, samples ~30 km apart showed the highest variation in the horizontal distribution. Boosting sampling efficiency (reducing sampling effort without compromising ecological inferences) can significantly contribute to enhanced biodiversity management and efficient biomonitoring plans.
Impact of multimorbidity on mortality in heart failure with reduced ejection fraction: which comorbidities matter most? An analysis of PARADIGM‐HF and ATMOSPHERE
Authors: Dewan Pooja , Ferreira João Pedro , Butt Jawad H. , Petrie Mark C. , Abraham William T. , Desai Akshay S. , Dickstein Kenneth , Køber Lars , Packer Milton , Rouleau Jean L. , Stewart Simon , Swedberg Karl , Zile Michael R. , Solomon Scott D. , Jhund Pardeep S. , McMurray John J.V. 
Published: April 2023

ABSTRACTAimsMultimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure (HF). How risk related to comorbidities compares at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels.Methods and resultsUsing two clinical trials in HF – the Prospective comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin‐Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial (PARADIGM‐HF) and the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure trials (ATMOSPHERE) – we identified the 10 most common comorbidities and examined 45 possible pairs. We calculated population attributable fractions (PAF) for all‐cause death and relative excess risk due to interaction with Cox proportional hazard models. Of 15 066 patients in the study, 14 133 (93.7%) had at least one and 11 867 (78.8%) had at least two of the 10 most prevalent comorbidities. The greatest individual risk among pairs was associated with peripheral artery disease (PAD) in combination with stroke (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.28–2.33) and anaemia (HR 1.71; 95% CI 1.39–2.11). The combination of chronic kidney disease (CKD) and hypertension had the highest PAF (5.65%; 95% CI 3.66–7.61). Two pairs demonstrated significant synergistic interaction (atrial fibrillation with CKD and coronary artery disease, respectively) and one an antagonistic interaction (anaemia and obesity).ConclusionsIn HF, the impact of multimorbidity differed at the individual patient and population level, depending on the prevalence of and the risk related to each comorbidity, and the interaction between individual comorbidities. Patients with coexistent PAD and stroke were at greatest individual risk whereas, from a population perspective, coexistent CKD and hypertension mattered most.
Microwave–vacuum extraction cum drying of tomato slices: Optimization and functional characterization
Authors: Alvi Tayyaba , Khan Muhammad Kashif Iqbal , Maan Abid Aslam , Rizwan Muhammad , Aamir Muhammad , Saeed Farhan , Ateeq Huda , Raza Muhammad Qasim , Afzaal Muhammad , Shah Mohd Asif 
Published: April 2023

AbstractFruits and vegetables have shorter shelf life due to their perishable nature. Tomato, being a nutritionally rich fruit needs to be preserved for a longer period. In this context, this study was designed to dry the tomato slices through microwave–vacuum drying. This process was optimized for moisture ratio and drying rate using response surface methodology (RSM). The process was investigated at different power levels (30, 50, 80, and 100 W), pressure (0, 15, 20, and 25 inHg), and time (0, 4, 6, and 10 min) using Box–Behnken design. Results indicated that color, energy efficiency, and drying characteristics were significantly affected by changing power, vacuum levels, and processing time. Besides, nine mathematical models were applied on experimental data to deeply understand the moisture ratio of tomato slices. Amongst, Midilli model was found best to describe the drying process at 100 W and 25 inHg supported by R2 (0.9989), RMSE (0.001), and X2 (1.34e−4). This study was focused on finding the optimal combinations of power, vacuum pressure, and time for better drying and reduced wastage of the fruit owing to its perishable nature. From all the microwave powers, higher microwave power and vacuum level showed better energy consumption, energy efficiencies, color retention, and rehydration capacity.
Innovations and challenges in design and construction of underground Mumbai Metro Line 3 – Lot UG‐04 and UG‐06
Authors: Srivastava Ashish , Trivedi Suyash , Khateeb Ateeq , Muniyappa Prathap , Grewal Harsimran , Gupta Navneet , Ramalingam Rakesh 
Published: April 2023

AbstractIndia is well on its way to create a world‐class Mass Rapid Transport system environment as an integral part of community infrastructure development. Mumbai Metro Line 3 is one such project being constructed in Mumbai city. It comprises 33.5 km‐long underground metro corridor running along Colaba to Bandra to Santacruz Electronic Export Processing Zone. It includes 27 stations (26 underground and 1 at grade), depot and associated twin‐tube tunnel. Mumbai Metro Rail Corporation Ltd., an affiliate organisation of Mumbai Metropolitan Region Development Authority, is responsible for the implementation of the project. Excavation and tunnelling works posed significant challenges as they cross densely inhabited zones of Mumbai. There were several buildings which were old and in delicate condition, many of which were heritage structures. In Mumbai – being a coastal city – the water table is almost at ground level which added to complications. There were several utilities, many of which were lifeline utilities, which could not be diverted or even closed, thus requiring support during excavation. Likewise, ensuring traffic movement with minimal disruptions with enormous excavation works for the project required several innovative solutions. Other criticalities included low overburden to the existing flyovers and to the air traffic control tower as well as saving a 100 year‐old banyan tree.
Single neurons in the human medial temporal lobe flexibly shift representations across spatial and memory tasks
Authors: Donoghue Thomas , Cao Runnan , Han Claire Z. , Holman Cameron Monteith , Brandmeir Nicholas J. , Wang Shuo , Jacobs Joshua 
Published: April 2023

AbstractInvestigations into how individual neurons encode behavioral variables of interest have revealed specific representations in single neurons, such as place and object cells, as well as a wide range of cells with conjunctive encodings or mixed selectivity. However, as most experiments examine neural activity within individual tasks, it is currently unclear if and how neural representations change across different task contexts. Within this discussion, the medial temporal lobe is particularly salient, as it is known to be important for multiple behaviors including spatial navigation and memory, however the relationship between these functions is currently unclear. Here, to investigate how representations in single neurons vary across different task contexts in the medial temporal lobe, we collected and analyzed single‐neuron activity from human participants as they completed a paired‐task session consisting of a passive‐viewing visual working memory and a spatial navigation and memory task. Five patients contributed 22 paired‐task sessions, which were spike sorted together to allow for the same putative single neurons to be compared between the different tasks. Within each task, we replicated concept‐related activations in the working memory task, as well as target‐location and serial‐position responsive cells in the navigation task. When comparing neuronal activity between tasks, we first established that a significant number of neurons maintained the same kind of representation, responding to stimuli presentations across tasks. Further, we found cells that changed the nature of their representation across tasks, including a significant number of cells that were stimulus responsive in the working memory task that responded to serial position in the spatial task. Overall, our results support a flexible encoding of multiple, distinct aspects of different tasks by single neurons in the human medial temporal lobe, whereby some individual neurons change the nature of their feature coding between task contexts.
Nasal swab as an alternative specimen for the detection of severe acute respiratory syndrome coronavirus 2
Authors: Nahar Kamrun , Begum Mst. Noorjahan , Tony Selim R. , Jubair Mohammad , Hossain Md. Abir , Karim Yeasir , Faisal Abdullah Al. , Hossain Mohammad Enayet , Rahman Mohammed Ziaur , Rahman Mustafizur 
Published: April 2023

AbstractBackground and AimsThe coronavirus disease 2019 (COVID‐19) has brought serious threats to public health worldwide. Nasopharyngeal, nasal swabs, and saliva specimens are used to detect severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, limited data are available on the performance of less invasive nasal swab for testing COVID‐19. This study aimed to compare the diagnostic performance of nasal swabs with nasopharyngeal swabs using real‐time reverse transcription polymerase chain reaction (RT‐PCR) considering viral load, onset of symptoms, and disease severity.MethodsA total of 449 suspected COVIDCOVID‐19 individuals were recruited. Both nasopharyngeal and nasal swabs were collected from the same individual. Viral RNA was extracted and tested by real‐time RT‐PCR. Metadata were collected using structured questionnaire and analyzed by SPSS and MedCalc software.ResultsThe overall sensitivity of the nasopharyngeal swab was 96.6%, and the nasal swab was 83.4%. The sensitivity of nasal swabs was more than 97.7% for low and moderate Ct values. Moreover, the performance of nasal swab was very high (>87%) for hospitalized patients and at the later stage >7 days of onset of symptoms.ConclusionLess invasive nasal swab sampling with adequate sensitivity can be used as an alternative to nasopharyngeal swabs for the detection of SARS‐CoV‐2 by real‐time RT‐PCR.