bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of musculoskeletal models, scaling methods, and performance criteria for estimating muscle excitations and fiber lengths across walking speeds
Authors: Luis Israel , Afschrift Maarten , De Groote Friedl , Gutierrez-Farewik Elena M.
Published: October 2022

Muscle-driven simulations have been widely adopted to study muscle-tendon behavior; several generic musculoskeletal models have been developed, and their biofidelity improved based on available experimental data and computational feasibility. It is, however, not clear which, if any, of these models accurately estimate muscle-tendon dynamics over a range of walking speeds. In addition, the interaction between model selection, performance criteria to solve muscle redundancy, and approaches for scaling muscle-tendon properties remain unclear. This study aims to compare estimated muscle excitations and muscle fiber lengths, qualitatively and quantitatively, from several model combinations to experimental observations. We tested three generic models proposed by Hamner et al., Rajagopal et al., and Lai-Arnold et al. in combination with performance criteria based on minimization of muscle effort to the power of 2, 3, 5, and 10, and four approaches to scale the muscle-tendon unit properties of maximum isometric force, optimal fiber length, and tendon slack length. We collected motion analysis and electromyography data in eight able-bodied subjects walking at seven speeds and compared agreement between estimated/modelled muscle excitations and observed muscle excitations from electromyography and computed normalized fiber lengths to values reported in the literature. We found that best agreement in on/off timing in vastus lateralis, vastus medialis, tibialis anterior, gastrocnemius lateralis, gastrocnemius medialis, and soleus was estimated with minimum squared muscle effort than to higher exponents, regardless of model and scaling approach. Also, minimum squared or cubed muscle effort with only a subset of muscle-tendon unit scaling approaches produced the best time-series agreement and best estimates of the increment of muscle excitation magnitude across walking speeds. There were discrepancies in estimated fiber lengths and muscle excitations among the models, with the largest discrepancy in the Hamner et al. model. The model proposed by Lai-Arnold et al. best estimated muscle excitation estimates overall, but failed to estimate realistic muscle fiber lengths, which were better estimated with the model proposed by Rajagopal et al. No single model combination estimated the most accurate muscle excitations for all muscles; commonly observed disagreements include onset delay, underestimated co-activation, and failure to estimate muscle excitation increments across walking speeds.
Interfacial engineered iron oxide nanoring for T2-weighted magnetic resonance imaging-guided magnetothermal-chemotherapy
Authors: Bao Jianfeng , Tu Hui , Li Jing , Dong Yanbo , Dang Le , Yurievna Korjova Elena , Zhang Fengshou , Xu Lei
Published: October 2022

Due to no penetration depth limitation, low cost, and easy control, magnetic nanoparticles mediated magnetic hyperthermia therapy (MHT) has shown great potential in experimental and clinal treatments of various diseases. However, the low heating conversion efficiencies and short circulation times are major drawback for most existing magnetic-thermal materials. Additionally, single MHT treatment always leads to resistance and recurrence. Herein, a highly efficient magnetic-thermal conversion, ferrimagnetic vortex nanoring Fe3O4 coated with hyaluronic acid (HA) nanoparticles (Fe3O4@HA, FVNH NPs) was firstly constructed. Additionally, the doxorubicin (DOX) was successfully enclosed inside the FVNH and released remotely for synergetic magnetic–thermal/chemo cancer therapy. Due to the ferrimagnetic vortex-domain state, the ring shape Fe3O4 displays a high specific absorption rate (SAR) under an external alternating magnetic field (AMF). Additionally, antitumor drug (DOX) can be encapsulated inside the single large hole of FVNH by the hyaluronic acid (HA) shell and quickly released in response the tumor acidic microenvironments and AMF. What’s more, the non-loaded FVNH NPs show good biocompatibility but high cytotoxicity after loading DOX under AMF. Furthermore, the synthesized FVNH can efficiently reduce the transverse relaxation time and enhance negative magnetic resonance imaging (MRI). The impressive in vivo systemic therapeutic efficacy of FVNH was also proved in this work. Taken together, the results of this study demonstrate that the synthesized FVNH NPs offer the promise of serving as multifunctional theranostic nanoplatforms for medical imaging-guided tumor therapies.
Physicochemical properties of bone marrow mesenchymal stem cells encapsulated in microcapsules combined with calcium phosphate cement and their ectopic bone formation
Authors: Yuan Yafei , Shen Lipei , Liu Tiankun , He Lin , Meng Dan , Jiang Qingsong
Published: October 2022

Calcium phosphate bone cement (CPC) serves as an excellent scaffold material for bone tissue engineering owing to its good biocompatibility, injectability, self-setting property and three-dimensional porous structure. However, its clinical use is limited due to the cytotoxic effect of its setting reaction on cells and difficulties in degradation into bone. In this study, bone marrow mesenchymal stem cells (BMSCs) were encapsulated in alginate chitosan alginate (ACA) microcapsules and compounded with calcium phosphate bone cement. Changes in the compressive strength, porosity, injectability and collapsibility of CPC at different volume ratios of microcapsules were evaluated. At a 40% volume ratio of microcapsules, the composite scaffold displayed high porosity and injectability with good collapsibility and compressive strength. Cell live/dead double staining, Cell Counting Kit-8 (CCK-8) assays and scanning electron microscopy were used to detect the viability, proliferation and adhesion of cells after cell microcapsules were combined with CPC. The results revealed that cells protected by microcapsules proliferated and adhered better than those that were directly combined with CPC paste, and cell microcapsules could effectively form macropores in scaffold material. The composite was subsequently implanted subcutaneously on the backs of nude mice, and ectopic osteogenesis of the scaffold was detected via haematoxylin-eosin (H&E), Masson’s trichrome and Goldner’s trichrome staining. CPC clearly displayed better new bone formation function and degradability after addition of pure microcapsules and cell microcapsules. Furthermore, the cell microcapsule treatment group showed greater osteogenesis than the pure microcapsule group. Collectively, these results indicate that BMSCs encapsulated in ACA microcapsules combined with CPC composite scaffolds have good application prospects as bone tissue engineering materials.
Dynamic alteration in SULmax predicts early pathological tumor response and short-term prognosis in non-small cell lung cancer treated with neoadjuvant immunochemotherapy
Authors: Sun Taotao , Huang Shujie , Jiang Yongluo , Yuan Hui , Wu Junhan , Liu Chao , Zhang Xiaochun , Tang Yong , Ben Xiaosong , Tang Jiming , Zhou Haiyu , Zhang Dongkun , Xie Liang , Chen Gang , Zhao Yumo , Wang Shuxia , Xu Hao , Qiao Guibin
Published: October 2022

Introduction: Biomarkers predicting tumor response to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) are still lacking despite great efforts. We aimed to assess the effectiveness of the immune PET Response Criteria in Solid Tumors via SULmax (iPERCIST-max) in predicting tumor response to neoadjuvant immunochemotherapy and short-term survival in locally advanced NSCLC.

Methods: In this prospective cohort study, we calculated SULmax, SULpeak, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their dynamic percentage changes in a training cohort. We then investigated the correlation between alterations in these parameters and pathological tumor responses. Subsequently, iPERCIST-max defined by the proportional changes in the SULmax response (△SULmax%) was constructed and internally validated using a time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC) value. A prospective cohort from the Sun Yat-Sen University Cancer Center (SYSUCC) was also included for external validation. The relationship between the iPERCIST-max responsiveness and event-free survival in the training cohort was also investigated.

Results: Fifty-five patients with NSCLC were included in this study from May 2019 to December 2021. Significant alterations in post-treatment SULmax (p < 0.001), SULpeak (p < 0.001), SULmean (p < 0.001), MTV (p < 0.001), TLG (p < 0.001), and tumor size (p < 0.001) were observed compared to baseline values. Significant differences in SULpeak, SULmax, and SULmean between major pathological response (mPR) and non-mPR statuses were observed. The optimal cutoff values of the SULmax response rate were −70.0% and −88.0% using the X-tile software. The univariate and multivariate binary logistic regression showed that iPERCIST-max is the only significant key predictor for mPR status [OR = 84.0, 95% confidence interval (CI): 7.84–900.12, p < 0.001]. The AUC value for iPERCIST-max was 0.896 (95% CI: 0.776–1.000, p < 0.001). Further, external validation showed that the AUC value for iPERCIST-max in the SYSUCC cohort was 0.889 (95% CI: 0.698–1.000, p = 0.05). Significantly better event-free survival (EFS) in iPERCIST-max responsive disease (31.5 months, 95% CI 27.9–35.1) than that in iPERCIST-max unresponsive disease (22.2 months, 95% CI: 17.3–27.1 months, p = 0.024) was observed.

Conclusion: iPERCIST-max could better predict both early pathological tumor response and short-term prognosis of NSCLC treated with neoadjuvant immunochemotherapy than commonly used criteria. Furthermore, large-scale prospective studies are required to confirm the generalizability of our findings.
In vivo targeting capacities of different nanoparticles to prostate tissues based on a mouse model of chronic bacterial prostatitis
Authors: Hu Ruimin , Yang Yang , Song Guojing , Zhao Fuhan , Chen Saipeng , Zhou Zhansong , Zheng Jun , Shen Wenhao
Published: October 2022

Chronic bacterial prostatitis usually occurs in men and seriously affects the quality of life of patients. The efficacy of chronic bacterial prostatitis treatment is limited by the difficulty for free drugs (e.g., antibiotics) to penetrate the prostate epithelium and target inflammatory tissues. The advent of nanotechnology offers the possibility to address this issue, such as the development of targeted nanoparticle delivery strategies that may overcome these important limitations. The physicochemical properties of nanoparticles, such as particle size, shape and surface modification ligands, determine their targeting effectiveness. In this study, nanoparticles with different physicochemical properties were prepared to explore and confirm their targeting capacities to inflammatory prostate tissues of chronic bacterial prostatitis, focusing on the effects of size and different modification ligands on the targeting performance. In vivo and ex vivo imaging results verified that folic acid-modified nanoparticles with a particle size of 180–190 nm via tail intravenous injection had the optimal targeting efficiency to prostate tissues. Our results provide an experimental basis and reference value for targeted therapy of prostate-related diseases with nanotechnology in the future.
Highly tumoricidal efficiency of non-oxidized MXene-Ti3C2Tx quantum dots on human uveal melanoma
Authors: Zhang Huankai , Li Xuesong , You Pan , Song Xian , Fan Qian , Tao Xutang , Qu Yi
Published: October 2022

Uveal melanoma (UM) is a highly malignant intraocular tumor with poor prognosis. Current topical ophthalmic therapies purpose to conserve the eye and useful vision. Due to the risks and limited clinical benefits, the topical treatments of UM remain challenging and complex. In this study, newly developed non-oxidized MXene-Ti3C2Tx quantum dots (NMQDs-Ti3C2Tx) are proposed for UM treatment. Surprisingly, NMQDs-Ti3C2Tx shows significant tumor-killing effects on UM cells in a dose-dependent manner and causes severe necrosis near the injection site on the xenograft UM tumor model. Moreover, NMQDs-Ti3C2Tx exhibits excellent biocompatibility with normal retina pigment epithelium (RPE) cells and does not cause any damage in C57BL/6 mice eyes. Mechanistically, NMQDs-Ti3C2Tx inhibits the proliferation, invasion, and migration of UM cells via its desirable reactive oxygen species (ROS) generation ability, which causes lipid peroxidation and mitophagy, triggering cell ferroptosis. Furthermore, NMQDs-Ti3C2Tx is detected accumulating in autolysosomes which exacerbates cell death. This work provides new light on the topical treatment of UM.
Viscoelastic damage evaluation of the axon
Authors: Hasan Fuad , Mahmud KAH Al , Khan Md. Ishak , Adnan Ashfaq
Published: October 2022

In this manuscript, we have studied the microstructure of the axonal cytoskeleton and adopted a bottom-up approach to evaluate the mechanical responses of axons. The cytoskeleton of the axon includes the microtubules (MT), Tau proteins (Tau), neurofilaments (NF), and microfilaments (MF). Although most of the rigidity of the axons is due to the MT, the viscoelastic response of axons comes from the Tau. Early studies have shown that NF and MF do not provide significant elasticity to the overall response of axons. Therefore, the most critical aspect of the mechanical response of axons is the microstructural topology of how MT and Tau are connected and construct the cross-linked network. Using a scanning electron microscope (SEM), the cross-sectional view of the axons revealed that the MTs are organized in a hexagonal array and cross-linked by Tau. Therefore, we have developed a hexagonal Representative Volume Element (RVE) of the axonal microstructure with MT and Tau as fibers. The matrix of the RVE is modeled by considering a combined effect of NF and MF. A parametric study is done by varying fiber geometric and mechanical properties. The Young’s modulus and spacing of MT are varied between 1.5 and 1.9 GPa and 20–38 nm, respectively. Tau is modeled as a 3-parameter General Maxwell viscoelastic material. The failure strains for MT and Tau are taken to be 50 and 40%, respectively. A total of 4 RVEs are prepared for finite element analysis, and six loading cases are inspected to quantify the three-dimensional (3D) viscoelastic relaxation response. The volume-averaged stress and strain are then used to fit the relaxation Prony series. Next, we imposed varying strain rates (between 10/sec to 50/sec) on the RVE and analyzed the axonal failure process. We have observed that the 40% failure strain of Tau is achieved in all strain rates before the MT reaches its failure strain of 50%. The corresponding axonal failure strain and stress vary between 6 and 11% and 5–19.8 MPa, respectively. This study can be used to model macroscale axonal aggregate typical of the white matter region of the brain tissue.
Cybergenetic control of microbial community composition
Authors: Lee Ting An , Steel Harrison
Published: October 2022

The use of bacterial communities in bioproduction instead of monocultures has potential advantages including increased productivity through division of labour, ability to utilise cheaper substrates, and robustness against perturbations. A key challenge in the application of engineered bacterial communities is the ability to reliably control the composition of the community in terms of its constituent species. This is crucial to prevent faster growing species from outcompeting others with a lower relative fitness, and to ensure that all species are present at an optimal ratio during different steps in a biotechnological process. In contrast to purely biological approaches such as synthetic quorum sensing circuits or paired auxotrophies, cybergenetic control techniques - those in which computers interface with living cells-are emerging as an alternative approach with many advantages. The community composition is measured through methods such as fluorescence intensity or flow cytometry, with measured data fed real-time into a computer. A control action is computed using a variety of possible control algorithms and then applied to the system, with actuation taking the form of chemical (e.g., inducers, nutrients) or physical (e.g., optogenetic, mechanical) inputs. Subsequent changes in composition are then measured and the cycle repeated, maintaining or driving the system to a desired state. This review discusses recent and future developments in methods for implementing cybergenetic control systems, contrasts their capabilities with those of traditional biological methods of population control, and discusses future directions and outstanding challenges for the field.
Cell-cell interactions and fluctuations in the direction of motility promote directed migration of osteoblasts in direct current electrotaxis
Authors: Dawson Jonathan Edward , Sellmann Tina , Porath Katrin , Bader Rainer , van Rienen Ursula , Appali Revathi , Köhling Rüdiger
Published: October 2022

Under both physiological (development, regeneration) and pathological conditions (cancer metastasis), cells migrate while sensing environmental cues in the form of mechanical, chemical or electrical stimuli. In the case of bone tissue, osteoblast migration is essential in bone regeneration. Although it is known that osteoblasts respond to exogenous electric fields, the underlying mechanism of electrotactic collective movement of human osteoblasts is unclear. Here, we present a computational model that describes the osteoblast cell migration in a direct current electric field as the motion of a collection of active self-propelled particles and takes into account fluctuations in the direction of single-cell migration, finite-range cell-cell interactions, and the interaction of a cell with the external electric field. By comparing this model with in vitro experiments in which human primary osteoblasts are exposed to a direct current electric field of different field strengths, we show that cell-cell interactions and fluctuations in the migration direction promote anode-directed collective migration of osteoblasts.
Post-occupancy evaluation and codesign in mental healthcare buildings: User’s input as a driver for functional and technical adaptations in post COVID-19 reality
Authors: Goulart Fernanda de Moraes , Ono Rosaria
Published: October 2022

During the COVID-19 pandemic, social distancing protocols imposed the suspension of many activities in mental healthcare facilities, limiting the use of the facility to people in comprehensive care. With the advancement of vaccination, these buildings are gradually reopening for community use. However, managers and workers now face challenges in accommodating new design demands related to reducing the risk of contamination by COVID-19 within the building. This research adopted a multi-method approach in two phases, combining a post-occupancy evaluation with a cocreation activity to help mental healthcare workers and patients to suggest design changes in their environment. Three Psychosocial Care Centers (CAPS) in São Paulo were selected as case-study buildings. The first phase was the Post-Occupancy Evaluation (POE), in which the lead researcher conducted a walkthrough with the facility administrator, applied questionnaires to 100 employees, and conducted a walking interview with 12 patients. During Phase 02, a codesign activity entitled “Dream CAPS” was conducted with 25 healthcare workers and 12 patients. In this activity, participants were asked to customize a physical model of a mental healthcare facility, choosing the wall and floor finishings, the types of openings (windows, doors), furniture, and ornaments. Afterward, they participated in an interview with illustrated cards. All activities were audio-recorded and textual analysis qualified and categorized the content. Objective and subjective data analysis identified five characteristics of the built environment that prevented or increased risk of COVID-19 spread: Places that support risk mitigation procedures, access and circulation control, extended use of outdoor spaces, natural and artificial air renovation systems, and materials resistant to terminal cleaning. Patients participated in the activities but did not express opinions on the impact of architecture on airborne disease prevention. Healthcare workers claimed that environments that improve mental health must be attractive and prone to social interaction and relaxation without compromising biological safety. The combination of post-occupancy evaluation and codesign proved an excellent tool to identify the demands of mental healthcare buildings and discuss the solutions that must be implemented to deal with contemporary and future crises in a pandemic context.
DNA damage checkpoint execution and the rules of its disengagement
Authors: Yam Candice Qiu Xia , Lim Hong Hwa , Surana Uttam
Published: October 2022

Chromosomes are susceptible to damage during their duplication and segregation or when exposed to genotoxic stresses. Left uncorrected, these lesions can result in genomic instability, leading to cells’ diminished fitness, unbridled proliferation or death. To prevent such fates, checkpoint controls transiently halt cell cycle progression to allow time for the implementation of corrective measures. Prominent among these is the DNA damage checkpoint which operates at G2/M transition to ensure that cells with damaged chromosomes do not enter the mitotic phase. The execution and maintenance of cell cycle arrest are essential aspects of G2/M checkpoint and have been studied in detail. Equally critical is cells’ ability to switch-off the checkpoint controls after a successful completion of corrective actions and to recommence cell cycle progression. Interestingly, when corrective measures fail, cells can mount an unusual cellular response, termed adaptation, where they escape checkpoint arrest and resume cell cycle progression with damaged chromosomes at the cost of genome instability or even death. Here, we discuss the DNA damage checkpoint, the mitotic networks it inhibits to prevent segregation of damaged chromosomes and the strategies cells employ to quench the checkpoint controls to override the G2/M arrest.
Self-doped N, S porous carbon from semi-coking wastewater-based phenolic resin for supercapacitor electrodes
Authors: Yan Long , Wang Xianjie , Wang Yufei , Li Jian , Liu Qianqian , Zhong Xiang , Chang Yuan , Li Qingchao , Verma Santosh Kumar
Published: October 2022

Contamination of phenolic compounds has devastating effects on the environment. Therefore, its harmless treatment and recycling have received extensive attention. Herein, a novel method for preparing N-S doped phenolic resin (NSPR) from phenols, N and S groups in semi-coking wastewater, and formaldehyde are developed. The KOH is consequently incorporated into the NSPR through simultaneous carbonization and activation in a single step to produce porous carbon material (NSPC). The as-obtained NSPC exhibits a high specific capacitance of 182 F g−1 at 0.5 A g−1, a high energy density of 9.1 Wh kg−1 at a power density of 0.15 kW kg−1, and remarkable cycling stability in aqueous KOH electrolyte. This outstanding electrochemical performance is attributed to its ultrahigh specific surface area (SSA, 2,523 m2 g−1), enormous total pore volume (Vt, 1.30 cm3 g−1), rational pore structure, and N-S heteroatom self-doping (0.76 at% N and 0.914 at% S), which ensures adequate charge storage, rapid electrolyte ion diffusion, and contributed pseudo-capacitance. This work not only provides a facile method for transforming phenolic wastewater into high-value products but also offers a cost-effective and high-performance porous carbon material for supercapacitors.
Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study
Authors: Hussain Rafaqat , Shah Mazloom , Iqbal Shahid , Rehman Wajid , Khan Shoaib , Rasheed Liaqat , Naz Haseena , Al-ghulikah Hanan A. , Elkaeed Eslam B. , Pashameah Rami Adel , Alzahrani Eman , Farouk Abd-ElAziem
Published: October 2022

Twenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety (1–25) and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.01 and 30.80 ± 0.80 μM (against α-amylase) in comparison to standard acarbose (12.80 ± 0.10 μM). Similarly, synthetics analogs also displayed a varied range of α-glucosidase activity ranging from 0.80 ± 0.01 μM to IC50 = 29.70 ± 0.40 μM (against α-glucosidase) as compared to standard acarbose (IC50 = 12.90 ± 0.10 μM). Among synthesized analogs, compound 22 showed excellent potency due to the presence of di-hydroxy substitutions at the 2,3-position of the aryl ring. For all analogs, the structure–activity relationship was carried out based on the pattern of substitutions around the aryl ring, and further, the potent analogs were subjected to a molecular docking study to analyze how active residues of targeted enzymes interact with active parts of newly prepared analogs. The result obtained shows that these compounds furnish several key interactions with enzyme active sites and, hence, enhanced their enzymatic activities.
Partial deligandation activated ZIF-67 for efficient electrocatalytic oxygen reduction reaction
Authors: Yang Xiaoli , Gu Jiali , Liu Chenhong , Bai Zhengyu , Yang Lin
Published: October 2022

Removing the blocked molecular groups and fully exposing the intrinsic active sites of metal-organic frameworks (MOFs) could give full play to their advantages of multi-active sites and multi-channel mass transfer, which will benefit the electrocatalytic oxygen reduction reaction (ORR) in fuel cells. Here, the partial diligandation-activated ZIF-67 (named as ZIF-67–400) with excellent ORR performance was obtained by simple low-temperature pyrolysis. The ORR electrocatalytic activity exhibits a half-wave potential of 0.82 V and the stability of maintaining 96% activity after 10 h of operation, which is comparable to commercial Pt/C. Further research studies reveal that the morphology, special dodecahedron configuration, and crystal structure of ZIF-67-400 are maintained well during the pyrolysis, but some hydrocarbon groups in the ligands are eliminated, resulting in the active sites being exposed and coordinated with the intrinsic porosity, improving the catalytic performance. This work may provide an alternative path for activating the electrocatalytic performance of metal-organic frameworks by low-temperature annealing.
“Upcycling” known molecules and targets for drug-resistant TB
Authors: Roubert Christine , Fontaine Evelyne , Upton Anna M
Published: October 2022

Despite reinvigorated efforts in Tuberculosis (TB) drug discovery over the past 20 years, relatively few new drugs and candidates have emerged with clear utility against drug resistant TB. Over the same period, significant technological advances and learnings around target value have taken place. This has offered opportunities to re-assess the potential for optimization of previously discovered chemical matter against Mycobacterium tuberculosis (M.tb) and for reconsideration of clinically validated targets encumbered by drug resistance. A re-assessment of discarded compounds and programs from the “golden age of antibiotics” has yielded new scaffolds and targets against TB and uncovered classes, for example beta-lactams, with previously unappreciated utility for TB. Leveraging validated classes and targets has also met with success: booster technologies and efforts to thwart efflux have improved the potential of ethionamide and spectinomycin classes. Multiple programs to rescue high value targets while avoiding cross-resistance are making progress. These attempts to make the most of known classes, drugs and targets complement efforts to discover new chemical matter against novel targets, enhancing the chances of success of discovering effective novel regimens against drug-resistant TB.
Interrogating the transmission dynamics of Trypanosoma cruzi (Trypanosomatida, Trypanosomatidae) by Triatoma venosa (Hemiptera: Reduviidae) after the elimination of vector transmission by Rhodnius prolixus in Boyacá eastern Colombia
Authors: Medina Manuel , Zuluaga Sara , Martínez María Fernanda , Bermúdez Juan Carlos , Hernández Carolina , Beltrán Virgilio , Velásquez-Ortiz Natalia , Muñoz Marina , Ramírez Juan David , Triana Omar , Cantillo-Barraza Omar
Published: October 2022

Chagas disease (CD) is a parasitic zoonosis (Trypanosoma cruzi) that is endemic in Colombia. Vector control of Rhodnius prolixus, the main domestic T. cruzi vector, has been achieved in a large part of the area with historically vector transmission of CD. It is necessary to understand the ecological behavior characteristics of local native vectors to ensure sustainability of the vector control programs. To evaluate the long-term success of a recent vector control campaign in the Boyacá department (Colombia), we used a combined strategy of entomological surveillance with co-existing canine surveillance from ten rural villages within six municipalities of the Tenza valley region (Boyacá, Colombia): Chinavita, Garagoa, Guateque, Somondoco, Sutatenza and Tenza, with historical reports of R. prolixus and secondary vectors. Collected triatomines and canine whole blood were analyzed for T. cruzi infection and genotyping. Triatomine bugs specimens were evaluated for blood meal source. Canine serology was performed using two distinct antibody assays. In total, 101 Triatoma venosa were collected by active search in domestic and peridomestic habitats. A natural infection prevalence of 13.9% (14/101) and four feeding sources were identified: human, dog, rat, and hen. A frequency infection of 46.5% (40/87) was observed from two independent serological tests and T. cruzi DNA was detected in 14 dogs (16.4%). Only TcIsylvatic DTU was detected. The results suggest that T. venosa present eco-epidemiological characteristics to maintain the transmission of T. cruzi in Tenza valley. This species has reinfested the intervened households and it has an active role in domestic and peridomestic transmission of T. cruzi due to their infection rates and feeding behavior. Therefore, this species should be considered as epidemiologically relevant for vector control strategies. Moreover, there is a need for human serological studies to have a close up of risk they are exposed to.
Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
Authors: Sethi Anurag , Taylor D. Leland , Ruby J. Graham , Venkataraman Jagadish , Sorokin Elena , Cule Madeleine , Melamud Eugene
Published: October 2022

Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, however, due to the lack of routine monitoring, the pathology remains severely under-diagnosed and prevalence in the general population is not known. We have developed a set of machine learning methods to quantitate levels of abdominal aortic calcification (AAC) in the UK Biobank imaging cohort and carried out the largest to-date analysis of genetic, biochemical, and epidemiological risk factors associated with the pathology. In a genetic association study, we identified three novel loci associated with AAC (FGF9, NAV9, and APOE), and replicated a previously reported association at the TWIST1/HDAC9 locus. We find that AAC is a highly prevalent pathology, with ~ 1 in 10 adults above the age of 40 showing significant levels of hydroxyapatite build-up (Kauppila score > 3). Presentation of AAC was strongly predictive of future cardiovascular events including stenosis of precerebral arteries (HR~1.5), myocardial infarction (HR~1.3), ischemic heart disease (HR~1.3), as well as other diseases such as chronic obstructive pulmonary disease (HR~1.3). Significantly, we find that the risk for myocardial infarction from elevated AAC (HR ~1.4) was comparable to the risk of hypercholesterolemia (HR~1.4), yet most people who develop AAC are not hypercholesterolemic. Furthermore, the overwhelming majority (98%) of individuals who develop pathology do so in the absence of known pre-existing risk conditions such as chronic kidney disease and diabetes (0.6% and 2.7% respectively). Our findings indicate that despite the high cardiovascular risk, calcification of large arteries remains a largely under-diagnosed lethal condition, and there is a clear need for increased awareness and monitoring of the pathology in the general population.
Proteomics and bioinformatics analysis of cardiovascular related proteins in offspring exposed to gestational diabetes mellitus
Authors: Pan Hai-Tao , Xiong Yi-Meng , Zhu Hong-Dan , Shi Xiao-Liang , Yu Bin , Ding Hai-Gang , Xu Ren-Jie , Ding Jin-Long , Zhang Tao , Zhang Juan
Published: October 2022

Introduction

Previous studies have demonstrated that exposed to the initial suboptimal intrauterine environment of gestational diabetes mellitus (GDM) may increase risk of cardiovascular disease in adulthood.

Methods

In order to investigate the underlying mechanisms involved in the increased risk of cardiovascular diseases (CVDs) in the offspring of GDM, we applied a high-throughput proteomics approach to compare the proteomic expression profile of human umbilical vessels of normal and GDM offspring.

Results

A total of significantly different 100 proteins were identified in umbilical vessels from GDM group compared with normal controls, among which 31 proteins were up-regulated, while 69 proteins were down-regulated. Differentially expressed proteins (DEPs) are validated using Western blotting analysis. The analysis of these differently expressed proteins (DEPs) related diseases and functions results, performed by Ingenuity Pathway Analysis (IPA) software. Based on “Diseases and Disorders” analysis, 17 proteins (ACTA2, ADAR, CBFB, DDAH1, FBN1, FGA, FGB, FGG, GLS, GSTM1, HBB, PGM3, PPP1R13L, S100A8, SLC12A4, TPP2, VCAN) were described to be associated with CVD, especially in Anemia, Thrombus and Myocardial infarction. Functional analysis indicated that DEPs involved in many cardiovascular functions, especially in “vasoconstriction of blood vessel” (related DEPs: ACTA2, DDAH1, FBN1, FGA, FGB, and FGG). Upstream regulator analyses of DEPs identifies STAT3 as inhibitor of ACTA2, FGA, FGB, and FGG.

Conclusion

The results of this study indicate that intrauterine hyperglycemia is associated with an elevated risk of cardiovascular risk in the offspring.
Aging and hypertension in kidney function decline: A 10 year population-based study
Authors: Jaques David A. , Vollenweider Peter , Bochud Murielle , Ponte Belen
Published: October 2022

Background

Aging is associated with a physiological decline in kidney function (KFD). In this study, we aimed to describe the impact of age on the rate of KFD and its interplay with risk factors for chronic kidney disease (CKD), considering mainly hypertension (HT), in the general population.

Materials and methods

Participants of European descent, aged 35–75, were recruited from a populational cohort in Lausanne, Switzerland. Participants with a 10 year follow-up were selected. KFD was defined as the difference in estimated glomerular filtration rate (eGFR) between baseline and follow-up, divided by the observation period. Multivariate linear regressions were used with KFD as the outcome and age as the main predictor. HT was tested as a modifying factor.

Results

We included 4,163 participants with mean age 52.2 ± 10.4, 44.7% men, 31.9% HT, and 5.0% diabetics. Mean baseline eGFR was 85.9 ± 14.6 ml/min/1.73 m2. Mean KFD was –0.49 ± 1.08 ml/min/1.73 m2 per year with 70% of participants decreasing their eGFR during follow-up. The relationship between age and KFD was non-linear and age was divided in tertiles. Old participants had faster rates of KFD as compared to young and middle-age participants (p < 0.001). A significant interaction was found between age and HT on KFD prediction (p < 0.001). In HT participants, KFD was significantly different across tertiles of age (p < 0.001). On contrary, KFD was not different across tertiles of age in non-HT participants.

Conclusion

A physiological KFD is present over time in the general population. Age contributes non-linearly to the rate of this decline with older subjects declining the fastest. The presence of HT is a major contributing factor in this setting as KFD worsened with age only in hypertensive participants. Thus, HT represents an important pathological factor aggravating the age-related physiological decline in eGFR in the general population.
Comparison between distinct insulin resistance indices in measuring the development of hypertension: The China Health and Nutrition Survey
Authors: Yuan Yue , Sun Wei , Kong Xiangqing
Published: October 2022

Aim

Our aim was to identify the relationship between several surrogate insulin resistance (IR) indices based on lipid products and the development of hypertension.

Materials and methods

A total of 3,281 participants aged ≥ 18 years enrolled in the China Health and Nutrition Survey from 2009 to 2015 and who were followed up for 6 years were included in the final analysis. Logistic regression was used to analyze the association between different IR indices and incident hypertension.

Results

There were 882 (28.9%) hypertensive participants in 2015. With regard to the homeostasis model assessment of insulin resistance (HOMA-IR) based on insulin level, subjects in the highest quartile of HOMA-IR values were more likely to develop hypertension [RR = 1.58 (1.26–1.98), P < 0.001] after being adjusted by sex and age, smoke habits, alcohol consumption, community type, married status, and education years in 2009. Subjects in the highest quartile of the triglyceride-glucose index (TyG) combined with body mass index (BMI) and waist circumference (WC) had more than two times the risk of hypertension after full adjustment compared with individuals in the lowest quartile (both P < 0.001), and the trend continued when adjusted for the HOMA-IR. Compared with those in the lowest quartile of TyG-BMI values, females in the highest quartile had a higher risk of developing hypertension than males [2.82 (2.01–3.97) vs. 2.56 (1.80–3.64)] after the full adjustment, and the trend existed independent of IR. Young participants in the highest quartile of the HOMA-IR had significantly higher risks of hypertension compared with subjects in the lowest quartile [1.67 (1.31–2.14), P < 0.005], and this trend was not significant in the elderly participants.

Conclusion

The results from our large-scale study elucidate the superiority of the TyG-BMI and TyG-WC compared with the HOMA-IR in the prediction of hypertension, which may be related to lipid deposition. The sex-specific predictive value is distinct for different IR indicators.
Serial thrombin generation and exploration of alternative anticoagulants in critically ill COVID-19 patients: Observations from Maastricht Intensive Care COVID Cohort
Authors: van de Berg Tom W. , Mulder Mark M. G. , Alnima Teba , Nagy Magdolna , van Oerle Rene , Beckers Erik A. M. , Hackeng Tilman M. , Hulshof Anne-Marije , Sels Jan-Willem E. M. , Henskens Yvonne M. C. , van der Horst Iwan C. C. , ten Cate Hugo , Spronk Henri M. H. , van Bussel Bas C. T. ,   MaastrICCht Collaborators
Published: October 2022

Background

COVID-19 associated coagulopathy (CAC) is associated with an increase in thromboembolic events. Current guidelines recommend prophylactic heparins in the management of CAC. However, the efficacy of this strategy in the intensive care population remains uncertain.

Objective

We aimed to measure thrombin generation (TG) to assess CAC in intensive care unit (ICU) patients receiving thromboprophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin (UFH). In addition, we performed statistical modeling to link TG parameters to patient characteristics and clinical parameters. Lastly, we studied the potency of different anticoagulants as an alternative to LMWH treatment in ex vivo COVID-19 plasma.

Patients/Methods

We included 33 patients with confirmed COVID-19 admitted at the ICU. TG was measured at least twice over the course of 6 weeks after admission. Thrombin generation parameters peak height and endogenous thrombin potential (ETP) were compared to healthy controls. Results were subsequently correlated with a patient characteristics and laboratory measurements. In vitro spiking in TG with rivaroxaban, dabigatran, argatroban and orgaran was performed and compared to LMWH.

Results

Anti-Xa levels of all patients remained within the therapeutic range throughout follow-up. At baseline, the mean (SE) endogenous thrombin potential (ETP) was 1,727 (170) nM min and 1,620 (460) nM min for ellagic acid (EA) and tissue factor (TF), respectively. In line with this we found a mean (SE) peak height of 353 (45) nM and 264 (96) nM for EA and TF. Although fluctuating across the weeks of follow-up, TG parameters remained elevated despite thromboprophylaxis. In vitro comparison of LMWHs and direct thrombin inhibitors (e.g., agratroban, dabigatran) revealed a higher efficacy in reducing coagulation potential for direct thrombin inhibition in both ellagic acid (EA) and tissue factor (TF) triggered TG.

Conclusion

In a sub-group of mechanically ventilated, critically ill COVID-19 patients, despite apparent adequate anti-coagulation doses evaluated by anti-Xa levels, thrombin generation potential remained high during ICU admission independent of age, sex, body mass index, APACHE II score, cardiovascular disease, and smoking status. These observations could, only partially, be explained by (anti)coagulation and thrombosis, inflammation, and multi-organ failure. Our in vitro data suggested that direct thrombin inhibition compared with LMWH might offer an alternate, more effective anticoagulant strategy in COVID-19.
Clinical characteristics of patients with heart failure and intracardiac thrombus
Authors: Zhai Mei , Huang Liyan , Liang Lin , Tian Pengchao , Zhao Lang , Zhao Xuemei , Huang Boping , Feng Jiayu , Huang Yan , Zhou Qiong , Zhang Yuhui , Zhang Jian
Published: October 2022

Background

Heart failure (HF) patients are in a hypercoagulable state that predisposes them to an intracardiac thrombus. We aim to assess the clinical features of patients with HF and intracardiac thrombus.

Methods

Patients diagnosed with HF with intracardiac thrombus were enrolled in this study. Patients' demographics, clinical comorbidities, laboratory tests, and cardiac imaging parameters are recorded. Baseline characteristics are described; the relationship between intracardiac thrombus location and cardiac underlying diseases, New York Heart Association (NYHA) class, and left ventricular ejection fraction (LVEF) are analyzed; and the anticoagulation rate is summarized.

Results

A total of 1,248 patients were included in the study. Most patients were men (72.2%) with a mean age of 54 years. The left ventricle is the most frequently involved (66.8%), and the prevalence of left ventricular thrombus is more in patients complicated with coronary artery diseases, ventricular noncompaction cardiomyopathy, and dilated cardiomyopathy (86.3%, 86.4%, and 78.2%, respectively). When combined with atrial fibrillation, atrial flutter, hypertrophic cardiomyopathy, restrictive cardiomyopathy, or valvular cardiomyopathy, the intracardiac thrombus is mostly likely to occur in the left atrium. The incidence rate of left cardiac thrombosis increased with the decline of LVEF, an increase of NYHA class, and enlargement of a cardiac chamber. Overall, the anticoagulation rate was 56.8%, with warfarin still the mainstay drug (45.1%), while the prescription of non-vitamin K antagonist oral anticoagulants rose year by year. As for imaging modalities for thrombus detection and diagnosis, transthoracic echocardiography was the most widely performed (75.1%).

Conclusion

This study summarizes the underlying disease constitution, thrombus location and related factors, imaging modalities, and antithrombotic profile in HF patients with intracardiac thrombus comprehensively.
Anomalous left coronary artery from the pulmonary artery: Outcomes and management of mitral valve
Authors: Yu Juemin , Ren Qiushi , Liu Xiaobing , Chen Tianyu , Liufu Rong , Wen Shusheng , Chen Jimei , Cen Jianzheng , Zhuang Jian
Published: October 2022

Objective

Use of concomitant mitral valve repair remains controversial in the anomalous left coronary artery from the pulmonary artery (ALCAPA) with mitral regurgitation (MR). This study aimed to evaluate postoperative mitral valve function and explore the indication for concomitant mitral valve repair.

Materials and methods

The medical records of 111 patients with ALCAPA and MR who underwent ALCAPA surgery between April 2006 and November 2020 were reviewed. The patients were categorized into three groups for comparison, namely, group I consisted of 38 patients with trivial or mild MR who underwent ALCAPA repair only; group II consisted of 37 patients with moderate or severe MR who similarly had only surgery of the ALCAPA performed; and group III consisted of 36 patients who had concomitant mitral valve repair for moderate or severe MR.

Result

Overall mortality was 7.2% (8 of 111). The mortality of group II (16.2%, 6 of 37) was higher than those of groups I (5.3%, 2 of 38) and III (0%, 0 of 36) (p = 0.027). All three patients who underwent mitral valve reintervention were in group II. At the last follow-up, none of the patients had more than moderate MR in group I. The percentage of patients with improved MR grade was 79.4% (27 of 34) in group III and 51.4% (19 of 37) in group II (p = 0.001). The multivariate logistic regression revealed that concomitant mitral valve repair (adjusted odds ratio = 4.492, 95% CI: 1.909–12.794; p < 0.001) was the major factor influencing MR grade improvement.

Conclusion

The long-term outcomes after ALCAPA repair were favorable. For mild MR, ALCAPA repair only can be performed. For moderate and severe MR, we suggest concomitant mitral valve repair.