tbuckley/cabot-search huggingface dataset:
Childhood and Early Onset Glaucoma Classification and Genetic Profile in a Large Australasian Disease Registry
Authors: Lachlan S.W. Knight, Jonathan B. Ruddle, Deepa A. Taranath, Ivan Goldberg, James E.H. Smith, Glen Gole, Mark Y. Chiang, Faren Willett, Guy D’Mellow, James Breen, Ayub Qassim, Sean Mullany, James E. Elder, Andrea L. Vincent, Sandra E. Staffieri, Lisa S. Kearns, David A. Mackey, Susie Luu, Owen M. Siggs, Emmanuelle Souzeau, Jamie E. Craig
Journal: Ophthalmology (2021)

To report the relative frequencies of childhood and early onset glaucoma subtypes and their genetic findings in a large single cohort.Retrospective clinical and molecular study.All individuals with childhood glaucoma (diagnosed 0 to <18 years) and early onset glaucoma (diagnosed 18 to <40 years) referred to a national disease registry.We retrospectively reviewed the referrals of all individuals with glaucoma diagnosed at <40 years of age recruited to the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG). Subtypes of glaucoma were determined using the Childhood Glaucoma Research Network (CGRN) classification system. DNA extracted from blood or saliva samples underwent sequencing of genes associated with glaucoma.The phenotype and genotype distribution of glaucoma diagnosed at <40 years of age.A total of 290 individuals (533 eyes) with childhood glaucoma and 370 individuals (686 eyes) with early onset glaucoma were referred to the ANZRAG. Primary glaucoma was the most prevalent condition in both cohorts. In the childhood cohort, 57.6% of individuals (167/290, 303 eyes) had primary congenital glaucoma (PCG), and 19.3% (56/290, 109 eyes) had juvenile open-angle glaucoma. Juvenile open-angle glaucoma constituted 73.2% of the early onset glaucoma cohort (271/370, 513 eyes). Genetic testing in probands resulted in a diagnostic yield of 24.7% (125/506) and a reclassification of glaucoma subtype in 10.4% of probands (13/125). The highest molecular diagnostic rate was achieved in probands with glaucoma associated with nonacquired ocular anomalies (56.5%). Biallelic variants in CYP1B1 (n = 29, 23.2%) and heterozygous variants in MYOC (n = 24, 19.2%) and FOXC1 (n = 21, 16.8%) were most commonly reported among probands with a molecular diagnosis. Biallelic CYP1B1 variants were reported in twice as many female individuals as male individuals with PCG (66.7% vs. 33.3%, P = 0.02).We report on the largest cohort of individuals with childhood and early onset glaucoma from Australasia using the CGRN classification. Primary glaucoma was most prevalent. Genetic diagnoses ascertained in 24.7% of probands supported clinical diagnoses and genetic counseling. International collaborative efforts are required to identify further genes because the majority of individuals still lack a clear molecular diagnosis.
Association Between Systemic Corticosteroid Treatment for Cutaneous Immune-Related Adverse Events and Survival Outcomes in Patients With Advanced Cancer
Authors: Leah L. Thompson, Jaewon Yoon, Nira A. Krasnow, Michael S. Chang, Edward B. Li, Devon E. McMahon, Steven T. Chen
Journal: JAMA Dermatology (2021)

This cohort study investigates the association of systemic corticosteroid exposures with infectious complications and survival outcomes among patients with a cutaneous immune-related adverse event.
Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers
Authors: Rivka R Colen, Christian Rolfo, Murat Ak, Mira Ayoub, Sara Ahmed, Nabil Elshafeey, Priyadarshini Mamindla, Pascal O Zinn, Chaan Ng, Raghu Vikram, Spyridon Bakas, Christine B Peterson, Jordi Rodon Ahnert, Vivek Subbiah, Daniel D Karp, Bettzy Stephen, Joud Hajjar, Aung Naing
Journal: Journal for ImmunoTherapy of Cancer (2021)

We present a radiomics-based model for predicting response to pembrolizumab in patients with advanced rare cancers.
Acute haemoptysis, fever and abdominal pain in an adolescent from northern Australia
Authors: Daniel K Yeoh, Timothy J Ford, Joanna Chua, Miriam Bennamoun, Christopher C Blyth, Anita J Campbell, Prasanthy Hamsanathan, Ben Harkin, Jovanka King, Lisa Matthews, Charlie McLeod, Rebecca Warren, Asha C Bowen, Melanie J Thompson, André Schultz
Journal: Thorax (2021)

<b>Objective:</b> To examine and compare bacteriological findings at autopsy of cases of sudden unexpected infant death and those of deaths of other cause. Design: autopsy report review of 130 SIDS cases (2004 definition), 32 cases of sudden unexpected death in infancy (SUDI) due to infection and 33 cases of non-infectious sudden deaths. <b>Setting: </b>Qualitative assessment of normally sterile site (NSS) (heart blood, spleen or cerebrospinal fluid) bacteriology in SIDS and age-matched comparison deaths that occurred in the late 1980s and early 1990s. <b>Main outcome measures:</b> comparative sterile site bacteriological findings. <b>Results: </b>Sterile site infection was uncommon in cases of sudden accidental death (e.g. motor vehicle accident or drowning, etc.) however, the finding of true pathogens such as Staphylococcus aureus in sterile sites in SIDS and deaths associated with infection was relatively common. 10.76% of SIDS had S. aureus in a sterile site, compared with 18.75% of cases of infection-related deaths. S. aureus was not found in sudden accidental deaths. The incidence of coliform bacteria in NSS in SIDS was not significantly different from that seen in deaths of other cause. NSS bacteriology yielded no growth in 45.4% of sudden accidental death, 43% of SIDS and 28.1% of infectious causes of death. <b>Conclusions: </b>The finding of S. aureus in NSS in a large proportion of cases of SIDS would indicate that a proportion of these babies died of staphylococcal disease. Although the differences in NSS isolation of Staphylococcuus aureus in the three infant groups did not quite achieve significance, nevertheless, on the basis of these findings and the characteristic virulence of S. aureus, it is recommended that sudden unexpected deaths from which Staphylococcus aureus is isolated from NSS be considered for reclassifiication. The incidence of coliform bacteria in NSS in SIDS is not significantly different from that in deaths of other cause (both accidental and infectious). From these findings it is recommended that the opinion of a consultant microbiologist be sought to interpret microbiological findings prior to finalising autopsy reports on SUDI.
A Type 2 Diabetes Subtype Responsive to ACCORD Intensive Glycemia Treatment
Authors: Arshiya Mariam, Galen Miller-Atkins, Kevin M. Pantalone, Robert S. Zimmerman, John Barnard, Michael W. Kattan, Hetal Shah, Howard L. McLeod, Alessandro Doria, Michael J. Wagner, John B. Buse, Alison A. Motsinger-Reif, Daniel M. Rotroff
Journal: Diabetes Care (2021)

OBJECTIVE Current type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed, suggesting potential benefit for some individuals. RESEARCH DESIGN AND METHODS ACCORD was a randomized controlled trial that investigated whether intensively treating glycemia in individuals with T2D would reduce CVD outcomes. Using a novel approach to cluster HbA1c trajectories, we identified groups in the intensive glycemia arm with modified CVD risk. Genome-wide analysis and polygenic score (PS) were developed to predict group membership. Mendelian randomization was performed to infer causality. RESULTS We identified four clinical groupings in the intensive glycemia arm, and clinical group 4 (C4) displayed fewer CVD (hazard ratio [HR] 0.34; P = 2.01 × 10−3) and microvascular outcomes (HR 0.86; P = 0.015) than those receiving standard treatment. A single-nucleotide polymorphism, rs220721, in MAS1 reached suggestive significance in C4 (P = 4.34 × 10−7). PS predicted C4 with high accuracy (area under the receiver operating characteristic curve 0.98), and this predicted C4 displayed reduced CVD risk with intensive versus standard glycemia treatment (HR 0.53; P = 4.02 × 10−6), but not reduced risk of microvascular outcomes (P &amp;lt; 0.05). Mendelian randomization indicated causality between PS, on-trial HbA1c, and reduction in CVD outcomes (P &amp;lt; 0.05). CONCLUSIONS We found evidence of a T2D clinical group in ACCORD that benefited from intensive glycemia treatment, and membership in this group could be predicted using genetic variants. This study generates new hypotheses with implications for precision medicine in T2D and represents an important development in this landmark clinical trial warranting further investigation.
Central, but not peripheral, nervous system ERK2 is essential for itch signals in murine allergic skin inflammation
Authors: Shinsuke Matsuo, Takashi Hashimoto, Fumhiro Matsuura, Osamu Imamura, Shogo Endo, Yasushi Satoh, Takahiro Satoh
Journal: Allergy (2021)

Itch is a common cutaneous symptom in a variety of dermatological diseases, but detailed neuropathological mechanisms remain to be fully elucidated. This study aimed to assess in vivo ERK2 functions in the nervous system for itch responses.We generated conditional knockout mice deficient in ERK2 of the central nervous system (CNS) or peripheral nervous system (PNS), respectively, and assessed chemical and mechanical itch responses in vivo.Chemical itch responses to histamine, but not to BAM8-22, were alleviated in CNS Erk2-deficient mice. In contrast, both histamine- and BAM8-22-induced mechanical itch (alloknesis) were alleviated in CNS Erk2-deficient mice. Neither chemical itch nor mechanical itch induced by these pruritogens was affected by PNS ERK2 deficiency. Spontaneous scratching behaviors during acute and chronic contact hypersensitivity were impaired in CNS Erk2-deficient mice, but not PNS Erk2-deficient mice. In addition, CNS ERK2 deficiency attenuated mechanical itch responses during chronic contact hypersensitivity. Again, PNS Erk2-deficient mice showed comparable responses of mechanical itch to control mice. In addition, alleviated mechanical itch in CNS Erk2-deficient mice was observed in IgE-mediated prurigo-like allergic skin inflammation. Mechanical itch induced by IL-31 was also alleviated by CNS ERK2 deficiency. Phosphorylated ERK1/2 was detected in neurokinin B-expressing cells of the spinal dorsal horn of control mice; these cells accumulated during the induction of chronic contact hypersensitivity. Notably, phosphorylated ERK1/2 was also localized in spinal urocortin3-expressing neurons that are known to transmit mechanical itch.Spinal cord ERK2 could be a potential therapeutic target for intractable itch in pruritic skin diseases.
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer
Authors: Aditya Bardia, Sara A. Hurvitz, Sara M. Tolaney, Delphine Loirat, Kevin Punie, Mafalda Oliveira, Adam Brufsky, Sagar D. Sardesai, Kevin Kalinsky, Amelia B. Zelnak, Robert Weaver, Tiffany Traina, Florence Dalenc, Philippe Aftimos, Filipa Lynce, Sami Diab, Javier Cortés, Joyce O’Shaughnessy, Véronique Diéras, Cristiano Ferrario, Peter Schmid, Lisa A. Carey, Luca Gianni, Martine J. Piccart, Sibylle Loibl, David M. Goldenberg, Quan Hong, Martin S. Olivo, Loretta M. Itri, Hope S. Rugo
Journal: New England Journal of Medicine (2021)

Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.
Progress in Immunization Safety Monitoring — Worldwide, 2010–2019
Authors: Omar Salman, Katherine Topf, Rebecca Chandler, Laura Conklin
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

High levels of coverage with safe and effective immunizations are critical to the successful control and prevention of vaccine-preventable diseases worldwide. In addition to stringent standards to regulate the safety of vaccines, robust postlicensure monitoring systems help ensure that the benefits of vaccines continue to outweigh the risks for the populations who receive them. National Expanded Programmes on Immunization (EPI) are typically responsible for identifying and investigating adverse events following immunization (AEFI), including assessment of causality. National regulatory authorities (NRAs) are mandated to perform postlicensure surveillance of adverse drug reactions, including those associated with receipt of vaccines. This report describes global progress toward meeting World Health Organization (WHO) indicators on minimal country capacity for vaccine safety surveillance and coordination of AEFI reporting between countries' EPI and NRAs. In 2019, among 194 countries, 129 (66.5%) reported having an operational national AEFI causality review committee, compared with 94 (48.5%) in 2010. During 2010-2019, the proportion of countries reporting ≥10 AEFI per 100,000 surviving infants per year (an indicator of country capacity to monitor immunization safety) increased, from 41.2% to 56.2%. In 2019, however, only 46 (23.7%) countries reported AEFI data from both EPI and NRAs. Although global progress has been made toward strengthening systems for vaccine safety monitoring over the past decade, new indicators for monitoring global immunization safety performance are needed to better reflect program functionality. Continued global efforts will be vital to address barriers to routine reporting of AEFI, build national capacity for AEFI investigation and data management, and improve sharing of AEFI data at national, regional, and global levels.
Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE‐MI): design and baseline characteristics
Authors: Karola S. Jering, Brian Claggett, Marc A. Pfeffer, Christopher Granger, Lars Køber, Eldrin F. Lewis, Aldo P. Maggioni, Douglas Mann, John J.V. McMurray, Jean‐Lucien Rouleau, Scott D. Solomon, Philippe G. Steg, Peter van der Meer, Margaret Wernsing, Katherine Carter, Weinong Guo, Yinong Zhou, Martin Lefkowitz, Jianjian Gong, Yi Wang, Bela Merkely, Stella M. Macin, Urmil Shah, Jose C. Nicolau, Eugene Braunwald
Journal: European Journal of Heart Failure (2021)
Response to “Reply to ‘A deep learning-based smartphone platform for cutaneous lupus erythematosus classification assistance: Simplifying the diagnosis of complicated diseases.’ Has the complicated disease been simplified too much?” Artificial intelligence system is helpful for diagnosis of cutaneous lupus erythematosus
Authors: Haijing Wu, Haipeng Chen, Xiaoqing Liu, Yizhou Yu, Qianjin Lu
Journal: Journal of the American Academy of Dermatology (2021)
Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity
Authors: Janie F. Shelton, Anjali J. Shastri, Chelsea Ye, Catherine H. Weldon, Teresa Filshtein-Sonmez, Daniella Coker, Antony Symons, Jorge Esparza-Gordillo, Adrian Chubb, Alison Fitch, Alison Kung, Amanda Altman, Andy Kill, Jason Tan, Jeff Pollard, Jey McCreight, Jess Bielenberg, John Matthews, Johnny Lee, Lindsey Tran, Michelle Agee, Monica Royce, Nate Tang, Pooja Gandhi, Raffaello d’Amore, Ruth Tennen, Scott Dvorak, Scott Hadly, Sungmin Park, Taylor Morrow, Trung Le, Yiwen Zheng, Stella Aslibekyan, Adam Auton
Journal: Nature Genetics (2021)
Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes
Authors: Pietro Mesirca, Shu Nakao, Sarah Dalgas Nissen, Gabriella Forte, Cali Anderson, Tariq Trussell, Jue Li, Charlotte Cox, Min Zi, Sunil Logantha, Sana Yaar, Helena Cartensen, Isabelle Bidaud, Luke Stuart, Luca Soattin, Gwilym M. Morris, Paula A. da Costa Martins, Elizabeth J. Cartwright, Delvac Oceandy, Matteo E. Mangoni, Thomas Jespersen, Rikke Buhl, Halina Dobrzynski, Mark R. Boyett, Alicia D’Souza
Journal: Circulation Research (2021)

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Transitional Metal‐Based Noncatalytic Medicine for Tumor Therapy
Authors: Wencheng Wu, Yinying Pu, Xiangyu Lu, Han Lin, Jianlin Shi
Journal: Advanced Healthcare Materials (2021)

Abstract Nanocatalytic medicine has been emerging as a highly promising strategy for cancer therapeutics since it enables tumor suppression by in situ generating toxic agents within tumors through catalytic reactions without using conventional highly toxic and nonselective chemodrugs. In the last several years, a number of nanocatalytic medicines have been used to steer catalytic reactions in endogenous or exogenous stimuli‐activated cancer therapy, such as chemodynamic therapy, photodynamic therapy, and sonodynamic therapy. In particular, transitional metal‐based nanocatalytic medicines with excellent catalytic activity and selectivity show significant clinical potentials, and significant progress has been achieved very recently. In this review, three types of typical transitional metal (Fe, Mn, and Cu)‐based nanocatalytic medicines are summarized, followed by detailed discussions on their catalytic mechanisms. Of note, the obstacles and challenges that will be encountered in the design and further clinical conversion of transitional metal‐based nanocatalytic medicine in the future are also outlooked.
Efficacy of Mycophenolate Mofetil in Patients with Diffuse Proliferative Lupus Nephritis
Authors: Tak Mao Chan, Fu Keung Li, Colin S.O. Tang, Raymond W.S. Wong, Guo Xiang Fang, Yu Lian Ji, Chak Sing Lau, Andrew K.M. Wong, Matthew K.L. Tong, Kwok Wah Chan, Kar Neng Lai
Journal: New England Journal of Medicine (2000)

The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects. Whether mycophenolate mofetil can be substituted for cyclophosphamide is not known.
Simultaneous Delivery of Multiple Antimicrobial Agents by Biphasic Scaffolds for Effective Treatment of Wound Biofilms
Authors: Yajuan Su, Alec McCarthy, Shannon L. Wong, Ronald R. Hollins, Guangshun Wang, Jingwei Xie
Journal: Advanced Healthcare Materials (2021)

Biofilms pose a major challenge to control wound-associated infections. Due to biofilm impenetrability, traditional antimicrobial agents are often ineffective in combating biofilms. Herein, a biphasic scaffold is reported as an antimicrobial delivery system by integrating nanofiber mats with dissolvable microneedle arrays for the effective treatment of bacterial biofilms. Different combinations of antimicrobial agents, including AgNO3 , Ga(NO3 )3 , and vancomycin, are incorporated into nanofiber mats by coaxial electrospinning, which enables sustained delivery of these drugs. The antimicrobial agents-incorporated dissolvable microneedle arrays allow direct penetration of drugs into biofilms. By optimizing the administration strategies, drug combinations, and microneedle densities, biphasic scaffolds are able to eradicate both methicillin-resistant Staphylococcus aureus (MRSA) and MRSA/Pseudomonas aeruginosa blend biofilms in an ex vivo human skin wound infection model without necessitating surgical debridement. Taken together, the combinatorial system comprises of nanofiber mats and microneedle arrays can provide an efficacious delivery of multiple antimicrobial agents for the treatment of bacterial biofilms in wounds.
Drug-Induced Immune Thrombocytopenia (DITP) Caused By Multiple Drug-Dependent Platelet-Reactive Antibodies (DDAbs) in Patients Undergoing Oxaliplatin-Containing Combination Chemotherapy for Metastatic Colon Cancer
Authors: Brian R. Curtis, Yen-Michael S. Hsu, Nikolai A. Podoltsev, Jill Lacy, Susanna A Curtis, Robert Andrew Desimone, Michael Samuel, Kristin Zutavern, Daniel Bougie, Richard H. Aster
Journal: Blood (2017)
Abstract 53: Implantation of Loop Recorder In Patients with Ehlers-Danlos Syndrome
Authors: Hemanshi Mistry, Sowmika Lingampally, Amna A Butt, Chandralekha Ashangari, Apeksha Bhattarai, Stacy E Hamid, Amer Suleman
Journal: Circulation Research (2017)

Background: Patients (pts) with Ehlers-Danlos Syndrome (EDS) have a higher incidence of syncope and have a higher rate of complications from incision related procedures. We serve a large population of pts with EDS and report our experience with pts with EDS who required Implantable loop recorder (ILR). Methods: We have conducted a retrospective study on a total of 94 pts with ILR implantation from 2014-2016. Out of 94 pts, there were 20 males (average age=50.8 + 20.143 yrs, 21.28%) and 74 females (average age= 47.59 + 17.296 yrs, 78.72%). Total of 24 (25.53%) pts with EDS who had ILR over the last 2 years. Pts were grouped into 3 categories (1) pts with EDS where ILR implantation was done with the standard technique (2) Our learning curve &amp; (3) the results after the standardized new technique for ILR. 1. Category 1 pts, we used the standard provided by the manufacturer to create a V-shaped cut, loop recorder was inserted; subsequently Dermabond was applied. 2. Category 2 pts, we modified the technique, made a more horizontal incision with the V-shaped blade and a 4-0 Vicryl suture was used to improve wound healing. 3. Category 3 pts, after standardizing the technique, we used the V-shaped blade provided with 4-0 Vicryl knotless continuous suture to tamponade the bleeding. The Dermabond was applied only after local hemostasis was observed. Findings: When the loop recorder was implanted using the standard technique, more of bleeding, bigger scars and multiple keloid formation was observed. In the category 1, we learned that if proper hemostasis is not obtained during the implantation, the patient tended to have more scars. In category 3, when 1-2 layers of Vicryl sutures were applied, the first layer of sutures were subcutaneous &amp; the second was under the skin and a knot less closure was done, hemostasis was obtained prior to applying Dermabond, patients did not have scar formation. Conclusions: We hereby conclude that EDS pts who required ILR, the wound should be closed with 1-2 layers of Vicryl using a knot-less closure technique which will leave a more aesthetically acceptable scar. We would also recommend that until further research is done, this same technique should be use in patients with other hereditary connective tissue disorders.