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Article ; Online: Inferring B Cell Phylogenies from Paired H and L Chain BCR Sequences with Dowser.

Jensen, Cole G / Sumner, Jacob A / Kleinstein, Steven H / Hoehn, Kenneth B

Journal of immunology (Baltimore, Md. : 1950)

2024

Abstract: Abs are vital to human immune responses and are composed of genetically variable H and L chains ... the history of mutations within a clone. Until recently, BCR sequencing technologies separated H and L chains ... but advancements in single-cell sequencing now pair H and L chains from individual cells. However, it is unclear ...

Abstract	Abs are vital to human immune responses and are composed of genetically variable H and L chains. These structures are initially expressed as BCRs. BCR diversity is shaped through somatic hypermutation and selection during immune responses. This evolutionary process produces B cell clones, cells that descend from a common ancestor but differ by mutations. Phylogenetic trees inferred from BCR sequences can reconstruct the history of mutations within a clone. Until recently, BCR sequencing technologies separated H and L chains, but advancements in single-cell sequencing now pair H and L chains from individual cells. However, it is unclear how these separate genes should be combined to infer B cell phylogenies. In this study, we investigated strategies for using paired H and L chain sequences to build phylogenetic trees. We found that incorporating L chains significantly improved tree accuracy and reproducibility across all methods tested. This improvement was greater than the difference between tree-building methods and persisted even when mixing bulk and single-cell sequencing data. However, we also found that many phylogenetic methods estimated significantly biased branch lengths when some L chains were missing, such as when mixing single-cell and bulk BCR data. This bias was eliminated using maximum likelihood methods with separate branch lengths for H and L chain gene partitions. Thus, we recommend using maximum likelihood methods with separate H and L chain partitions, especially when mixing data types. We implemented these methods in the R package Dowser: https://dowser.readthedocs.io.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300851
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Article: Common Pediatric Hand Anomalies.

McCarter, Jacob H / Zeledon, Ricardo A / Cole, Samuel H / Layon, Sarah A / Nguyen, Jenny Lee

Seminars in plastic surgery

2023 Volume 37, Issue 4, Page(s) 275–286

Abstract: Upper extremity congenital anomalies in the newborn are second only to congenital heart anomalies. Some of the more commonly encountered upper extremity anomalies are trigger thumb, thumb hypoplasia, polydactyly, syndactyly, and amniotic band syndrome. ... ...

Abstract	Upper extremity congenital anomalies in the newborn are second only to congenital heart anomalies. Some of the more commonly encountered upper extremity anomalies are trigger thumb, thumb hypoplasia, polydactyly, syndactyly, and amniotic band syndrome. While some conditions occur in isolation, others are known to commonly occur in association with syndromes. Familiarity with these conditions is important not only to provide adequate evaluation and workup of these patients but also to deliver appropriate surgical intervention and prepare parents with appropriate expectations. In this article, we outline the etiology, classification, surgical management, and outcomes of these five commonly encountered upper extremity congenital anomalies.
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2077828-4
ISSN	1535-2188
ISSN	1535-2188
DOI	10.1055/s-0043-1777096
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Article: Inferring B cell phylogenies from paired heavy and light chain BCR sequences with Dowser.

Jensen, Cole G / Sumner, Jacob A / Kleinstein, Steven H / Hoehn, Kenneth B

bioRxiv : the preprint server for biology

2023

Abstract: Antibodies are vital to human immune responses and are composed of genetically variable heavy and light chains. These structures are initially expressed as B cell receptors (BCRs). BCR diversity is shaped through somatic hypermutation and selection ... ...

Abstract	Antibodies are vital to human immune responses and are composed of genetically variable heavy and light chains. These structures are initially expressed as B cell receptors (BCRs). BCR diversity is shaped through somatic hypermutation and selection during immune responses. This evolutionary process produces B cell clones, cells that descend from a common ancestor but differ by mutations. Phylogenetic trees inferred from BCR sequences can reconstruct the history of mutations within a clone. Until recently, BCR sequencing technologies separated heavy and light chains, but advancements in single cell sequencing now pair heavy and light chains from individual cells. However, it is unclear how these separate genes should be combined to infer B cell phylogenies. In this study, we investigated strategies for using paired heavy and light chain sequences to build phylogenetic trees. We found incorporating light chains significantly improved tree accuracy and reproducibility across all methods tested. This improvement was greater than the difference between tree building methods and persisted even when mixing bulk and single cell sequencing data. However, we also found that many phylogenetic methods estimated significantly biased branch lengths when some light chains were missing, such as when mixing single cell and bulk BCR data. This bias was eliminated using maximum likelihood methods with separate branch lengths for heavy and light chain gene partitions. Thus, we recommend using maximum likelihood methods with separate heavy and light chain partitions, especially when mixing data types. We implemented these methods in the R package Dowser: https://dowser.readthedocs.io.
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.29.560187
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Smallholder aquaculture diversifies livelihoods and diets thus improving food security status

Alexander M. Kaminski / Steven M. Cole / Jacob Johnson / Shakuntala H. Thilsted / Mary Lundeba / Sven Genschick / David C. Little

Agriculture & Food Security, Vol 13, Iss 1, Pp 1-

evidence from northern Zambia

2024 Volume 21

Abstract: Abstract Background Much has been made of the potential for aquaculture to improve rural livelihoods and food and nutrition security in Africa, though little evidence exists to back such claims. This study, conducted in northern Zambia, assessed the ... ...

Abstract	Abstract Background Much has been made of the potential for aquaculture to improve rural livelihoods and food and nutrition security in Africa, though little evidence exists to back such claims. This study, conducted in northern Zambia, assessed the benefits of adopting aquaculture by comparing a sample of households with (n = 177) and without fishponds (n = 174). Results On-farm food production was assessed by summing all crop and livestock activities and calculating a production diversity score (PDS) of key food groups. Aquaculture households had greater crop diversification and were more associated with key nutritious foods grown on the farm, possibly due to additional water irrigation capabilities. A greater diversity of cultivated crops led to better household dietary diversity scores (HDDS). We further assessed the frequency of consumption of 53 food items (including 30 fish species) over a period of 4 weeks via a Food Frequency Questionnaire (FFQ). Using the Simpson’s Index, aquaculture households had greater diversity and evenness in the distribution of foods and fish species consumed, particularly for foods grown on the farm. Using livelihood and dietary factors in a multilevel probit regression on the Household Food Insecurity Access Scale (HFIAS), we found that adopting aquaculture gave households almost two times more likelihood of improving their food security status. Households could further improve their food security outcomes by growing and consuming certain vegetables, especially those that could be integrated along pond dykes. Conclusions The study suggests three clear pathways to food security. (1) Increasing wealth and income from the sale of fish and integrated vegetables and/or crops, which can be used to purchase a diversity of foods. (2) Increasing food and nutrition security via the direct consumption of fish and vegetables grown on the farm. (3) Improving irrigation capabilities in integrated aquaculture–agriculture systems that has direct impact on pathways 1 and 2. Aquaculture should ...
Keywords	Aquaculture ; Crop diversification ; Dietary diversity ; Production diversity ; Tilapia ; Zambia ; Agriculture ; S ; Nutrition. Foods and food supply ; TX341-641
Subject code	590
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cyfip2 controls the acoustic startle threshold through FMRP, actin polymerization, and GABA

Deslauriers, Jacob C / Ghotkar, Rohit P / Russ, Lindsey A / Jarman, Jordan A / Martin, Rubia M / Tippett, Rachel G / Sumathipala, Sureni H / Burton, Derek F / Cole, D Chris / Marsden, Kurt C

bioRxiv : the preprint server for biology

2024

Abstract: Animals process a constant stream of sensory input, and to survive they must detect and respond to dangerous stimuli while ignoring innocuous or irrelevant ones. Behavioral responses are elicited when certain properties of a stimulus such as its ... ...

Abstract	Animals process a constant stream of sensory input, and to survive they must detect and respond to dangerous stimuli while ignoring innocuous or irrelevant ones. Behavioral responses are elicited when certain properties of a stimulus such as its intensity or size reach a critical value, and such behavioral thresholds can be a simple and effective mechanism to filter sensory information. For example, the acoustic startle response is a conserved and stereotyped defensive behavior induced by sudden loud sounds, but dysregulation of the threshold to initiate this behavior can result in startle hypersensitivity that is associated with sensory processing disorders including schizophrenia and autism. Through a previous forward genetic screen for regulators of the startle threshold a nonsense mutation in
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.22.573054
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Common Pediatric Hand Anomalies

McCarter, Jacob H. / Zeledon, Ricardo A. / Cole, Samuel H. / Layon, Sarah A. / Nguyen, Jenny Lee

Seminars in Plastic Surgery

(Pediatric Plastic Surgery)

2023 Volume 37, Issue 04, Page(s) 275–286

Series title	Pediatric Plastic Surgery
Abstract	Upper extremity congenital anomalies in the newborn are second only to congenital heart anomalies. Some of the more commonly encountered upper extremity anomalies are trigger thumb, thumb hypoplasia, polydactyly, syndactyly, and amniotic band syndrome. While some conditions occur in isolation, others are known to commonly occur in association with syndromes. Familiarity with these conditions is important not only to provide adequate evaluation and workup of these patients but also to deliver appropriate surgical intervention and prepare parents with appropriate expectations. In this article, we outline the etiology, classification, surgical management, and outcomes of these five commonly encountered upper extremity congenital anomalies.
Keywords	upper extremity ; congenital hand ; thumb hypoplasia ; syndactyly ; trigger thumb ; amniotic band syndrome ; polydactyly
Language	English
Publishing date	2023-11-01
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2077828-4
ISSN	1536-0067 ; 1535-2188
ISSN (online)	1536-0067
ISSN	1535-2188
DOI	10.1055/s-0043-1777096
Database	Thieme publisher's database

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Article ; Online: Dupilumab efficacy in high sleep disturbance management among patients with type 2 asthma.

Maspero, Jorge F / Shafazand, Shirin / Cole, Jeremy / Pavord, Ian D / Busse, William W / Msihid, Jérôme / Gall, Rebecca / Soler, Xavier / Radwan, Amr / Khan, Asif H / de Prado Gómez, Lucia / Jacob-Nara, Juby A

Respiratory medicine

2023 Volume 218, Page(s) 107344

Abstract: Background: Patients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) ...

Abstract	Background: Patients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD. Methods: QUEST (NCT02414854) data were used in this post hoc analysis. A composite endpoint from validated patient-reported outcomes was developed to identify patients with HSD using sleep-related items from the ACQ-5, Asthma-Related Quality-of-Life Questionnaire, Rhino-Conjunctivitis Quality-of-Life Questionnaire, and Sino-Nasal Outcome Test-22. Impairment in at least 1 item was considered an indication of HSD. Change from baseline to Week 52 in nighttime symptoms, ACQ-5 score, lung function, annualized severe exacerbation rates (AER), and short-acting β-agonists use during treatment was used to assess dupilumab efficacy. Results: In type 2 asthma patients, 64% had HSD at baseline; of those with ACQ-5 ≥2.5 at baseline, 82% had HSD. In this population, dupilumab reduced nighttime symptoms and ACQ-5 score by 0.31 and 0.56 points, respectively, by Week 52 versus placebo, and led to a 66% reduction in AER during QUEST and 0.34 L improvement in pre-bronchodilator (pre-BD) forced expiratory volume in 1 s (FEV Conclusion: A majority of patients with moderate-to-severe type 2 asthma with ACQ-5 ≥2.5 at baseline had HSD. Dupilumab reduced nighttime symptoms and exacerbations, and improved lung function, overall asthma control, and quality of life. Further studies are needed to confirm the association between ACQ-5 score ≥2.5 and higher sleep disturbance rates.
MeSH term(s)	Humans ; Anti-Asthmatic Agents ; Antibodies, Monoclonal/therapeutic use ; Quality of Life ; Asthma/complications ; Asthma/drug therapy ; Asthma/chemically induced ; Double-Blind Method ; Treatment Outcome
Chemical Substances	dupilumab (420K487FSG) ; Anti-Asthmatic Agents ; Antibodies, Monoclonal
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1003348-8
ISSN	1532-3064 ; 0954-6111
ISSN (online)	1532-3064
ISSN	0954-6111
DOI	10.1016/j.rmed.2023.107344
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Article ; Online: Perspectives on unhealthy alcohol use among men who have sex with men prescribed HIV pre-exposure prophylaxis

Sabrina H. Strong / Benjamin J. Oldfield / Jacob J. van den Berg / Christopher A. Cole / Emma Biegacki / Onyema Ogbuagu / Michael Virata / Philip A. Chan / E. Jennifer Edelman

Preventive Medicine Reports, Vol 37, Iss , Pp 102553- (2024)

A qualitative study

2024

Abstract: Unhealthy alcohol use is a common, often unaddressed behavior associated with increased risk for acquisition of HIV and may also be associated with decreased adherence to oral pre-exposure prophylaxis (PrEP) among gay, bisexual, and other men who have ... ...

Abstract	Unhealthy alcohol use is a common, often unaddressed behavior associated with increased risk for acquisition of HIV and may also be associated with decreased adherence to oral pre-exposure prophylaxis (PrEP) among gay, bisexual, and other men who have sex with men (MSM) living in the United States. To inform future alcohol-reduction interventions among individuals engaging in PrEP care, we sought to explore perspectives on alcohol use, PrEP adherence, and the acceptability of alcohol use treatment options for MSM prescribed oral formulations of PrEP in the Northeastern United States. Between February 2019 and July 2020, we conducted semi-structured interviews with 15 MSM without HIV who were prescribed PrEP and screened positive for unhealthy alcohol use with AUDIT-C ≥ 4 and were receiving care in Providence, Rhode Island or New Haven, Connecticut. Interviews were coded and analyzed using thematic analysis. Three themes emerged: 1) Consequences of fluctuations in drinking 2) Alcohol use negatively impacts health and relationships; and 3) Desire for a multimodal approach to treatment of unhealthy alcohol use. Our findings support the need to raise awareness of potential alcohol-related harms, address the spectrum of unhealthy alcohol use among MSM prescribed PrEP, and the acceptability and preferences for alcohol reduction interventions within PrEP programs.
Keywords	PrEP ; HIV ; Alcohol ; Men who have sex with men ; Qualitative research ; Medicine ; R
Subject code	360
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Novel Low-Cost Ventilator for Use in a Worldwide Pandemic: The Portsmouth Ventilator.

Cole, Jacob H / Hughey, Scott B / Rector, Christopher H / Booth, Gregory J

Critical care explorations

2020 Volume 2, Issue 12, Page(s) e0292

Abstract: ... with predicted tidal volumes of 300-800 mL, positive end-expiratory pressure 0-20 cm H: Main results ...

Abstract	The ongoing severe acute respiratory syndrome coronavirus 2 or coronavirus disease 2019 pandemic has demonstrated the potential need for a low-cost, rapidly deployable ventilator. Based on this premise, we sought to design a ventilator with the following criteria: 1) standard components that are accessible to the public, 2) "open-source" compatibility to allow anyone to easily recreate the system, 3) ability to ventilate in acute respiratory distress syndrome, and 4) lowest possible cost to provide adequate oxygenation and ventilation. Design: We pursued development of a pneumatic-type ventilator. The basic design involves three electrically controlled solenoid valves, a pressure chamber, the patient breathing circuit, a positive end-expiratory pressure valve, and an electronics control system. Multiple safety elements were built into the design. The user-friendly interface allows simple control of ventilator settings. The ventilator delivers a hybrid form of pneumatic, assist-control ventilation, with predicted tidal volumes of 300-800 mL, positive end-expiratory pressure 0-20 cm H Main results: The ventilator was extensively tested with two separate high-fidelity lung simulators and a porcine in vivo model. Both lung simulators were able to simulate a variety of pathologic states, including obstructive lung disease and acute respiratory distress syndrome. The ventilator performed well across all simulated scenarios. Similarly, a porcine in vivo model was used to assess performance in live tissue, with a specific emphasis on gas exchange. The ventilator performed well in vivo and demonstrated noninferior ventilation and oxygenation when compared with the standard ventilator. Conclusions: The Portsmouth Ventilator was able to perform well across all simulated pathologies and in vivo. All components may be acquired by the public for a cost of approximately $250 U.S.D. Although this ventilator has limited functionality compared with modern ventilators, the simple design appears to be safe and would allow for rapid mass production if ventilator surge demand exceeded supply.
Language	English
Publishing date	2020-12-02
Publishing country	United States
Document type	Journal Article
ISSN	2639-8028
ISSN (online)	2639-8028
DOI	10.1097/CCE.0000000000000292
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Cadaveric Porcine Spines as a Model for the Human Epidural Space.

Cole, Jacob H / Fishback, Joanna E / Hughey, Scott B

Comparative medicine

2019 Volume 69, Issue 4, Page(s) 308–310

Abstract: Most patients who undergo epidural anesthesia are pregnant and thus a protected population, which has limited investigations of the human epidural space. Among the several species studied as models for the human spine, the porcine spine has been used as ... ...

Abstract	Most patients who undergo epidural anesthesia are pregnant and thus a protected population, which has limited investigations of the human epidural space. Among the several species studied as models for the human spine, the porcine spine has been used as a model for spine instrumentation. Although the spread of colored dye within the porcine epidural space has been investigated, no model has demonstrated in situ spread by using radiopaque contrast dye. To this end, we here used 10 Yorkshire swine cadavers through an approved tissue sharing agreement. Epidural catheters were placed by using a landmark-based loss-of-resistance technique; placement was confirmed through radiography. The catheters were connected to epidural infusion pumps to ensure consistent dosing, 2-mL boluses of contrast dye were injected into the space, and radiographs were taken and recorded after each bolus. The total spread of the contrast dye was analyzed. We demonstrated consistent and reliable spread of fluid in the epidural space among the animals used, with low variability between animals of different weights. Our results support the use of the epidural space of cadaveric swine as a model for the human epidural space. Furthermore, the technique for epidural administration by using the landmark-based loss-of-resistance demonstrated in this model was validated, thus supporting future investigations of medication delivery into the epidural space.
MeSH term(s)	Anesthesia, Epidural/methods ; Animals ; Cadaver ; Contrast Media/therapeutic use ; Disease Models, Animal ; Epidural Space/anatomy & histology ; Female ; Humans ; Swine
Chemical Substances	Contrast Media
Language	English
Publishing date	2019-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2006425-1
ISSN	1532-0820 ; 0023-6764
ISSN	1532-0820 ; 0023-6764
DOI	10.30802/AALAS-CM-18-000133
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