tbuckley/cabot-search huggingface dataset:
Immunomodulation and osseointegration activities of Na2TiO3 nanorods-arrayed coatings doped with different Sr content
Authors: Dongmei Yu, Shuo Guo, Meng Yu, Wenwen Liu, Xiaokang Li, Dafu Chen, Bo Li, Zheng Guo, Yong Han
Journal: Bioactive Materials (2021)

To endow Ti-based orthopedic implants immunomodulatory capability and thus enhanced osseointegration, different amounts of Sr are doped in Na2TiO3 nanorods in the arrays with identical nanotopographic parameters (rod diameter, length and inter-rod spacing) by substitution of Na+ using hydrothermal treatment. The obtained arrays are denoted as STSr2, STSr4, and STSr7, where the arabic numbers indicate the incorporating amounts of Sr in Na2TiO3. The modulation effects of the Sr-doped nanorods arrays on macrophage polarization and osteogenetic functions of osteoblasts are investigated, together with the array without Sr (ST). Moreover, osseointegration of these arrays are also assayed in rat femoral condyles. Sr-doped nanorods arrays accelerate M1 (pro-inflammatory phenotype)-to-M2 (anti-inflammatory phenotype) transformation of the adhered macrophages, enhancing secretion of pro-osteogenetic cytokines and growth factors (TGF-β1 and BMP2), moreover, the Sr doped arrays directly enhance osteogenetic functions of osteoblasts. The enhancement of paracrine of M2 macrophages and osteogenetic function of osteoblasts is promoted with the increase of Sr incorporating amounts. Consequently, Sr doped arrays show significantly enhanced osseointegration in vivo compared to ST, and STSr7 exhibits the best performance. Our work sheds a new light on the design of surface chemical components and structures for orthopedic implants to enhance their osseointegration.
Polymer Composite Sponges with Inherent Antibacterial, Hemostatic, Inflammation‐Modulating and Proregenerative Performances for Methicillin‐Resistant <i>Staphylococcus aureus</i>‐Infected Wound Healing
Authors: Wenshuai Liu, Chunfang Yang, Rui Gao, Chao Zhang, Wenbin Ou‐Yang, Zujian Feng, Chuangnian Zhang, Xiangbin Pan, Pingsheng Huang, Deling Kong, Weiwei Wang
Journal: Advanced Healthcare Materials (2021)

Abstract Clinical wound management remains a major challenge due to massive bleeding, bacterial infection, and difficult wound healing after tissue trauma. To simultaneously address these issues, composite polymer sponges for accelerating drug‐resistant bacterial infected wound healing are fabricated by facilely mixing sodium polyacrylate (PAAS), double quaternary ammonium salts‐conjugated chitosan (QAS‐CS), and collagen (COL) in aqueous solution, followed by lyophilization. Composite sponges (PAAS/QAS‐CS/COL, PQC) show highly porous microstructures (porosity ≈90%) with moderate compress modulus (≈0.3 MPa), tensile strength (0.004 MPa), and high swelling ratio (≈3500%). Importantly, PQC sponge demonstrates superior hemostasis ability over commercially available CS sponge by inducing rapid hemagglutination, and exhibits significantly better antibacterial activity against both methicillin‐resistant Staphylococcus aureus (MRSA) and Escherichia coli by destroying cell membrane and causing the leakage of bioactive components such as potassium ion and β ‐galactosidase from treated bacterial. Furthermore, PQC sponge can efficiently promote cell proliferation. Significantly, the sponge greatly expedites the regeneration of MRSA‐infected full‐thickness skin wound in rabbit by successfully eradicating bacterial infection, and reducing inflammation. PQC sponge also improves both early angiogenesis and blood vessel maturation at the wound site. Overall, this multifunctional sponge is a promising wound dressing for clinical use and holds great potential for rapid clinical translation.
Phase II Trial of Symptom Screening With Targeted Early Palliative Care for Patients With Advanced Cancer
Authors: Camilla Zimmermann, Ashley Pope, Breffni Hannon, Monika K. Krzyzanowska, Gary Rodin, Madeline Li, Doris Howell, Jennifer J. Knox, Natasha B. Leighl, Srikala Sridhar, Amit M. Oza, Rebecca Prince, Stephanie Lheureux, Aaron R. Hansen, Anne Rydall, Brittany Chow, Leonie Herx, Christopher M. Booth, Deborah Dudgeon, Neesha Dhani, Geoffrey Liu, Philippe L. Bedard, Jean Mathews, Nadia Swami, Lisa W. Le
Journal: Journal of the National Comprehensive Cancer Network (2021)

Routine early palliative care (EPC) improves quality of life (QoL) for patients with advanced cancer, but it may not be necessary for all patients. We assessed the feasibility of Symptom screening with Targeted Early Palliative care (STEP) in a phase II trial.Patients with advanced cancer were recruited from medical oncology clinics. Symptoms were screened at each visit using the Edmonton Symptom Assessment System-revised (ESAS-r); moderate to severe scores (screen-positive) triggered an email to a palliative care nurse, who called the patient and offered EPC. Patient-reported outcomes of QoL, depression, symptom control, and satisfaction with care were measured at baseline and at 2, 4, and 6 months. The primary aim was to determine feasibility, according to predefined criteria. Secondary aims were to assess whether STEP identified patients with worse patient-reported outcomes and whether screen-positive patients who accepted and received EPC had better outcomes over time than those who did not receive EPC.In total, 116 patients were enrolled, of which 89 (77%) completed screening for ≥70% of visits. Of the 70 screen-positive patients, 39 (56%) received EPC during the 6-month study and 4 (6%) received EPC after the study end. Measure completion was 76% at 2 months, 68% at 4 months, and 63% at 6 months. Among screen-negative patients, QoL, depression, and symptom control were substantially better than for screen-positive patients at baseline (all P<.0001) and remained stable over time. Among screen-positive patients, mood and symptom control improved over time for those who accepted and received EPC and worsened for those who did not receive EPC (P<.01 for trend over time), with no difference in QoL or satisfaction with care.STEP is feasible in ambulatory patients with advanced cancer and distinguishes between patients who remain stable without EPC and those who benefit from targeted EPC. Acceptance of the triggered EPC visit should be encouraged.gov identifier: NCT04044040.
NHS recovery plan for England is “beyond urgent” given length of waiting times, says Labour
Authors: Adrian O’Dowd
Journal: BMJ (2021)

Patients routinely have to wait longer than the promised 18 weeks for NHS treatment in England, an analysis of official data by the Labour Party has shown.1

The party has urged the government to produce an NHS recovery plan before the end of this year setting out what action is being taken to reduce waiting lists and ensure that the service has enough staff and equipment to deliver the care needed.

The analysis of NHS England’s waiting times data found that in 83 hospitals patients waiting for specific surgeries or treatments, including oral surgery, ear nose and throat surgery, and ophthalmology, could …
Major Depressive Episode Severity Among Adults from Marginalized Racial and Ethnic Backgrounds in the US
Authors: Michael William Flores, Margo Moyer, Caryn R. R. Rodgers, Benjamin Lê Cook
Journal: JAMA Psychiatry (2021)

Depression is the leading cause of disability and disease burden in the US. 1,2Research using the National Comorbidity Survey (fielded 1990-1992) showed that while lifetime and pastyear rates of major depressive disorder were lower among individuals from minoritized racial and ethnic groups compared with White adults, 3 major depressive disorder persistence was greater for Black and Latino adults. 3Analysis of the National Survey of American Life (fielded 2001-2003) found similar or lower major depressive disorder prevalence among Black adults compared with White adults but greater major depressive disorder chronicity, severity, and disability. 4We provide an update of these findings, analyzing nationally representative data to estimate differences in major depressive episode (MDE) prevalence, persistence, and severity among racial and ethnic groups.
Clinical definition of acquired resistance to immunotherapy in patients with metastatic non-small-cell lung cancer
Authors: A.J. Schoenfeld, S.J. Antonia, M.M. Awad, E. Felip, J. Gainor, S.N. Gettinger, F.S. Hodi, M.L. Johnson, N.B. Leighl, C.M. Lovly, T. Mok, M. Perol, M. Reck, B. Solomon, J.-C. Soria, D.S.W. Tan, S. Peters, M.D. Hellmann
Journal: Annals of Oncology (2021)
The regional decline and rise of tick-borne encephalitis incidence do not correlate with Lyme borreliosis, Austria, 2005 to 2018
Authors: Karin Stiasny, Isabel Santonja, Heidemarie Holzmann, Astrid Essl, Gerold Stanek, Michael Kundi, Franz X Heinz
Journal: Eurosurveillance (2021)

BackgroundTick-borne encephalitis (TBE) virus is a human pathogen that is expanding its endemic zones in Europe, emerging in previously unaffected regions. In Austria, increasing incidence in alpine regions in the west has been countered by a decline in traditional endemic areas to the east of the country.AimTo shed light on the cause of this disparity, we compared the temporal changes of human TBE incidences in all federal provinces of Austria with those of Lyme borreliosis (LB), which has the same tick vector and rodent reservoir.MethodsThis comparative analysis was based on the surveillance of hospitalised TBE cases by the National Reference Center for TBE and on the analysis of hospitalised LB cases from hospital discharge records across all of Austria from 2005 to 2018.ResultsThe incidences of the two diseases and their annual fluctuations were not geographically concordant. Neither the decline in TBE in the eastern lowlands nor the increase in western alpine regions is paralleled by similar changes in the incidence of LB.ConclusionThe discrepancy between changes in incidence of TBE and LB support the contributions of virus-specific factors beyond the mere availability of tick vectors and/or human outdoor activity, which are a prerequisite for the transmission of both diseases. A better understanding of parameters controlling human pathogenicity and the maintenance of TBE virus in its natural vector-host cycle will generate further insights into the focal nature of TBE and can potentially improve forecasts of TBE risk on smaller regional scales.
Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes
Authors: Zachary T. Yoneda, Katherine C. Anderson, Joseph A. Quintana, Matthew J. O’Neill, Richard A. Sims, Andrew M. Glazer, Christian M. Shaffer, Diane M. Crawford, Thomas Stricker, Fei Ye, Quinn Wells, Lynne W. Stevenson, Gregory F. Michaud, Dawood Darbar, Steven A. Lubitz, Patrick T. Ellinor, Dan M. Roden, M. Benjamin Shoemaker
Journal: JAMA Cardiology (2021)

Early-onset atrial fibrillation (AF) can be the initial manifestation of a more serious underlying inherited cardiomyopathy or arrhythmia syndrome.
Sulfated Alginate Hydrogels Prolong the Therapeutic Potential of MSC Spheroids by Sequestering the Secretome
Authors: Marissa Gionet‐Gonzales, Alena Casella, Daphne Diloretto, Clara Ginnell, Katherine H. Griffin, Anne Bigot, J. Kent Leach
Journal: Advanced Healthcare Materials (2021)

Abstract Cell‐based approaches to tissue repair suffer from rapid cell death upon implantation, limiting the window for therapeutic intervention. Despite robust lineage‐specific differentiation potential in vitro, the function of transplanted mesenchymal stromal cells (MSCs) in vivo is largely attributed to their potent secretome comprising a variety of growth factors (GFs). Furthermore, GF secretion is markedly increased when MSCs are formed into spheroids. Native GFs are sequestered within the extracellular matrix (ECM) via sulfated glycosaminoglycans, increasing the potency of GF signaling compared to their unbound form. To address the critical need to prolong the efficacy of transplanted cells, alginate hydrogels are modified with sulfate groups to sequester endogenous heparin‐binding GFs secreted by MSC spheroids. The influence of crosslinking method and alginate modification is assessed on mechanical properties, degradation rate, and degree of sulfate modification. Sulfated alginate hydrogels sequester a mixture of MSC‐secreted endogenous biomolecules, thereby prolonging the therapeutic effect of MSC spheroids for tissue regeneration. GFs are sequestered for longer durations within sulfated hydrogels and retain their bioactivity to regulate endothelial cell tubulogenesis and myoblast infiltration. This platform has the potential to prolong the therapeutic benefit of the MSC secretome and serve as a valuable tool for investigating GF sequestration.
First treatment of Crohn’s disease refractory anastomotic stricture with a lumen-apposing metallic stent suitable for colonoscopy
Authors: Gabriel Marcellier, Diane Lorenzo, Abdellah Hedjoudje, Benedicte Jais, Yoram Bouhnik, Frederic Prat
Journal: Endoscopy (2021)

A 58-year-old patient with Crohn's disease and prior ileocecal resection, experienced repeated bouts of bowel occlusion related to a short and fibrotic anastomotic stricture despite several endoscopic dilations. To avoid further surgery, endoscopic stenting was chosen to relieve symptoms and prevent relapses.
Opioid Use Disorder Treatment for People Involved in the US Criminal Justice System—Promising Advances and Critical Implementation Challenges
Authors: Tyler N. A. Winkelman, Rachel Sandler Silva
Journal: JAMA Network Open (2021)

Joshua D. Lee, MD, MSc; Mia Malone, BA; Ryan McDonald, MA; Anna Cheng, BA; Kumar Vasudevan, MD; Babak Tofighi, MD; Ann Garment, MD; Barbara Porter, MD; Keith S. Goldfeld, DrPH; Michael Matteo; Jasdeep Mangat, MD; Monica Katyal, JD, MPH; Jonathan Giftos, MD; Ross MacDonald, MD
SO-30 Efficacy and safety of neoadjuvant short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma: Averectal study
Authors: A. Shamseddine, Y. Zeidan, Y. Bouferraa, R. Turfa, J. Kattan, D. Mukherji, S. Temraz, K. Alqasem, R. Amarin, T. Al Awabdeh, S. Deeba, S. Doughan, I. Mohamad, M. Elkhaldi, F. Daoud, M. Al Masri, A. Dabous, A. Hushki, M. Charafeddine, M. Al Darazi, F. Geara
Journal: Annals of Oncology (2021)
Assessment of Hospital Characteristics and Interhospital Transfer Patterns of Adults With Emergency General Surgery Conditions
Authors: Cindy Y. Teng, Billie S. Davis, Matthew R. Rosengart, Kathleen M. Carley, Jeremy M. Kahn
Journal: JAMA Network Open (2021)

Although patients with emergency general surgery (EGS) conditions frequently undergo interhospital transfers, the transfer patterns and associated factors are not well understood.
Alzheimer's disease-causing presenilin-1 mutations have deleterious effects on mitochondrial function
Authors: Jihoon Han, Heejin Park, Chinmoyee Maharana, A-Ryeong Gwon, Jinsu Park, Seung Hyun Baek, Han-Gyu Bae, Yoonsuk Cho, Hark Kyun Kim, Jae Hoon Sul, Jeongmi Lee, Eunae Kim, Junsik Kim, Yongeun Cho, Sunyoung Park, Leon F Palomera, Thiruma V Arumugam, Mark P Mattson, Dong-Gyu Jo
Journal: Theranostics (2021)

Mitochondrial dysfunction and oxidative stress are frequently observed in the early stages of Alzheimer's disease (AD). Studies have shown that presenilin-1 (PS1), the catalytic subunit of γ-secretase whose mutation is linked to familial AD (FAD), localizes to the mitochondrial membrane and regulates its homeostasis. Thus, we investigated how five PS1 mutations (A431E, E280A, H163R, M146V, and Δexon9) observed in FAD affect mitochondrial functions. Methods: We used H4 glioblastoma cell lines genetically engineered to inducibly express either the wild-type PS1 or one of the five PS1 mutants in order to examine mitochondrial morphology, dynamics, membrane potential, ATP production, mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), oxidative stress, and bioenergetics. Furthermore, we used brains of PS1M146V knock-in mice, 3xTg-AD mice, and human AD patients in order to investigate the role of PS1 in regulating MAMs formation. Results: Each PS1 mutant exhibited slightly different mitochondrial dysfunction. Δexon9 mutant induced mitochondrial fragmentation while A431E, E280A, H163R, and M146V mutants increased MAMs formation. A431E, E280A, M146V, and Δexon9 mutants also induced mitochondrial ROS production. A431E mutant impaired both complex I and peroxidase activity while M146V mutant only impaired peroxidase activity. All PS1 mutants compromised mitochondrial membrane potential and cellular ATP levels were reduced by A431E, M146V, and Δexon9 mutants. Through comparative profiling of hippocampal gene expression in PS1M146V knock-in mice, we found that PS1M146V upregulates Atlastin 2 (ATL2) expression level, which increases ER-mitochondria contacts. Down-regulation of ATL2 after PS1 mutant induction rescued abnormally elevated ER-mitochondria interactions back to the normal level. Moreover, ATL2 expression levels were significantly elevated in the brains of 3xTg-AD mice and AD patients. Conclusions: Overall, our findings suggest that each of the five FAD-linked PS1 mutations has a deleterious effect on mitochondrial functions in a variety of ways. The adverse effects of PS1 mutations on mitochondria may contribute to MAMs formation and oxidative stress resulting in an accelerated age of disease onset in people harboring mutant PS1.
The lymphatic vasculature: An active and dynamic player in cancer progression
Authors: Sara Rezzola, Elena C. Sigmund, Cornelia Halin, Roberto Ronca
Journal: Medicinal Research Reviews (2021)

The lymphatic vasculature has been widely described and explored for its key functions in fluid homeostasis and in the organization and modulation of the immune response. Besides transporting immune cells, lymphatic vessels play relevant roles in tumor growth and tumor cell dissemination. Cancer cells that have invaded into afferent lymphatics are propagated to tumor-draining lymph nodes (LNs), which represent an important hub for metastatic cell arrest and growth, immune modulation, and secondary dissemination to distant sites. In recent years many studies have reported new mechanisms by which the lymphatic vasculature affects cancer progression, ranging from induction of lymphangiogenesis to metastatic niche preconditioning or immune modulation. In this review, we provide an up-to-date description of lymphatic organization and function in peripheral tissues and in LNs and the changes induced to this system by tumor growth and progression. We will specifically focus on the reported interactions that occur between tumor cells and lymphatic endothelial cells (LECs), as well as on interactions between immune cells and LECs, both in the tumor microenvironment and in tumor-draining LNs. Moreover, the most recent prognostic and therapeutic implications of lymphatics in cancer will be reported and discussed in light of the new immune-modulatory roles that have been ascribed to LECs.
Recombination Marks the Evolutionary Dynamics of a Recently Endogenized Retrovirus
Authors: Lei Yang, Raunaq Malhotra, Rayan Chikhi, Daniel Elleder, Theodora Kaiser, Jesse Rong, Paul Medvedev, Mary Poss
Journal: Molecular Biology and Evolution (2021)

Abstract All vertebrate genomes have been colonized by retroviruses along their evolutionary trajectory. Although endogenous retroviruses (ERVs) can contribute important physiological functions to contemporary hosts, such benefits are attributed to long-term coevolution of ERV and host because germline infections are rare and expansion is slow, and because the host effectively silences them. The genomes of several outbred species including mule deer (Odocoileus hemionus) are currently being colonized by ERVs, which provides an opportunity to study ERV dynamics at a time when few are fixed. We previously established the locus-specific distribution of cervid ERV (CrERV) in populations of mule deer. In this study, we determine the molecular evolutionary processes acting on CrERV at each locus in the context of phylogenetic origin, genome location, and population prevalence. A mule deer genome was de novo assembled from short- and long-insert mate pair reads and CrERV sequence generated at each locus. We report that CrERV composition and diversity have recently measurably increased by horizontal acquisition of a new retrovirus lineage. This new lineage has further expanded CrERV burden and CrERV genomic diversity by activating and recombining with existing CrERV. Resulting interlineage recombinants then endogenize and subsequently expand. CrERV loci are significantly closer to genes than expected if integration were random and gene proximity might explain the recent expansion of one recombinant CrERV lineage. Thus, in mule deer, retroviral colonization is a dynamic period in the molecular evolution of CrERV that also provides a burst of genomic diversity to the host population.
GenTB: A user-friendly genome-based predictor for tuberculosis resistance powered by machine learning
Authors: Matthias I. Gröschel, Martin Owens, Luca Freschi, Roger Vargas, Maximilian G. Marin, Jody Phelan, Zamin Iqbal, Avika Dixit, Maha R. Farhat
Journal: Genome Medicine (2021)

Abstract Background Multidrug-resistant Mycobacterium tuberculosis ( Mtb ) is a significant global public health threat. Genotypic resistance prediction from Mtb DNA sequences offers an alternative to laboratory-based drug-susceptibility testing. User-friendly and accurate resistance prediction tools are needed to enable public health and clinical practitioners to rapidly diagnose resistance and inform treatment regimens. Results We present Translational Genomics platform for Tuberculosis (GenTB), a free and open web-based application to predict antibiotic resistance from next-generation sequence data. The user can choose between two potential predictors, a Random Forest (RF) classifier and a Wide and Deep Neural Network (WDNN) to predict phenotypic resistance to 13 and 10 anti-tuberculosis drugs, respectively. We benchmark GenTB’s predictive performance along with leading TB resistance prediction tools (Mykrobe and TB-Profiler) using a ground truth dataset of 20,408 isolates with laboratory-based drug susceptibility data. All four tools reliably predicted resistance to first-line tuberculosis drugs but had varying performance for second-line drugs. The mean sensitivities for GenTB-RF and GenTB-WDNN across the nine shared drugs were 77.6% (95% CI 76.6–78.5%) and 75.4% (95% CI 74.5–76.4%), respectively, and marginally higher than the sensitivities of TB-Profiler at 74.4% (95% CI 73.4–75.3%) and Mykrobe at 71.9% (95% CI 70.9–72.9%). The higher sensitivities were at an expense of ≤ 1.5% lower specificity: Mykrobe 97.6% (95% CI 97.5–97.7%), TB-Profiler 96.9% (95% CI 96.7 to 97.0%), GenTB-WDNN 96.2% (95% CI 96.0 to 96.4%), and GenTB-RF 96.1% (95% CI 96.0 to 96.3%). Averaged across the four tools, genotypic resistance sensitivity was 11% and 9% lower for isoniazid and rifampicin respectively, on isolates sequenced at low depth (&lt; 10× across 95% of the genome) emphasizing the need to quality control input sequence data before prediction. We discuss differences between tools in reporting results to the user including variants underlying the resistance calls and any novel or indeterminate variants Conclusions GenTB is an easy-to-use online tool to rapidly and accurately predict resistance to anti-tuberculosis drugs. GenTB can be accessed online at https://gentb.hms.harvard.edu , and the source code is available at https://github.com/farhat-lab/gentb-site .