bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Kidney Injury: Epidemiology, Diagnosis, Prognosis, and Future Directions
Authors: Briosa Neves Joana , Jorge Sofia , Lopes José António
Published: February 2023

Acute kidney injury (AKI) is a common problem highly associated with hospitalisation. AKI is the cause of harmful short-term consequences: longer hospital stays, greater disability after discharge, and greater risk of in-hospital mortality, as well as adverse long-term outcomes, such as progression to chronic kidney disease, development of cardiovascular disease, and increased risk of long-term mortality. The concept of AKI has changed since the introduction of the ‘Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease’ (RIFLE) classification. More recently, the ‘Kidney Disease Improving Global Outcomes’ (KDIGO) classification appears to have provided increased diagnostic sensitivity and outcome-prediction capability. Novel biomarkers and further research on the role of the immune system in AKI may help improve the diagnosis, severity, outcome evaluation, and treatment of the condition. In this review we describe the epidemiology, diagnosis, and prognosis of AKI, as well as possible future directions for its clinical management.
Brain Health: Translating Scientific Evidence Into Clinical Practice in Multiple Sclerosis
Authors: Thomas Joan
Published: February 2023

Brain volume loss (BVL) progresses more rapidly in patients with multiple sclerosis (MS) than in healthy individuals, and brain atrophy begins early in the course of the disease. The objective of this symposium was to emphasise the importance of care and preservation of the brain within treatment protocols for MS so that early and appropriate management can be initiated to preserve brain volume and function. Prof Per Solberg Sørensen chaired the symposium and welcomed the speakers. Prof Heinz Wiendl gave a presentation on BVL in MS and described its underlying pathophysiology. Dr Andreas Lysandropoulos illustrated how information on BVL is clinically relevant and can be taken from clinical studies to assist clinical practice and decision-making. The final presentation was given by Prof Andrew Chan who highlighted the important role of brain atrophy in decision-making for early treatment and presented recent data for two treatments for MS: teriflunomide and the monoclonal antibody alemtuzumab. The symposium was concluded by a short question and answer session.
Status Epilepticus in Critically Ill Patients
Authors: Rocco Monica , Caputo Cristina , Fegiz Alessandra , Maggi Luigi , De Blasi Roberto Alberto
Published: February 2023

Status epilepticus (SE) is a common diagnosis in critically ill patients that may bear significant morbidity and mortality. Nowadays it is defined as continuous seizure activity lasting for more than 5 mins and requiring a specific treatment. A generalised convulsive state is a medical emergency burdened by high mortality, especially in the elderly, because repeated seizures swiftly induce significant metabolic and cardiocirculatory derangement. Two different kinds of SE are commonly recognised, depending on the presence of convulsion: convulsive SE and non-convulsive SE, which have different electroencephalographic patterns and require different therapies. In this review we provide an overview of this intriguing issue, focussing on critically ill patients.
ANALISA EFFISIENSI PLTU PAITON KETIKA HIGH PRESSURE HEATER (HPH 7) INSERVICE DAN OUTSERVICE
Authors: Untoro Sigit , Ismail Nova Risdiyanto , Farid Akhmad , Suwandono Purbo
Published: February 2023

National electricity needs are always increasing, for that the efficiency of power plants needs to be maintained and expected to be improved. To maintain the efficiency of the power plant, it is necessary to feed water system as a provider of feed water before entering the boiler in good condition and one of the equipment is the High Pressure Heater (HPH). In Paiton Power Plant there are HPH numbers 5.6 and 7. This research aims to compare the efficiency of power plants and the losses caused when pltu operates in hph 7 inservice and outservice conditions. The research method used is a simulation in the simulator room of PLTU PT. PJB UP Paiton 1 & 2.  From the data obtained then done calculations. Research produces the efficiency value of PLTU when in HPH 7 inservice condition is 33.40% and when outservice is 29.20%. The need for coal to increase the temperature lost due to HPH 7 outservice amounted to 11.11 Tons / hour, so that the losses caused by the increase in coal flow amounted to Rp 1,204.896.000 per year.
PENGARUH METODE PROSES MANUFAKTUR TERHADAP KEKUATAN BENDING KOMPOSIT SERAT KULIT POHON WARU SEBAGAI MATERIAL TERBARUKAN UNTUK PESAWAT NIRAWAK
Authors: Herman Ahmat , Hermawan Dadang , Fadhillah Arief Rizki
Published: February 2023

Perkembangan teknologi komposit saat ini banyak mengarah pada komposit alam/ Nature Composites (NACO). Komposit alam memiliki beberapa keunggulan, antara lain: dapat didaur ulang atau ramah lingkungan, memiliki sifat mekanik yang spesifik, ringan, memiliki sifat isolator panas dan suara, tahan korosi, serta dapat dijadikan sebagai penghambat listrik yang baik selain itu juga ramah lingkungan. Salah satu komposit alam yang saat ini sedang banyak dikembangkan dan diteliti yaitu komposit serat kulit waru. Komposit ini merupakan salah satu inovasi teknologi material maju yang memanfaatkan serat alam sebagai material reinforcing phase yang dikombinasikan dengan resin sintetis sebagai material matrix phase. Beberapa penelitian menunjukkan komposit serat kulit waru memiliki kekuatan tarik, impak dan bending yang cukup baik, Berdasarkan hasil penelitian komposit serat kulit pohon waru, maka dapat dilihat bahwa komposit ini memiliki potensi yang cukup baik dari segi sifat mekaniknya, sehingga dapat diimplementasikan pada pesawat nirawak dengan spesifikasi, antara lain: ringan, kaku, tidak mudah patah, tangguh serta tahan terhadap getaran dan korosi. Tujuan dari penelitian ini untuk mengetahui pengaruh metode proses manufaktur terhadap sifat mekanik kekuatan bending komposit serat kulit pohon waru sebagai material terbarukan untuk  pesawat nirawak. Dengan 3 macam metode manufaktur yaitu, Hand lay up, Press, dan Vacuum infusion resin, Selain dilakukan pengujian bending, dalam penelitian ini juga dilakukan foto mikro dan foto patahan untuk mengetahui bagaimana struktur dari bahan uji yang sudah diuji dengan metode Bending tersebut. Hasil pengujian bending komposit serat kulit pohon waru tersebut, kekuatan bending yang baik terdapat pada proses manufaktur Press. Berdasarkan hasil foto patahan dan foto mikro komposit serat kulit pohon waru menunjukan ikatan antara resin bisphenol LP-1Q pada metode manufaktur Vacuum infusion resin memiliki  ikatan paling baik dan resin dapat menutup dengan sempurna dan mengisi serat kulit pohon waru secara keseluruhan
Ritande kan stödja barns och elevers lärande i naturvetenskap
Authors: Höst Gunnar
Published: February 2023

Att rita kan hjälpa barn att lära sig naturvetenskap och om hur bilder används inom naturvetenskapen. Forskare har undersökt hur lärare genomför aktiviteter där barn och elever i yngre åldrar får rita i den naturvetenskapliga undervisningen. Resultaten visar hur upplägget påverkar vilket lärande som blir möjligt. Att lärarens syfte, normer och det material som finns tillgängligt samspelar har betydelse för barns och elevers lärande.
Chemical modification by peroxynitrite enhances TLR4 activation of the grass pollen allergen Phl p 5
Authors: Reinmuth-Selzle Kathrin , Bellinghausen Iris , Leifke Anna Lena , Backes Anna T. , Bothen Nadine , Ziegler Kira , Weller Michael G. , Saloga Joachim , Schuppan Detlef , Lucas Kurt , Pöschl Ulrich , Fröhlich-Nowoisky Janine
Published: February 2023

The chemical modification of aeroallergens by reactive oxygen and nitrogen species (ROS/RNS) may contribute to the growing prevalence of respiratory allergies in industrialized countries. Post-translational modifications can alter the immunological properties of proteins, but the underlying mechanisms and effects are not well understood. In this study, we investigate the Toll-like receptor 4 (TLR4) activation of the major birch and grass pollen allergens Bet v 1 and Phl p 5, and how the physiological oxidant peroxynitrite (ONOO–) changes the TLR4 activation through protein nitration and the formation of protein dimers and higher oligomers. Of the two allergens, Bet v 1 exhibited no TLR4 activation, but we found TLR4 activation of Phl p 5, which increased after modification with ONOO– and may play a role in the sensitization against this grass pollen allergen. We attribute the TLR4 activation mainly to the two-domain structure of Phl p 5 which may promote TLR4 dimerization and activation. The enhanced TLR4 signaling of the modified allergen indicates that the ONOO–-induced modifications affect relevant protein-receptor interactions. This may lead to increased sensitization to the grass pollen allergen and thus contribute to the increasing prevalence of allergies in the Anthropocene, the present era of globally pervasive anthropogenic influence on the environment.
Efficient hydroxylation of flavonoids by using whole-cell P450 sca-2 biocatalyst in Escherichia coli
Authors: Hu Baodong , Zhao Xinrui , Zhou Jingwen , Li Jianghua , Chen Jian , Du Guocheng
Published: February 2023

The hydroxylation is an important way to generate the functionalized derivatives of flavonoids. However, the efficient hydroxylation of flavonoids by bacterial P450 enzymes is rarely reported. Here, a bacterial P450 sca-2mut whole-cell biocatalyst with an outstanding 3′-hydroxylation activity for the efficient hydroxylation of a variety of flavonoids was first reported. The whole-cell activity of sca-2mut was enhanced using a novel combination of flavodoxin Fld and flavodoxin reductase Fpr from Escherichia coli. In addition, the double mutant of sca-2mut (R88A/S96A) exhibited an improved hydroxylation performance for flavonoids through the enzymatic engineering. Moreover, the whole-cell activity of sca-2mut (R88A/S96A) was further enhanced by the optimization of whole-cell biocatalytic conditions. Finally, eriodictyol, dihydroquercetin, luteolin, and 7,3′,4′-trihydroxyisoflavone, as examples of flavanone, flavanonol, flavone, and isoflavone, were produced by whole-cell biocatalysis using naringenin, dihydrokaempferol, apigenin, and daidzein as the substrates, with the conversion yield of 77%, 66%, 32%, and 75%, respectively. The strategy used in this study provided an effective method for the further hydroxylation of other high value-added compounds.
Advanced glycation end products regulate the receptor of AGEs epigenetically
Authors: Wu Xiaoqing , Shi Xuanren , Chen Xiaoyong , Yin Zhanhai
Published: February 2023

Advanced glycation end-products (AGEs) can boost their receptor of AGE (RAGE) expression through the downstream signaling pathway to facilitate AGE–RAGE interaction. In this regulation process, the primary signaling pathways are NF-κB and STAT3. However, the inhibition of these transcription factors cannot completely block the upregulation of RAGE, which indicates AGEs may also impact RAGE expression via other pathways. In this study, we revealed that AGEs can exhibit epigenetic impacts on RAGE expression. Here, we used carboxymethyl-lysine (CML) and carboxyethyl-lysine (CEL) to treat liver cells and discovered that AGEs can promote the demethylation of the RAGE promoter region. To verify this epigenetic modification, we employed dCAS9-DNMT3a with sgRNA to specifically modify the RAGE promoter region against the effect of carboxymethyl-lysine and carboxyethyl-lysine. The elevated RAGE expressions were partially repressed after AGE-induced hypomethylation statuses were reversed. Additionally, TET1 were also upregulated in AGE-treated cells, indicating AGEs may epigenetically modulate RAGE through the elevating TET1 level.
Sensitive detection of noradrenaline in human whole blood based on Au nanoparticles embedded vertically-ordered silica nanochannels modified pre-activated glassy carbon electrodes
Authors: Huang Liyuan , Su Ruobing , Xi Fengna
Published: February 2023

Sensitive determination of noradrenaline (NE), the pain-related neurotransmitters and hormone, in complex whole blood is of great significance. In this work, an electrochemical sensor was simply constructed on the pre-activated glassy carbon electrode (p-GCE) modified with vertically-ordered silica nanochannels thin film bearing amine groups (NH2-VMSF) and in-situ deposited Au nanoparticles (AuNPs). The simple and green electrochemical polarization was employed to pre-activate GCE to realize the stable binding of NH2-VMSF on the surface of electrode without the use of any adhesive layer. NH2-VMSF was conveniently and rapidly grown on p-GCE by electrochemically assisted self-assembly (EASA). With amine group as the anchor sites, AuNPs were in-situ electrochemically deposited on the nanochannels to improve the electrochemical signals of NE. Owing to signal amplification from gold nanoparticles, the fabricated AuNPs@NH2-VMSF/p-GCE sensor can achieve electrochemical detection of NE ranged from 50 nM to 2 μM and from 2 μM to 50 μM with a low limit of detection (LOD) of 10 nM. The constructed sensor exhibited high selectivity and can be easily regenerated and reused. Owing to the anti-fouling ability of nanochannel array, direct electroanalysis of NE in human whole blood was also realized.
Lowering the computational barrier: Partially Bayesian neural networks for transparency in medical imaging AI
Authors: Prabhudesai Snehal , Hauth Jeremiah , Guo Dingkun , Rao Arvind , Banovic Nikola , Huan Xun
Published: February 2023

Deep Neural Networks (DNNs) can provide clinicians with fast and accurate predictions that are highly valuable for high-stakes medical decision-making, such as in brain tumor segmentation and treatment planning. However, these models largely lack transparency about the uncertainty in their predictions, potentially giving clinicians a false sense of reliability that may lead to grave consequences in patient care. Growing calls for Transparent and Responsible AI have promoted Uncertainty Quantification (UQ) to capture and communicate uncertainty in a systematic and principled manner. However, traditional Bayesian UQ methods remain prohibitively costly for large, million-dimensional tumor segmentation DNNs such as the U-Net. In this work, we discuss a computationally-efficient UQ approach via the partially Bayesian neural networks (pBNN). In pBNN, only a single layer, strategically selected based on gradient-based sensitivity analysis, is targeted for Bayesian inference. We illustrate the effectiveness of pBNN in capturing the full uncertainty for a 7.8-million parameter U-Net. We also demonstrate how practitioners and model developers can use the pBNN's predictions to better understand the model's capabilities and behavior.
Clinical and electrocardiographic outcomes evaluated by telemedicine of outpatients with clinical suspicion of COVID-19 treated with chloroquine compounds in Brazil†
Authors: Nascimento Bruno R. , Paixão Gabriela M. M. , Tonaco Luìs Antônio B. , Alves Ana Carolina D. , Peixoto David C. , Ribeiro Leonardo B. , Mendes Mayara S. , Gomes Paulo R. , Pires Magda C. , Ribeiro Antonio Luiz P.
Published: February 2023

Aims

To evaluate clinical and electrocardiographic outcomes of patients with COVID-19, comparing those using chloroquine compounds (chloroquine) to individuals without specific treatment.

Methods

Outpatients with suspected COVID-19 in Brazil who had at least one tele-electrocardiography (ECG) recorded in a telehealth system were enrolled in two arms (Group 1: chloroquine and Group 2: without specific treatment) and one registry (Group 3: other treatments). Outcomes were assessed through follow-up calls (phone contact, days 3 and 14) and linkage to national mortality and hospitalization databases. The primary outcome was composed of: hospitalization, intensive care admission, mechanical ventilation, and all-cause death, and the ECG outcome was the occurrence of major abnormalities by the Minnesota code. Significant variables in univariable logistic regression were included in 4 models: 1-unadjusted; 2-adjusted for age and sex; 3-model 2 + cardiovascular risk factors and 4-model 3 + COVID-19 symptoms.

Results

In 303 days, 712 (10.2%) patients were allocated in group 1, 3,623 (52.1%) in group 2 and 2,622 (37.7%) in group 3; 1,969 had successful phone follow-up (G1: 260, G2: 871, and G3: 838). A late follow-up ECG was obtained for 917 (27.2%) patients [group 1: 81 (11.4%), group 2: 512 (14.1%), group 3: 334 (12.7%)]. In adjusted models, chloroquine was independently associated with greater chance of the composite clinical outcome: phone contact (model 4): OR = 3.24 (95% CI 2.31–4.54), p < 0.001. Chloroquine was also independently associated with higher mortality, assessed by phone + administrative data (model 3): OR = 1.67 (95% CI 1.20–2.28). However, chloroquine did not associate with the occurrence of major ECG abnormalities [model 3; OR = 0.80 (95% CI 0.63–1.02, p = 0.07)]. Abstracts with partial results of this work was accepted in the American Heart Association Scientific Sessions, November 2022, in Chicago, IL, USA.

Conclusion

Chloroquine was associated with a higher risk of poor outcomes in patients suspected to have COVID-19 when compared to those who received standard care. Follow-up ECGs were obtained in only 13.2% of patients and did not show any significant differences in major abnormalities amongst the three groups. In the absence of early ECG changes, other side effects, late arrhythmias or deferral of care may be hypothesized to explain the worse outcomes.
Causal relationship between atrial fibrillation and leukocyte telomere length: A two sample, bidirectional Mendelian randomization study
Authors: Sha Zimo , Hou Tianzhichao , Zhou Taojie , Dai Yang , Bao Yangyang , Jin Qi , Ye Jing , Lu Yiming , Wu Liqun
Published: February 2023

Background

Atrial fibrillation (AF) is an age-related disease, while telomeres play a central role in aging. But the relationship between AF and telomere length (LTL) is still controversial. This study aims to examine the potential causal association between AF and LTL by using Mendelian randomization (MR).

Methods

Bidirectional two-sample MR, expression and protein quantitative trait loci (eQTL and pQTL)-based MR were performed using genetic variants from United Kingdom Biobank, FinnGen, and a meta-analysis study, which comprised nearly 1 million participants in the Atrial Fibrillation Study and 470,000 participants in the Telomere Length Study. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, complementary analysis approaches and sensitivity analysis were applied.

Results

The forward MR revealed a significant causal estimate for the genetically predicted AF with LTL shortening [IVW: odds ratio (OR) = 0.989, p = 0.007; eQTL-IVW: OR = 0.988, p = 0.005; pQTL-IVW: OR = 0.975, p < 0.005]. But in the reverse MR analysis, genetically predicted LTL has no significant correlation with AF (IVW: OR = 0.995, p = 0.916; eQTL-IVW: OR = 0.999, p = 0.995; pQTL-IVW: OR = 1.055, p = 0.570). The FinnGen replication data yielded similar findings. Sensitivity analysis ensured the stability of the results.

Conclusion

The presence of AF leads to LTL shortening rather than the other way around. Aggressive intervention for AF may delay the telomere attrition.
Effects of norepinephrine on plaque hypoxia in atherosclerotic rabbits
Authors: Wang Jia-Yu , Liu Kun , Wang Yu-Bo , Deng You-Bin , Sun Jie
Published: February 2023

Background

Hypoxia plays a vital role throughout the whole process of atherosclerotic vulnerable plaque formation, which may be induced by a reduced oxygen supply. The vasa vasorum can be affected by norepinephrine (NE) and cause a reduced oxygen supply, ultimately leading to plaque hypoxia. This study aimed to investigate the effects of norepinephrine, which can increase the tension of the vasa vasorum, on plaque hypoxia, evaluated by contrast-enhanced ultrasound imaging.

Methods

Atherosclerosis (AS) was induced in New Zealand white rabbits by a combination of a cholesterol-rich diet and aortic balloon dilation. After the atherosclerotic model was well established, NE was intravenously administered three times per day for 2 weeks. Contrast-enhanced ultrasound (CEUS) and immunohistochemistry staining were performed to evaluate the expression of hypoxia-inducible factor alpha (HIF-α) and vascular endothelial growth factor (VEGF) in atherosclerotic plaques.

Results

The plaque blood flow decreased after long-term norepinephrine administration. The expression of HIF-α and VEGF in atherosclerotic plaques concentrated in the outer medial layers increased, which indicated that NE might cause plaque hypoxia by contraction of the vasa vasorum.

Conclusion

Apparent hypoxia of atherosclerotic plaques after long-term NE administration was mainly caused by decreased plaque blood flow due to the contraction of the vasa vasorum and high blood pressure.
Roles of biomaterials in modulating the innate immune response in ocular therapy
Authors: Rafiei Mehrnoosh , Chung Jin Teng , Chau Ying
Published: February 2023

The eye is a hard-to-treat organ due to its poor regenerative capacity and susceptibility to inflammation; as a result, it has an immune privilege mechanism. In the case of ocular degenerative disorders, chronic and uncontrolled ocular inflammations can overcome this immune response to initiate and exacerbate tissue degeneration, ultimately leading to blindness. Recent landmark discoveries on the key roles of the ocular innate immune system in regulating acute and chronic inflammations as well as tissue fibrosis and homeostasis have shed light on the value of novel treatment interventions in modulating ocular immune responses at the molecular, cellular, and tissue levels. This strategy can be attained by using therapeutics to target resident phagocytes and antigen-presenting cells, namely, microglia and dendritic cells, as well as infiltrating neutrophils and macrophages. Biomaterials are foreign materials to the host and interact with innate immune cells. To leverage such intrinsic immunomodulatory properties, biomaterials such as implants, injectable depots, and nano/micro particles can be used alone as a treatment or with different payloads as carriers in immune-related ocular disorders. This article discusses how physicochemical properties such as biodegradability, size, shape, and charge affect biomaterials’ interaction with the eye’s innate immune system, therefore influencing outcomes towards pro- or anti-inflammatory responses. Knowledge about the eye’s immunological response is required for designing tolerogenic biomaterials including intraocular lenses, cellular scaffolds, therapeutic molecule depots, or carriers of gene therapies. The discussion presented in this review will shed light on the potential use of biomaterials to direct immune responses toward favorable treatment outcomes.
Late quaternary glacial history of the La Ji Shan: Implications for the LGM on the northeastern Tibetan Plateau
Authors: Cui Hang , Mou Haizhen , Jing Tao
Published: February 2023

Previous studies have suggested that the Bayan Har Shan and Lake Donggi Cona areas on the northeastern Tibetan Plateau were not glaciated during the Last Glacial Maximum (LGM; MIS2). However, the La Ji Shan, which is at a lower elevation than the Bayan Har Shan and Lake Donggi Cona areas but has similar annual precipitation, experienced a glacial event during the LGM. To investigate this discrepancy, factors controlling glacier development in the Bayan Har Shan, Lake Donggi Cona, and La Ji Shan were examined. First, a coupled mass balance and ice flow model was used to reconstruct the LGM climatic conditions in the La Ji Shan, and then the factors controlling glacier development were assessed based on the modeled LGM climatic conditions. With LGM precipitation being 70%–80% of present-day values, the modeled LGM temperature decrease was 3.9°C–4.3°C, which is consistent with other reconstructed LGM climatic conditions on the Tibetan Plateau. A comparison of the topography and climate of the La Ji Shan, Bayan Har Shan and Lake Donggi Cona areas indicates that a lower LGM summit height above the LGM equilibrium line altitude (ELA) and LGM annual precipitation at the LGM ELA are the main reason for the lack of LGM glacial expansion in the Bayan Har Shan and Lake Donggi Cona areas.
Nuclear magnetic resonance response characteristics and quantitative evaluation method of fluid saturation of lacustrine shale oil
Authors: Fan Ruiqi , Liao Guangzhi , Mao Rui , Luo Xingping , Hou Lianhua , Zhang Hao , Tian Hua , Wang Gang , Qin Zhijun , Xiao Lizhi
Published: February 2023

The quantitative evaluation of fluid saturation is important for formation evaluation of shale oil. However, there is currently no effective method to identify the fluid occurrence state and quantitative evaluate the fluid saturation of lacustrine shale oil because of the complexity of diagenetic minerals and pore types. In this paper, a method is proposed for the quantitative evaluation of fluid saturation based on nuclear magnetic resonance (NMR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements for shale samples of Fengcheng Formation, Mahu sag in Junggar Basin, China. These studies revealed that the shale oil rocks mainly contain quartz, feldspar, dolomite, calcite and clay minerals, both develop organic and inorganic pores. The fluids mainly occur in the form of bitumen, clay bound water, bound water, bound oil and movable oil in this study area. Based on the findings from these experiments, a mixed rock index (MI) and mud index (SI) were proposed to divide the shale oil formations into three types, including sand shale, dolomitic shale and mudstone. A T1−T2 2D NMR fluid occurrence state characterization map was established to identify the different fluids by the MI, SI and NMR characteristics. Furthermore, a method was proposed to quantitatively calculate the coefficient distribution of bound and movable fluids for shale oil in different formations. Finally, the proposed method was successfully applied into the lacustrine shale oil in the Fengcheng Formation to identify fluid occurrence state and evaluate fluid saturation quantitatively.
The association between hemoglobin A1c and all-cause mortality in the ICU: A cross-section study based on MIMIC-IV 2.0
Authors: Liu Chunxia , Pang Ke , Tong Jianbin , Ouyang Wen , Li Liang , Tang Yongzhong
Published: February 2023

Background

Hyperglycemia has been reported to be associated with the outcomes of patients in the intensive care unit (ICU). However, the relationship between hemoglobin A1c (HbA1c) and long-term or short-term mortality in the ICU is still unknown. This study used the Medical Information Mart for Intensive Care (MIMIC)-IV database to investigate the relationship between HbA1c and long-term or short-term mortality among ICU patients without a diabetes diagnosis.

Methods

A total of 3,154 critically ill patients without a diabetes diagnosis who had HbA1c measurements were extracted and analyzed from the MIMIC-IV. The primary outcome was 1-year mortality, while the secondary outcomes were 30-day mortality and 90-day mortality after ICU discharge. HbA1c levels were classified into four levels according to three HbA1c values (5.0%, 5.7%, and 6.5%). The Cox regression model was used to investigate the relationship between the highest HbA1c measurement and mortality. Finally, this correlation was validated using the XGBoost machine learning model and Cox regression after propensity score matching (PSM).

Results

The study eventually included 3,154 critically ill patients without diabetes who had HbA1c measurements in the database. HbA1c levels of below 5.0% or above 6.5% were significantly associated with 1-year mortality after adjusting for covariates in Cox regression (HR: 1.37; 95% CI: 1.02–1.84 or HR: 1.62; 95% CI: 1.20–2.18). In addition, HbA1c 6.5% was linked to 30-day mortality (HR: 1.81; 95% CI: 1.21–2.71) and 90-day mortality (HR: 1.62; 95% CI: 1.14–2.29). The restricted cubic spline demonstrated a U-shaped relationship between HbA1c levels and 1-year mortality. The AUCs of the training and testing datasets in the XGBoost model were 0.928 and 0.826, respectively, while the SHAP plot revealed that HbA1c was somewhat important for the 1-year mortality. Higher HbA1c levels in Cox regression were still significantly associated with 1-year mortality after PSM for other factors,

Conclusions

The 1-year mortality, 30-day mortality, and 90-day mortality rates for critically ill patients after discharge from ICU are significantly associated with HbA1c. HbA1c < 5.0% and ≥6.5% would increase 30-day, 90-day, and 1-year mortality, while levels between 5.0% and 6.5% of HbA1c did not significantly affect these outcomes.
Enhancing the metabolic benefits of exercise: Is timing the key?
Authors: Bennett Samuel , Sato Shogo
Published: February 2023

Physical activity represents a potent, non-pharmacological intervention delaying the onset of over 40 chronic metabolic and cardiovascular diseases, including type 2 diabetes, coronary heart disease, and reducing all-cause mortality. Acute exercise improves glucose homeostasis, with regular participation in physical activity promoting long-term improvements in insulin sensitivity spanning healthy and disease population groups. At the skeletal muscle level, exercise promotes significant cellular reprogramming of metabolic pathways through the activation of mechano- and metabolic sensors, which coordinate downstream activation of transcription factors, augmenting target gene transcription associated with substrate metabolism and mitochondrial biogenesis. It is well established that frequency, intensity, duration, and modality of exercise play a critical role in the type and magnitude of adaptation; albeit, exercise is increasingly considered a vital lifestyle factor with a critical role in the entrainment of the biological clock. Recent research efforts revealed the time-of-day-dependent impact of exercise on metabolism, adaptation, performance, and subsequent health outcomes. The synchrony between external environmental and behavioural cues with internal molecular circadian clock activity is a crucial regulator of circadian homeostasis in physiology and metabolism, defining distinct metabolic and physiological responses to exercise unique to the time of day. Optimising exercise outcomes following when to exercise would be essential to establishing personalised exercise medicine depending on exercise objectives linked to disease states. We aim to provide an overview of the bimodal impact of exercise timing, i.e. the role of exercise as a time-giver (zeitgeber) to improve circadian clock alignment and the underpinning clock control of metabolism and the temporal impact of exercise timing on the metabolic and functional outcomes associated with exercise. We will propose research opportunities that may further our understanding of the metabolic rewiring induced by specific exercise timing.
Habitat quality evolution characteristics and multi-scenario prediction in Shenzhen based on PLUS and InVEST models
Authors: Wang Jiangbo , Wu Yufan , Gou Aiping
Published: February 2023

Based on the PLUS model, research proposed a method to adjust the probability of land use transition to reduce the calculation error of the number of pixels. The refined algorithm is applied to simulate Shenzhen land use situation in 2030 under a progressive scenario using three periods of Shenzhen land use data in 2000, 2010 and 2020. Then, InVEST model was employed to evaluate the distribution situation and future trends of habitat quality in Shenzhen during the study period. Following are the conclusions: 1) The construction land in Shenzhen expanded rapidly and the ecological land gradually shrank during the research period. The proportion of artificial surface area increased by about 45.4% (304.98 km2) within 20 years. 2) By simulating the land use situation of Shenzhen in 2030, the results revealed that the land use change of Shenzhen in the future is mainly concentrated in the central and western regions. 3) The overall average habitat quality of Shenzhen was at a medium level, but the habitat quality showed a continuous degradation trend in each year throughout the study period. Spatially, the habitat quality degradation are mainly concentrated in Shenzhen’s central and western region. 4) Under the natural development scenario, Shenzhen’s habitat quality would experience a sharp decline by 2030. The habitat quality of the conservation area is guaranteed to a certain degree, but the artificial surface expansion outside the area will still affect the habitat quality in the boundary constraint scenario; Only in scenario of ecological priority, the habitat quality of Shenzhen has been restored and improved to a large extent. 5) In order to slow down the degradation trend and improve the regional ecological environment. It is necessary not only to strictly implement various protection boundaries delineated in the context of Territorial Spatial Planning, but also to implement the policy of “Clear waters and green mountains are as good as mountains of gold and silver” in the process of urban development. Government should reasonably control the scale of cities, optimize the ecological compensation mechanism, and implement ecological restoration policies such as returning farmland to forests and returning farmland to grassland.
Modeling principles, criteria and indicators to assess water sector governance for climate compatibility and sustainability
Authors: Iqbal Kanwar Muhammad Javed , Khan Muhammad Irfan , Mikhaylov Alexey , Shah Ashfaq Ahmad , Yadykin Vladimir , Leal Filho Walter , Tariq Muhammad Atiq Ur Rehman , Ullah Wahid
Published: February 2023

The United Nations SDGs Report 2020 revealed that climatic variability victimized masses across the globe in 2018 and the global average temperature would rise to 3.2°C during this century. The GHG emission reduction targets for 2030 were prioritized under the Paris Climate Agreement (PCA) of 2015 to keep the rise in global temperature below 1.5°C. Here, parallel action for climate adaptation is on top of it. However, targets for both adaptation and mitigation are lagging. Climatic variations will continue more likely with similar trends thus influencing the development needs vis-à-vis environmental security and sustainability of resources. It entails climate compatibility, particularly for the water security agenda for SDG-13 and Paris Climate Agreement (PCA), which requires an inclusive governance regime and ownership for national and sub-national scenarios. In this context, this paper aimed to assess existing water sector governance for climate compatible development (CCD) by taking the case of Pakistan which is among the top 10 countries vulnerable to climate change. Considering the limitations of available methodologies due to the involvement of various aspects and concepts of governance, an integrated multivariate mix-method model was formulated by combining rules and rights-oriented approaches. This MCDA-based model integrates six novel climate governance principles against six basic components of the basic institutional governance framework; Simple Multi-attribute Rating Technique (SMART) with a set of sectoral indicators of 09 criteria of climate compatible development (CCD). It proved well for this water sector case study with cross-sectional data from 340 key informant interviews (KIIs) and 17 focus group discussions (FGDs) in Pakistan, validated statistically. It can be used for periodic sectoral governance assessments for CCD.
The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment
Authors: Keerthana Chenicheri Kizhakkeveettil , Rayginia Tennyson Prakash , Shifana Sadiq Chembothumparambil , Anto Nikhil Ponnoor , Kalimuthu Kalishwaralal , Isakov Noah , Anto Ruby John
Published: February 2023

Adenosine monophosphate-activated protein kinase (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. AMPK contributes to diverse metabolic and physiological effects besides its fundamental role in glucose and lipid metabolism. Aberrancy in AMPK signaling is one of the determining factors which lead to the development of chronic diseases such as obesity, inflammation, diabetes, and cancer. The activation of AMPK and its downstream signaling cascades orchestrate dynamic changes in the tumor cellular bioenergetics. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways. In addition, AMPK plays a central role in potentiating the phenotypic and functional reprogramming of various classes of immune cells which reside in the tumor microenvironment (TME). Furthermore, AMPK-mediated inflammatory responses facilitate the recruitment of certain types of immune cells to the TME, which impedes the development, progression, and metastasis of cancer. Thus, AMPK appears to play an important role in the regulation of anti-tumor immune response by regulating the metabolic plasticity of various immune cells. AMPK effectuates the metabolic modulation of anti-tumor immunity via nutrient regulation in the TME and by virtue of its molecular crosstalk with major immune checkpoints. Several studies including that from our lab emphasize on the role of AMPK in regulating the anticancer effects of several phytochemicals, which are potential anticancer drug candidates. The scope of this review encompasses the significance of the AMPK signaling in cancer metabolism and its influence on the key drivers of immune responses within the TME, with a special emphasis on the potential use of phytochemicals to target AMPK and combat cancer by modulating the tumor metabolism.
Trophic ecology of midwater zooplankton along a productivity gradient in the Southeast Pacific
Authors: Fernández-Urruzola Igor , Bode Antonio , Loick-Wilde Natalie , Schneider Wolfgang , Lindsay Dhugal , Escribano Ruben
Published: February 2023

The environmental regulation of planktonic food web structure is a key determinant for the efficiency of energy transfer through trophic levels, with direct implications for the amount of energy that is available to top-consumers and deep-sea communities. Yet, the complex trophic interplay between the different components of plankton communities under contrasting environmental conditions remains unresolved. Here, we present a comprehensive field study based on compound-specific isotope analysis of amino acids that aims to explore depth-resolved changes in the trophic strategies of various size-classes of mesozooplankton from distinct habitats across the Southeast Pacific. According to the δ15N values of the so-called source amino acids such as phenylalanine, we first identified a clear shift in nitrogen sources for biological production, from nitrate in the productive upwelling waters of the Humboldt Current System to increased inputs of diazotroph-N within the ultra-oligotrophic South Pacific gyre. These shifts in the productivity and in the source of N at the base of the food web were not accompanied by significant changes in the trophic position (TP) of mesozooplankton, which were mainly omnivores (TP = 2.8 ± 0.3, n = 65) in all ecoregions. However, although the planktonic food web length remained relatively unaltered along the productivity gradient, the microbial contribution to mid-trophic level consumers appeared to be more important at relatively high productivities, likely due to more intense remineralization processes in a late successional stage of the upwelling throughout the coastal-transition zone. Altogether, this research work will contribute to a better understanding of the food web functioning in one of the least explored marine regions of the world’s oceans.
Deep learning methods for drug response prediction in cancer: Predominant and emerging trends
Authors: Partin Alexander , Brettin Thomas S. , Zhu Yitan , Narykov Oleksandr , Clyde Austin , Overbeek Jamie , Stevens Rick L.
Published: February 2023

Cancer claims millions of lives yearly worldwide. While many therapies have been made available in recent years, by in large cancer remains unsolved. Exploiting computational predictive models to study and treat cancer holds great promise in improving drug development and personalized design of treatment plans, ultimately suppressing tumors, alleviating suffering, and prolonging lives of patients. A wave of recent papers demonstrates promising results in predicting cancer response to drug treatments while utilizing deep learning methods. These papers investigate diverse data representations, neural network architectures, learning methodologies, and evaluations schemes. However, deciphering promising predominant and emerging trends is difficult due to the variety of explored methods and lack of standardized framework for comparing drug response prediction models. To obtain a comprehensive landscape of deep learning methods, we conducted an extensive search and analysis of deep learning models that predict the response to single drug treatments. A total of 61 deep learning-based models have been curated, and summary plots were generated. Based on the analysis, observable patterns and prevalence of methods have been revealed. This review allows to better understand the current state of the field and identify major challenges and promising solution paths.
Case report: Unusual viral evolutions following antiviral therapies in a patient with concurrent hepatitis B virus and hepatitis C virus infection
Authors: Su Yi-Tse , Chang Ming-Ling , Liaw Yun-Fan
Published: February 2023

Concurrent hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is not uncommon as the two viruses shared the similar transmission routes. HCV is usually the dominant virus to suppress HBV, and HBV reactivation may occur during or after the course of anti-HCV treatment. By contrast, HCV reactivation after anti-HBV therapy in the concurrent HBV- and HCV-infected patients was rarely noted. Here, we reported the unusual viral evolutions of a patient with concurrent HBV and HCV infection, in whom HCV reactivation occurred during the entecavir therapy to rescue the severe HBV flare, while the following anti-HCV combination therapy with pegylated interferon and ribavirin elicited the second HBV flare despite sustained virological response to HCV infection, and further entecavir therapy healed the flare.
Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19
Authors: Bruzzone Chiara , Conde Ricardo , Embade Nieves , Mato José M. , Millet Oscar
Published: February 2023

COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.
Effects of (S)-ketamine on depression-like behaviors in a chronic variable stress model: a role of brain lipidome
Authors: Zhou Cuihong , Zhao Xinxin , Ma Xinxu , Ma Hongzhe , Li Rui , Hu Guangtao , Wang Huaning , Peng Zhengwu , Cai Min
Published: February 2023

Introduction: Compelling evidence indicates that a single sub-anesthetic dose of (S)-ketamine elicits rapid and robust antidepressant effects. However, the underlying mechanisms behind the antidepressant effects of (S)-ketamine remain unclear.

Methods: Here, using a chronic variable stress (CVS) model in mice, we analyzed changes inthe lipid compositions of the hippocampus and prefrontal cortex (PFC) with a mass spectrometry-based lipidomic approach.

Results: Similar to previous research outcomes, the current study also showed that (S)-ketamine reversed depressive-like behaviors in mice produced by CVS procedures. Moreover, CVS induced changes inthe lipid compositions of the hippocampus and PFC, notably in the contents of sphingolipids, glycerolipids, and fatty acyls. With the administration of (S)-ketamine, CVS-induced lipid disturbances were partially normalized, particularly in the hippocampus.

Conclusion: Altogether, our results indicated that (S)-ketamine could rescue CVS-induced depressive-like behaviors in mice through region-specific modulation of the brain lipidome, contributing to the understanding of (S)-ketamine’s antidepressant effects.
Motor and cognitive deficits limit the ability to flexibly modulate spatiotemporal gait features in older adults with mild cognitive impairment
Authors: Rosenberg Michael C. , Slusarenko Alexandra , Cao Ke , Lucas McKay J. , Emmery Laura , Kesar Trisha M. , Hackney Madeleine E.
Published: February 2023

Introduction:Dance-based therapies are an emerging form of movement therapy aiming to improve motor and cognitive function in older adults with mild cognitive impairments (MCIs). Despite the promising effects of dance-based therapies on function, it remains unclear how age-related declines in motor and cognitive function affect movement capacity and influence which movements and rhythms maximize dance therapy efficacy. Here, we evaluated the effects of age and MCI on the ability to accurately modulate spatial (i.e., joint kinematics), temporal (i.e., step timing), and spatiotemporal features of gait to achieve spatial and temporal targets during walking.

Methods:We developed novel rhythmic movement sequences—nine spatial, nine temporal, and four spatiotemporal—that deviated from typical spatial and temporal features of walking. Healthy young adults (HYA), healthy older adults (HOA), and adults with MCI were trained on each gait modification before performing the modification overground, with kinematic data recorded using wearable sensors.

Results:HOA performed spatial (p= 0.010) and spatiotemporal (p= 0.048) gait modifications less accurately than HYA. Individuals with MCI performed spatiotemporal gait modifications less accurately than HOA (p= 0.017). Spatial modifications to the swing phase of gait (p= 0.006, Cohen’sd= −1.3), and four- and six-stepDuplerhythms during temporal modifications (p≤ 0.030, Cohen’sd≤ 0.9) elicited the largest differences in gait performance in HYA vs. HOA and HOA vs. MCI, respectively.

Discussion:These findings suggest that age-related declines in strength and balance reduce the ability to accurately modulate spatial gait features, while declines in working memory in individuals with MCI may reduce the ability to perform longer temporal gait modification sequences. Differences in rhythmic movement sequence performance highlight motor and cognitive factors potentially underlying deficits in gait modulation capacity, which may guide therapy personalization and provide more sensitive indices to track intervention efficacy.