tbuckley/cabot-search huggingface dataset:
The 2024 Europe report of the Lancet Countdown on health and climate change: unprecedented warming demands unprecedented action
Authors: Kim R van Daalen, Cathryn Tonne, Jan C Semenza, Joacim Rocklöv, Anil Markandya, Niheer Dasandi, Slava Jankin, Hicham Achebak, Joan Ballester, Hannah Bechara, Thessa M Beck, Max W Callaghan, Bruno M Carvalho, Jonathan Chambers, Marta Cirah Pradas, Orin Courtenay, Shouro Dasgupta, Matthew J Eckelman, Zia Farooq, Peter Fransson, Elisa Gallo, Olga Gasparyan, Nube Gonzalez-Reviriego, Ian Hamilton, Risto Hänninen, Charles Hatfield, Kehan He, Aleksandra Kazmierczak, Vladimir Kendrovski, Harry Kennard, Gregor Kiesewetter, Rostislav Kouznetsov, Hedi Katre Kriit, Alba Llabrés-Brustenga, Simon J Lloyd, Martín Lotto Batista, Carla Maia, Jaime Martinez-Urtaza, Zhifu Mi, Carles Milà, Jan C Minx, Mark Nieuwenhuijsen, Julia Palamarchuk, Dafni Kalatzi Pantera, Marcos Quijal-Zamorano, Peter Rafaj, Elizabeth J Z Robinson, Nacho Sánchez-Valdivia, Daniel Scamman, Oliver Schmoll, Maquins Odhiambo Sewe, Jodi D Sherman, Pratik Singh, Elena Sirotkina, Henrik Sjödin, Mikhail Sofiev, Balakrishnan Solaraju-Murali, Marco Springmann, Marina Treskova, Joaquin Triñanes, Eline Vanuytrecht, Fabian Wagner, Maria Walawender, Laura Warnecke, Ran Zhang, Marina Romanello, Josep M Antó, Maria Nilsson, Rachel Lowe
Journal: The Lancet Public Health (2024)
ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair
Authors: Renshuai Hua, Chenxi Zhao, Zhengyu Xu, Derong Liu, Wenyuan Shen, Wenlu Yuan, Yan Li, Jun Ma, Zhishuo Wang, Shiqing Feng
Journal: Bioactive Materials (2024)

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord, and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI. Although human umbilical cord mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments and promote neural regeneration in SCI, their efficacy is greatly limited by the local microenvironment after SCI. Therefore, in this study, we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor, in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence, and combined with the reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair. Meanwhile, we also modified the classic ferroptosis inhibitor Ferrostatin-1 (Fer-1) and synthesized a new prodrug Feborastatin-1 (Feb-1). The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI, and promoted the recovery of neurological function in rats with SCI. This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.
Biodegradable Zn-2Cu-0.5Zr alloy promotes the bone repair of senile osteoporotic fractures via the immune-modulation of macrophages
Authors: Huanzhong Ji, Gang Shen, Hanghang Liu, Yao Liu, Junyu Qian, GuoJiang Wan, En Luo
Journal: Bioactive Materials (2024)

Delayed bone-healing of senile osteoporotic fractures remains a clinical challenge due to the alterations caused by aging in bone and immune systems. The novel biomaterials that address the deficiencies in both skeletal cells and immune systems are required to effectively treat the bone injuries of older patients. Zinc (Zn) has shown promise as a biodegradable material for use in orthopedic implants. To address the bone-healing deficiencies in elderly patients with bone injuries, we developed a biodegradable Zn-based alloy (Zn–2Cu-0.5Zr) with enhanced mechanical properties, including a yield strength of 198.7 MPa and ultimate tensile strength of 217.6 MPa, surpassing those of pure Zn and Zn–2Cu alloys. Cytotoxicity tests conducted on bone marrow mesenchymal stem cells (BMSCs) and MC3T3-E1 cells demonstrated that the extracts from Zn–2Cu-0.5Zr alloy exhibited no observable cytotoxic effects. Furthermore, the extracts of Zn–2Cu-0.5Zr alloy exhibited significant anti-inflammatory effects through regulation of inflammation-related cytokine production and modulation of macrophage polarization. The improved immune-osteo microenvironment subsequently contributed to osteogenic differentiation of BMSCs. The potential therapeutic application of Zn–2Cu-0.5Zr in senile osteoporotic fracture was tested using a rat model of age-related osteoporosis. The Zn–2Cu-0.5Zr alloy met the requirements for load-bearing applications and accelerated the healing process in a tibial fracture in aged rats. The imaging and histological analyses showed that it could accelerate the bone-repair process and promote the fracture healing in senile osteoporotic rats. These findings suggest that the novel Zn–2Cu-0.5Zr alloy holds potential for influencing the immunomodulatory function of macrophages and facilitating bone repair in elderly individuals with osteoporosis.
Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects
Authors: Pan Huang, Quanbin Dong, Yifeng Wang, Yunfan Tian, Shunhe Wang, Chengcheng Zhang, Leilei Yu, Fengwei Tian, Xiaoxiang Gao, Hang Guo, Shanrong Yi, Mingyang Li, Yang Liu, Qingsong Zhang, Wenwei Lu, Gang Wang, Bo Yang, Shumao Cui, Dongxu Hua, Xiuchao Wang, Yuwen Jiao, Lu Liu, Qiufeng Deng, Beining Ma, Tingting Wu, Huayiyang Zou, Jing Shi, Haifeng Zhang, Daming Fan, Yanhui Sheng, Jianxin Zhao, Liming Tang, Hao Zhang, Wei Sun, Wei Chen, Xiangqing Kong, Lianmin Chen, Qixiao Zhai
Journal: Cell Genomics (2024)

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.
Contemporary g<scp>uideline‐directed</scp> medical therapy in de novo, chronic, and worsening heart failure patients: First data from the <scp>TITRATE‐HF</scp> study
Authors: Jishnu Malgie, Mariëlle I. Wilde, Pascal R.D. Clephas, Mireille E. Emans, Stefan Koudstaal, Jeroen Schaap, Arend Mosterd, Jan van Ramshorst, Alexander J. Wardeh, Sandra van Wijk, Mieke van den Heuvel, Eric Wierda, C. Jan Willem Borleffs, Colette Saraber, Saskia L.M.A. Beeres, Roland van Kimmenade, Wouter Jansen Klomp, Robert Denham, Carlos A. da Fonseca, IJsbrand T. Klip, Olivier C. Manintveld, Robert M.A. van der Boon, Clara E.E. van Ofwegen, Ayten Yilmaz, Ron Pisters, Gerard C.M. Linssen, Nikola Faber, Loek van Heerebeek, Julio E.C. van de Swaluw, Lex J. Bouhuijzen, Marco C. Post, Aaf F.M. Kuijper, Ka wai Wu, Eugène A. van Beek, Tim Hesselink, Lennaert Kleijn, Maurice J.M. Kurvers, René A. Tio, Jorina Langerveld, Bas M. van Dalen, J.W. Martijn van Eck, M. Louis Handoko, Walter R.M. Hermans, Hetty J.J. Koornstra‐Wortel, Mariusz K. Szymanski, Dennis Rooker, Kenneth Tandjung, Sabine C.M. Eijsbouts, Folkert W. Asselbergs, Peter van der Meer, Hans‐Peter Brunner‐La Rocca, Rudolf A. de Boer, Jasper J. Brugts
Journal: European Journal of Heart Failure (2024)

Abstract Aims Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real‐world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE‐HF study started to prospectively investigate the use, sequencing, and titration of guideline‐directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. Methods and results TITRATE‐HF is an ongoing long‐term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63–78), 29% were female, and median ejection fraction was 35% (IQR 25–40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non‐use in HFrEF patients was related to side‐effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. Conclusion This first analysis of the TITRATE‐HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.
Renal function and natriuresis‐guided diuretic therapy – a pre‐specified analysis from the PUSH‐AHF trial
Authors: Kevin Damman, Iris E. Beldhuis, Peter van der Meer, Jan A. Krikken, Jenifer E. Coster, Wybe Nieuwland, Dirk J. van Veldhuisen, Adriaan A. Voors, Jozine M. ter Maaten
Journal: European Journal of Heart Failure (2024)

Abstract Aim In a randomized controlled trial, we recently showed that a natriuresis‐guided diuretic approach improved natriuresis and diuresis in patients with acute heart failure (HF). In this pre‐specified analysis, we investigated the association between (worsening) renal function, outcomes and the effect of intensive natriuresis‐guided loop diuretic therapy as compared with standard of care. Methods and results The Pragmatic Urinary Sodium‐based algoritHm in Acute Heart Failure (PUSH‐AHF) trial randomized patients to natriuresis‐guided diuretic therapy or standard of care. Serum creatinine and estimated glomerular filtration rate (eGFR) were assessed at fixed timepoints, and worsening renal function (WRF) was assessed at 72 h. The primary outcome was the interaction between randomized treatment allocation, baseline eGFR and the dual primary outcome of PUSH‐AHF: total natriuresis at 24 h and time to all‐cause mortality or HF rehospitalization at 180 days. In 309 patients, median baseline eGFR was 53 (35–73) ml/min/1.73 m 2 , and 58% had eGFR &lt;60 ml/min/1.73 m 2 . Baseline eGFR did not significantly modify the treatment effect of natriuresis‐guided diuretic therapy on natriuresis at 24 h ( p for interaction = 0.730). However, baseline eGFR significantly modified the effect on all‐cause mortality and HF rehospitalization ( p for interaction = 0.017): the risk of this second primary outcome was lower in patients with lower eGFR who were randomized to the natriuresis‐guided group. In the natriuresis‐guided arm, eGFR decreased more (−11.0 vs. −6.91 ml/min/1.73 m 2 ; p = 0.002) during the first 3 days, but this effect was attenuated at discharge (−10.3 vs. −8.69 ml/min/1.73 m 2 ; p = 0.38). WRF was more frequently observed in patients randomized to natriuresis‐guided treatment, but was not associated with worse clinical outcomes. Conclusions Natriuresis‐guided diuretic treatment improved diuresis and natriuresis irrespective of baseline eGFR and occurrence of WRF, was effective even in patients with low eGFR, and the observed effect on eGFR was transient and not associated with worse clinical outcomes.
Cardiovascular-Kidney-Metabolic Overlap in Heart Failure With Mildly Reduced or Preserved Ejection Fraction
Authors: John W. Ostrominski, Brian L. Claggett, Zi Michael Miao, Finnian R. Mc Causland, Inder S. Anand, Akshay S. Desai, Pardeep S. Jhund, Carolyn S.P. Lam, Marc A. Pfeffer, Bertram Pitt, Faiez Zannad, Michael R. Zile, Antonieta Bomfim Wirtz, James Lay-Flurrie, Prabhakar Viswanathan, John J.V. McMurray, Scott D. Solomon, Muthiah Vaduganathan
Journal: Journal of the American College of Cardiology (2024)
Titration of Medications After Acute Heart Failure Is Safe, Tolerated, and Effective Regardless of Risk
Authors: Andrew P Ambrosy, Alex J Chang, Beth Davison, Adriaan Voors, Alain Cohen-Solal, Albertino Damasceno, Antoine Kimmoun, Carolyn S P Lam, Christopher Edwards, Daniela Tomasoni, Etienne Gayat, Gerasimos Filippatos, Hadiza Saidu, Jan Biegus, Jelena Celutkiene, Jozine M Ter Maaten, Kamilė Čerlinskaitė-Bajorė, Karen Sliwa, Koji Takagi, Marco Metra, Maria Novosadova, Marianela Barros, Marianna Adamo, Matteo Pagnesi, Mattia Arrigo, Ovidiu Chioncel, Rafael Diaz, Peter S Pang, Piotr Ponikowski, Gad Cotter, Alexandre Mebazaa
Journal: JACC Heart Failure (2024)
Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec‐15 axis in immune escape
Authors: Xin‐Yu Zhang, Jian‐Bo Shi, Shu‐Fang Jin, Rui‐Jie Wang, Ming‐Yu Li, Zhi‐Yuan Zhang, Xi Yang, Hai‐Long Ma
Journal: Cancer Communications (2024)

Abstract Background Metabolic reprograming and immune escape are two hallmarks of cancer. However, how metabolic disorders drive immune escape in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, the aim of the present study was to investigate the metabolic landscape of HNSCC and its mechanism of driving immune escape. Methods Analysis of paired tumor tissues and adjacent normal tissues from 69 HNSCC patients was performed using liquid/gas chromatography‐mass spectrometry and RNA‐sequencing. The tumor‐promoting function of kynurenine (Kyn) was explored in vitro and in vivo. The downstream target of Kyn was investigated in CD8 + T cells. The regulation of CD8 + T cells was investigated after Siglec‐15 overexpression in vivo. An engineering nanoparticle was established to deliver Siglec‐15 small interfering RNA (siS15), and its association with immunotherapy response were investigated. The association between Siglec‐15 and CD8 + programmed cell death 1 (PD‐1) + T cells was analyzed in a HNSCC patient cohort. Results A total of 178 metabolites showed significant dysregulation in HNSCC, including carbohydrates, lipids and lipid‐like molecules, and amino acids. Among these, amino acid metabolism was the most significantly altered, especially Kyn, which promoted tumor proliferation and metastasis. In addition, most immune checkpoint molecules were upregulated in Kyn‐high patients based on RNA‐sequencing. Furthermore, tumor‐derived Kyn was transferred into CD8 + T cells and induced T cell functional exhaustion, and blocking Kyn transporters restored its killing activity. Accroding to the results, mechanistically, Kyn transcriptionally regulated the expression of Siglec‐15 via aryl hydrocarbon receptor (AhR), and overexpression of Siglec‐15 promoted immune escape by suppressing T cell infiltration and activation. Targeting AhR in vivo reduced Kyn‐mediated Siglec‐15 expression and promoted intratumoral CD8 + T cell infiltration and killing capacity. Finally, a NH 2 ‐modified mesoporous silica nanoparticle was designed to deliver siS15, which restored CD8 + T cell function status and enhanced anti‐PD‐1 efficacy in tumor‐bearing immunocompetent mice. Clinically, Siglec‐15 was positively correlated with AhR expression and CD8 + PD‐1 + T cell infiltration in HNSCC tissues. Conclusions The findings describe the metabolic landscape of HNSCC comprehensively and reveal that the Kyn/Siglec‐15 axis may be a novel potential immunometabolism mechanism, providing a promising therapeutic strategy for cancers.
Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial
Authors: Hong-Han Ge, Ning Cui, Xiao-Hong Yin, Li-Fen Hu, Zhi-You Wang, Yi-Mei Yuan, Ming Yue, Hong-Di Lv, Zhen Wang, Wen-Wen Zhang, Lan Zhang, Lan Yuan, Xue-Juan Fan, Xin Yang, Yong-Xiang Wu, Guang-Qian Si, Zhen-Yu Hu, Hao Li, Xiao-Ai Zhang, Peng-Tao Bao, Wei Liu
Journal: Journal of Infection (2024)

Highlights•Tocilizumab therapy can reduce the fatality for severe SFTS patients.•A combined therapy of tocilizumab plus corticosteroids was recommended for SFTS.•Patients treated with tocilizumab did not experience more serious coinfections.SummaryBackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy.MethodsWe conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317).Results63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone.ConclusionsA significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.
Impact of pruritus on patient fatigue: a cross-sectional study
Authors: Luis F Andrade, Zaim Haq, Parsa Abdi, Michael J Diaz, Gil Yosipovitch
Journal: British Journal of Dermatology (2024)

Through an analysis of 114 015 adult patients in the NIH All of Us research programme – an initiative structured to incorporate populations that have been historically under-represented in biomedical research – we concluded that diagnoses of chronic pruritus and pruritus-related conditions were significantly associated with increased fatigue compared with age-, sex- and race/ethnicity propensity-matched controls without pruritus.
Bilaterally Aligned Electroosmotic Flow Generated by Porous Microneedle Device for Dual‐Mode Delivery
Authors: Gaobo Wang, Kosuke Kato, Sae Ichinose, Daisuke Inoue, Airi Kobayashi, Hitoshi Terui, Soichiro Tottori, Makoto Kanzaki, Matsuhiko Nishizawa
Journal: Advanced Healthcare Materials (2024)

Here, a novel porous microneedle (PMN) device with bilaterally aligned electroosmotic flow (EOF) enabling controllable dual-mode delivery of molecules is developed. The PMNs placed at anode and cathode compartments are modified with anionic poly-2-acrylamido-2-methyl-1-propanesulfonic acid and cationic poly-(3-acrylamidopropyl) trimethylammonium, respectively. The direction of EOF generated by PMN at the cathode compartment is, therefore, reversed from cathode to anode, countering the unwanted cathodal suctioning of interstitial fluid caused by reverse iontophoresis. With the bilateral alignment of EOF, the versatility of the proposed device is evaluated by delivering molecules with different charges and sizes using Franz cell. In addition, a 3D printed probe device is developed to ease practical handling and minimize electrical stimulation by integrating two PMNs in closed proximity. Finally, the performance of the integrated probe device is demonstrated by dual delivery of a variety of molecules (methylene blue, rhodamine B, and fluorescein isothiocyanate-dextran) using pig skin and vaccination using mice with delivered ovalbumin.
Modifying the Backbone Chemistry of PEG‐Based Bottlebrush Block Copolymers for the Formation of Long‐Circulating Nanoparticles
Authors: Julian Grundler, Chang‐Hee Whang, Kwangsoo Shin, N. Anna Savan, Mingjiang Zhong, W. Mark Saltzman
Journal: Advanced Healthcare Materials (2024)

Nanoparticle physicochemical properties have received great attention in optimizing the performance of nanoparticles for biomedical applications. For example, surface functionalization with small molecules or linear hydrophilic polymers is commonly used to tune the interaction of nanoparticles with proteins and cells. However, it is challenging to control the location of functional groups within the shell for conventional nanoparticles. Nanoparticle surfaces composed of shape-persistent bottlebrush polymers allow hierarchical control over the nanoparticle shell but the effect of the bottlebrush backbone on biological interactions is still unknown. The synthesis is reported of novel heterobifunctional poly(ethylene glycol) (PEG)-norbornene macromonomers modified with various small molecules to form bottlebrush polymers with different backbone chemistries. It is demonstrated that micellar nanoparticles composed of poly(lactic acid) (PLA)-PEG bottlebrush block copolymer (BBCP) with neutral and cationic backbone modifications exhibit significantly reduced cellular uptake compared to conventional unmodified BBCPs. Furthermore, the nanoparticles display long blood circulation half-lives of ≈22 hours and enhanced tumor accumulation in mice. Overall, this work sheds light on the importance of the bottlebrush polymer backbone and provides a strategy to improve the performance of nanoparticles in biomedical applications.
Thrombogenicity of biodegradable metals
Authors: D.E.J. Anderson, H.H. Le, H. Vu, J. Johnson, J.E. Aslan, J. Goldman, M.T. Hinds
Journal: Bioactive Materials (2024)

Biodegradable metals offer a promising means to ameliorate many of the long-term risks associated with vascular devices made of conventional biostable stent metals. While numerous biodegradable metal alloys have been developed and characterized in animal models, knowledge of their blood reactivity and thrombogenicity remains unknown. Metal hemocompatibility is particularly valuable because current generation drug-eluting stents pose a significant long-term thrombosis risk. In this study, four pure metals, widely used as degradable base materials (Fe, Zn, Mg, and Mo), and three alloys commonly used in cardiovascular devices [NiTi, CoCr, and stainless steel (SS)] were evaluated. This work examined how each of these metals activate platelets, coagulation factors, and inflammation using in vitro hemocompatibility assays and a clinically relevant ex vivo non-human primate arteriovenous shunt model. Testing found that while all metals promoted a downstream activation of platelets and coagulation in flowing whole blood, platelet and fibrin attachment to Mg was markedly reduced. Additionally, Fe and Mo trended toward higher platelet attachment and contact pathway activation. Overall, the results suggest that Mg may delay clot initiation, but not eliminate clot formation, indicating the importance of understanding thrombosis in Mg alloys that are currently being developed for clinical use as biodegradable stents.