tbuckley/cabot-search huggingface dataset:
<i>Streptococcus</i> species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice
Authors: Rabia Moentadj, Yiwen Wang, Kate Bowerman, Linda Rehaume, Hendrik Nel, Paraic O Cuiv, Juliette Stephens, Amalina Baharom, Muralidhara Maradana, Vanessa Lakis, Mark Morrison, Timothy Wells, Philip Hugenholtz, Helen Benham, Kim-Anh Le Cao, Ranjeny Thomas
Journal: Annals of the Rheumatic Diseases (2021)

Analysis of oral dysbiosis in individuals sharing genetic and environmental risk factors with rheumatoid arthritis (RA) patients may illuminate how microbiota contribute to disease susceptibility. We studied the oral microbiota in a prospective cohort of patients with RA, first-degree relatives (FDR) and healthy controls (HC), then genomically and functionally characterised streptococcal species from each group to understand their potential contribution to RA development.After DNA extraction from tongue swabs, targeted 16S rRNA gene sequencing and statistical analysis, we defined a microbial dysbiosis score based on an operational taxonomic unit signature of disease. After selective culture from swabs, we identified streptococci by sequencing. We examined the ability of streptococcal cell walls (SCW) from isolates to induce cytokines from splenocytes and arthritis in ZAP-70-mutant SKG mice.RA and FDR were more likely to have periodontitis symptoms. An oral microbial dysbiosis score discriminated RA and HC subjects and predicted similarity of FDR to RA. Streptococcaceae were major contributors to the score. We identified 10 out of 15 streptococcal isolates as S. parasalivarius sp. nov., a distinct sister species to S. salivarius. Tumour necrosis factor and interleukin 6 production in vitro differed in response to individual S. parasalivarius isolates, suggesting strain specific effects on innate immunity. Cytokine secretion was associated with the presence of proteins potentially involved in S. parasalivarius SCW synthesis. Systemic administration of SCW from RA and HC-associated S. parasalivarius strains induced similar chronic arthritis.Dysbiosis-associated periodontal inflammation and barrier dysfunction may permit arthritogenic insoluble pro-inflammatory pathogen-associated molecules, like SCW, to reach synovial tissue.
Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia
Authors: Xiaowei Zhu, Bo Zhou, Reenal Pattni, Kelly Gleason, Chunfeng Tan, Agnieszka Kalinowski, Steven Sloan, Anna-Sophie Fiston-Lavier, Jessica Mariani, Dmitri Petrov, Ben A. Barres, Laramie Duncan, Alexej Abyzov, Hannes Vogel, Xiaowei Zhu, Bo Zhou, Alexander Urban, Christopher Walsh, Javier Ganz, Mollie Woodworth, Pengpeng Li, Rachel Rodin, Robert Hill, Sara Bizzotto, Zinan Zhou, Alice Lee, Alissa D’Gama, Alon Galor, Craig Bohrson, Daniel Kwon, Doga Gulhan, Elaine Lim, Isidro Cortes, Joe Luquette, Maxwell Sherman, Michael Coulter, Michael Lodato, Peter Park, Rebeca Monroy, Sonia Kim, Yanmei Dou, Andrew Chess, Attila Jones, Chaggai Rosenbluh, Schahram Akbarian, Ben Langmead, Jeremy Thorpe, Jonathan Pevsner, Rob Scharpf, Sean Cho, Flora Vaccarino, Liana Fasching, Simone Tomasi, Nenad Sestan, Sirisha Pochareddy, Andrew Jaffe, Apua Paquola, Daniel Weinberger, Jennifer Erwin, Jooheon Shin, Richard Straub, Rujuta Narurkar, Anjene Addington, David Panchision, Doug Meinecke, Geetha Senthil, Lora Bingaman, Tara Dutka, Thomas Lehner, Alexej Abyzov, Taejeong Bae, Laura Saucedo-Cuevas, Tara Conniff, Diane A. Flasch, Trenton J. Frisbie, Jeffrey M. Kidd, Mandy M. Lam, John B. Moldovan, John V. Moran, Kenneth Y. Kwan, Ryan E. Mills, Sarah Emery, Weichen Zhou, Yifan Wang, Kenneth Daily, Mette Peters, Fred Gage, Meiyan Wang, Patrick Reed, Sara Linker, Ani Sarkar, Aitor Serres, David Juan, Inna Povolotskaya, Irene Lobon, Manuel Solis, Raquel Garcia, Tomas Marques-Bonet, Gary Mathern, Jing Gu, Joseph Gleeson, Laurel Ball, Renee George, Tiziano Pramparo, Aakrosh Ratan, Mike J. McConnell, John V. Moran, Flora M. Vaccarino, Carol A. Tamminga, Douglas F. Levinson, Alexander E. Urban
Journal: Nature Neuroscience (2021)
Uptake of and factors associated with testing for sexually transmitted infections in community-based settings among youth in Zimbabwe: a mixed-methods study
Authors: Kevin Martin, Ioana D Olaru, Nyasha Buwu, Tsitsi Bandason, Michael Marks, Ethel Dauya, Joice Muzangwa, David Mabey, Chido Dziva Chikwari, Suzanna C Francis, Mandikudza Tembo, Constancia Mavodza, Victoria Simms, Constance R S Mackworth-Young, Anna Machiha, Katharina Kranzer, Rashida A Ferrand
Journal: The Lancet Child & Adolescent Health (2021)

BackgroundThe prevalence of sexually transmitted infections (STIs) among youth is high in sub-Saharan Africa. We investigated the uptake of testing for and prevalence of Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhoea) infections among youth in community-based settings in Zimbabwe, and explored the facilitators and barriers to testing.MethodsThis study was nested within a cluster randomised trial of community-based delivery of integrated HIV and sexual and reproductive health services for youth aged 16–24 years. Chlamydia and gonorrhoea testing via urine samples using the Xpert CT/NG test was offered in the four intervention clusters in Harare, Zimbabwe. Factors associated with testing uptake were investigated in a subset of participants (n=257) using hierarchical multivariate logistic regression. In-depth interviews with a separate purposively selected sample (n=26) explored facilitators and barriers to STI testing and partner notification and were analysed using thematic analysis.FindingsBetween June 1, 2019, and Jan 31, 2020, there were 6200 attendances by 4440 participants (78·2% women, 21·8% men) median age 20·3 (IQR 17·9–22·8) years. 1478 participants had 1501 tests done, and 248 tests were positive and 1253 tests were negative for chlamydia or gonorrhoea, or both. STI test uptake was 33·3% (95% CI 31·9–34·7), increasing from 11·7% in June, 2019, to 37·1% in January, 2020. The prevalence of chlamydia or gonorrhoea, or both, was 16·5% (95% CI 14·7–18·5; 248 of 1501), with only seven participants (3%) showing symptoms. The overall yield of testing was 4·0% (95% CI 3·5–4·5; 248 of 6200). Uptake was associated with having symptoms (adjusted odds ratio [OR] 14·8, 95% CI 1·66–132·07) and negatively associated with being single (adjusted OR 0·33, 95% CI 0·13–0·84) or having a boyfriend or girlfriend (adjusted OR 0·19, 95% CI 0·087–0·43) compared with being married, and being a student compared with being employed (adjusted OR 0·26, 95% CI 0·10–0·68). Perceived risk and symptoms of STIs were motivators for testing whereas misinformation, anticipated stigma, and concern about confidentiality were barriers.InterpretationThe prevalence of chlamydia or gonorrhoea, or both, was high among youth but only a minority were symptomatic. Therefore most infections would remain untreated without access to STI testing. Provision of education, counselling, and confidentiality are essential to improve uptake and acceptability of STI testing.FundingWellcome Trust.
Productivity Benefits of Preventing Type 2 Diabetes in Australia: A 10-Year Analysis
Authors: Kirthi Menon, Barbora de Courten, Danny Liew, Zanfina Ademi, Alice J. Owen, Dianna J. Magliano, Ella Zomer
Journal: Diabetes Care (2021)

OBJECTIVE Diabetes imposes a heavy burden on both health and productivity. In this study, we sought to estimate the potential productivity gains associated with the prevention of type 2 diabetes over the next 10 years in Australia. RESEARCH DESIGN AND METHODS Dynamic life table models were constructed to estimate years of life lived and productivity-adjusted life-years (PALYs) lived by Australians aged 20–69 years over the period from 2020 to 2029. The models distinguished people with and without type 2 diabetes. PALYs were ascribed a financial value equivalent to gross domestic product (GDP) per full-time worker in Australia (∼200,000 Australian dollars [AUD]). The model simulation was first undertaken assuming currently expected trends in the incidence of type 2 diabetes and then repeated assuming hypothetically that the incidence was reduced. The difference between the modeled outputs reflected the impact of new cases of type 2 diabetes on productivity as well as the potential benefits of prevention. An annual 5% discount rate was applied to all outcomes. RESULTS Over the next decade, 140 million years of life and 87 million PALYs will be lived by Australians of working age, contributing AUD 18.0 trillion to the country’s GDP. A 10% reduction in the incidence of type 2 diabetes would result in a gain of 2,510 PALYs and AUD 532 million in GDP. CONCLUSIONS This study illustrates the health and economic impact of type 2 diabetes and the gains that could be potentially achieved from the implementation of effective prevention strategies. However, cost-effectiveness evaluations of these prevention strategies are needed.
Mystery of Biphasic Defibrillation Waveform Efficacy: Is it Calcium?⁎⁎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: James P. Daubert, Shey-Shing Sheu
Journal: Journal of the American College of Cardiology (2008)
Abstract 118: Resuscitative Transfusion With Hemoglobin Vesicles in the Management of Post-Partum Hemorrhage
Authors: Kohsuke Hagisawa, Manabu Kinoshita, Hiroki Ishibashi, Hiromi Sakai
Journal: Circulation (2019)

Background: We developed a Hemoglobin vesicles (HbV), which are artificial substitute for Red blood cells (RBCs). Objective: To evaluate the efficacy of HbV for alternative treatment instead of RBCs transfusion in rabbits with hemorrhagic shock due to post-partum hemorrhage. Methods: New Zealand white rabbits at late gestation underwent uncontrolled hemorrhagic shock by transecting a right mid-artery in the myometrium, after cesarean section of right side uterus. Initially, in the simulated ordinal treatment of bleeding, rabbits received colloid fluids (Voluven®) through an femoral vein with equivalent volume of the bleeding every 5 minutes. Once blood loss achieved 100ml, animals subsequently faced on critical hemorrhagic situation, where mean arterial pressure (MAP) reduced to approximately 48mmHg. They were randomly divided into three isovolemic resuscitation regimens: continuing colloid fluid resuscitation (n=4); transfusion of autologous washed RBCs with plasma (n=4); HbV infusion combining 5% human serum albumin (n=4). After 60 minutes of bleeding, all animals underwent surgical control of bleeding and cesarean section of left side uterus. Results: At the point of critical hemorrhagic situation, Hb concentration reduced to 4.8 g/dl. At the end of resuscitation, HbV infusion regained MAP and restored Hb concentration as well as RBCs transfusion, besides colloid fluid resuscitation exaggerated the severe hemorrhagic shock as shown in the table. Conclusions: HbV treatment may be effective in the management of post-partum hemorrhagic shock.
Ian Archibald McGlashan
Authors: Julian McGlashan, Nick McGlashan, Kate McGlashan
Journal: BMJ (2021)

Ian Archibald McGlashan was born in Glasgow, Scotland. During the second world war the family home was moved to Maybole in Ayrshire, where he went to primary school. His life nearly ended at the age of 8 when he contracted diphtheria. Fortunately, his mother has had the foresight to ensure that he had had the newly introduced vaccine, which probably helped save his life. He then attended secondary school at Carrick Academy in Greenock after the family moved to Gourock on the estuary of the Clyde. His father worked for the Ministry of Supply and spent the war time in London. When the war ended Ian, aged 15, his mother, and his two sisters were reunited with his father in Woolwich, London. Ian completed his secondary education at Shooters Hill Grammar School. He was captain of the first XV rugby team and a good athletic sprinter. Although he obtained four good …
How Have Multigene Panels Changed the Clinical Practice of Genetic Counseling and Testing
Authors: Robert Pilarski
Journal: Journal of the National Comprehensive Cancer Network (2021)

Historically, genetic testing (and billing) for hereditary cancer risk was essentially performed gene by gene, with clinicians ordering testing only for the genes most likely to explain a patient’s or family’s cancer presentation, with laboratories typically charging $1,000 to $1,500 for each gene that was sequenced. Given the expense, only patients at high risk of having a hereditary syndrome were offered testing. With the introduction of next-generation sequencing technologies, however, laboratories are able to test for multiple genes at the same time with greater efficiency, significantly decreased costs, and relatively little increased expense when adding additional genes. This has drastically altered clinical practice so that clinicians now typically order testing for a panel of multiple genes for most patients. Although this approach has streamlined the diagnostic odyssey, it has introduced several problems, as well, including difficulties in choosing the appropriate panel test for a given patient, assessing the significance of identified genetic variants (including variants of uncertain significance [VUS]), and understanding the disease risks and management associated with pathogenic variants in a given gene. Many laboratories offer testing for genes that have limited data supporting their associated cancer risks, which then leads to an inability to set management guidelines based on that gene. In addition, testing larger numbers of genes increases the likelihood of finding one or more VUS, which introduce their own management issues. Thus, although panel testing has certainly moved clinical practice forward in many ways, it has also raised its own set of problems that increase the complexity of genetic counseling and highlight the need for education of community practitioners on the complexities and nuances of this testing. Whenever possible, testing should be performed by, or in consultation with, cancer genetics professionals.
Methylene Blue for the Treatment of Intractable Pain From Oral Mucositis Related to Cancer Treatment: An Uncontrolled Cohort
Authors: Carlos J. Roldan, Matthew Chung, Lei Feng, Eduardo Bruera
Journal: Journal of the National Comprehensive Cancer Network (2021)

Oral mucositis is a complication of cancer therapy, causing severe pain that affects oral functioning, nutrition, and quality of life, as well as therapy nonadherence or dose-limiting toxicity. Anecdotal experience has suggested that methylene blue (MB) oral rinse may be an effective and safe treatment of this oral pain.To evaluate the efficacy and safety of MB oral rinse for the treatment of oral pain due to mucositis in patients with cancer, we retrospectively evaluated patients who experienced refractory pain despite conventional therapy.We identified 281 patients who received MB oral rinse. Most were receiving treatment for leukemia (n=85; 30.3%) and head and neck squamous cell carcinoma (n=84; 29.9%). The most common treatments were radiation therapy alone (n=108; 38.4%) and chemoradiation (n=86; 30.6%). Median duration of symptoms was 14 days. Mean (SD) numeric rating scale pain scores were 7.7 (1.83; median, 8) before MB oral rinse and 2.51 (2.76; median, 2) after MB oral rinse (P<.0001). Most patients achieved pain control within the first 3 doses. The effectiveness of MB oral rinse was independent of patient age, sex, cancer type, cancer stage, MB dilution, and pain duration or baseline pain scores. The lowest response to treatment was reported in individuals with esophageal mucositis. Few patients experienced adverse effects of MB oral rinse (n=13; 4.6%); 10 had a transient burning sensation, 2 had transient blue discoloration of the teeth and mouth, and 1 had increased pain.MB oral rinse is an effective and safe treatment for refractory pain from oral mucositis related to cancer treatment.
Plasma Soluble Suppression of Tumorigenicity-2 Associates with Ventilator Liberation in Acute Hypoxemic Respiratory Failure
Authors: Jehan Alladina, Sean D. Levy, Josalyn L. Cho, Kelsey L. Brait, Sowmya R. Rao, Alexander Camacho, Kathryn A. Hibbert, R. Scott Harris, Benjamin D. Medoff, James L. Januzzi, B. Taylor Thompson, Ednan K. Bajwa
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Standard physiologic assessments of extubation readiness in patients with acute hypoxemic respiratory failure (AHRF) may not reflect lung injury resolution and could adversely affect clinical decision-making and patient outcomes. Objectives: We hypothesized that elevations in inflammatory plasma biomarkers sST2 (soluble suppression of tumorigenicity-2) and IL-6 indicate ongoing lung injury in AHRF and better inform patient outcomes compared with standard clinical assessments. Methods: We measured daily plasma biomarkers and physiologic variables in 200 patients with AHRF for up to 9 days after intubation. We tested the associations of baseline values with the primary outcome of unassisted breathing at Day 29. We analyzed the ability of serial biomarker measurements to inform successful ventilator liberation. Measurements and Main Results: Baseline sST2 concentrations were higher in patients dead or mechanically ventilated versus breathing unassisted at Day 29 (491.7 ng/ml [interquartile range (IQR), 294.5-670.1 ng/ml] vs. 314.4 ng/ml [IQR, 127.5-550.1 ng/ml]; P = 0.0003). Higher sST2 concentrations over time were associated with a decreased probability of ventilator liberation (hazard ratio, 0.80 per log-unit increase; 95% confidence interval [CI], 0.75-0.83; P = 0.03). Patients with higher sST2 concentrations on the day of liberation were more likely to fail liberation compared with patients who remained successfully liberated (320.9 ng/ml [IQR, 181.1- 495.6 ng/ml] vs. 161.6 ng/ml [IQR, 95.8-292.5 ng/ml]; P = 0.002). Elevated sST2 concentrations on the day of liberation decreased the odds of successful liberation when adjusted for standard physiologic parameters (odds ratio, 0.325; 95% CI, 0.119-0.885; P = 0.03). IL-6 concentrations did not associate with outcomes. Conclusions: Using sST2 concentrations to guide ventilator management may more accurately reflect underlying lung injury and outperform traditional measures of readiness for ventilator liberation.
Lifetime Pesticide Use and Monoclonal Gammopathy of Undetermined Significance in a Prospective Cohort of Male Farmers
Authors: Jonathan N. Hofmann, Laura E. Beane Freeman, Kazunori Murata, Gabriella Andreotti, Joseph J. Shearer, Katie Thoren, Lakshmi Ramanathan, Christine G. Parks, Stella Koutros, Catherine C. Lerro, Danping Liu, Nathaniel Rothman, Charles F. Lynch, Barry I. Graubard, Dale P. Sandler, Michael C. Alavanja, Ola Landgren
Journal: Environmental Health Perspectives (2021)

Background: Farmers have a higher incidence of multiple myeloma, and there is suggestive evidence of an elevated prevalence of its precursor, monoclonal gammopathy of undetermined significance (MGUS), relative to the general population. Pesticide exposures are suspected to play a role; however, the biologic plausibility for associations with multiple myeloma remains unclear. Objectives: Our objectives were to examine the prevalence of MGUS and evaluate associations with a wide range of pesticides in a large sample of farmers. Methods: We obtained sera and assessed MGUS among 1,638 male farmers ≥50 years of age in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate associations with MGUS for recent use (within the 12 months before phlebotomy) and cumulative intensity-weighted lifetime days of use of specific pesticides. Results: The age-standardized MGUS prevalence was significantly elevated among AHS farmers (7.7%) compared with demographically similar men in the National Health and Nutrition Examination Survey (2.8%) or Olmsted County, Minnesota (3.8%; p<0.001). Recent use of permethrin was associated with MGUS [recent use vs. no recent use, OR=1.82 (95% CI: 1.06, 3.13)], especially among those who had also used it in the past [recent and past use vs. never use, OR=2.49 (95% CI: 1.32, 4.69)]. High intensity-weighted lifetime use of the organochlorine insecticides aldrin and dieldrin was associated with MGUS relative to those who never used either of these pesticides [OR=2.42 (95% CI: 1.29, 4.54); ptrend=0.006]. We also observed a positive association with high lifetime use of petroleum oil/distillates as an herbicide, as well as an inverse association with fonofos use. Discussion: This is the largest investigation of MGUS in farmers and the first to identify an association with MGUS for permethrin, a pyrethroid insecticide previously associated with multiple myeloma. Given the continued widespread use of permethrin in various residential and commercial settings, our findings may have important implications for exposed individuals in the general population. https://doi.org/10.1289/EHP6960
Stereotypic neutralizing V <sub>H</sub> antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals
Authors: Sang Il Kim, Jinsung Noh, Sujeong Kim, Younggeun Choi, Duck Kyun Yoo, Yonghee Lee, Hyunho Lee, Jongtak Jung, Chang Kyung Kang, Kyoung-Ho Song, Pyoeng Gyun Choe, Hong Bin Kim, Eu Suk Kim, Nam-Joong Kim, Moon-Woo Seong, Wan Beom Park, Myoung-don Oh, Sunghoon Kwon, Junho Chung
Journal: Science Translational Medicine (2021)

Stereotypic antibody clonotypes exist in healthy individuals and may provide protective immunity against viral infections by neutralization. We observed that 13 of 17 patients with COVID-19 had stereotypic variable heavy chain (V
ヒト多発性骨髄腫の染色体転座 t(14;16)(q32;q23)の新規遺伝子導入マウスモデル
Authors: Morito Naoki, Yoh Keigyou, Maeda Atsuko, Nakano Takako, Fujita Akiko, Kusakabe Manabu, Hamada Michito, Kudo Takashi, Yamagata Kunihiro, Takahashi Satoru
Journal: Cancer Research (2011)
David Arnott Player: public health activist and director general of the Health Education Council
Authors: Rebecca Wallersteiner
Journal: BMJ (2021)

Photo credit: The Scotsman

David Player, physician, public health activist, and director general of the Health Education Council, has died at the age of 93.

Player was born in Queen’s Park, Glasgow, to John, a detective chief inspector, and Agnes (nee Gray). He was educated at Bellahouston Academy in Govanhill, where he enjoyed playing football and cricket, later playing both sports for British Army teams during his national service. He was the first student from Bellahouston to win a scholarship to study medicine at Glasgow University.

At university, he developed an awareness of the necessity for deep structural change that led to his later becoming active in the Labour party. After graduating he served as a doctor in the British Army in Hong Kong, where he was a captain with the Royal Army Medical Corps and learnt Mandarin, before returning to work in the emergency department at Glasgow Royal Infirmary. In the evenings, he trained in psychiatry in Dumfries. In the 1950s, he moved to Cumbria and entered general practice, serving mining villages where poverty and poor working conditions were widespread. Many of his patients had respiratory illnesses, and his concern for them prompted his move into preventive medicine. This also encouraged him to return to Glasgow University to gain a diploma in public health in 1960.

He met Anne Darragh while they were both undertaking postgraduate training at Dumfries Royal Infirmary, and they married in 1955 and had two sons, John and Stewart. Anne died in …