tbuckley/cabot-search huggingface dataset:
Antibiotic-loaded amphora-shaped pores on a titanium implant surface enhance osteointegration and prevent infections
Authors: Viviane Ständert, Kai Borcherding, Nicole Bormann, Gerhard Schmidmaier, Ingo Grunwald, Britt Wildemann
Journal: Bioactive Materials (2021)

Artificial prostheses for joint replacement are indispensable in orthopedic surgery. Unfortunately, the implanted surface is attractive to not only host cells but also bacteria. To enable better osteointegration, a mechanically stable porous structure was created on a titanium surface using laser treatment and metallic silver particles were embedded in a hydrophilic titanium oxide layer on top. The laser structuring resulted in unique amphora-shaped pores. Due to their hydrophilic surface conditions and capillary forces, the pores can be loaded preoperative with the antibiotic of choice/need, such as gentamicin. Cytotoxicity and differentiation assays with primary human osteoblast-like cells revealed no negative effect of the surface modification with or without gentamicin loading. An in vivo biocompatibility study showed significantly enhanced osteointegration as measured by push-out testing and histomorphometry 56 days after the implantation of the K-wires into rat femora. Using a S. aureus infection model, the porous, silver-coated K-wires slightly reduced the signs of bone destruction, while the wires were still colonized after 28 days. Loading the amphora-shaped pores with gentamicin significantly reduced the histopathological signs of bone destruction and no bacteria were detected on the wires. Taken together, this novel surface modification can be applied to new or established orthopedic implants. It enables preoperative loading with the antibiotic of choice/need without further equipment or post-coating, and supports osteointegration without a negative effect of the released dug, such as gentamicin.
Correspondence on ‘Risk of venous thromboembolism in rheumatoid arthritis, and its association with disease activity: a nationwide cohort study from Sweden’
Authors: Maria I Zervou, George N Goulielmos
Journal: Annals of the Rheumatic Diseases (2021)

We read with great interest an article by Molander et al 1 demonstrating a strong association between clinical rheumatoid arthritis (RA) disease activity, measured by Disease Avtivity Score-28 (DAS28) ESR, and the risk of venous thromboembolism (VTE). In the framework of this elegant nationwide register-based cohort study that enrolled 46 316 patients, it was found that the risk ratio for VTE in patients with RA was 1.88 (95% CI 1.65 to 2.15), while among patients with RA, the risk for VTE increased with increasing RA disease activity. Noteworthy, compared with the general population, also patients with RA in DAS28 ESR remission were at elevated VTE risk.1 Therefore, the authors nicely suggested that RA disease activity can be used as an additional tool for VTE risk stratification in patients with RA. RA is an …
SARS-CoV-2 infection and viral load are associated with the upper respiratory tract microbiome
Authors: Christian Rosas-Salazar, Kyle S. Kimura, Meghan H. Shilts, Britton A. Strickland, Michael H. Freeman, Bronson C. Wessinger, Veerain Gupta, Hunter M. Brown, Seesandra V. Rajagopala, Justin H. Turner, Suman R. Das
Journal: Journal of Allergy and Clinical Immunology (2021)
Increasing Post-Myocardial Infarction Heart Failure Incidence in Elderly Patients: A Call for Action⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Chang-seng Liang, Joseph D. Delehanty
Journal: Journal of the American College of Cardiology (2009)
Morphine acts on spinal dynorphin neurons to cause itch through disinhibition
Authors: Eileen Nguyen, Grace Lim, Huiping Ding, Junichi Hachisuka, Mei-Chuan Ko, Sarah E. Ross
Journal: Science Translational Medicine (2021)

Morphine-induced itch is mediated by a specific population of dynorphin-expressing spinal inhibitory neurons in mice.
Soluble Intercellular Adhesion Molecule-1 Associated with Endothelial Dysfunction and the Echographic Analysis with the Impairment Musculoskeletal in Obesity
Authors: Leticia Manuel-Apolinar, Alejandra Martínez Coria, Norma Angélica Estrada-Cruz, Daniel H. Montes-Cortes
Journal: Metabolism (2021)
A Multicenter Study of Recombinant Factor VIII (Recombinate): Safety, Efficacy, and Inhibitor Risk in Previously Untreated Patients With Hemophilia A
Authors: G.L. Bray, E.D. Gomperts, S. Courier, R. Gruppo, E.M. Gordon, M. Manco-Johnson, A. Shapiro, E. Scheibel, G. White, M. Lee
Journal: Blood (1994)
Quantifying Variation in Treatment Utilization for Type 2 Diabetes Across Five Major University of California Health Systems
Authors: Thomas A. Peterson, Valy Fontil, Suneil K. Koliwad, Ayan Patel, Atul J. Butte
Journal: Diabetes Care (2021)

OBJECTIVE Using the newly created University of California (UC) Health Data Warehouse, we present the first study to analyze antihyperglycemic treatment utilization across the five large UC academic health systems (Davis, Irvine, Los Angeles, San Diego, and San Francisco). RESEARCH DESIGN AND METHODS This retrospective analysis used deidentified electronic health records (EHRs; 2014–2019) including 97,231 patients with type 2 diabetes from 1,003 UC-affiliated clinical settings. Significant differences between health systems and individual providers were identified using binomial probabilities with cohort matching. RESULTS Our analysis reveals statistically different treatment utilization patterns not only between health systems but also among individual providers within health systems. We identified 21 differences among health systems and 29 differences among individual providers within these health systems, with respect to treatment intensifications within existing guidelines on top of either metformin monotherapy or dual therapy with metformin and a sulfonylurea. Next, we identified variation for medications within the same class (e.g., glipizide vs. glyburide among sulfonylureas), with 33 differences among health systems and 86 among individual providers. Finally, we identified 2 health systems and 55 individual providers who more frequently used medications with known cardioprotective benefits for patients with high cardiovascular disease risk, but also 1 health system and 8 providers who prescribed such medications less frequently for these patients. CONCLUSIONS Our study used cohort-matching techniques to highlight real-world variation in care between health systems and individual providers. This demonstrates the power of EHRs to quantify differences in treatment utilization, a necessary step toward standardizing precision care for large populations.
Clinical Characteristics of SARS-CoV2 Infected and Exposed Patients at a Tertiary Care Allergy/Immunology Program in Florida
Authors: Mary Ann Miranda, Joseph Dasso, Maryssa Ellison, Jessica Trotter, Priyanka Timothy, Maria Chitty-Lopez, Carla Duff, Daime Nieves, Emma Westermann-Clark, Nathan Tang, Mandel Sher, Mark Ballow, Jennifer Leiding, Panida Sriaroon, Jolan Walter
Journal: Journal of Allergy and Clinical Immunology (2021)

Immunocompromised persons are logically thought to have increased risk of severe SARS-CoV-2 infection (COVID-19) and Florida has one of the highest number of COVID-19 cases nationally. How allergic and immunologic disorders affect the clinical course of COVID-19 is not fully understood. Hence, we characterized the demographics, symptoms, diagnosis, comorbidities, and disease severity of patients in our academic allergy/immunology program in Florida with SARS-CoV2 infection or direct exposure to household contacts. Infection was confirmed by viral nucleic acid testing or antibody serology. We performed a referral-based retrospective chart review of patients described above. Of 18 patients, most had allergic conditions (60%) and/or antibody deficiency (55%). One patient was asymptomatic with severe T-cell lymphopenia and another had combined immunodeficiency and untreated hypogammaglobulinemia. The median age of 12 symptomatic patients with COVID-19 was 18 years with similar sex distribution and divided equally as to staying home, going to emergency department or becoming hospitalized (33% each). Six patients with COVID-19 household contacts were asymptomatic (2 PCR negative, 1 IgG seropositive, 3 not tested). Six of 18 had serological testing and 3 (50%) were positive for SARS-CoV2 IgG antibody. All hospitalized patients had comorbidities of asthma and/or obesity. All patients were treated supportively and none required respiratory support or died. This observational study suggests that in our predominantly pediatric population with allergic and immune disorders, mostly young adults become infected and symptomatic. Comorbidity with asthma and obesity increases hospitalization. Whether non-asthmatic allergic disorders and/or immunodeficiency affects infectivity or morbidity is unclear.
In Search of the Optimal Target for Phosphate Control: Episode 1
Authors: Ron Wald, Michael W. Walsh
Journal: Journal of the American Society of Nephrology (2021)

Hyperphosphatemia is near ubiquitous among patients receiving maintenance dialysis. Compelling experimental data suggest that hyperphosphatemia is directly toxic to the vasculature.[1][1] Numerous epidemiologic studies demonstrated an association between elevated serum phosphate and mortality.[2][2
Design of Temperature-Responsive Cell Culture Surfaces for Cell Sheet Engineering
Authors: Y. Akiyama
Journal: Cyborg and Bionic Systems (2021)

Temperature-responsive cell culture surfaces, which modulate cell attachment/detachment characteristics with temperature, have been used to fabricate cell sheets. Extensive study on fabrication of cell sheet with the temperature-responsive cell culture surface, manipulation, and transplantation of the cell sheet has established the interdisciplinary field of cell sheet engineering, in which engineering, biological, and medical fields closely collaborate. Such collaboration has pioneered cell sheet engineering, making it a promising and attractive technology in tissue engineering and regenerative medicine. This review introduces concepts of cell sheet engineering, followed by designs for the fabrication of various types of temperature-responsive cell culture surfaces and technologies for cell sheet manipulation. The development of various methods for the fabrication of temperature-responsive cell culture surfaces was also summarized. The availability of cell sheet engineering for the treatment and regeneration of damaged human tissue has also been described, providing examples of the clinical application of cell sheet transplantation in humans.
Carbon nanomaterials for cardiovascular theranostics: Promises and challenges
Authors: Keshav Narayan Alagarsamy, Sajitha Mathan, Weiang Yan, Alireza Rafieerad, Saravanan Sekaran, Hanna Manego, Sanjiv Dhingra
Journal: Bioactive Materials (2021)

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Heart attack and stroke cause irreversible tissue damage. The currently available treatment options are limited to "damage-control" rather than tissue repair. The recent advances in nanomaterials have offered novel approaches to restore tissue function after injury. In particular, carbon nanomaterials (CNMs) have shown significant promise to bridge the gap in clinical translation of biomaterial based therapies. This family of carbon allotropes (including graphenes, carbon nanotubes and fullerenes) have unique physiochemical properties, including exceptional mechanical strength, electrical conductivity, chemical behaviour, thermal stability and optical properties. These intrinsic properties make CNMs ideal materials for use in cardiovascular theranostics. This review is focused on recent efforts in the diagnosis and treatment of heart diseases using graphenes and carbon nanotubes. The first section introduces currently available derivatives of graphenes and carbon nanotubes and discusses some of the key characteristics of these materials. The second section covers their application in drug delivery, biosensors, tissue engineering and immunomodulation with a focus on cardiovascular applications. The final section discusses current shortcomings and limitations of CNMs in cardiovascular applications and reviews ongoing efforts to address these concerns and to bring CNMs from bench to bedside.
The chromosome-level reference genome assembly for Dendrobium officinale and its utility of functional genomics research and molecular breeding study
Authors: Zhitao Niu, Fei Zhu, Yajuan Fan, Chao Li, Benhou Zhang, Shuying Zhu, Zhenyu Hou, Mengting Wang, Jiapeng Yang, Qingyun Xue, Wei Liu, Xiaoyu Ding
Journal: Acta Pharmaceutica Sinica B (2021)

Dendrobium officinale, an important medicinal plant of the genus Dendrobium in Orchidaceae family, has been used as traditional Chinese medicine (TCM) for nearly thousands of years. Here, we report the first chromosome-level reference genome of D. officinale, based on PacBio long-reads, Illumina short-reads and Hi-C data. The high-quality assembled genome is 1.23 Gb long, with contig N50 of 1.44 Mb. A total of 93.53% genome sequences were assembled into 19 pseudochromosomes with a super scaffold N50 of 63.07 Mb. Through comparative genomic analysis, we explored the expanded gene families of D. officinale, and also their impact on environmental adaptation and biosynthesis of secondary metabolites. We further performed detailed transcriptional analysis of D. officinale, and identified the candidate genes involved in the biosynthesis of three main active ingredients, including polysaccharides, alkaloids and flavonoids. In addition, the MODIFYING WALL LIGNIN-1 (MWL1) gene, which inferred from Genome-Wide Association Studies (GWAS) based on the resequencing date from D. officinale and five related species and their morphologic features, may contribute to the plant production (yield of stems) of D. officinale. Therefore, the high-quality reference genome reported in this study could benefits functional genomics research and molecular breeding of D. officinale.
How Did We Get a COVID-19 Vaccine in Less Than 1 Year?
Authors: E. John Wherry, Elizabeth M. Jaffee, Nicholas Warren, Gypsyamber D'Souza, Antoni Ribas
Journal: Clinical Cancer Research (2021)

Abstract The successful development of COVID-19 vaccines within an unprecedented short time needs to be followed by rapid vaccine uptake, in particular, in high-risk populations such as patients with cancer. It is important for the scientific research community and cancer physicians to convey the knowledge behind the COVID-19 vaccine development and contribute to build the required trust on their use.
Phase II trial of pegylated liposomal doxorubicin-cyclophosphamide combination as first-line chemotherapy in elderly metastatic breast cancer patients
Authors: P. R. Dufour, F. Rousseau, N. Meyer, T. Delozier, D. Serin, M. Nabet, L. Djafari, J. Kurtz
Journal: Journal of Clinical Oncology (2007)

19565 Background: Although the majority of metastatic breast cancer (MBC) patients (pts) responds to endocrine therapy, treatment failure is a concern, as well as front-line therapy for pts with ER/PR negative disease.The combination of anthracyclines (A) and cyclophosphamide (C) is active in younger pts, but cardiac toxicity of A in elderly MBC pts has to be considered. Pegylated liposomal doxorubicin (PLD) (Caelyx®) is active in MBC and has much less cardiotoxicity than A, and we present the preliminary data of the PLD/C in elderly MBC pts. Methods: This was a multicentric phase II trial. Inclusion criteria included: pts aged between 65 and 75, histologically proven measurable MBC, ECOG PS 0–1, LVEF = 50%, first-line chemotherapy for MBC. Prior adjuvant chemotherapy was allowed if stopped for = 6 or 12 months without and with anthracyclines, respectively. Endocrine therapy either in the adjuvant or metastatic setting had to be stopped for = 1 month. All pts gave a written informed consent. The treatment schedule was : PLD 40mg/m 2 and C 500mg/m 2 d1 every 4 weeks. Efficacy as well as response duration and tolerance were the primary and secondary end-points, respectively. Results: 35 patients were enrolled (Median age 71.3, range 65.6–75.9). A total of 166 cycles have been administered. The median number of cycles was 6 (range 1–9). No toxic death was reported, one patient died of diabetes mellitus decompensation. No congestive heart failure or decrease in LVEF was reported, although 1 pt experience grade 3 dyspnea and stopped treatment. Other (gr3–4) NCI-CTC toxicity included: neutropenia in 7 (gr3) and 3 (gr4) pts; gr3 mucositis (4). No febrile neutropenia was reported. Grade 3 hand-foot syndrome occurred in 1 pt, whereas treatment was stopped due to a generalized rash in 1 pt. An objective response (CR + PR) was achieved in 10 (28,6%) pts (1 CR and 8 PR), and a disease control in 24 (68.6%) with a progression free survival of 8.8 months and a median survival of 20.4 months Conclusions: The LPD-C combination is active in elderly MBC pts, with an acceptable toxicity profile. No significant financial relationships to disclose.
Oncogenetic landscape of lymphomagenesis in coeliac disease
Authors: Sascha Cording, Ludovic Lhermitte, Georgia Malamut, Sofia Berrabah, Amélie Trinquand, Nicolas Guegan, Patrick Villarese, Sophie Kaltenbach, Bertrand Meresse, Sherine Khater, Michael Dussiot, Marc Bras, Morgane Cheminant, Bruno Tesson, Christine Bole-Feysot, Julie Bruneau, Thierry Jo Molina, David Sibon, Elizabeth Macintyre, Olivier Hermine, Christophe Cellier, Vahid Asnafi, Nadine Cerf-Bensussan
Journal: Gut (2021)

Enteropathy-associated T-cell lymphoma (EATL) is a rare but severe complication of coeliac disease (CeD), often preceded by low-grade clonal intraepithelial lymphoproliferation, referred to as type II refractory CeD (RCDII). Knowledge on underlying oncogenic mechanisms remains scarce. Here, we analysed and compared the mutational landscape of RCDII and EATL in order to identify genetic drivers of CeD-associated lymphomagenesis.Pure populations of RCDII-cells derived from intestinal biopsies (n=9) or sorted from blood (n=2) were analysed by whole exome sequencing, comparative genomic hybridisation and RNA sequencing. Biopsies from RCDII (n=50), EATL (n=19), type I refractory CeD (n=7) and uncomplicated CeD (n=18) were analysed by targeted next-generation sequencing. Moreover, functional in vitro studies and drug testing were performed in RCDII-derived cell lines.80% of RCDII and 90% of EATL displayed somatic gain-of-functions mutations in the JAK1-STAT3 pathway, including a remarkable p.G1097 hotspot mutation in the JAK1 kinase domain in approximately 50% of cases. Other recurrent somatic events were deleterious mutations in nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) regulators TNFAIP3 and TNIP3 and potentially oncogenic mutations in TET2, KMT2D and DDX3X. JAK1 inhibitors, and the proteasome inhibitor bortezomib could block survival and proliferation of malignant RCDII-cell lines.Mutations activating the JAK1-STAT3 pathway appear to be the main drivers of CeD-associated lymphomagenesis. In concert with mutations in negative regulators of NF-κB, they may favour the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine. The identified mutations are attractive therapeutic targets to treat RCDII and block progression towards EATL.
Poverty, health, and covid-19
Authors: Margaret Whitehead, David Taylor-Robinson, Ben Barr
Journal: BMJ (2021)

Covid-19 does not strike at random-mortality is much higher in elderly people, poorer groups, and ethnic minorities, and its economic effect is also unevenly distributed across the population.The economic fallout is likely to be felt for years.Without concerted preventive action worse off families and communities will be disproportionately affected, increasing health inequalities in the UK and globally.
Use of Helmet CPAP in COVID-19 – A practical review
Authors: H. Amirfarzan, M. Cereda, T.G. Gaulton, K.B. Leissner, A. Cortegiani, R. Schumann, C. Gregoretti
Journal: Pulmonology (2021)

Helmet CPAP (H-CPAP) has been recommended in many guidelines as a noninvasive respiratory support during COVID-19 pandemic in many countries around the world. It has the least amount of particle dispersion and air contamination among all noninvasive devices and may mitigate the ICU bed shortage during a COVID surge as well as a decreased need for intubation/mechanical ventilation. It can be attached to many oxygen delivery sources. The MaxVenturi setup is preferred as it allows for natural humidification, low noise burden, and easy transition to HFNC during breaks and it is the recommended transport set-up. The patients can safely be proned with the helmet. It can also be used to wean the patients from invasive mechanical ventilation. Our article reviews in depth the pathophysiology of COVID-19 ARDS, provides rationale of using H-CPAP, suggests a respiratory failure algorithm, guides through its setup and discusses the issues and concerns around using it.
Heterogeneity of HSCs in a Mouse Model of NASH
Authors: Sara Brin Rosenthal, Xiao Liu, Souradipta Ganguly, Debanjan Dhar, Martina P. Pasillas, Eugenia Ricciardelli, Rick Z. Li, Ty D. Troutman, Tatiana Kisseleva, Christopher K. Glass, David A. Brenner
Journal: Hepatology (2021)

In clinical and experimental NASH, the origin of the scar-forming myofibroblast is the HSC. We used foz/foz mice on a Western diet to characterize in detail the phenotypic changes of HSCs in a NASH model.We examined the single-cell expression profiles (scRNA sequencing) of HSCs purified from the normal livers of foz/foz mice on a chow diet, in NASH with fibrosis of foz/foz mice on a Western diet, and in livers during regression of NASH after switching back to a chow diet. Selected genes were analyzed using immunohistochemistry, quantitative real-time PCR, and short hairpin RNA knockdown in primary mouse HSCs. Our analysis of the normal liver identified two distinct clusters of quiescent HSCs that correspond to their acinar position of either pericentral vein or periportal vein. The NASH livers had four distinct HSC clusters, including one representing the classic fibrogenic myofibroblast. The three other HSC clusters consisted of a proliferating cluster, an intermediate activated cluster, and an immune and inflammatory cluster. The livers with NASH regression had one cluster of inactivated HSCs, which was similar to, but distinct from, the quiescent HSCs.Analysis of single-cell RNA sequencing in combination with an interrogation of previous studies revealed an unanticipated heterogeneity of HSC phenotypes under normal and injured states.