tbuckley/cabot-search huggingface dataset:
First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes
Authors: Jenna J. Guthmiller, Julianna Han, Lei Li, Alec W. Freyn, Sean T. H. Liu, Olivia Stovicek, Christopher T. Stamper, Haley L. Dugan, Micah E. Tepora, Henry A. Utset, Dalia J. Bitar, Natalie J. Hamel, Siriruk Changrob, Nai-Ying Zheng, Min Huang, Florian Krammer, Raffael Nachbagauer, Peter Palese, Andrew B. Ward, Patrick C. Wilson
Journal: Science Translational Medicine (2021)

Broadly neutralizing antibodies are critical for protection against both drifted and shifted influenza viruses. Here, we reveal that first exposure to the 2009 pandemic H1N1 influenza virus recalls memory B cells that are specific to the conserved receptor-binding site (RBS) or lateral patch epitopes of the hemagglutinin (HA) head domain. Monoclonal antibodies (mAbs) generated against these epitopes are broadly neutralizing against H1N1 viruses spanning 40 years of viral evolution and provide potent protection in vivo. Lateral patch-targeting antibodies demonstrated near universal binding to H1 viruses, and RBS-binding antibodies commonly cross-reacted with H3N2 viruses and influenza B viruses. Lateral patch-targeting mAbs were restricted to expressing the variable heavy-chain gene VH3-23 with or without the variable kappa-chain gene VK1-33 and often had a Y-x-R motif within the heavy-chain complementarity determining region 3 to make key contacts with HA. Moreover, lateral patch antibodies that used both VH3-23 and VK1-33 maintained neutralizing capability with recent pH1N1 strains that acquired mutations near the lateral patch. RBS-binding mAbs used a diverse repertoire but targeted the RBS epitope similarly and made extensive contacts with the major antigenic site Sb. Together, our data indicate that RBS- and lateral patch-targeting clones are abundant within the human memory B cell pool, and universal vaccine strategies should aim to drive antibodies against both conserved head and stalk epitopes.
Surgical services: Northern Ireland must speed up action to tackle UK’s worst waiting lists, says royal college
Authors: Matthew Limb
Journal: BMJ (2021)

The Royal College of Surgeons of England has launched a 10 step plan to restore surgical services in Northern Ireland and tackle the patient harm arising from the UK’s worst waiting lists.

The college warned of unprecedented pressures on hospitals, as many patients now needed emergency care because their conditions had deteriorated while waiting. In a report on its plans it said that the risk of harm from long waiting lists was “already being observed in all surgical specialties.” It added, “The health minister has stated it will take 10 years to sort the backlog in elective care. This is a catastrophic assessment.”

The college’s report, titled Recovery: 10 Steps Not 10 Years , calls for quicker action including an …
Interspecific interactions that affect ageing: Age-distorters manipulate host ageing to their own evolutionary benefits
Authors: Jérôme Teulière, Charles Bernard, Eric Bapteste
Journal: Ageing Research Reviews (2021)

Genetic causes for ageing are traditionally investigated within a species. Yet, the lifecycles of many organisms intersect. Additional evolutionary and genetic causes of ageing, external to a focal species/organism, may thus be overlooked. Here, we introduce the phrase and concept of age-distorters and its evidence. Age-distorters carry ageing interfering genes, used to manipulate the biological age of other entities upon which the reproduction of age-distorters relies, e.g. age-distorters bias the reproduction/maintenance trade-offs of cells/organisms for their own evolutionary interests. Candidate age-distorters include viruses, parasites and symbionts, operating through specific, genetically encoded interferences resulting from co-evolution and arms race between manipulative non-kins and manipulable species. This interference results in organismal ageing when age-distorters prompt manipulated organisms to favor their reproduction at the expense of their maintenance, turning these hosts into expanded disposable soma. By relying on reproduction/maintenance trade-offs affecting disposable entities, which are left ageing to the reproductive benefit of other physically connected lineages with conflicting evolutionary interests, the concept of age-distorters expands the logic of the Disposable Soma theory beyond species with fixed germen/soma distinctions. Moreover, acknowledging age-distorters as external sources of mutation accumulation and antagonistic pleiotropic genes expands the scope of the mutation accumulation and of the antagonistic pleiotropy theories.
Retrograde nerve growth factor signaling modulates tooth mechanical hyperalgesia induced by orthodontic tooth movement via acid-sensing ion channel 3
Authors: Meiya Gao, Xinyu Yan, Yanzhu Lu, Linghuan Ren, Shizhen Zhang, Xiaoqi Zhang, Qianyun Kuang, Lu Liu, Jing Zhou, Yan Wang, Wenli Lai, Hu Long
Journal: International Journal of Oral Science (2021)

Abstract Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia. Nerve growth factor (NGF) is upregulated in periodontium and may modulate tooth mechanical hyperalgesia. The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms. Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague–Dawley rats. Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia (TG). Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG. The administration of agonists, antagonists, and virus vectors into TG and periodontium was conducted. Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal. Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium (mainly in periodontal fibroblasts) and TG. Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1. Acid-sensing ion channel 3 (ASIC3) and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement. The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG, respectively. NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist (APETx2). Moreover, NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist (GMQ). NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression. Taken together, in response to force stimuli, periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG, where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3. NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.
Sonosensitizer‐Functionalized Graphene Nanoribbons for Adhesion Blocking and Sonodynamic Ablation of Ovarian Cancer Spheroids
Authors: Hak Rae Lee, Dae Woo Kim, Victoria O. Jones, Yunkyu Choi, Vivian E. Ferry, Melissa A. Geller, Samira M. Azarin
Journal: Advanced Healthcare Materials (2021)

Advanced stage ovarian cancer is challenging to treat due to widespread seeding of tumor spheroids throughout the mesothelial lining of the peritoneal cavity. In this work, a therapeutic strategy using graphene nanoribbons (GNR) functionalized with 4-arm polyethylene glycol (PEG) and chlorin e6 (Ce6), a sonosensitizer, to target metastatic ovarian cancer spheroids is reported. GNR-PEG-Ce6 adsorbs onto the spheroids and disrupts their adhesion to extracellular matrix proteins or LP-9 mesothelial cells. Furthermore, for spheroids that do adhere, GNR-PEG-Ce6 delays spheroid disaggregation and spreading as well as mesothelial clearance, key metastatic processes following adhesion. Owing to the sonodynamic effects of Ce6 and its localized delivery via the biomaterial, GNR-PEG-Ce6 can kill ovarian cancer spheroids adhered to LP-9 cell monolayers when combined with mild ultrasound irradiation. The interaction with GNR-PEG-Ce6 also loosens cell-cell adhesions within the spheroids, rendering them more susceptible to treatment with the chemotherapeutic agents cisplatin and paclitaxel, which typically have difficulty in penetrating ovarian cancer spheroids. Thus, this material can facilitate effective chemotherapeutic and sonodynamic combination therapies. Finally, the adhesion inhibiting and sonodynamic effects of GNR-PEG-Ce6 are also validated with tumor spheroids derived from the ascites fluid of ovarian cancer patients, providing evidence of the translational potential of this biomaterial approach.
Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel
Authors: Zehao Jing, Renhua Ni, Jiedong Wang, Xinhong Lin, Daoyang Fan, Qingguang Wei, Teng Zhang, Yufeng Zheng, Hong Cai, Zhongjun Liu
Journal: Bioactive Materials (2021)

Surgical resection and perioperative adjuvant chemotherapy-based therapies have improved the prognosis of patients with osteosarcoma; however, intraoperative bone defects, local tumour recurrence, and chemotherapy-induced adverse effects still affect the quality of life of patients. Emerging 3D-printed titanium alloy (Ti6Al4V) implants have advantages over traditional implants in bone repair, including lower elastic modulus, lower stiffness, better bone conduction, more bone in-growth, stronger mechanical interlocking, and lager drug-loading capacity by their inherent porous structure. Here, cisplatin, a clinical first-line anti-osteosarcoma drug, was loaded into Ti6Al4V implants, within a PLGA-PEG-PLGA thermo-sensitive hydrogel, to construct bone substitutes with both anti-osteosarcoma and bone-repair functions. The optimal concentrations of cisplatin (0.8 and 1.6 mg/mL) were first determined in vitro. Thereafter, the anti-tumour effect and biosafety of the cisplatin/hydrogel-loaded implants, as well as their bone-repair potential were evaluated in vivo in tumour-bearing mouse, and bone defect rabbit models, respectively. The loading of cisplatin reduced tumour volume by more than two-thirds (from 641.1 to 201.4 mm3) with negligible organ damage, achieving better anti-tumour effects while avoiding the adverse effects of systemic cisplatin delivery. Although bone repair was hindered by cisplatin loading at 4 weeks, no difference was observed at 8 weeks in the context of implants with versus without cisplatin, indicating acceptable long-term stability of all implants (with 8.48%–10.04% bone in-growth and 16.94%–20.53% osseointegration). Overall, cisplatin/hydrogel-loaded 3D-printed Ti6Al4V implants are safe and effective for treating osteosarcoma-caused bone defects, and should be considered for clinical use.
AB0338 PREGNANCY OUTCOMES IN ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: P. Alba, Y. Tissera, N. Cucchiaro, V. Savio, R. Serrano Morales, M. I. Quaglia, J. A. Albiero, V. Juarez, C. A. Gobbi, M. Yorio, M. E. Crespo Espindola
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic lupus erythematosus (SLE) is a autoimmune disease that affects adolescents and young women of childbearing age. In spite of the improvement in fetal and maternal SLE pregnancy outcome in the last decades, they have increased risk of adverse outcomes including disease flare, abortions, preeclampsia (PE) and premature birth (PB). However, pregnancy outcomes among adolescents with SLE have not been well explored. Objectives: To evaluate maternal and fetal outcomes in pregnant adolescents with SLE. Methods: We retrospectively studied all pregnant SLE adolescent patients, who attended to 3 Maternity Hospitals in Argentina in the last 5 years. Demographic, clinical, and laboratory data were collected. The presence of Antiphospholipid Syndrome (APS) and the Antiphospholipid antibodies (AA), and maternal and fetal outcome were evaluated. Adolescent pregnancy was defined it is happened between 10 and 19 years old. Lupus activity was evaluated by SELENA SLEDAI at the conception and each trimester of pregnancy and puerperium. Results: 32 pregnancies in 21 patients were included. Mean age was 18 years old, 66% was mestizo ethnicity and mean disease duration of 2 years. Renal involvement was found in 19, Mucocutaneous in 21, and hematological in 14 patients. 4 patients had positive Anti-SSA/Ro antibodies, 1 Anti-SSB/La, 2 Lupus anticoagulant, 6 Ig G ACL, 3 Ig M ACL, and 8 patients fulfilled APS criteria. Activity disease was 0 SELENA SLEDAI in 1 ° trimester, 4 in 2°,3° trimester and puerperium. Maternal and fetal outcomes are shown in Table 1. Cesarean section was performed in 58%(n=18) of the patients, 6 had abortions and 1 fetal death. Table 1. Maternal outcomes Disease Flares 13(41%) 7 renal (PE)/Hellp 6 (19%) Gestational Diabetes 1 (3%) Maternal outcomes Spontaneous Membrane Rupture 1 (3%) Mortality 0 Fetal outcome Live birth 24 (75%) Gestational age (weeks) 32 (32-38) Weight (grs) 2805 (2100-3340) IUGR 5 (16%) PB 8 (25%) Conclusion: Maternal and fetal complications were high in adolescent pregnancy with SLE, including disease activity, PE and PB. A tight control of patients should be performed before and after conception. These patients should be managed by a multidisciplinary team, thus allowing an improvement of maternal and fetal prognosis. References: [1]Ling N, Lawson E, von Scheven E. Adverse Pregnancy outcome in adolescents and young women with systemic lupus erythematosus: a national estimate. Pediatric Rheumatology 2018, 16:26. [2]FraserA, Brockert J, Ward R: Association of young maternal age with adverse reproductive outcomes. N Engl J Med 1995, 223:1113-1117. 26. Disclosure of Interests: None declared
Pulse oximetry is an essential tool that saves lives: a call for standardisation
Authors: Catia Cilloniz, Anita Simonds, Kjeld Hansen, Josep Alouch, Heather Zar, Yoichi Nakanishi, Stephanie Levine, Mark Cohen, Charles Dela Cruz, Scott E. Evans, Maurizio Sanguinetti, Jordi Vila, Jesús Díez Manglano, Ricard Ferrer, Lucio Criado, José Polo García, Zaira Correcher, Diana Rodriguez-Hurtado, Carmen Terrazas, Carmen Muñoz-Almagro, Carolina Garcia-Vidal, Zeina Aoun, Israel Amirav
Journal: European Respiratory Journal (2021)

Pneumonia is a leading global cause of morbidity and mortality, particularly amongst adults aged >70 years and children. Annual deaths due to pneumonia in these groups was estimated at more than one million and 672 000 worldwide for both groups, respectively, in 2019 [1]. The importance of pneumonia is highlighted by impact of the current coronavirus disease 2019 (COVID-19) pandemic on vulnerable populations. Yet, despite the high impact of pneumonia worldwide, diagnosing pneumonia, especially in children in low- and middle-income countries, remains a big challenge. Frequent clinical signs of pneumonia (cough and difficult or rapid breathing) are non-specific and can overlap with other prevalent diseases in these settings, such as malaria. Equally important, data provided by the World Health Organization (WHO) revealed that 40% of children with pneumonia symptoms in the 40 countries reporting 90% of child pneumonia deaths never receive medical care for their pneumonia [2]. Furthermore, overdiagnosis of bacterial pneumonia and unnecessary administration of antibiotics poses an extra challenge, particularly in countries with limited resources for diagnostic procedures. A call to action to immediately review the accuracy of pulse oximeters so that all patients receive optimal and equitable diagnosis and treatment for hypoxaemia <https://bit.ly/2RSPDCT>
Prevalence and clinical outcomes of dystrophin‐associated dilated cardiomyopathy without severe skeletal myopathy
Authors: Maria A. Restrepo‐Cordoba, Karim Wahbi, Anca R. Florian, Juan Jiménez‐Jáimez, Luisa Politano, Michael Arad, Vicente Climent‐Paya, Ana Garcia‐Alvarez, Rasmus B. Hansen, José M. Larrañaga‐Moreira, Milos Kubanek, Luis R. Lopes, Andrea Ros, Ruxandra Jurcut, Torsten B. Rasmussen, Luis Ruiz‐Guerrero, Regina Pribe‐Wolferts, Julian Palomino‐Doza, Zofia Bilinska, José F. Rodríguez‐Palomares, Rosa L.E. Van Loon, María Teresa Basurte Elorz, Giovanni Quarta, Maria Robledo Iñarritu, Job A.J. Verdonschot, Tanya Stojkovic, Zornitsa Shomanova, Francisco Bermudez‐Jimenez, Alberto Palladino, Dov Freimark, Maria I. García‐Álvarez, Paloma Jorda, Fernando Dominguez, Juan Pablo Ochoa, Francesca Girolami, Ramon Brugada, Benjamin Meder, Roberto Barriales‐Villa, Jens Mogensen, Pascal Laforêt, Ali Yilmaz, Perry Elliott, Pablo Garcia‐Pavia
Journal: European Journal of Heart Failure (2021)
Effect of anti‐IL‐5 biologics on weight and body mass index
Authors: Ruth P. Cusack, Chynna Huang, Nicola LaVigne, Imran Satia, Parameswaran Nair, Paul M. O'Byrne
Journal: Allergy (2021)

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AB0486 ONE-YEAR DIRECT COSTS OF BIOLOGICAL THERAPY IN ANKYLOSING SPONDYLITIS AND ITS PREDICTIVE FACTORS: DATA FROM THE MOROCCAN RBSMR REGISTRY
Authors: S. Bahloul, H. Rkain, S. Fellous, S. Ahid, R. Abouqal, T. Latifa, I. Hmamouchi, L. Achemlal, I. El Bouchti, A. EL Maghraoui, I. Ghozlani, H. Hassikou, T. Harzy, I. Linda, O. Mkinsi, R. Niamane, R. Bahiri, F. Allali
Journal: Annals of the Rheumatic Diseases (2021)

Background: NA Objectives: To estimate the annual direct costs of biological therapies in Spondyloarthropathies (SpA) and to establish possible factors associated with those costs. Methods: The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR). We included SpA patients with available 1-year data. Variables related to socioeconomic status, disease and biological therapy were collected. Differences in costs across groups were tested by Mann–Whitney and Kruskal–Wallis tests. Correlations analysis was performed in search of factors associated with high costs. Results: We included 89 SpA patients. The mean age was 40.6± 13.6 years, with male predominance 68.9 %. Patients received one of the following therapies: TNF-blockers (n =79), Biosimilar of TNF-blockers (n =8) and Il17-blockers (n =2). Median one-year biologic costs per patient were 9 569, 39 €. The total annual of biotherapies in AS patients was 851 675, 98 €. Figure 1 Annual mean drug costs per treated patient (€: Euro) The costs are presented in Euro using an exchange rate of (1 Moroccan Dirham = 0.091Euro). TNF-blockers constituted 95 % of the total annual budget. Biosimilar of TNF-blockers and Il17-blockers represented 3 % and 2 % of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. No correlation was found between the annual direct costs of biotherapies and body mass index nor with BASFI or BASDAI. Conclusion: In Morocco, a developing country, the annual direct costs of biological therapies are high in AS patients. Our results may contribute to the development of strategies for better governance of these costs. Disclosure of Interests: None declared.
Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues
Authors: Xiaohui Wu, Xin Wang, Xiaobin Chen, Xiaowei Yang, Qian Ma, Guohua Xu, Lin Yu, Jiandong Ding
Journal: Bioactive Materials (2021)

It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo. Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.
In type 2 diabetes, SGLT2 inhibitors reduce all-cause, but not cardiovascular, mortality vs. GLP-1 RAs
Authors: Michael Tanner
Journal: Annals of Internal Medicine (2021)

Source Citation Palmer SC, Tendal B, Mustafa RA, et al. Sodium–glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2021;372:m4573. 33441402
Risks and Benefits of Benzodiazepines—Reply
Authors: Matthew E. Hirschtritt, Mark Olfson, Kurt Kroenke
Journal: JAMA (2021)

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Non-additive association analysis using proxy phenotypes identifies novel cattle syndromes
Authors: Edwardo G. M. Reynolds, Catherine Neeley, Thomas J. Lopdell, Michael Keehan, Keren Dittmer, Chad S. Harland, Christine Couldrey, Thomas J. J. Johnson, Kathryn Tiplady, Gemma Worth, Mark Walker, Stephen R. Davis, Richard G. Sherlock, Katie Carnie, Bevin L. Harris, Carole Charlier, Michel Georges, Richard J. Spelman, Dorian J. Garrick, Mathew D. Littlejohn
Journal: Nature Genetics (2021)