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Article ; Online: Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

Gupta, Samir / Subhedar, Nimish V / Bell, Jennifer L / Field, David / Bowler, Ursula / Hutchison, Elizabeth / Johnson, Sam / Kelsall, Wilf / Pepperell, Justine / Roberts, Tracy / Sinha, Sunil / Stanbury, Kayleigh / Wyllie, Jonathan / Hardy, Pollyanna / Juszczak, Edmund

The New England journal of medicine

2024 Volume 390, Issue 4, Page(s) 314–325

Abstract: Background: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known.: Methods: We ... ...

Abstract	Background: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. Results: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. Conclusions: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).
MeSH term(s)	Humans ; Infant, Newborn ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Bronchopulmonary Dysplasia/etiology ; Bronchopulmonary Dysplasia/mortality ; Ductus Arteriosus, Patent/complications ; Ductus Arteriosus, Patent/drug therapy ; Ductus Arteriosus, Patent/mortality ; Ibuprofen/administration & dosage ; Ibuprofen/adverse effects ; Ibuprofen/therapeutic use ; Infant, Extremely Premature ; Cyclooxygenase Inhibitors/administration & dosage ; Cyclooxygenase Inhibitors/adverse effects ; Cyclooxygenase Inhibitors/therapeutic use ; Double-Blind Method ; Time Factors ; Treatment Outcome
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Ibuprofen (WK2XYI10QM) ; Cyclooxygenase Inhibitors
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Randomized Controlled Trial ; Multicenter Study ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMoa2305582
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Article ; Online: Utility of peripheral protein biomarkers for the prediction of incident interstitial features: a multicentre retrospective cohort study.

Ash, Samuel / Doyle, Tracy J / Choi, Bina / San Jose Estepar, Ruben / Castro, Victor / Enzer, Nicholas / Kalhan, Ravi / Liu, Gabrielle / Bowler, Russell / Wilson, David O / San Jose Estepar, Raul / Rosas, Ivan O / Washko, George R

BMJ open respiratory research

2024 Volume 11, Issue 1

Abstract: Introduction/rationale: Protein biomarkers may help enable the prediction of incident interstitial features on chest CT.: Methods: We identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and without ... ...

Abstract	Introduction/rationale: Protein biomarkers may help enable the prediction of incident interstitial features on chest CT. Methods: We identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and without objectively measured interstitial features at baseline using a univariate screen (t-test false discovery rate, FDR p<0.001), and which of those were associated with interstitial features longitudinally (multivariable mixed effects model FDR p<0.05). To predict incident interstitial features, we trained four random forest classifiers in a two-thirds random subset of COPDGene: (1) imaging and demographic information, (2) univariate screen biomarkers, (3) multivariable confirmation biomarkers and (4) multivariable confirmation biomarkers available in a separate testing cohort (Pittsburgh Lung Screening Study (PLuSS)). We evaluated classifier performance in the remaining one-third of COPDGene, and, for the final model, also in PLuSS. Results: In COPDGene, 1305 biomarkers were available and 20 differed between those with and without interstitial features at baseline. Of these, 11 were associated with feature progression over a mean of 5.5 years of follow-up, and of these 4 were available in PLuSS, (angiopoietin-2, matrix metalloproteinase 7, macrophage inflammatory protein 1 alpha) over a mean of 8.8 years of follow-up. The area under the curve (AUC) of classifiers using demographics and imaging features in COPDGene and PLuSS were 0.69 and 0.59, respectively. In COPDGene, the AUC of the univariate screen classifier was 0.78 and of the multivariable confirmation classifier was 0.76. The AUC of the final classifier in COPDGene was 0.75 and in PLuSS was 0.76. The outcome for all of the models was the development of incident interstitial features. Conclusions: Multiple novel and previously identified proteomic biomarkers are associated with interstitial features on chest CT and may enable the prediction of incident interstitial diseases such as idiopathic pulmonary fibrosis.
MeSH term(s)	Humans ; Retrospective Studies ; Proteomics ; Idiopathic Pulmonary Fibrosis ; Biomarkers ; Tomography, X-Ray Computed
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	2736454-9
ISSN	2052-4439 ; 2052-4439
ISSN (online)	2052-4439
ISSN	2052-4439
DOI	10.1136/bmjresp-2023-002219
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Article: Modern concept of vascular cognitive impairment.

Bowler, J V

British medical bulletin

2007 Volume 83, Page(s) 291–305

Abstract: Background: Vascular cognitive impairment (VCI) has superseded vascular dementia and multi-infarct dementia as the concept to be used in cognitive decline due to cerebrovascular disease.: Method: The literature was reviewed with regard to the concept ...

Abstract	Background: Vascular cognitive impairment (VCI) has superseded vascular dementia and multi-infarct dementia as the concept to be used in cognitive decline due to cerebrovascular disease. Method: The literature was reviewed with regard to the concept of VCI and its incidence, pathophysiological substrate, clinical features and management. Results: A change in the diagnostic paradigm from the current Alzheimer-based definition of vascular dementia to VCI will allow the earlier identification of cases and will identify a different population from that recognized using the current criteria for vascular dementia. Conclusions: Case identification at the earliest possible stage affords the greatest opportunity for treatment that may slow the rate of progression.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/complications ; Cerebrovascular Disorders/complications ; Cognition Disorders/diagnosis ; Cognition Disorders/epidemiology ; Cognition Disorders/etiology ; Dementia, Vascular/diagnosis ; Dementia, Vascular/epidemiology ; Dementia, Vascular/etiology ; Diagnosis, Differential ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prognosis ; Risk Factors
Language	English
Publishing date	2007
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	213294-1
ISSN	1471-8391 ; 0007-1420
ISSN (online)	1471-8391
ISSN	0007-1420
DOI	10.1093/bmb/ldm021
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Article: Domain Adaptation and Federated Learning for Ultrasonic Monitoring of Beer Fermentation

Bowler, Alexander L. / Pound, Michael P. / Watson, Nicholas J.

Fermentation. 2021 Nov. 01, v. 7, no. 4

2021

Abstract: Beer fermentation processes are traditionally monitored through sampling and off-line wort density measurements. In-line and on-line sensors would provide real-time data on the fermentation progress whilst minimising human involvement, enabling ... ...

Abstract	Beer fermentation processes are traditionally monitored through sampling and off-line wort density measurements. In-line and on-line sensors would provide real-time data on the fermentation progress whilst minimising human involvement, enabling identification of lagging fermentations or prediction of ethanol production end points. Ultrasonic sensors have previously been used for in-line and on-line fermentation monitoring and are increasingly being combined with machine learning models to interpret the sensor measurements. However, fermentation processes typically last many days and so impose a significant time investment to collect data from a sufficient number of batches for machine learning model training. This expenditure of effort must be multiplied if different fermentation processes must be monitored, such as varying formulations in craft breweries. In this work, three methodologies are evaluated to use previously collected ultrasonic sensor data from laboratory scale fermentations to improve machine learning model accuracy on an industrial scale fermentation process. These methodologies include training models on both domains simultaneously, training models in a federated learning strategy to preserve data privacy, and fine-tuning the best performing models on the industrial scale data. All methodologies provided increased prediction accuracy compared with training based solely on the industrial fermentation data. The federated learning methodology performed best, achieving higher accuracy for 14 out of 16 machine learning tasks compared with the base case model.
Keywords	ethanol production ; fermentation ; humans ; models ; prediction ; ultrasonics
Language	English
Dates of publication	2021-1101
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2813985-9
ISSN	2311-5637
ISSN	2311-5637
DOI	10.3390/fermentation7040253
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Article ; Online: Small molecules disaggregate alpha-synuclein and prevent seeding from patient brain-derived fibrils.

Murray, Kevin A / Hu, Carolyn J / Pan, Hope / Lu, Jiahui / Abskharon, Romany / Bowler, Jeannette T / Rosenberg, Gregory M / Williams, Christopher K / Elezi, Gazmend / Balbirnie, Melinda / Faull, Kym F / Vinters, Harry V / Seidler, Paul M / Eisenberg, David S

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 7, Page(s) e2217835120

Abstract: The amyloid aggregation of alpha-synuclein within the brain is associated with the pathogenesis of Parkinson's disease (PD) and other related synucleinopathies, including multiple system atrophy (MSA). Alpha-synuclein aggregates are a major therapeutic ... ...

Abstract	The amyloid aggregation of alpha-synuclein within the brain is associated with the pathogenesis of Parkinson's disease (PD) and other related synucleinopathies, including multiple system atrophy (MSA). Alpha-synuclein aggregates are a major therapeutic target for treatment of these diseases. We identify two small molecules capable of disassembling preformed alpha-synuclein fibrils. The compounds, termed CNS-11 and CNS-11g, disaggregate recombinant alpha-synuclein fibrils in vitro, prevent the intracellular seeded aggregation of alpha-synuclein fibrils, and mitigate alpha-synuclein fibril cytotoxicity in neuronal cells. Furthermore, we demonstrate that both compounds disassemble fibrils extracted from MSA patient brains and prevent their intracellular seeding. They also reduce in vivo alpha-synuclein aggregates in
MeSH term(s)	Mice ; Animals ; alpha-Synuclein/metabolism ; Synucleinopathies/pathology ; Caenorhabditis elegans/metabolism ; Parkinson Disease/pathology ; Multiple System Atrophy/pathology ; Brain/metabolism ; Amyloid/metabolism
Chemical Substances	alpha-Synuclein ; Amyloid
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2217835120
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Zs.A 1148: Show issues

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Article ; Online: Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

Kim, John S / Sun, Yifei / Balte, Pallavi / Cushman, Mary / Boyle, Rebekah / Tracy, Russell P / Styer, Linda M / Bell, Taison D / Anderson, Michaela R / Allen, Norrina B / Schreiner, Pamela J / Bowler, Russell P / Schwartz, David A / Lee, Joyce S / Xanthakis, Vanessa / Doyle, Margaret F / Regan, Elizabeth A / Make, Barry J / Kanaya, Alka M /

Wenzel, Sally E / Coresh, Josef / Isasi, Carmen R / Raffield, Laura M / Elkind, Mitchell S V / Howard, Virginia J / Ortega, Victor E / Woodruff, Prescott / Cole, Shelley A / Henderson, Joel M / Mantis, Nicholas J / Parker, Monica M / Demmer, Ryan T / Oelsner, Elizabeth C

Nature communications

2024 Volume 15, Issue 1, Page(s) 1492

Abstract: This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood ... ...

Abstract	This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.
MeSH term(s)	Adult ; Humans ; Female ; Male ; Aged ; 2019-nCoV Vaccine mRNA-1273 ; Antibody Formation ; BNT162 Vaccine ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19 Vaccines ; SARS-CoV-2 ; Antibodies, Viral ; Demography ; Vaccination
Chemical Substances	2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine ; COVID-19 Vaccines ; Antibodies, Viral
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45468-9
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Article ; Online: Time processing in neurological and psychiatric conditions.

Hinault, Thomas / D'Argembeau, Arnaud / Bowler, Dermot M / La Corte, Valentina / Desaunay, Pierre / Provasi, Joelle / Platel, Hervé / Tran The, Jessica / Charretier, Laura / Giersch, Anne / Droit-Volet, Sylvie

Neuroscience and biobehavioral reviews

2023 Volume 154, Page(s) 105430

Abstract: A central question in understanding cognition and pathology-related cognitive changes is how we process time. However, time processing difficulties across several neurological and psychiatric conditions remain seldom investigated. The aim of this review ... ...

Abstract	A central question in understanding cognition and pathology-related cognitive changes is how we process time. However, time processing difficulties across several neurological and psychiatric conditions remain seldom investigated. The aim of this review is to develop a unifying taxonomy of time processing, and a neuropsychological perspective on temporal difficulties. Four main temporal judgments are discussed: duration processing, simultaneity and synchrony, passage of time, and mental time travel. We present an integrated theoretical framework of timing difficulties across psychiatric and neurological conditions based on selected patient populations. This framework provides new mechanistic insights on both (a) the processes involved in each temporal judgement, and (b) temporal difficulties across pathologies. By identifying underlying transdiagnostic time-processing mechanisms, this framework opens fruitful avenues for future research.
MeSH term(s)	Humans ; Time Perception ; Mental Disorders/psychology ; Cognition ; Judgment ; Auditory Perception
Language	English
Publishing date	2023-10-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2023.105430
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Article ; Online: Mucosal-homing natural killer cells are associated with aging in persons living with HIV.

Kroll, Kyle W / Shah, Spandan V / Lucar, Olivier A / Premeaux, Thomas A / Shikuma, Cecilia M / Corley, Michael J / Mosher, Matthew / Woolley, Griffin / Bowler, Scott / Ndhlovu, Lishomwa C / Reeves, R Keith

Cell reports. Medicine

2022 Volume 3, Issue 10, Page(s) 100773

Abstract: Natural killer (NK) cells are critical modulators of HIV transmission and disease. Recent evidence suggests a loss of NK cell cytotoxicity during aging, yet analysis of NK cell biology and aging in people with HIV (PWH) is lacking. Herein, we perform ... ...

Abstract	Natural killer (NK) cells are critical modulators of HIV transmission and disease. Recent evidence suggests a loss of NK cell cytotoxicity during aging, yet analysis of NK cell biology and aging in people with HIV (PWH) is lacking. Herein, we perform comprehensive analyses of people aging with and without HIV to determine age-related NK phenotypic changes. Utilizing high-dimensional flow cytometry, we analyze 30 immune-related proteins on peripheral NK cells from healthy donors, PWH with viral suppression, and viremic PWH. NK cell phenotypes are dynamic across aging but change significantly in HIV and on antiretroviral drug therapy (ART). NK cells in healthy aging show increasing ⍺4β7 and decreasing CCR7 expression and a reverse phenomenon in PWH. These HIV-associated trafficking patterns could be due to NK cell recruitment to HIV reservoir formation in lymphoid tissue or failed mucosal signaling in the HIV-infected gut but appear to be tight delineators of age-related NK cell changes.
MeSH term(s)	Humans ; HIV-1 ; Receptors, CCR7/metabolism ; Killer Cells, Natural/metabolism ; Anti-Retroviral Agents/metabolism ; HIV Infections/drug therapy
Chemical Substances	Receptors, CCR7 ; Anti-Retroviral Agents
Language	English
Publishing date	2022-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100773
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Article ; Online: Bcl-xL targeting eliminates ageing tumor-promoting neutrophils and inhibits lung tumor growth.

Bodac, Anita / Mayet, Abdullah / Rana, Sarika / Pascual, Justine / Bowler, Amber D / Roh, Vincent / Fournier, Nadine / Craciun, Ligia / Demetter, Pieter / Radtke, Freddy / Meylan, Etienne

EMBO molecular medicine

2023 Volume 16, Issue 1, Page(s) 158–184

Abstract: Elevated peripheral blood and tumor-infiltrating neutrophils are often associated with a poor patient prognosis. However, therapeutic strategies to target these cells are difficult to implement due to the life-threatening risk of neutropenia. In a ... ...

Abstract	Elevated peripheral blood and tumor-infiltrating neutrophils are often associated with a poor patient prognosis. However, therapeutic strategies to target these cells are difficult to implement due to the life-threatening risk of neutropenia. In a genetically engineered mouse model of lung adenocarcinoma, tumor-associated neutrophils (TAN) demonstrate tumor-supportive capacities and have a prolonged lifespan compared to circulating neutrophils. Here, we show that tumor cell-derived GM-CSF triggers the expression of the anti-apoptotic Bcl-xL protein and enhances neutrophil survival through JAK/STAT signaling. Targeting Bcl-xL activity with a specific BH3 mimetic, A-1331852, blocked the induced neutrophil survival without impacting their normal lifespan. Specifically, oral administration with A-1331852 decreased TAN survival and abundance, and reduced tumor growth without causing neutropenia. We also show that G-CSF, a drug used to combat neutropenia in patients receiving chemotherapy, increased the proportion of young TANs and augmented the anti-tumor effect resulting from Bcl-xL blockade. Finally, our human tumor data indicate the same role for Bcl-xL on pro-tumoral neutrophil survival. These results altogether provide preclinical evidence for safe neutrophil targeting based on their aberrant intra-tumor longevity.
MeSH term(s)	Animals ; Humans ; Mice ; Aging ; Apoptosis ; Apoptosis Regulatory Proteins/metabolism ; bcl-X Protein ; Cell Line, Tumor ; Lung Neoplasms/pathology ; Neutropenia/drug therapy ; Neutropenia/metabolism ; Neutropenia/pathology ; Neutrophils/metabolism
Chemical Substances	Apoptosis Regulatory Proteins ; bcl-X Protein ; Bcl2l1 protein, mouse
Language	English
Publishing date	2023-12-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.1038/s44321-023-00013-x
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Article: Vascular cognitive impairment.

Bowler, J V

Journal of neurology, neurosurgery, and psychiatry

2005 Volume 76 Suppl 5, Page(s) v35–44

MeSH term(s)	CADASIL/diagnosis ; CADASIL/epidemiology ; CADASIL/physiopathology ; CADASIL/psychology ; CADASIL/therapy ; Cerebrovascular Disorders/diagnosis ; Cerebrovascular Disorders/epidemiology ; Cerebrovascular Disorders/physiopathology ; Cerebrovascular Disorders/psychology ; Cerebrovascular Disorders/therapy ; Cognition Disorders/diagnosis ; Cognition Disorders/epidemiology ; Cognition Disorders/physiopathology ; Cognition Disorders/psychology ; Cognition Disorders/therapy ; Dementia, Vascular/diagnosis ; Dementia, Vascular/epidemiology ; Dementia, Vascular/physiopathology ; Dementia, Vascular/psychology ; Dementia, Vascular/therapy ; Humans ; Prognosis
Language	English
Publishing date	2005-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp.2005.082313
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