bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of spectroscopic process analytical technology for rapid quality evaluation during preparation of CHO cell culture media
Authors: Ou Jianfa , Cui Wanyue , Zhao Yuxiang , Tang Yawen , Williams Alexander , Wasalathanthri Dhanuka , Xu Jianlin , Lee Jongchan , Borys Michael C. , Khetan Anurag
Published: May 2024

Media preparation parameters contribute significantly to media quality, cell culture performance, productivity, and product quality. Establishing proper media preparation procedures is critical for ensuring a robust CHO cell culture process. Process analytical technology (PAT) enables unique ways to quantify assessments and improve media quality. Here, cell culture media were prepared under a wide range of temperatures (40–80°C) and pH (7.6–10.0). Media quality profiles were compared using three real‐time PATs: Fourier‐transform infrared (FTIR) spectroscopy, Raman spectroscopy, and excitation‐emission matrix (EEM) spectroscopy. FTIR and Raman spectroscopies identified shifts in media quality under high preparation temperature (80°C) and at differing preparation pH which negatively impacted monoclonal antibody (mAb) production. In fed‐batch processes for production of three different mAbs, viable cell density (VCD) and cell viability were mostly unaffected under all media preparation temperatures, while titer and cell specific productivity of mAb decreased when cultured in basal and feed media prepared at 80°C. High feed preparation pH alone was tolerated but cell growth and productivity profiles deviated from the control condition. Further, charge variants (main, acidic, basic species) and glycosylation (G0F, afucosylation, and high mannose) were examined. Statistically significant differences were observed for one or more of these quality attributes with any shifts in media preparation. In this study, we demonstrated strong associations between media preparation conditions and cell growth, productivity, and product quality. The rapid evaluation of media by PAT implementation enabled more comprehensive understanding of different parameters on media quality and consequential effects on CHO cell culture.
Developing tardigrade‐inspired material: Track membranes functionalized with Dsup protein for cell‐free DNA isolation
Authors: Zarubin Mikhail , Andreev Evgeny , Kravchenko Elena , Pinaeva Uliana , Nechaev Alexander , Apel Pavel
Published: May 2024

When developing functionalized biomaterials, the proteins from extremophilic organisms, in particular unique tardigrade disordered proteins, are of great value. The damage suppressor protein (Dsup), initially discovered in the tardigrade Ramazzottius varieornatus and found to be an efficient DNA protector under oxidative and irradiation stress, has been hypothesized to possess a good potential for the development of the material, which can isolate cell‐free DNA. With this in mind, DNA‐nonadsorbing polyethylene terephthalate track membranes have been functionalized using the Dsup protein via covalent bonding with glutaraldehyde. The filtration experiments have verified the ability of track membranes with the immobilized Dsup protein to adsorb cell‐free DNA, with an accumulation capacity of 70 ± 19 mg m−2. The resulting track membrane‐based biomaterial might be used in various devices for filtration and separation of cell‐free DNA molecules from biological solutions and environmental samples, and also for their accumulation, storage, and further manipulation.
Construction and validation of “WCH‐nomogram” for predicting the prognosis after resection of colorectal liver metastases
Authors: Jiang Chuang , Liu Weixing , Jin Zechuan , Lan Ling , Xu Lin , Du Ao , Peng Song , Zeng Yong , Wang Haichuan , Liao Mingheng , Zhou Jin
Published: May 2024

Background

The prognostic predictive tool for patients with colorectal liver metastasis (CRLM) is limited and the criteria for administering preoperative neoadjuvant chemotherapy in CRLM patients remain controversial.

Methods

This study enrolled 532 CRLM patients at West China Hospital (WCH) from January 2009 to December 2019. Prognostic factors were identified from the training cohort to construct a WCH‐nomogram and evaluating accuracy in the validation cohort. Receiver operating characteristic (ROC) curve analysis was used to compare the prediction accuracy with other existing prediction tools.

Results

From the analysis of the training cohort, four independent prognostic risk factors, namely tumor marker score, KRAS mutation, primary lymph node metastasis, and tumor burden score were identified on which a WCH‐nomogram was constructed. The C‐index of the two cohorts were 0.674 (95% CI: 0.634–0.713) and 0.655 (95% CI: 0.586–0.723), respectively, which was better than the previously reported predication scores (CRS, m‐CS and GAME score). ROC curves showed AUCs for predicting 1‐, 3‐, and 5‐year overall survival (OS) of 0.758, 0.709, and 0.717 in the training cohort, and 0.860, 0.669, and 0.692 in the validation cohort, respectively. A cutoff value of 114.5 points was obtained for the WCH‐nomogram total score based on the maximum Youden index of the ROC curve of 5‐year OS. Risk stratification showed significantly better prognosis in the low‐risk group, however, the high‐risk group was more likely to benefit from neoadjuvant chemotherapy.

Conclusions

The WCH‐nomogram demonstrates superior prognostic stratification compared to prior scoring systems, effectively identifying CRLM patients who may benefit the most from neoadjuvant chemotherapy.
A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population
Authors: Zou Yuanlin , Zhu Jicun , Song Caijuan , Li Tiandong , Wang Keyan , Shi Jianxiang , Ye Hua , Wang Peng
Published: May 2024

Aims

This study aimed to investigate environmental factors and genetic variant loci associated with hepatocellular carcinoma (HCC) in Chinese population and construct a weighted genetic risk score (wGRS) and polygenic risk score (PRS).

Methods

A case–control study was applied to confirm the single nucleotide polymorphisms (SNPs) and environmental variables linked to HCC in the Chinese population, which had been screened by meta‐analyses. wGRS and PRS were built in training sets and validation sets. Area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were applied to evaluate the performance of the models.

Results

A total of 13 SNPs were included in both risk prediction models. Compared with wGRS, PRS had better accuracy and discrimination ability in predicting HCC risk. The AUC for PRS in combination with drinking history, cirrhosis, HBV infection, and family history of HCC in training sets and validation sets (AUC: 0.86, 95% CI: 0.84–0.89; AUC: 0.85, 95% CI: 0.81–0.89) increased at least 20% than the AUC for PRS alone (AUC: 0.63, 95% CI: 0.60–0.67; AUC: 0.65, 95% CI: 0.60–0.71).

Conclusions

A novel model combining PRS with alcohol history, HBV infection, cirrhosis, and family history of HCC could be applied as an effective tool for risk prediction of HCC, which could discriminate at‐risk individuals for precise prevention.
A nomogram to predict the risk of venous thromboembolism in patients with colon cancer in China
Authors: Yang Yuanyuan , Zhan Jiayi , Li Xiaosheng , Hua Jun , Lei Haike , Chen Xiaoliang
Published: May 2024

Objective

To create a nomogram for predicting the likelihood of venous thromboembolism (VTE) in colon cancer patients from China.

Methods

The data of colon cancer patients from Chongqing University Cancer Hospital between 2019 and 2022 were analyzed. Patients were divided into training set and internal validation set by random split‐sample method in a split ratio of 7:3. The univariable and multivariable logistic analysis gradually identified the independent risk factors for VTE. A nomogram was created using all the variables that had a significance level of p < 0.05 in the multivariable logistic analysis and those with clinical significance. Calibration curves and clinical decision curve analysis (DCA) were used to assess model's fitting performance and clinical value. Harrell's C‐index (concordance statistic) and the area under the receiver operating characteristic curves (AUC) were used to evaluate the predictive effectiveness of models.

Results

A total of 1996 patients were ultimately included. There were 1398 patients in the training set and 598 patients in the internal validation set. The nomogram included age, chemotherapy, targeted therapy, hypertension, activated partial thromboplastin time, prothrombin time, platelet, absolute lymphocyte count, and D‐dimer. The C‐index of nomogram and Khorana score were 0.754 (95% CI 0.711–0.798), 0.520 (95% CI 0.477–0.563) in the training cohort and 0.713 (95% CI 0.643–0.784), 0.542 (95% CI 0.473–0.612) in the internal validation cohort.

Conclusions

We have established and validated a nomogram to predict the VTE risk of colon cancer patients in China, which encompasses a diverse age range, a significant population size, and various clinical factors. It facilitates the identification of high‐risk groups and may enable the implementation of targeted preventive measures.
Clinical outcomes of pomalidomide‐based and daratumumab‐based therapies in patients with relapsed/refractory multiple myeloma: A real‐world cohort study in China
Authors: Han Xiaoyan , Jiang Xincheng , He Jingsong , Zheng Gaofeng , Xiong Yaqin , Wen Yanling , Yang Yang , He Donghua , Chen Qingxiao , Zhao Yi , Li Yi , Wu Wenjun , Cai Zhen
Published: May 2024

Background

Comparative investigations evaluating the efficacy of pomalidomide‐based (Pom‐based) versus daratumumab‐based (Dara‐based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real‐world studies.

Methods

This retrospective cohort study included 140 RRMM patients treated with Pom‐based or Dara‐based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023.

Results

The overall response rates (ORR) for Pom‐based (n = 48), Dara‐based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression‐free survival (PFS) was 5.7 months (95% CI: 5.0–6.5) for the Pom‐based group, 10.5 months (5.2–15.8) for the Dara‐based group, and 6.7 months (4.0–9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara‐based vs. Pom‐based, DPd vs. Pom‐based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double‐refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara‐based regimens over Pom‐based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara‐based and DPd regimens (Pom‐based 39.6% vs. Dara‐based 64.7% vs. DPd 70.8%, p = 0.009).

Conclusions

In real‐world settings, Pom‐based, Dara‐based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara‐based therapy yielded superior clinical response and PFS compared to Pom‐based therapy.
Exploring Cutting‐Edge Approaches in Anaerobic Digestion and Anaerobic Digestate Management
Authors: Mariappan Iyyadurai , Prabhakaran Rajkumar , Vivekanand Vivekanand , Poomani Merlin Sobia , Muthan Krishnaveni , Dhandayuthapani Sivanesan , Sivasamy Sivabalan , Regurajan Rathika , Subramanian Venkatesh
Published: May 2024

Exploring alternative energy sources is vital amid increasing human fuel consumption. Globally, biogas, rich in methane, hydrogen sulfide, and carbon dioxide, addresses energy demands through biomass anaerobic digestion (AD). Efficient digestate management, employing techniques like solid‐liquid separation and composting, is crucial for environmental protection. The goal is to optimize nutrient‐rich byproduct utilization while minimizing negative impacts. This review analyzes diverse substrates, emphasizing challenges and benefits. Key considerations include nutrient ratios, moisture content, co‐digestion, organic loading rate, and retention time. The study explores temperature's impact on microbial growth, biogas impurities, and upgradation techniques, including biological methods. Fermentation, microbial electrochemical techniques, and biochar use for enhanced AD are introduced. Discussing digestate's multifaceted aspects, the review highlights its nutrient value and diverse applications in aquaculture, animal feed, fermentation, bioremediation, and fine chemical production.
Rb‐Promoted Au/CeO2 Nanocatalyst for Remarkably‐Enhanced Aniline Conversion to Azoxybenzene with Ultrahigh Selectivity
Authors: Khan Afsar , Ju Peiwen , Han Zhengwei , Xie Yu , Gan Ziyu , Zhong Hui , He Zhiguo , Xie Weiqi
Published: May 2024

Aromatic azo compounds have proven to be a relevant class of building blocks in chemical synthesis. However, uncontrollable selectivity towards azo compounds and low reactant conversion in traditional synthetic methods seriously impede their applications. Herein, Rb‐doped Au/CeO2 nanocatalyst (Rb−Au/CeO2) was prepared and utilized as a highly efficient supported metal catalyst for the selective oxidation of anilines to azocompounds using hydrogen peroxide as an oxidant, which reached ultrahigh selectivity (92 %) towards azoxybenzene and complete aniline conversion (100 %). The addition of Rb+ accelerates the electron transformation of Au to produce Au+, which is ready for catalysis. This research presents a promising Rb‐doped strategy for achieving complete aniline conversion and high selectivity towards azoxybenzene, opening up new possibilities for the application of aromatic azo compounds in chemical synthesis.
New Architecture Based on Metal‐Organic Frameworks and Spin Crossover Complexes to Detect Volatile Organic Compounds
Authors: Cuza Emmelyne , Patriarche Gilles , Serre Christian , Tissot Antoine
Published: May 2024

We present here the encapsulation of a spin crossover complex C1 [FeII(L)] (L: 4‐amino‐, 2‐(2‐pyridinylmethylene)hydrazide) inside MOF‐808(Zr), a chemically robust Metal‐Organic Framework. The compound C1⊂MOF‐808 retains its crystallinity as well as a partial porosity compared to pristine MOF and shows solvatochromism under Volatile Organic compounds (VOCs) sorption associated to a spin state change of the guest complex. More specifically, this compound shows an interesting reversible color change under formaldehyde and formic acid vapor sorption and can therefore be considered as a new kind of optical VOCs chemosensor, opening new doors for developing a broad range of VOCs optical sensors.
1,2,3‐Triazole‐Containing Azamacrocycles from Chiral Triazolopeptoids: Synthesis and Solid‐State Studies
Authors: Araszczuk Alicja M. , Pierri Giovanni , Schettini Rosaria , Costabile Chiara , Della Sala Giorgio , Di Marino Luca , Tedesco Consiglia , De Riccardis Francesco , Izzo Irene
Published: May 2024

Two new chiral 1,2,3‐triazole‐containing macrocyclic oligoamides (i. e.: triazolopeptoid 4 and 5) were obtained through solid‐phase synthesis of linear precursors followed by high dilution macrocyclization reaction. Theoretical (DFT) and spectroscopic (NMR) studies revealed the intricate interplay between the Nα‐chiral side chains and their conformational attitudes. BH3‐mediated reduction of the tertiary amide groups of known 1–3 and newly synthesized 4 gave novel azamacrocycles 6–9. Detection of borane complexes of azamacrocycles 6 and 9 (i. e.: 10 and 11), corroborated by X‐ray diffraction studies, demonstrated the peculiar properties of 1,2,3‐triazole‐containing macrorings.
Myosin phosphatase targeting subunit1 controls localization and motility of Rab7‐containing vesicles: Is myosin phosphatase a cytoplasmic dynein regulator?
Authors: Matsumura Fumio , Murayama Takashi , Kuriyama Ryoko , Matsumura Aya , Yamashiro Shigeko
Published: May 2024

Myosin phosphatase targeting subunit1 (MYPT1) is a critical subunit of myosin phosphatase (MP), which brings PP1Cδ phosphatase and its substrate together. We previously showed that MYPT1 depletion resulted in oblique chromatid segregation. Therefore, we hypothesized that MYPT1 may control microtubule‐dependent motor activity. Dynein, a minus‐end microtubule motor, is known to be involved in mitotic spindle assembly. We thus examined whether MYPT1 and dynein may interact. Proximity ligation assay and co‐immunoprecipitation revealed that MYPT1 and dynein intermediate chain (DIC) were associated. We found that DIC phosphorylation is increased in MYPT1‐depleted cells in vivo, and that MP was able to dephosphorylate DIC in vitro. MYPT1 depletion also altered the localization and motility of Rab7‐containing vesicles. MYPT1‐depletion dispersed the perinuclear Rab7 localization to the peripheral in interphase cells. The dispersed Rab7 localization was rescued by microinjection of a constitutively active, truncated MYPT1 mutant, supporting that MP is responsible for the altered Rab7 localization. Analyses of Rab7 vesicle trafficking also revealed that minus‐end transport was reduced in MYPT1‐depleted cells. These results suggest an unexpected role of MP: MP controls dynein activity in both mitotic and interphase cells, possibly by dephosphorylating dynein subunits including DIC.
The synergy mechanism of CsSnI3 and LiTFSI enhancing the electrochemical performance of PEO‐based solid‐state batteries
Authors: Sun Rui , Zhu Ruixiao , Li Jiafeng , Wang Zhongxiao , Zhu Yuting , Yin Longwei , Wang Chengxiang , Wang Rutao , Zhang Zhiwei
Published: May 2024

Lithium metal solid‐state battery is the first choice of batteries for electromobiles and consumer electronic products because of the specific capacity of 3860 mAh g−1 and high electrochemical potential (−3.04 V) of Li metal. Flexible polymer solid electrolytes have become the optimal solution to produce high energy density lithium batteries with arbitrary size and shape. In this work, we introduce a halide perovskite, CsSnI3, into the polyethylene oxide/lithium bis‐(trifluoromethanesuphone)imide (PEO–LiTFSI) polymer matrix. The CsSnI3 could form a LixSn alloy with Li, leading to homogenization of the electric field and Li+‐flux at the interface, Sn atom also bonds with the TFSI− anion to provide more dissociated Li+. Besides that, the I atom could interact with Li to form an electronic insulation with a strong blocking effect on electron tunneling. As a proof of concept, the synergy mechanism of the PEO–LiTFSI–CsSnI3 electrolyte improves the stable cycle life of the symmetric battery to more than 500 h, and the Li+ conductivity raised to 6.1 × 10−4 S cm−1 at 60°C. The application of the “zwitter ions analog” halide perovskite in PEO–LiTFSI provides a new choice among various methods to improve the electrochemical performance of polymer solid‐state batteries.
Assessing nasal airway resistance and symmetry: An approach to global perspective through computational fluid dynamics
Authors: Burgos Manuel A. , Bastir Markus , Pérez‐Ramos Alejandro , Sanz‐Prieto Daniel , Heuzé Yann , Maréchal Laura , Esteban‐Ortega Francisco
Published: May 2024

This study aimed to explore the variability in nasal airflow patterns among different sexes and populations using computational fluid dynamics (CFD). We focused on evaluating the universality and applicability of dimensionless parameters R (bilateral nasal resistance) and ϕ (nasal flow asymmetry), initially established in a Caucasian Spanish cohort, across a broader spectrum of human populations to assess normal breathing function in healthy airways. In this retrospective study, CT scans from Cambodia (20 males, 20 females), Russia (20 males, 18 females), and Spain (19 males, 19 females) were analyzed. A standardized CFD workflow was implemented to calculate R‐ϕ parameters from these scans. Statistical analyses were conducted to assess and compare these parameters across different sexes and populations, emphasizing their distribution and variances. Our results indicated no significant sex‐based differences in the R parameter across the populations. However, moderate sexual dimorphism in the ϕ parameter was observed in the Cambodian group. Notably, no geographical differences were found in either R or ϕ parameters, suggesting consistent nasal airflow characteristics across the diverse human groups studied. The study also emphasized the importance of using dimensionless variables to effectively analyze the relationships between form and function in nasal airflow. The observed consistency of R‐ϕ parameters across various populations highlights their potential as reliable indicators in both medical practice and further CFD research, particularly in diverse human populations. Our findings suggest the potential applicability of dimensionless CFD parameters in analyzing nasal airflow, highlighting their utility across diverse demographic and geographic contexts. This research advances our understanding of nasal airflow dynamics and underscores the need for additional studies to validate these parameters in broader population cohorts. The approach of employing dimensionless parameters paves the way for future research that eliminates confounding size effects, enabling more accurate comparisons across different populations and sexes. The implications of this study are significant for the advancement of personalized medicine and the development of diagnostic tools that accommodate individual variations in nasal airflow.
Cation Dependence of Enniatin B/Membrane‐Interactions Assessed Using Surface‐Enhanced Infrared Absorption (SEIRA) Spectroscopy
Authors: Gonzalez Barbara Daiana , Forbrig Enrico , Yao Guiyang , Kielb Patrycja , Mroginski Maria Andrea , Hildebrandt Peter , Kozuch Jacek
Published: May 2024

Enniatins are mycotoxins with well‐known antibacterial, antifungal, antihelmintic and antiviral activity, which have recently come to attention as potential mitochondriotoxic anticancer agents. The cytotoxicity of enniatins is traced back to ionophoric properties, in which the cyclodepsipeptidic structure results in enniatin:cation‐complexes of various stoichiometries proposed as membrane‐active species. In this work, we employed a combination of surface‐enhanced infrared absorption (SEIRA) spectroscopy, tethered bilayer lipid membranes (tBLMs) and density functional theory (DFT)‐based computational spectroscopy to monitor the cation‐dependence (Mz+=Na+, K+, Cs+, Li+, Mg2+, Ca2+) on the mechanism of enniatin B (EB) incorporation into membranes and identify the functionally relevant EBn : Mz+ complexes formed. We find that Na+ promotes a cooperative incorporation, modelled via an autocatalytic mechanism and mediated by a distorted 2 : 1‐EB2 : Na+ complex. K+ (and Cs+) leads to a direct but less efficient insertion into membranes due to the adoption of “ideal” EB2 : K+ sandwich complexes. In contrast, the presence of Li+, Mg2+, and Ca2+ causes a (partial) extraction of EB from the membrane via the formation of “belted” 1 : 1‐EB : Mz+ complexes, which screen the cationic charge less efficiently. Our results point to a relevance of the cation dependence for the transport into the malignant cells where the mitochondriotoxic anticancer activity is exerted.
Iron as Recyclable Metal Fuel: Unraveling Oxidation Behavior and Cyclization Effects Through Thermogravimetric Analysis, Wide‐Angle X‐ray Scattering and Mössbauer Spectroscopy
Authors: Kuhn Carola , Knapp Anna , Deutschmann Max P. , Spielmann Jonas , Tischer Steffen , Kramm Ulrike I. , Nirschl Hermann , Deutschmann Olaf
Published: May 2024

The carbon‐free chemical storage and release of renewable energy is an important task to drastically reduce CO2 emissions. The high specific energy density of iron and its recyclability makes it a promising storage material. Energy release by oxidation with air can be realized by the combustion of micron‐sized iron powders in retro‐fitted coal fired power plants and in fixed‐bed reactors under milder conditions. An experimental parameter study of iron powder oxidation with air was conducted based on thermogravimetric analysis in combination with wide‐angle X‐ray scattering and Mössbauer spectroscopy. In agreement with literature the oxidation was found to consist of a very fast initial oxidation of the outer particle layer followed by much slower oxidation due to diffusion of iron ions through the Fe2O3/Fe3O4 layer being the rate‐limiting step. Scanning electron microscopy analysis of the iron particle before and after oxidation reveal a strong particle morphology transformation. This impact on the reaction was studied by cyclization experiments. Up to 10 oxidation‐reduction cycles show that both, oxidation and reduction rates, increase strongly with cycling due to increased porosity.
Hyperlactataemia is a marker of reduced exercise capacity in heart failure with preserved ejection fraction
Authors: Nan Tie Emilia , Wolsk Emil , Nanayakkara Shane , Vizi Donna , Mariani Justin , Moller Jacob Eifer , Hassager Christian , Gustafsson Finn , Kaye David M.
Published: May 2024

Aims

Heart failure with preserved ejection fraction (HFpEF) is associated with an array of central and peripheral haemodynamic and metabolic changes. The exact pathogenesis of exercise limitation in HFpEF remains uncertain. Our aim was to compare lactate accumulation and central haemodynamic responses to exercise in patients with HFpEF, non‐cardiac dyspnoea (NCD), and healthy volunteers.

Methods and results

Right heart catheterization with mixed venous blood gas and lactate measurements was performed at rest and during symptom‐limited supine exercise. Multivariable analyses were conducted to determine the relationship between haemodynamic and biochemical parameters and their association with exercise capacity. Of 362 subjects, 198 (55%) had HFpEF, 103 (28%) had NCD, and 61 (17%) were healthy volunteers. This included 139 (70%) females with HFpEF, 77 (75%) in NCD (P = 0.41 HFpEF vs. NCD), and 31 (51%) in healthy volunteers (P < 0.001 HFpEF vs. volunteers). The median age was 71 (65, 75) years in HFpEF, 66 (57, 72) years in NCD, and 49 (38, 65) years in healthy volunteers (HFpEF vs. NCD or volunteer, both P < 0.001). Peak workload was lower in HFpEF compared with healthy volunteers [52 W (interquartile range 31–73), 150 W (125–175), P < 0.001], but not NCD [53 W (33, 75), P = 0.85]. Exercise lactate indexed to workload was higher in HFpEF at 0.08 mmol/L/W (0.05–0.11), 0.06 mmol/L/W (0.05–0.08; P = 0.016) in NCD, and 0.04 mmol/L/W (0.03–0.05; P < 0.001) in volunteers. Exercise cardiac index was 4.5 L/min/m2 (3.7–5.5) in HFpEF, 5.2 L/min/m2 (4.3–6.2; P < 0.001) in NCD, and 9.1 L/min/m2 (8.0–9.9; P < 0.001) in volunteers. Oxygen delivery in HFpEF was lower at 1553 mL/min (1175–1986) vs. 1758 mL/min (1361–2282; P = 0.024) in NCD and 3117 mL/min (2667–3502; P < 0.001) in the volunteer group during exercise. Predictors of higher exercise lactate levels in HFpEF following adjustment included female sex and chronic kidney disease (both P < 0.001).

Conclusions

HFpEF is associated with reduced exercise capacity secondary to both central and peripheral factors that alter oxygen utilization. This results in hyperlactataemia. In HFpEF, plasma lactate responses to exercise may be a marker of haemodynamic and cardiometabolic derangements and represent an important target for future potential therapies.
Artificial intelligence‐assisted automated heart failure detection and classification from electronic health records
Authors: Oo Mon Myat , Gao Chuang , Cole Christian , Hummel Yoran , Guignard‐Duff Magalie , Jefferson Emily , Hare James , Voors Adriaan A. , de Boer Rudolf A. , Lam Carolyn S.P. , Mordi Ify R. , Tromp Jasper , Lang Chim C.
Published: May 2024

Aims

Electronic health records (EHR) linked to Digital Imaging and Communications in Medicine (DICOM), biological specimens, and deep learning (DL) algorithms could potentially improve patient care through automated case detection and surveillance. We hypothesized that by applying keyword searches to routinely stored EHR, in conjunction with AI‐powered automated reading of DICOM echocardiography images and analysing biomarkers from routinely stored plasma samples, we were able to identify heart failure (HF) patients.

Methods and results

We used EHR data between 1993 and 2021 from Tayside and Fife (~20% of the Scottish population). We implemented a keyword search strategy complemented by filtering based on International Classification of Diseases (ICD) codes and prescription data to EHR data set. We then applied DL for the automated interpretation of echocardiographic DICOM images. These methods were then integrated with the analysis of routinely stored plasma samples to identify and categorize patients into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and controls without HF. The final diagnosis was verified through a manual review of medical records, measured natriuretic peptides in stored blood samples, and by comparing clinical outcomes among groups. In our study, we selected the patient cohort through an algorithmic workflow. This process started with 60 850 EHR data and resulted in a final cohort of 578 patients, divided into 186 controls, 236 with HFpEF, and 156 with HFrEF, after excluding individuals with mismatched data or significant valvular heart disease. The analysis of baseline characteristics revealed that compared with controls, patients with HFrEF and HFpEF were generally older, had higher BMI, and showed a greater prevalence of co‐morbidities such as diabetes, COPD, and CKD. Echocardiographic analysis, enhanced by DL, provided high coverage, and detailed insights into cardiac function, showing significant differences in parameters such as left ventricular diameter, ejection fraction, and myocardial strain among the groups. Clinical outcomes highlighted a higher risk of hospitalization and mortality for HF patients compared with controls, with particularly elevated risk ratios for both HFrEF and HFpEF groups. The concordance between the algorithmic selection of patients and manual validation demonstrated high accuracy, supporting the effectiveness of our approach in identifying and classifying HF subtypes, which could significantly impact future HF diagnosis and management strategies.

Conclusions

Our study highlights the feasibility of combining keyword searches in EHR, DL automated echocardiographic interpretation, and biobank resources to identify HF subtypes.
Diastereoselective Aldol Reaction of α‐Azido Ketones with α‐CF3 Pyruvate to Organoazides with Vicinal Tetrasubstituted Carbons
Authors: Gao Yang , Zhang Xue‐Xin , Tu Zhi , Yu Jin‐Sheng , Zhou Jian
Published: May 2024

A direct diastereoselective aldol reaction of cyclic or acyclic α‐azido ketones with α‐trifluoromethyl (CF3) pyruvate catalysed by DABCO is developed, which allowed the facile access of CF3‐containing multifunctional organoazides with vicinal tetrasubstituted carbons in good to high yields and diastereoselectivities. Moreover, phenylethynyl trifluoro‐ and difluoromethyl ketones are also viable substrates. Up to 50 % enantioselectivity could be obtained in the initial exploration of the catalytic asymmetric variant.
Does a broad‐spectrum cannabidiol supplement improve performance in a 10‐min cycle ergometer performance‐test?
Authors: Gillham Scott H. , Starke Lynn , Welch Lauren , Mather Edward , Whitelegg Thomas , Chester Neil , Owens Daniel J. , Bampouras Theodoros , Close Graeme L.
Published: May 2024

Cannabidiol (CBD) is a non‐intoxicating phytocannabinoid which has been proposed to possess anti‐inflammatory and analgesic properties. Given the potential for perceptions of pain to limit exercise performance, the aim of the present study was to investigate if 3 weeks of daily CBD supplementation (150 mg day−1) improved performance in a 10‐min performance‐trial on a cycle ergometer. In a randomized, double‐blind and placebo‐controlled study, 22 healthy participants (n = 11 male and n = 11 female) completed two 10‐min performance trials on a WattBike cycle ergometer interspersed with a 3‐week supplementation period. Supplementation involved either 150 mg day−1 oral CBD or 150 mg day−1 of a visually identical placebo (PLA). During trials, ratings of perceived exertion (RPE [6–20]), heart rate (HR) and blood lactate (BLa) were collected every 2 min. Mean power (W) was also taken throughout the exercise at each time point. All data were analyzed using two‐way ANOVAs. There were no significant differences (P > 0.05) between CBD or PLA groups for mean power (W) during the 10‐min performance trial. There were also no significant differences (P > 0.05) in any of the physiological or perceptual parameters (HR, BLa and RPE) between conditions. Three weeks supplementation of a broad‐spectrum CBD supplement did not improve performance via any change in RPE during a 10‐min time trial on a cycle ergometer, and as such, this evidence does not support the claim that broad‐spectrum CBD supplements could be performance‐enhancing in this exercise modality.
The evolution of crystal‐poor rhyolite in the middle Okinawa Trough and its implications for the state of magma chamber
Authors: Luo Xinyu , Zeng Zhigang , Chen Zuxing , Zhang Yuxiang , Du Xiaoning , Qi Haiyan
Published: May 2024

The crystal‐poor rhyolitic pumice is the product of extreme magma differentiation and is characterized by highly vesicular, honeycomb‐like structure. However, little is known about the evolutionary history and the time of volatile saturation of the pumice‐forming melt. A crystal‐poor rhyolitic pumice (TVG7‐1) has been collected from the Yoron Hole hydrothermal field in the middle Okinawa Trough, a young continental margin back‐arc basin in the western Pacific. This study conducted a detailed analysis on the texture and in situ chemical composition of plagioclase, orthopyroxene and Fe‐Ti oxides to reveal the evolution process, storage state and eruption triggers of eruptible silicic melt. Texture and zoning of specific minerals and mineral populations suggest a magmatic evolution history of open system. Additionally, the hollow reentrant texture, as well as results from plagioclase‐liquid hygrometers, confirm a water‐rich melt pocket. The exsolution of volatiles (H2O, etc.), in this melt pocket, will contribute to local oxidation conditions, which may have been recorded by the concordant behaviour of FeO and An in plagioclase. Then, the overpressure caused by volatile exsolution would destabilize the magma chamber, which will eventually be broken by magma mixing/recharge, and lead to violent melt evacuation. Consequently, crystal size distribution (CSD) provides a new perspective on understanding the kinetic effect of magma mixing/recharge in the Okinawa Trough, especially on the mineral populations. Our study reveals the petrogenesis of crystal‐poor rhyolite within the framework of the mush model, refines the magma evolution history and demonstrates that pumice magma reaches volatile saturation before the eruption.
Development and influencing factors of middle‐deep tight sandstone reservoir ‘sweet spots’ in fault basin—Taking the Eocene Shahejie Formation in Suning area of Raoyang Sag in Bohai Bay basin as an example
Authors: Pu Qiongyao , Wang Ping , Wang Hongmei , Xie Jun , Guo Fajun , Guan Huajiao , Li Ping , Cui Jie
Published: May 2024

This study takes the tight sandstone of the lower sub‐member of the first member of the Eocene Shahejie Formation (Es1x) in the Suning area, Raoyang Sag, Bohai Bay Basin. Furthermore, it determines the rock type of the middle‐deep tight sandstone through lithologic profiling, core observation and log data analysis. The genetic control factors of tight sandstone in the study area are analysed using conventional thin section, pore‐casted thin section and scanning electron microscope, and the characteristics and genetic control factors of tight sandstone reservoirs are summarized. The research results show that the tight sandstones in this area are primarily feldspathic sandstone and feldspathic lithic sandstone, with high quartz contents, around 61.50%. The average porosity of the reservoir in the study area is 4.69%, and the average permeability is 2.92 mD, which are characteristics of low‐porosity and low‐permeability reservoirs. Through research, it has been found that the distribution of sedimentary facies and diagenesis in the study area control the development and distribution of ‘sweet spots’. Both compaction and cementation reduce the physical properties of the reservoir, while dissolution can increase porosity, thereby increasing the physical properties of the reservoir; dissolution resulted in an increase of approximately 3.57%–3.69% in the porosity of the tight reservoir in the study area, with an average porosity increase of 3.63%, and is the main controlling factor for the development of ‘sweet spots’ in the reservoir. The results provide an important basis for guiding the exploration and development of tight sandstone oil and gas in the lower sub‐member of the first member of the Eocene Shahejie Formation (Es1x)in the Suning area.
Cognitive function in different motor subtypes of Parkinson's disease: A systematic review protocol
Authors: Child Brittany , Saywell Isaac , da Silva Robyn , Collins‐Praino Lyndsey , Baetu Irina
Published: May 2024

Background and Aims

As the fastest‐growing neurological disorder globally, a better understanding of Parkinson's disease (PD) is needed to improve patient outcomes and reduce the increasing economic and healthcare burden associated with the disease. Whilst classified as a movement disorder, this disease is highly heterogeneous, encompassing a broad range of both motor and non‐motor symptoms (NMS). Cognitive impairment, presenting as either mild cognitive impairment or PD‐dementia, is one of the most prevalent and disabling NMS. To better understand heterogeneity in PD, researchers have sought to identify subtypes of individuals who share similar symptom profiles. To date, this research has predominantly focused on motor subtyping, with many studies comparing these motor subtypes on non‐motor outcomes, such as cognitive impairment. However, despite evidence of a motor‐cognitive relationship in healthy aging, findings regarding the presence of a motor‐cognitive relationship in PD are inconsistent. In our proposed systematic review, we will investigate motor subtyping studies that have evaluated the relationship between motor and cognitive function in PD. We aim to examine what is currently known about the relationship between motor and cognitive impairment in PD and evaluate the state of the field with respect to the subtyping methods and quality of cognitive assessment tools used.

Methods

Systematic literature searches will be conducted in PubMed, PsycINFO, CINAHL, Scopus, and Web of Science.

Results

Results will be synthesized using meta‐analysis and, where meta‐analysis is not feasible, narrative synthesis.

Conclusion

Despite the preponderance of motor subtyping research in PD, our study will be the first to systematically review evidence regarding the association between motor subtypes and cognitive impairment. Understanding the nature of the motor‐cognitive relationship in PD may lead to important insights regarding shared underlying disease pathology, which would have significant implications for early diagnosis, prognosis, and treatment of cognitive impairment in PD.
Knowledge and factors associated with active management of the third stage of labor in sub‐Saharan Africa: A systematic review and meta‐analysis
Authors: Abebe Gelaw Kelemu , Atalay Yibeltal Assefa , Azeze Gedion Asnake , Yitayew Alemker Molla , Gebeyehu Natnael Atnafu
Published: May 2024

Background

Postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality in sub‐Saharan Africa. Implementing active management in the third stage of labor has significantly reduced the incidence of PPH. Thus, understanding the level of healthcare providers' knowledge of active management in the third stage of labor can inform guidelines, policies, and practices for effectively preventing PPH.

Objective

This review aimed to assess the level of healthcare providers' knowledge and associated factors of active management in the third stage of labor in sub‐Saharan Africa.

Search Strategy

We conducted a search using PubMed, Scopus, Web of Science, Google Scholar, Cochrane Library, and the African Journals online international databases.

Selection Criteria

The inclusion criteria were determined before the review of the articles and adhere to the criteria of population, intervention, comparison, and outcome.

Data Collection and Analysis

Statistical analysis was performed using STATA data analysis software version 14, while Microsoft Excel was utilized for data abstraction. We checked publication bias using a funnel plot and Egger and Begg regression tests. A P value less than 0.05 was considered statistically significant, suggesting the presence of presence publication bias. The I2 statistic was used to assess heterogeneity between studies. The study's overall effect was evaluated using the random effects model.

Main Result

The study included 20 studies to conduct a pooled prevalence analysis. The overall prevalence of healthcare providers' knowledge of active management of third‐stage labor in sub‐Saharan Africa was 47.975% (95% CI: 32.585, 63.365). Having pre‐ and in‐service training (AOR: 2.25, 95% CI: 1.00, 5.08), having a higher degree (AOR: 1.98, 95% CI: 1.39, 2.82), and having good practices (AOR: 8.91, 95% CI: 4.58, 17.40) were significantly associated with healthcare provider's knowledge regarding active management third stage of labor.

Conclusions

The overall healthcare providers' knowledge of active management of the third stage of labor (AMTSL) was low in sub‐Saharan Africa. Obstetric healthcare providers should undertake comprehensive training covering all AMTSL components through pre‐ and in‐service diploma training programs.
Emerging near‐infrared luminescent materials for next‐generation broadband optical communications
Authors: Xu Beibei , Jin Chaoyuan , Park Jae‐Seong , Liu Huiyun , Lin Xing , Cui Junjie , Chen Daoyuan , Qiu Jianrong
Published: May 2024

The rapid development of emerging technologies observed in recent years, such as artificial intelligence, machine learning, mobile internet, big data, cloud computing, and the Internet of Everything, are generating escalating demands for expanding the capacity density, and speed in next‐generation optical communications. This poses a significant challenge to existing communication techniques. Within this context, the integration of near‐infrared broadband, tunable, and high‐gain luminescent materials into silicon optical circuits or fiber architectures to transmit and modulate light shows enormous potential for advancing next‐generation communication techniques. Here, this review provides an overview of the recent breakthroughs in near‐infrared luminescent epitaxial/colloidal quantum dots, and metal‐active‐center‐doped materials for broadband optical amplifiers and tunable lasers. We also expound on efforts to enhance the bandwidth and gain of these materials‐based amplifiers and lasers, exploring the challenges associate with developing ultra‐broadband and high‐speed optical communication systems. Additionally, the potential applications in Fifth Generation Fixed Networks, integration with 5G and 6G wireless networks, compensation for current Si electronic based CMOS for high computing capability, and the prospects of these light sources for next‐generation optoelectronic devices are discussed.

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Pet loss support for clients and staff: the importance of clear communication
Authors: James Diane
Published: May 2024

Anyone who works in the health and welfare sphere is aware of death, but it's not a topic that many people want to think about or find easy to work with. In relation to pets, the role that those in the veterinary world play in this ending brings many added pressures, from emotion and stress, to client reactions and moral injury, to name just a few. This article aims to address many of the areas that result from loss, and reiterates the importance of being mindful that empathy, compassion and communication relating to loss will vary from person to person and can improve or decline over time.
Bafi A1 inhibits nano‐copper oxide‐induced mitochondrial damage by reducing the release of copper from lysosomes
Authors: Huang Zhi , Lin Mo , Wang Lei , Dou Liangding , Hou Xin , Zhang Jinwen , Huang Yongchao , Wei Lifang , An Ran , Wang Dai , Yao Youliang , Guo Dongbei , Li Zhibo , Zhang Yongxing
Published: May 2024

This study demonstrated that both copper oxide nanoparticles (CuO‐NPs) and copper nanoparticles (Cu‐NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO‐NPs and Cu‐NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas‐2B cells. However, it is clear that CuO‐NPs exhibit a more pronounced detrimental effect compared with Cu‐NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO‐NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S‐acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO‐NPs. This observation suggests that the toxicity of CuO‐NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu‐NPs.
Microvesicles derived from dermal myofibroblasts modify the integrity of the blood and lymphatic barriers using distinct endocytosis pathways
Authors: Arif Syrine , Richer Megan , Larochelle Sébastien , Moulin Véronique J.
Published: May 2024

Microvesicles (MVs) are a subtype of extracellular vesicles that can transfer biological information from their producer cells to target cells. This communication can in turn affect both normal and pathological processes. Mounting evidence has revealed that dermal wound myofibroblasts (Wmyo) produce MVs, which can transfer biomolecules impacting receptor cells such as human dermal microvascular endothelial cells (HDMECs). While the effects of MVs on HDMECs are generally well described in the literature, little is known about the transport of MVs across the HDMEC barrier, and their potential effect on the barrier integrity remains unknown. Here, we investigated these roles of Wmyo‐derived MVs on two sub‐populations of HDMECs, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs). Using an in vitro model to mimic the endothelial barrier, we showed that MVs crossed the LEC barrier but not the BEC barrier. In addition, we demonstrated that MVs were able to influence the cell‐cell junctions of HDMECs. Specifically, we observed that after internalization via the predominantly caveolin‐dependent pathway, MVs induced the opening of junctions in BECs. Conversely, in LECs, MVs mainly use the macropinocytosis pathway and induce closure of these junctions. Moreover, proteins in the MV membrane were responsible for this effect, but not specifically those belonging to the VEGF family. Finally, we found that once the LEC barrier permeability was reduced by MV stimuli, MVs ceased to cross the barrier. Conversely, when the BEC barrier was rendered permeable following stimulation with MVs, they were subsequently able to cross the barrier via the paracellular pathway. Taken together, these results suggest that the study of Wmyo‐derived MVs offers valuable insights into their interaction with the HDMEC barrier in the context of wound healing. They highlight the potential significance of these MVs in the overall process.