tbuckley/cabot-search huggingface dataset:
Experimental Human Pneumococcal Colonization in Older Adults Is Feasible and Safe, Not Immunogenic
Authors: Hugh Adler, Esther L. German, Elena Mitsi, Elissavet Nikolaou, Sherin Pojar, Caz Hales, Rachel Robinson, Victoria Connor, Helen Hill, Angela D. Hyder-Wright, Lepa Lazarova, Catherine Lowe, Emma L. Smith, India Wheeler, Seher R. Zaidi, Simon P. Jochems, Dessi Loukov, Jesús Reiné, Carla Solórzano-Gonzalez, Polly de Gorguette d’Argoeuves, Tessa Jones, David Goldblatt, Tao Chen, Stephen J. Aston, Neil French, Andrea M. Collins, Stephen B. Gordon, Daniela M. Ferreira, Jamie Rylance
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease.Objectives: To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge.Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B; 80,000 cfu in each nostril). Colonization was determined by bacterial culture of nasal wash, and humoral immune responses were assessed by anticapsular and antiprotein IgG concentrations.Measurements and Main Results: Experimental colonization was established in 39% of participants (25/64) with no adverse events. Colonization occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonization. Colonization did not confer serotype-specific immune boosting, with a geometric mean titer (95% confidence interval) of 2.7 μg/ml (1.9-3.8) before the challenge versus 3.0 (1.9-4.7) 4 weeks after colonization (P = 0.53). Furthermore, pneumococcal challenge without colonization led to a drop in specific antibody concentrations from 2.8 μg/ml (2.0-3.9) to 2.2 μg/ml (1.6-3.0) after the challenge (P = 0.006). Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%).Conclusions: In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.
Advances and novel developments in allergic rhinitis
Authors: Yifan Meng, Chengshuo Wang, Luo Zhang
Journal: Allergy (2020)

Abstract Allergic rhinitis (AR) is an upper airway disease with high prevalence in the world, and therefore needs to be thoroughly investigated and treated accordingly. Although the mechanisms underlying the pathology and treatment of AR have been widely studied, many aspects of AR are still unclear and warrant further investigations. The purpose of the present review was therefore to report recently published papers, which highlight the novel mechanisms and treatments of AR. These include role of environment, important proteins and cells, and some other factors in the pathogenesis of AR; as well as the role of immunotherapy and biologics in the treatment of AR.
Recovered COVID-19 patients with recurrent viral RNA exhibit lower levels of anti-RBD antibodies
Authors: Bingfeng Liu, Yaling Shi, Wanying Zhang, Rong Li, Zhangping He, Xiaofan Yang, Yuejun Pan, Xilong Deng, Mingkai Tan, Lingzhai Zhao, Fan Zou, Yiwen Zhang, Ting Pan, Junsong Zhang, Xu Zhang, Fei Xiao, Fang Li, Kai Deng, Hui Zhang
Journal: Cellular and Molecular Immunology (2020)

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global pandemic.Most discharge criteria for patients with COVID-19 recommend two consecutive negative reverse-transcriptase polymerase-chain reaction (RT-PCR) test results from respiratory specimens over a 24-hour interval.2][3][4][5][6][7][8] Two cohort studies reported that 14.5% (38/262) and 16.7% (69/414) of patients with COVID-19 retesting were positive for SARS-CoV-2 RNA after discharge. 2,6The potential causes of RP specimens may be related to several aspects, such as virological factors, including residual viral reservoir, intermittent viral release, tissue distribution or false negatives, as well as immunological and sampling methodological factors. 3,9,10Given that an increasing number of RP cases have been reported worldwide, this phenomenon cannot be simply ascribed to false-negative testing.It indeed occurs, as truly discharged patients could suffer reactivation or could be reinfected with SARS-CoV-2. 3 The risk of possible retransmission still exists, and the serological characteristics remain largely unknown, which could jeopardize the management of recovered In this study, we collected blood samples from 47 recovered patients.The median age of the patients was 49 years (range: 17-82 years), and 55.3% of them were women. Acrding to the Chinese national treatment guidelines, their symptoms were classified as moderate (36 patients) or severe (11 patients), and the median disease duration (from the onset of illness to the last RNA-negative conversion before RP status) was 15 days (range: 1-40 days).Eight of the 47 recovered patients displayed RP anal or throat swab samples from 8 to 39 days after viral shedding, and 39 patients remained persistently RNA negative (PRN).None of the conditions of these RP patients were severe before recovery (Fig. S1a).The median disease duration was 16.5 days for RP patients (ranging from 10 to 24 days), which was not significantly different from that of PRN patients (15 days, ranging from 1 to 40 days) (Fig. S1b).Moreover, the RP patients were significantly younger than the PRN patients (median 34.5 years vs. 54 years, p = 0.019), which is consistent with previous reports (Fig. S1c).1,2
Efficacy, Improved Quality of Life, and Cost-effectiveness of Partial Breast Irradiation
Authors: Chirag Shah, Douglas Arthur, Frank Vicini
Journal: JAMA Oncology (2020)

This Viewpoint provides an evaluation of partial breast irradiation as an alternative to standard and hypofractionated whole-breast irradiation in terms of its ability to reduce duration of treatment and provide equivalent outcomes, comparable or reduced adverse effects, and cost-effectiveness
Cutaneous manifestations in COVID-19: A case series from a hospital in an area with high infection rates
Authors: A. Connolly, I. Spring, C. Cotter, M. Philippidou, J. Salisbury, D. Creamer, T. Basu, S. Rai, K. Irving, E. Harwood, S. Walsh
Journal: British Journal of Dermatology (2020)

Cutaneous manifestations of COVID-19 infection have been described in the literature since the onset of the pandemic  No formal classification system has been suggested, but cases reported in the literature demonstrate various subtypes, including urticarial, maculopapular, papulovesicular, purpuric and livedoid lesions  The pathogenesis of the cutaneous response is not fully understood, but may represent inflammatory and thromboinflammatory processes  Our institution in South London has treated one of the largest numbers of inpatients with confirmed COVID-19 infection in the U K , with 2989 cases recorded between 1 February 2020 and 29 June 2020  We describe the spectrum of cutaneous disease associated with COVID-19 infection presenting to an acute liaison dermatology service over a 4-month period from March to June 2020  From a large number of referrals of COVID-19-positive patients with skin disease, 13 cases of cutaneous presentations thought to be caused by COVID-19 infection were identified [eight males, five females;mean age 44 years (range 15-59)]  We included cases from outpatient (n = 8), inpatient (n = 2) and intensive care (n = 3) departments  Eight of 13 had positive COVID-19 antigen testing, while five of 13 had symptoms indicative of COVID-19 infection but were not offered a test  Clinical manifestations included perniosis (n = 3), livedo (n = 2), urticaria (n = 2), maculopapular exanthema (n = 2), vasculitis (n = 1), panniculitis (n = 1), eccrine squamous syringometaplasia (n = 1) and digital vein thrombosis (n = 1)  Five of 13 had a skin biopsy that supported the clinical diagnosis  Skin disease in COVID-19 infection reflects viral exanthematous inflammation in many cases  Thromboinflammatory pathologies also contribute to some COVID-19 dermatoses  Vascular and vaso-occlusive pathologies occur prominently in the lungs and kidneys, as well as the skin, and appear to have pathogenetic specificity for COVID-19  Immunostaining of lung tissue with an antibody to the Rp3 NP protein of severe acute respiratory syndrome-coronavirus 2 has revealed prominent expression on alveolar epithelial cells  Immunostaining of skin sections might provide further evidence for a direct viral effect in COVID-19 dermatoses  Our findings are comparable with those of European colleagues regarding the spectrum, the latency and the duration of the cutaneous symptoms  We would like to add our description of three new cutaneous manifestations of COVID-19 infection - panniculitis, eccrine squamous syringometaplasia and digital vein thrombosis - to the body of literature on this topic
CardioMEMS-Guided CAR T Cell Therapy for Lymphoma in a Patient With Anthracycline-Induced Cardiomyopathy
Authors: Anthony J. Kanelidis, Jayant Raikhelkar, Gene Kim, Gabriel Sayer, Michael R. Bishop, Tamar S. Polonsky, Nir Uriel
Journal: JACC CardioOncology (2020)

A 66-year-old woman with advanced diffuse large B-cell lymphoma (DLBCL) was referred for chimeric antigen receptor (CAR) T cell therapy. She was diagnosed with DLBCL 6 years prior to presentation and had no significant past medical history. She received a total of 10 cycles of rituximab,
The Alternative Splicing Factor, MBNL1, Inhibits Glioblastoma Tumor Initiation and Progression by Reducing Hypoxia-Induced Stemness
Authors: Dillon M. Voss, Anthony Sloan, Raffaella Spina, Heather M. Ames, Eli E. Bar
Journal: Cancer Research (2020)

Muscleblind-like proteins (MBNL) belong to a family of tissue-specific regulators of RNA metabolism that control premessenger RNA splicing. Inactivation of MBNL causes an adult-to-fetal alternative splicing transition, resulting in the development of myotonic dystrophy. We have previously shown that the aggressive brain cancer, glioblastoma (GBM), maintains stem-like features (glioma stem cell, GSC) through hypoxia-induced responses. Accordingly, we hypothesize here that hypoxia-induced responses in GBM might also include MBNL-based alternative splicing to promote tumor progression. When cultured in hypoxia condition, GSCs rapidly exported muscleblind-like-1 (MBNL1) out of the nucleus, resulting in significant inhibition of MBNL1 activity. Notably, hypoxia-regulated inhibition of MBNL1 also resulted in evidence of adult-to-fetal alternative splicing transitions. Forced expression of a constitutively active isoform of MBNL1 inhibited GSC self-renewal and tumor initiation in orthotopic transplantation models. Induced expression of MBNL1 in established orthotopic tumors dramatically inhibited tumor progression, resulting in significantly prolonged survival. This study reveals that MBNL1 plays an essential role in GBM stemness and tumor progression, where hypoxic responses within the tumor inhibit MBNL1 activity, promoting stem-like phenotypes and tumor growth. Reversing these effects on MBNL1 may therefore, yield potent tumor suppressor activities, uncovering new therapeutic opportunities to counter this disease. SIGNIFICANCE: This study describes an unexpected mechanism by which RNA-binding protein, MBNL1, activity is inhibited in hypoxia by a simple isoform switch to regulate glioma stem cell self-renewal, tumorigenicity, and progression.
Outcomes of a new slowly resorbable biosynthetic mesh (Phasix™) in potentially contaminated incisional hernias: A prospective, multi-center, single-arm trial
Authors: Mathilde MJ. van Rooijen, An P. Jairam, Tim Tollens, Lars N. Jørgensen, Tammo S. de Vries Reilingh, Guillaume Piessen, Ferdinand Köckerling, Marc Miserez, Alastair CJ. Windsor, Frederik Berrevoet, René H. Fortelny, Bertrand Dousset, Guido Woeste, Henderik L. van Westreenen, Francesco Gossetti, Johan F. Lange, Geert WM. Tetteroo, Andreas Koch, Leonard F. Kroese, Johannes Jeekel
Journal: International Journal of Surgery (2020)

Resorbable biomaterials have been developed to reduce the amount of foreign material remaining in the body after hernia repair over the long-term. However, on the short-term, these resorbable materials should render acceptable results with regard to complications, infections, and reoperations to be considered for repair. Additionally, the rate of resorption should not be any faster than collagen deposition and maturation; leading to early hernia recurrence. Therefore, the objective of this study was to collect data on the short-term performance of a new resorbable biosynthetic mesh (Phasix™) in patients requiring Ventral Hernia Working Group (VHWG) Grade 3 midline incisional hernia repair.A prospective, multi-center, single-arm trial was conducted at surgical departments in 15 hospitals across Europe. Patients aged ≥18, scheduled to undergo elective Ventral Hernia Working Group Grade 3 hernia repair of a hernia larger than 10 cm2 were included. Hernia repair was performed with Phasix™ Mesh in sublay position when achievable. The primary outcome was the rate of surgical site occurrence (SSO), including infections, that required intervention until 3 months after repair.In total, 84 patients were treated with Phasix™ Mesh. Twenty-two patients (26.2%) developed 32 surgical site occurrences. These included 11 surgical site infections, 9 wound dehiscences, 7 seromas, 2 hematomas, 2 skin necroses, and 1 fistula. No significant differences in surgical site occurrence development were found between groups repaired with or without component separation technique, and between clean-contaminated or contaminated wound sites. At three months, there were no hernia recurrences.Phasix™ Mesh demonstrated acceptable postoperative surgical site occurrence rates in patients with a Ventral Hernia Working Group Grade 3 hernia. Longer follow-up is needed to evaluate the recurrence rate and the effects on quality of life. This study is ongoing through 24 months of follow-up.
FDG PET/CT Findings of Melanoma in a Renal Allograft
Authors: Pengcheng Ran, Leilei Huang, Fanhang Meng, Yupin Liu
Journal: Clinical Nuclear Medicine (2020)

Renal melanoma is rare. We present a case with FDG-avid melanoma arising from renal allograft. This case indicates that melanoma can occur in the allograft, and it should be considered as a differential diagnosis of focal abnormal FDG uptake in the renal allograft.
Shared and Tissue-Specific Genetic Features of Primary Myelofibrosis, Hepatic Fibrosis, Idiopathic Pulmonary Fibrosis and Kidney Fibrosis
Authors: Anders B Dohlman, Rosa S Kim, Hadassa Hirschfield, Lilian Varricchio, Fiorella Ciaffoni, Massimiliano Dall'ora, Yujin Hoshida, Naftali Kaminski, Giovanni Barosi, Vittorio Rosti, Scott Friedman, Ronald Hoffman, Anna Rita Migliaccio
Journal: Blood (2017)
Plasma cadmium is associated with increased risk of long-term kidney graft failure
Authors: Camilo G. Sotomayor, Dion Groothof, Joppe J. Vodegel, Michele F. Eisenga, Tim J. Knobbe, Jan IJmker, Rosa G.M. Lammerts, Martin H. de Borst, Stefan P. Berger, Ilja M. Nolte, Ramón Rodrigo, Riemer H.J.A. Slart, Gerjan J. Navis, Daan J. Touw, Stephan J.L. Bakker
Journal: Kidney International (2020)

The kidney is one of the most sensitive organs to cadmium-induced toxicity, particularly in conditions of long-term oxidative stress. We hypothesized that, in kidney transplant recipients, nephrotoxic exposure to cadmium represents an overlooked hazard for optimal graft function. To test this, we performed a prospective cohort study and included 672 outpatient kidney transplant recipients with a functioning graft of beyond one year. The median plasma cadmium was 58 ng/L. During a median 4.9 years of follow-up, 78 kidney transplant recipients developed graft failure with a significantly different distribution across tertiles of plasma cadmium (13, 26, and 39 events, respectively). Plasma cadmium was associated with an increased risk of graft failure (hazard ratio 1.96, 95% confidence interval 1.56‒2.47 per log2 ng/L). Similarly, a dose-response relationship was observed over increasing tertiles of plasma cadmium, after adjustments for potential confounders (donor, recipient, transplant and lifestyle characteristics), robust in both competing risk and sensitivity analyses. These findings were also consistent for kidney function decline (graft failure or doubling of serum creatinine). Thus, plasma cadmium is independently associated with an increased risk of long-term kidney graft failure and decline in kidney function. Further studies are needed to investigate whether exposure to cadmium represents an otherwise overlooked modifiable risk factor for adverse long-term graft outcomes in different populations.
T T King
Authors: Andrew King
Journal: BMJ (2020)

Tom King (“TTK”) was one of a small cohort of internationally famous neurosurgeons from the UK. At the London Hospital, he and his ENT colleague, Andrew Morrison, pioneered new surgical techniques for acoustic neuroma, notably the translabyrinthine route. At the British Skull Base Society meeting that took place only a week after he died, he was recognised as one of the founders of modern skull base surgery in the UK. Most neurosurgeons attending the meeting …
Modularity in Protein Evolution: Modular Organization and De Novo Domain Evolution in Mollusk Metallothioneins
Authors: Sara Calatayud, Mario Garcia-Risco, Veronika Pedrini-Martha, Douglas J Eernisse, Reinhard Dallinger, Òscar Palacios, Mercè Capdevila, Ricard Albalat
Journal: Molecular Biology and Evolution (2020)

Metallothioneins (MTs) are proteins devoted to the control of metal homeostasis and detoxification, and therefore, MTs have been crucial for the adaptation of the living beings to variable situations of metal bioavailability. The evolution of MTs is, however, not yet fully understood, and to provide new insights into it, we have investigated the MTs in the diverse classes of Mollusks. We have shown that most molluskan MTs are bimodular proteins that combine six domains-α, β1, β2, β3, γ, and δ-in a lineage-specific manner. We have functionally characterized the Neritimorpha β3β1 and the Patellogastropoda γβ1 MTs, demonstrating the metal-binding capacity of the new γ domain. Our results have revealed a modular organization of mollusk MT, whose evolution has been impacted by duplication, loss, and de novo emergence of domains. MTs represent a paradigmatic example of modular evolution probably driven by the structural and functional requirements of metal binding.
Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-Week results from the Dutch BioDay registry
Authors: Lieneke F.M. Ariëns, Jorien van der Schaft, Lotte S. Spekhorst, Daphne S. Bakker, Geertruida L.E. Romeijn, Tessa A. Kouwenhoven, Marijke Kamsteeg, Angelique N. Voorberg, Albert J. Oosting, Ilona de Ridder, Annemieke Sloeserwij, Inge Haeck, Judith L. Thijs, Marie L.A. Schuttelaar, Marjolein S. de Bruin-Weller
Journal: Journal of the American Academy of Dermatology (2020)
鉄欠乏性貧血における静脈内フェルモキシトール対第二鉄カルボキシマルトの比較安全性:無作為化試験【JST・京大機械翻訳】
Authors: Adkinson N. Franklin, E Strauss William, C Macdougall Iain, E Bernard Kristine, Auerbach Michael, F Kaper Robert, M Chertow Glenn, S Krop Julie
Journal: American Journal of Hematology (2018)
Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer
Authors: Olivia Le Saux, Isabelle Ray-Coquard, S. Intidhar Labidi-Galy
Journal: Seminars in Cancer Biology (2020)

Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8+ T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.). Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated. Each approach faces distinct challenges that will be reviewed here. Robust immunogenomics studies conducted in parallel of the ongoing trials will help into refining optimal immunotherapy combination for this lethal disease and identify predictive biomarkers.
Postoperative Pelvic Radiotherapy in Patients With Endometrial Cancer May Increase the Risk for Secondary Pelvic Cancers: A Post Hoc Analysis of Results From the TME, PORTEC-1, and PORTEC-2 Trials Reply
Authors: L.M. Wiltink, R.A. Nout, M. Fiocco, C.L. Creutzberg, C.A.M. Marijnen
Journal: Journal of Clinical Oncology (2017)
Continuous Positive Airway Pressure Does Not Improve Nonalcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea. A Randomized Clinical Trial
Authors: Susanna S. S. Ng, Vincent W. S. Wong, Grace L. H. Wong, Winnie C. W. Chu, Tat-On Chan, Kin-Wang To, Fanny W. S. Ko, Ka-Pang Chan, David S. Hui
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Obstructive sleep apnea (OSA) is associated with development of nonalcoholic fatty liver disease (NAFLD). The effects of continuous positive airway pressure (CPAP) on NAFLD in patients with concomitant OSA are unknown.Objectives: To investigate the effects of autoadjusting CPAP versus subtherapeutic CPAP treatment over 6 months on NAFLD activities.Methods: Patients with NAFLD and OSA, as defined by respiratory event index ≥5/h diagnosed by a validated level 3 Embletta device, were randomized into group A) autoadjusting CPAP (4-20 cm H2O) or group B) subtherapeutic CPAP (pressure fixed at 4 cm H2O). The primary endpoint was the difference in changes in intrahepatic triglyceride as measured by proton magnetic resonance spectroscopy after 6 months of therapy. Key secondary endpoints included changes in controlled attenuation parameter (CAP) and liver stiffness measurement measured with transient elastography, and serum cytokeratin-18 fragment.Measurements and Main Results: A total of 120 patients were randomized equally into two groups. There were significant correlations between CAP and respiratory event index (r = 0.203, P = 0.026), percentage of total recording time with SaO2 < 90% (r = 0.265, P = 0.003), and oxygen desaturation index (r = 0.214, P = 0.019). After 6 months of treatment, there were no significant differences of changes in primary and secondary endpoints between the two treatment groups. Regression analysis showed that weight change over 6 months correlated with changes in both intrahepatic triglyceride and CAP (P < 0.001).Conclusions: Despite significant correlations between hepatic steatosis and markers of severity of OSA, CPAP alone did not improve hepatic steatosis and fibrosis. However, the additional role of weight reduction through lifestyle modification deserves further investigation.
進行性胃または胃食道腺癌におけるシスプラチン/S-1とシスプラチン/フルオロウラシル静注を比較した多施設共同第III相試験:FLAGS試験
Authors: A Ajani Jaffer, Rodriguez Wuilbert, Bodoky Gyorgy, Moiseyenko Vladimir, Lichinitser Mikhail, Gorbunova Vera, Vynnychenko Ihor, Garin August, Lang Istvan, Falcon Silvia
Journal: Journal of Clinical Oncology (2010)