bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation-based User-centered Design: An Approach to Device Development during COVID-19
Authors: Colman Nora , Saldana Christopher , Craig Kentez , Edwards Nicole , McGough Jennifer , Mason Carrie , Hebbar Kiran B.
Published: July 2021

Introduction:

Since the onset of COVID-19, intubations have become very high risk for clinical teams. Barrier devices during endotracheal intubation protect clinicians from the aerosols generated. Simulation-based user-centered design (UCD) was an iterative design process used to develop a pediatric intubation aerosol containment system (IACS). Simulation was anchored in human factor engineering and UCD to better understand clinicians’ complex interaction with the IACS device, elicit user wants and needs, identify design inefficiencies, and unveil safety concerns.

Methods:

This study was a prospective observational study of a simulation-based investigation used to design a pediatric IACS rapidly. Debriefing and Failure Mode and Effect Analysis identified latent conditions related to 5 device prototypes. Design iterations made were based on feedback provided to the engineering team after each simulation.

Results:

Simulation identified 32 latent conditions, resulting in 5 iterations of the IACS prototype. The prototypes included an (1) intubation box; (2) IACS shield; (3) IACS frame with PVC pipes; (4) IACS plexiglass frame, and finally, (5) IACS frame without a plexiglass top.

Conclusions:

Integration of simulation with human factor ergonomics and UCD, in partnership with mechanical engineers, facilitated a novel context to design and redesign a pediatric IACS to meet user needs and address safety concerns.
Quantifying Discharge Medication Reconciliation Errors at 2 Pediatric Hospitals
Authors: Morse Keith E. , Chadwick Whitney A. , Paul Wendy , Haaland Wren , Pageler Natalie M. , Tarrago Rod
Published: July 2021

Introduction:

Medication reconciliation errors (MREs) are common and can lead to significant patient harm. Quality improvement efforts to identify and reduce these errors typically rely on resource-intensive chart reviews or adverse event reporting. Quantifying these errors hospital-wide is complicated and rarely done. The purpose of this study is to define a set of 6 MREs that can be easily identified across an entire healthcare organization and report their prevalence at 2 pediatric hospitals.

Methods:

An algorithmic analysis of discharge medication lists and confirmation by clinician reviewers was used to find the prevalence of the 6 discharge MREs at 2 pediatric hospitals. These errors represent deviations from the standards for medication instruction completeness, clarity, and safety. The 6 error types are Duplication, Missing Route, Missing Dose, Missing Frequency, Unlisted Medication, and See Instructions errors.

Results:

This study analyzed 67,339 discharge medications and detected MREs commonly at both hospitals. For Institution A, a total of 4,234 errors were identified, with 29.9% of discharges containing at least one error and an average of 0.7 errors per discharge. For Institution B, a total of 5,942 errors were identified, with 42.2% of discharges containing at least 1 error and an average of 1.6 errors per discharge. The most common error types were Duplication and See Instructions errors.

Conclusion:

The presented method shows these MREs to be a common finding in pediatric care. This work offers a tool to strengthen hospital-wide quality improvement efforts to reduce pediatric medication errors.
A Quality Improvement Approach to Influence Value-based Mucolytic Use in the PICU
Authors: Gillis Holly Catherine , Dolan Kevin , Sargel Cheryl L. , Thompson R. Zachary , Lutmer Jeffrey E.
Published: July 2021

Introduction:

High-cost medication administration, despite lacking evidence for use, results in poor healthcare value. This work aimed to reduce dornase-alfa utilization in critically ill mechanically ventilated children.

Methods:

The project employed an observational pre-post design to develop a value-based clinical pathway to guide provider choice in mucolytic utilization in a quaternary pediatric intensive care unit. This pathway was designed to continue using low-cost mucolytic aerosols (hypertonic saline, N-acetylcysteine) but decrease new starts and total doses per 100 patient days (P100PD) dornase-alfa among patients for whom there is little to no supporting evidence. Interventions included a departmental journal club for fellow and attending physicians and a rolling introduction of the pathway to residents and respiratory therapists. Control charts serially tracked ordering changes and location-specific dornase alfa orders.

Results:

New dornase-alfa starts P100PD decreased by 53% (1.17–0.55), and total doses P100PD decreased by 75% (16–4). N-acetylcysteine ordering more than doubled; however, total doses of P100PD remained unchanged after the intervention. The use of 3% sodium chloride increased significantly from 0.28 to 4.15 new starts and 4.37 to 38.84 total doses P100PD. Mechanical ventilation days P100PD decreased, suggesting there were no measured adverse effects of pathway implementation. The reduction in dornase-alfa utilization resulted in a cumulative and sustained 59% mucolytic cost reduction ($2183.08–$885.77 P100PD).

Conclusion:

A clinical pathway prioritizing pharmacoeconomics when evidence for use is lacking can improve health care value without adversely affecting patient outcomes.
Standardized Neurodevelopmental Surveillance of High-risk Infants Using Telehealth: Implementation Study during COVID-19
Authors: Maitre Nathalie L. , Benninger Kristen L. , Neel Mary Lauren , Haase Jennifer A. , Pietruszewski Lindsay , Levengood Katelyn , Adderley Kathleen , Batterson Nancy , Hague Kaleigh , Lightfoot Megan , Weiss Sarah , Lewandowski Dennis J. , Larson Heather
Published: July 2021

Introduction:

Neurodevelopmental surveillance is critical for high-risk infants following neonatal intensive care discharge and is traditionally performed in-person. COVID-19 interruption of regular surveillance necessitated a rapid development of telehealth models for effective and standardized care.

Methods:

We used implementation science and lean methodologies to develop an effective telehealth neurodevelopmental surveillance program for high-risk infants. Interventions included reorganization of visit flow processes and a telehealth toolkit for standardized neurological and developmental assessments. We tested and improved our intervention through plan-do-study-act cycles, value-added analysis, and parent- and provider-satisfaction questionnaires. Process metrics (standard elements, subspecialty referrals, diagnostic tests, and prescriptions ordered) were compared in group-level analyses between telehealth patients (N = 97) March 16, 2020–July 1, 2020 and a matched in-person cohort at the same period the previous year. Run charts examined shifts in balancing measures (provider efficiency and missed visits) over 8 weeks before and after implementation.

Results:

Primary outcomes were visit completion (100%), patient parent satisfaction (>90% strongly agreed or agreed telehealth procedures were valuable and easy to use) and ability to accurately diagnose cerebral palsy (no statistical difference with comparison visits). Providers (N = 6) rated telehealth experiences favorably. Process metrics indicated no differences between telehealth and in-person visits (all P > 0.05). Following telehealth implementation, provider efficiency increased to near baseline (median 88.9% versus 91.7%) and median missed visits decreased to 0% from 20% (in-person).

Conclusions:

Implementation of telehealth for neurodevelopmental surveillance in a tertiary high-risk infant follow-up clinic successfully provided standardized and timely care during stay-at-home orders; broader telehealth applications may overcome access barriers in this field.
Replacing Computed Tomography with “Rapid” Magnetic Resonance Imaging for Ventricular Shunt Imaging
Authors: Marin Jennifer R. , Tyler-Kabara Elizabeth C. , Anderson Casey , Butler Gabriella , Charles Shaquille , Furtado Andre , Rosen Johanna R.
Published: July 2021

Introduction:

Children with ventricular shunts undergo frequent neuroimaging, and therefore, radiation exposures, to evaluate shunt malfunctions. The objective of this study was to safely reduce radiation exposure in this population by reducing computed tomography (CT) and increasing “rapid” magnetic resonance imaging (rMRI-shunt) among patients warranting neuroimaging for possible shunt malfunction.

Methods:

This was a single-center quality improvement study in a tertiary care pediatric emergency department (ED). We implemented a multidisciplinary guideline for ED shunt evaluation, which promoted the use of rMRI-shunt over CT. We included patients younger than 18 years undergoing an ED shunt evaluation during 11 months of the preintervention and 25 months of the intervention study periods. The primary outcome was the CT rate, and we evaluated the relevant process and balancing measures.

Results:

There were 266 encounters preintervention and 488 during the intervention periods with similar neuroimaging rates (80.7% versus 81.5%, P = 0.8.) CT decreased from 90.1% to 34.8% (difference −55.3%, 95% confidence interval [CI]: −71.1, −25.8), and rMRI-shunt increased from 9.9% to 65.2% (difference 55.3%, 95% CI: 25.8, 71.1) during the preintervention and intervention periods, respectively. There were increases in the mean time to neuroimaging (53.1 min; [95% CI: 41.6, 64.6]) and ED length of stay (LOS) (52.3 min; [95% CI: 36.8, 67.6]), without changes in total neuroimaging, 72-hour revisits, or follow-up neuroimaging.

Conclusions:

Multidisciplinary implementation of a standardized guideline reduced CT and increased rMRI-shunt use in a pediatric ED setting. Clinicians should balance the reduction in radiation exposure with ED rMRI-shunt for patients with ventricular shunts against the increased time of obtaining imaging and LOS.
The Child Health PSO at 10 Years: An Emerging Learning Network
Authors: Levy Fiona H. , Conrad Katherine A. , Kemper Carol , Green Michaeleen
Published: July 2021

Introduction:

The 2005 Patient Safety and Quality Improvement Act, actualized as a Learning Network (LN), has enabled the Child Health Patient Safety Organization (PSO) to play a vital and novel role in improving the quality and safety of care. This article describes the Child Health PSO and proposes PSOs as a new construct for LNs.

Methods:

A PSOs ability to affect patient care depends on member organizations’ integration of PSO output into their individual Learning Healthcare Systems. Therefore, the Child Health PSO developed tenets of an LN to improve member engagement in PSO outputs.

Results:

All Child Health PSO members participate in case-based learning, requiring ongoing and robust participation by all members. The engagement has been strong, with 86% of children’s hospitals achieving a case learning activity metric and 60% of children’s hospitals submitting cases. From this LNs perspective, 53% of children’s hospitals are considered highly engaged.

Conclusions:

In the last 10 years, the Child Health PSO has evolved as a viable LN and, to sustain this, has set a target of 100% of participating children’s hospitals being highly engaged. The previously inconceivable notion of sharing information to improve patient safety among hospitals is now an expected result of the formation of trusting relationships under a federally certified PSO. According to participants, collaboration is an essential element that empowers individual children’s hospitals to eliminate preventable harm.
Positive Multifocal PSMA PET/CT in a Patient With Prostate Cancer and Follicular Lymphoma
Authors: Dendl Katharina , Merkel Andreas , Kratochwil Clemens , Choyke Peter L. , Kleist Christian , Cardinale Jens , Haberkorn Uwe , Giesel Frederik L.
Published: July 2021

Prostate-specific membrane antigen (PSMA) PET/CT is a highly reliable nuclear tracer for diagnostic imaging of prostate cancer. However, PSMA is also expressed by some nonprostatic tissues such as benign tumors, inflammatory processes, and malignant neoplasms. This case presents a patient with prostate cancer and follicular lymphoma undergoing PSMA PET/CT. Remarkably, both tumor entities were clearly detected in the scan. Yet, the 2 malignancies demonstrated rather different ranges in terms of SUVmax uptake values and therefore still enabled precise and accurate discrimination of prostate cancer and follicular lymphoma.
68Ga-DOTATATE PET/CT in Primary Pulmonary Lymphoepithelioma-Like Carcinoma
Authors: Shang Qihang , Pang Yizhen , Meng Tinghua , Hao Bing , Chen Haojun
Published: July 2021

Primary pulmonary lymphoepithelioma-like carcinomas (LELCs) are extremely rare tumors with better prognosis than other types of lung malignancies. In this case, we present 18F-FDG and 68Ga-DOTATATE PET/CT findings in a 52-year-old woman with pathologically confirmed pulmonary LELC. The pulmonary LELC presented mild 18F-FDG but avid 68Ga-DOTATATE uptake, indicating that the somatostatin receptor 2 may be highly expressed in LELCs. Therefore, 68Ga-DOTATATE PET/CT is a useful tool for tumor detection and initial staging in patients with LELCs.
Surgical Management of Bilateral Osteoradionecrosis of the Mandible
Authors: Li Xiaoguang , Han Yu , Tang Xiao , Zhu Fengshuo , He Yue
Published: July 2021

Purpose:

The purpose of this study was to evaluate our 10 years clinical experience in surgical management of patients with bilateral osteoradionecrosis (BORN) of the mandible in head and neck malignancies patients.

Materials and Methods:

The authors reviewed 22 patients with bilateral mandibular bone mineral density changed in image who had failed to respond to conservative treatments. They were treated by radical resection and reconstruction with free flaps immediately or second-stage at our institution between January 2008 and January 2018.

Results:

Nine patients received immediate bilateral mandibular radical resection. Six bone flaps (4 fibula osteocutaneous [fibular OC], 1 fibular OC + pectoralis major myocutaneous flap [PMMF] and 1 fibular OC + anterolateral thigh flap [ALTF]) and 3 soft flaps (1 PMMF, 1 PMMF + titanium plate and 1 ALTF) were used. Three (33.3%) of these patients complications occurred in the immediate postoperative period, but all patients have an acceptable follow-up outcomes. In remaining 13 patients who only experienced immediate unilateral mandible resection for the first time. Complications occurred in 1 patient (7.7%), and all patients have a good outcome in the immediate postoperative period. In follow-up, 1 patient titanium plate exposed, and 6 patients (46.2%) contralateral mandible ORN developed that underwent radical resection in second time. Three fibular OC, 2 PMMF, and 1 latissimus dorsi myocutaneous flap were used. The overall outcome of our experience with the use of bone or soft tissue transfers in managing BORN of mandible is encouraging.

Conclusions:

An individualized management plan should be given for each patient depending on their own local and general condition. Radical resection followed by vascularized flaps reconstruction is an acceptable and reliable procedure for patients with BORN of the mandible.
Immediate Resection and Reconstruction of Encephalocele in the Craniofacial Region
Authors: Shamaeraotan Ahati , Wei Jiang-Rong , Ma Da-Liang , Zhao Bin , Jia Qi , Li Jun , Wang Fan , Zhao Bo-Xi
Published: July 2021

Introduction:

Congenital meningoencephalocele is a herniation of brain and meninges through a skull base defect. It may result not only in neural defects, sensorimotor deficits, neurological morbidities, visual impairment, impaired nasal function, and a potential risk of intracranial infection. Goals of surgery include removal or repositioning of nonfunctional cerebral tissue, closure of the dura, and reconstruction of skeletal and cutaneous structures.

Materials and Methods:

The authors present the case of a 4-months-old infant who was found to have a frontoethmoidal encephalomeningocele that was only discovered after birth, the volume increased gradually. After multiple department discussions, the procedures were planned in 2-staged surgical protocol comprising of the first stage urgently performed by neurosurgeon and craniomaxillofacial surgeon, which aimed at removal or repositioning of nonfunctional cerebral tissue, closure of the dura, and reconstruction of skeletal; then second stage was performed by plastic surgeon to correct craniofacial hard and soft tissue deformities.

Results and Conclusions:

The surgical procedures for frontoethmoidal encephalomeningocele are complicated, particularly for the infant. In order to achieve the final surgical purpose, it needs multiple department cooperation to make the surgical plans.
The Effect of Septoplasty on Endothelial Function in Patients With Marked Nasal Septal Deviation
Authors: Dağistan Hakan , Turan Yasar
Published: July 2021

Background:

It is known that nasal septal deviation (NSD) has negative effects on the cardiovascular system, but the possible pathophysiological mechanisms of these effects still need to be explained. The aim of this study was to investigate the endothelial dysfunction (ED) caused by NSD and the effects of septoplasty on it.

Methods:

The study included 40 patients between the ages of 18 to 50 years with a marked NSD indication for septoplasty and 40 healthy age-and gender-matched individuals. Nasal obstruction symptom evaluation scale was used to evaluate the severity of nasal obstruction and the effectiveness of septoplasty. All participants underwent detailed cardiac examination and ultrasonographic measurement of flow-mediated dilatation (FMD). The same cardiac evaluations and nasal obstruction symptom evaluation scale assessments were repeated in the patient group at the postoperative 3rd month.

Results:

The mean FMD value in the control group was significantly higher than preoperative FMD in the patient group (9.1 ± 2.9 versus 7.6 ± 2.4, P 
= 0.024). In the patient group, preoperative and postoperative FMD values were measured as 7.6 ± 2.4 and 9.0 ± 2.7, respectively, and there was a significant difference between them (P = 0.032). There was no significant difference in FMD values between the control group and postoperative patient group (P = 0.925).

Conclusions:

This study shows that NSD can cause ED, which is a precursor of atherosclerosis, and that successful septoplasty can improve ED.
Endoscopic Endonasal Removal of Stray Bullets in the Fossa Pterygopalatine in Innocent Young Bystanders of Conflicts in Somalia in a Period of Six Months
Authors: Tekin Ahmet M. , Elsamanody Ahmed N. , Ali Ismail M. , Topsakal Vedat
Published: July 2021

In Somalia, which is located in the horn of Africa, a fragile and insecure state structure allowed the strengthening of terrorist groups provoking armed conflicts. Stray bullet injuries can be defined as an accidental bullet wound caused by an anonymous attacker and are usually associated with celebratory gunfire or urban violence. The anatomy of the pterygopalatine fossa (PPF) is complex and penetrating foreign body injuries pose even a greater challenge for the surgeon to operate in this area. Endoscopic approaches facilitate the removal of foreign bodies from the paranasal sinuses, orbital cavity, and aerodigestive system, minimizing potential risks. This study presents a series of removal of stray bullets found in the PPF, as a result of urban violence in Somalia in a period of 6 months. Patient demographics, foreign body origin, treatment modalities, and surgery details were evaluated and assessed. All patients were male and aged 16, 2, and 24 years, respectively. The surgeries were quite straightforward with surgery times recorded as 25, 44, and 22 minutes, respectively. The endoscopic endonasal approach proved to provide safe and sufficient access for removal. Surprisingly, even the foreign body in the PPF of a 2-year-old patient could be removed with an endoscopic endonasal approach and did not require an external approach. The management of foreign body removal in the PPF is challenging due to the potential risks of iatrogenic vascular and nervous tissue injury. The endoscopic endonasal approach for removal proved efficient in 3 cases regardless of age and anatomical dimensions.
Barriers of Adherence to a Gluten-Free Diet in Iranian Adults With Celiac Disease
Authors: Akhavan Sabbagh Mojgan , Mahdavi Reza , Shirmohammadi Masood , Nikniaz Zeinab
Published: July 2021

This cross-sectional study aimed to evaluate and classify barriers to adherence to the gluten-free diet in 137 Iranian adults with celiac disease. We used a 23-point Likert questionnaire and exploratory factor analysis to identify and classify the barriers. Adherence to gluten-free diet was assessed by measuring the serum level of anti-tTG-IgA. The correlation between the barriers and adherence to gluten-free diet was assessed using logistic regression. A total of 117 subjects completed the study. Seven factors were extracted: “gluten-free diet restrictions,” “self-awareness and social awareness,” “psychological barriers,” “education,” “situational barriers and gatherings,” “lack of access/labeling,” and “cost.” There was a significant correlation between the situational barriers and gatherings and nonadherence to the diet in the adjusted model (odds ratio = 1.63; 95% confidence interval [1.03, 2.54], p = .03). Nutritionists and physicians should consider these barriers when consulting patients with celiac disease.
High Rates of Incisional Hernia After Laparoscopic Right Colectomy With Midline Extraction Site
Authors: Greemland Itzhak , Raveh Guy , Gavrielli Shlomo , Sadot Eran , Kashtan Hanoch , Wasserberg Nir
Published: July 2021

Background:

Laparoscopic surgery aims at reducing wound complications and improving cosmetics, among other advantages. High rates of postoperative ventral hernia (POVH) are observed after laparoscopic-assisted colectomies.

Materials and Methods:

In a 2011 to 2016 retrospective study of all patients at Rabin Medical Center, we examined POVH prevalence after right hemicolectomy for neoplasia and correlation to specimen extraction site. We also compared laparoscopic-assisted colectomy to hand-assisted laparoscopic colectomy. Included were patients who had postoperative abdominal computed tomography or magnetic resonance imaging scan as part of their routine oncological follow-up to 6 months postsurgery. Patients were excluded for conversion to laparotomy, and prior abdominal surgeries after right colectomy and before follow-up computed tomography/magnetic resonance imaging scan. Demographic and surgical data were collected from patient electronic records, and scans reviewed for POVH by a designated radiologist.

Results:

Of 370 patients, 138 (mean age 70.09 y, 58 males) were included: 54 (39.1%) were diagnosed with POVH, 42/72 (58.3%) at midline extraction site, and 12/66 (18.8%) at off-midline extraction sites (P<0.0001). Surgical site infections and patients positive for tumor metastasis were associated with higher POVH rates. Most (74%) POVHs were identified within 18 months postsurgery (P<0.0001). Body mass index, age, sex, diabetes mellitus, smoking, tumor size, lymph nodes positive for metastasis, and hand-assisted laparoscopic colectomy were not associated with POVH prevalence.

Conclusion:

High rates of radiologically diagnosed POVH were found after laparoscopic-assisted colectomy, with association to midline extraction site, surgical site infections, and positive tumor distant metastasis.
Low-frequency sampling rates are effective to record bottlenose dolphins
Authors: Romeu Bianca , Machado Alexandre M. S. , Daura-Jorge Fábio G. , Cremer Marta J. , de Moraes Alves Ana Kássia , Simões-Lopes Paulo C.
Published: July 2021

Acoustic monitoring in cetacean studies is an effective but expensive approach. This is partly because of the high sampling rate required by acoustic devices when recording high-frequency echolocation clicks. However, the proportion of echolocation clicks recorded at different frequencies is unknown for many species, including bottlenose dolphins. Here, we investigated the echolocation clicks of two subspecies of bottlenose dolphins in the western South Atlantic Ocean. The possibility of recording echolocation clicks at 24 and 48 kHz was assessed by two approaches. First, we considered the clicks in the frequency range up to 96 kHz. We found a loss of 0.95–13.90% of echolocation clicks in the frequency range below 24 kHz, and 0.01–0.42% below 48 kHz, to each subspecies. Then, we evaluated these recordings downsampled at 48 and 96 kHz and confirmed that echolocation clicks are recorded at these lower frequencies, with some loss. Therefore, despite reaching high frequencies, the clicks can also be recorded at lower frequencies because echolocation clicks from bottlenose dolphins are broadband. We concluded that ecological studies based on the presence–absence data are still effective for bottlenose dolphins when acoustic devices with a limited sampling rate are used.
Eco-friendly methoximation of aromatic aldehydes and ketones using MnCl
2
.4H
2
O as an easily accessible and efficient catalyst
Authors: Ontivero Melina C. , Kaufman Teodoro S. , Cortés Iván , Bracca Andrea B. J.
Published: July 2021

Methoximes are important as a class of intermediates and products, among fine chemicals and specialties. The development of a new, facile and efficient method for their synthesis is reported. The methoximes were properly accessed from the corresponding aromatic aldehydes and ketones in good to excellent yields, under mild conditions, employing the inexpensive and environmentally friendly MnCl
2
.4H
2
O as a catalyst (at low loading and without the addition of ligand), in EtOH at 50°C. The scope of the process was systematically assessed.
Dominance style is a key predictor of vocal use and evolution across nonhuman primates
Authors: Kavanagh Eithne , Street Sally E. , Angwela Felix O. , Bergman Thore J. , Blaszczyk Maryjka B. , Bolt Laura M. , Briseño-Jaramillo Margarita , Brown Michelle , Chen-Kraus Chloe , Clay Zanna , Coye Camille , Thompson Melissa Emery , Estrada Alejandro , Fichtel Claudia , Fruth Barbara , Gamba Marco , Giacoma Cristina , Graham Kirsty E. , Green Samantha , Grueter Cyril C. , Gupta Shreejata , Gustison Morgan L. , Hagberg Lindsey , Hedwig Daniela , Jack Katharine M. , Kappeler Peter M. , King-Bailey Gillian , Kuběnová Barbora , Lemasson Alban , Inglis David MacGregor , Machanda Zarin , MacIntosh Andrew , Majolo Bonaventura , Marshall Sophie , Mercier Stephanie , Micheletta Jérôme , Muller Martin , Notman Hugh , Ouattara Karim , Ostner Julia , Pavelka Mary S. M. , Peckre Louise R. , Petersdorf Megan , Quintero Fredy , Ramos-Fernández Gabriel , Robbins Martha M. , Salmi Roberta , Schamberg Isaac , Schoof Valérie A. M. , Schülke Oliver , Semple Stuart , Silk Joan B. , Sosa-Lopéz J. Roberto , Torti Valeria , Valente Daria , Ventura Raffaella , van de Waal Erica , Weyher Anna H. , Wilke Claudia , Wrangham Richard , Young Christopher , Zanoli Anna , Zuberbühler Klaus , Lameira Adriano R. , Slocombe Katie
Published: July 2021

Animal communication has long been thought to be subject to pressures and constraints associated with social relationships. However, our understanding of how the nature and quality of social relationships relates to the use and evolution of communication is limited by a lack of directly comparable methods across multiple levels of analysis. Here, we analysed observational data from 111 wild groups belonging to 26 non-human primate species, to test how vocal communication relates to dominance style (the strictness with which a dominance hierarchy is enforced, ranging from ‘despotic’ to ‘tolerant’). At the individual-level, we found that dominant individuals who were more tolerant vocalized at a higher rate than their despotic counterparts. This indicates that tolerance within a relationship may place pressure on the dominant partner to communicate more during social interactions. At the species-level, however, despotic species exhibited a larger repertoire of hierarchy-related vocalizations than their tolerant counterparts. Findings suggest primate signals are used and evolve in tandem with the nature of interactions that characterize individuals' social relationships.
Growth strategies of a model picoplankter depend on social milieu and
p
CO
2
Authors: Collins Sinead , Schaum C. Elisa
Published: July 2021

Phytoplankton exist in genetically diverse populations, but are often studied as single lineages (single strains), so that interpreting single-lineage studies relies critically on understanding how microbial growth differs with social milieu, defined as the presence or absence of conspecifics. The properties of lineages grown alone often fail to predict the growth of these same lineages in the presence of conspecifics, and this discrepancy points towards an opportunity to improve our understanding of the factors that affect lineage growth rates. We demonstrate that different lineages of a marine picoplankter modulate their maximum lineage growth rate in response to the presence of non-self conspecifics, even when resource competition is effectively absent. This explains why growth rates of lineages in isolation do not reliably predict their growth rates in mixed culture, or the lineage composition of assemblages under conditions of rapid growth. The diversity of growth strategies observed here are consistent with lineage-specific energy allocation that depends on social milieu. Since lineage growth is only one of many traits determining fitness in natural assemblages, we hypothesize that intraspecific variation in growth strategies should be common, with more strategies possible in ameliorated environments that support higher maximum growth rates, such as high CO
2
for many marine picoplankton.
Leucobacter chromiisoli sp. nov., isolated from chromium-containing chemical plant soil
Authors: Xu Zhe , Li Xiaoguang , Tian Jiewei , Gan Longzhan , Tian Yongqiang
Published: July 2021

A Gram-stain-positive, rod-shaped, aerobic, non-motile, non-sporulating bacterial strain, designated CSA1T, was isolated from chromium-containing soil sampled at a chemical plant. Growth of strain CSA1T occurred at pH 6–10 (optimum, pH 7), 15–45 °C (optimum, 30 °C) and in the presence of 0.5–6.5 % (w/v) NaCl (optimum, 2 %). The 16S rRNA gene sequence of strain CSA1T revealed the highest similarity to

Leucobacter ruminantium

A2T (97.5 %),

Leucobacter tardus

K 70/01T (97.3 %),

Leucobacter humi

Re6T (96.6 %),

Leucobacter kyeonggiensis

F3-P9T (96.2 %),

Leucobacter zeae

CC-MF41T (96.1 %) and

Leucobacter weissii

S27T (96.0 %). The draft genome of CSA1T was approximately 3 350 931 bp in size with a G+C content of 70.6 mol%. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values among strain CSA1T and the selected

Leucobacter

species were 74.0–79.2 % (ANIb), 84.3–87.1 % (ANIm) and 21.5–25.4 % (dDDH), which are below the recommended cutoff values for species delineation. The major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unknown glycolipid. The predominant menaquinones were MK-11, MK-8 and MK-6. The cell-wall amino acids were 2,4-diaminobutyric acid, alanine, glycine, glutamic acid and threonine. From the phenotypic, chemotaxonomic and molecular features, strain CSA1T was considered to represent a novel species of the genus

Leucobacter

, for which the name Leucobacter chromiisoli sp. nov. is proposed. The type strain is CSA1T (=JCM 34359T=CGMCC 1.18746T).
Streptococcus pneumoniae colonisation associates with impaired adaptive immune responses against SARS-CoV-2
Authors: Mitsi Elena , Reiné Jesús , Urban Britta C , Solórzano Carla , Nikolaou Elissavet , Hyder-Wright Angela D. , Pojar Sherin , Howard Ashleigh , Hitchins Lisa , Glynn Sharon , Farrar Madlen , Liatsikos Konstantinos , Collins Andrea M , Walker Naomi F , Hill Helen , German Esther L , Cheliotis Katerina S , Byrne Rachel L , Williams Christopher T. , Cubas-Atienzar Ana I , Flecher Tom , Adams Emily R , Draper Simon J , Pulido David , Beavon Rohini , Theilacker Christian , Begier Elizabeth , Jodar Luis , Gessner Bradford D , Ferreira Daniela M
Published: July 2021

Although recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, secondary pneumococcal pneumonia has been reported as infrequent. This apparent contradiction may be explained by interactions of SARS-CoV-2 and pneumococcus in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses. Here, we investigated the relationship of these two respiratory pathogens in two distinct cohorts of a) healthcare workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and b) patients with moderate to severe disease who presented to hospital. We assessed the effect of co-infection on host antibody, cellular and inflammatory responses to the virus. In both cohorts, pneumococcal colonisation was associated with diminished anti-viral immune responses, which affected primarily mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients. Our findings suggest that S. pneumoniae modulates host immunity to SARS-CoV-2 and raises the question if pneumococcal carriage also enables immune escape of other respiratory viruses through a similar mechanism and facilitates reinfection occurrence.
A locus conferring tolerance to Theileria infection in African cattle
Authors: Wragg D. , Cook E.A.J. , de Late P. Latre , Sitt T. , Hemmink J.D. , Chepkowny M. , Njeru R. , Poole E.J. , Powell J. , Paxton E. , Callaby R. , Talenti A. , Miyunga A.A. , Ndambuki G. , Mwaura S. , Auty H. , Matika O. , Hassan M. , Marshall K. , Connelley T. , Morrison L.J. , Bronsvoort B.M.deC. , Morrison W.I. , Toye P.G. , Prendergast J.G.D.
Published: July 2021

East Coast fever, a tick-borne cattle disease caused by theTheileria parvaparasite, is among the biggest natural killers of cattle in East Africa, leading to over 1 million deaths annually. Here we report on the genetic analysis of a cohort of Boran cattle demonstrating heritable tolerance to infection byT. parva(h2= 0.65, s.e. 0.57). Through a linkage analysis we identify a 6 Mb genomic region onBos tauruschromosome 15 that is significantly associated with survival outcome followingT. parvaexposure. Testing this locus in an independent cohort of animals replicates this association with survival followingT. parvainfection. A stop gained polymorphism in this region was found to be highly associated with survival across both related and unrelated animals, with only one of the 20 homozygote carriers (T/T) of this change succumbing to the disease in contrast to 44 out of 97 animals homozygote for the reference allele (C/C). Consequently, we present a genetic locus linked to tolerance of one of Africa’s most important cattle diseases, raising the promise of marker-assisted selection for cattle that are less susceptible to infection byT. parva.

Author Summary

More than a million cattle die of East Coast fever in Africa each year, the impact of which disproportionately falls onto low-income, smallholder farmers. The lack of a widely accessible vaccine, heavy reliance on chemicals to control the tick vector and inadequate drug treatments means that new approaches for controlling the disease are urgently required. Through a genetic study of an extended pedigree of Boran cattle that are more than three times less likely to succumb to the disease than matched controls, we identify a region on chromosome 15 of the cattle genome associated with a high level of tolerance to the disease. We show that a variant in this region is also associated with survival in an independent cohort, and is linked to rates of cell expansion during infection. This genetic variant can therefore support marker-assisted selection, allowing farmers to breed tolerant cattle and offers a route to introduce this beneficial DNA to non-native breeds, enabling reduced disease incidence and increased productivity, which would be of benefit to millions of rural smallholder farmers across Africa.
Modelling and assessing additional transmission routes for porcine reproductive and respiratory syndrome virus: vehicle movements and feed ingredients
Authors: Galvis Jason A. , Corzo Cesar A. , Machado Gustavo
Published: July 2021

Accounting for multiple modes of livestock disease dissemination in epidemiological models remains a challenge. We developed and calibrated a mathematical model for transmission of porcine reproductive and respiratory syndrome virus (PRRSV), tailored to fit nine modes of between-farm transmission pathways including: farm-to-farm proximity (local transmission), contact network of batches of pigs transferred between farms (pig movements), re-break probabilities for farms with previous PRRSV outbreaks, with the addition of four different contact networks of transportation vehicles (vehicles to transport pigs to farms, pigs to markets, feed and crew) and the amount of animal by-products within feed ingredients (e.g. animal fat or meat and bone meal). The model was calibrated on weekly PRRSV outbreaks data. We assessed the role of each transmission pathway considering the dynamics of specific types of production (i.e., sow, nursery). Although our results estimated that the networks formed by transportation vehicles were more densely connected than the network of pigs transported between-farms, pig movements and farm proximity were the main PRRSV transmission routes regardless of farm types. Among the four vehicle networks, vehicles transporting pigs to farms explained a large proportion of infections, sow = 20.9%; nursery = 15%; and finisher = 20.6%. The animal by-products showed a limited association with PRRSV outbreaks through descriptive analysis, and our model results showed that the contribution of animal fat contributed only 2.5% and meat and bone meal only 0.03% of the infected sow farms. Our work demonstrated the contribution of multiple routes of PRRSV dissemination, which has not been deeply explored before. It also provides strong evidence to support the need for cautious, measured PRRSV control strategies for transportation vehicles and further research for feed by-products modeling. Finally, this study provides valuable information and opportunities for the swine industry to focus effort on the most relevant modes of PRRSV between-farm transmission.
Development of an ASO therapy for Angelman syndrome by targeting an evolutionarily conserved region at the start of theUBE3A-AStranscript
Authors: Dindot Scott V. , Christian Sarah , Murphy William J. , Berent Allyson , Panagoulias Jennifer , Schlafer Annalise , Ballard Johnathan , Radeva Kamelia , Robinson Ruth , Myers Luke , Jepp Thomas , Shaheen Hillary , Hillman Paul , Konganti Kranti , Hillhouse Andrew , Bredemeyer Kevin R. , Black Lauren , Douville Julie ,   the FIRE consortium
Published: July 2021

Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A (UBE3A) gene. The paternalUBE3Aallele is imprinted in neurons of the central nervous system (CNS) by theUBE3Aantisense (UBE3A-AS) transcript, which represents the distal end of theSNHG14transcription unit. Reactivating the expression of the paternalUBE3Aallele in the CNS has long been pursued as a therapeutic option for Angelman syndrome. Here, we designed and optimized antisense oligonucleotides (ASO) targeting an evolutionarily conserved region demarcating the start of the humanUBE3A-AStranscript and show that ASOs targeting this region can reverse imprinting ofUBE3Ain cultured Angelman syndrome neurons and throughout the CNS of a non-human primate model. Findings from this study advanced the first investigational molecular therapy for Angelman syndrome into clinical development (ClinicalTrials.gov,NCT04259281).

Here, we describe the preclinical studies supporting the first investigational molecular therapy for Angelman syndrome to advance into clinical development (ClinicalTrials.gov,NCT04259281).
Heterogeneity and dynamics of ERK and Akt activation by G protein-coupled receptors depend on the activated heterotrimeric G proteins
Authors: Chavez-Abiega Sergei , Grönloh Max L.B. , Gadella T.W.J. , Bruggeman Frank J. , Goedhart J.
Published: July 2021

Kinases are fundamental regulators of cellular functions and play key roles in GPCR-mediated signaling pathways. Kinase activities are generally inferred from cell lysates, hiding the heterogeneity of the individual cellular responses to extracellular stimuli. Here, we study the dynamics and heterogeneity of ERK and Akt in genetically identical cells in response to activation of endogenously expressed GPCRs. We use kinase translocation reporters, high-content imaging, automated segmentation and clustering methods to assess cell-to-cell signaling heterogeneity. We observed ligand-concentration dependent response kinetics to histamine, a2-adrenergic, and S1P receptor stimulation that varied between cells. By using G protein inhibitors, we observed that Gq mediated the ERK and Akt responses to histamine. In contrast, Gi was necessary for ERK and Akt activation in response to α2-adrenergic receptor activation. ERK and Akt were also strongly activated by S1P, showing high heterogeneity at the single cell level, especially for ERK. In all cases, the cellular heterogeneity was not explained by distinct pre-stimulation levels or saturation of the measured response. Cluster analysis of time-series derived from 68,000 cells obtained under the different conditions revealed several distinct populations of cells that display similar response dynamics. The single-cell ERK responses to histamine and brimonidine showed remarkably similar dynamics, despite the activation of different heterotrimeric G proteins. In contrast, the ERK response dynamics to S1P showed high heterogeneity, which was reduced by the inhibition of Gi. To conclude, we have set up an imaging and analysis strategy that reveals substantial cell-to-cell heterogeneity in kinase activity driven by GPCRs.

Abstract Figure
Optogenetic actuator/ERK biosensor circuits identify MAPK network nodes that shape ERK dynamics
Authors: Dessauges Coralie , Mikelson Jan , Dobrzyński Maciej , Jacques Marc-Antoine , Frismantiene Agne , Gagliardi Paolo Armando , Khammash Mustafa , Pertz Olivier
Published: July 2021

Combining single-cell measurements of ERK activity dynamics with perturbations provides insights into the MAPK network topology. We built circuits consisting of an optogenetic actuator to activate MAPK signaling and an ERK biosensor to measure single-cell ERK dynamics. This allowed us to conduct RNAi screens to investigate the role of 50 MAPK proteins in ERK dynamics. We found that the MAPK network is robust against most node perturbations. We observed that the ERK-RAF and the ERK-RSK2-SOS negative feedbacks operate simultaneously to regulate ERK dynamics. Bypassing the RSK2-mediated feedback, either by direct optogenetic activation of RAS, or by RSK2 perturbation, sensitized ERK dynamics to further perturbations. Similarly, targeting this feedback in a human ErbB2-dependent oncogenic signaling model increased the efficiency of a MEK inhibitor. The RSK2-mediated feedback is thus important for the ability of the MAPK network to produce consistent ERK outputs and its perturbation can enhance the efficiency of MAPK inhibitors.
Phytoplankton exudates provide full nutrition to a subset of accompanying heterotrophic bacteria via carbon, nitrogen and phosphorus allocation
Authors: Eigemann Falk , Rahav Eyal , Grossart Hans-Peter , Aharonovich Dikla , Sher Daniel , Vogts Angela , Voss Maren
Published: July 2021

Marine bacteria rely on phytoplankton exudates as carbon sources (DOCp). Yet, it is unclear to what extent phytoplankton exudates also provide nutrients such as phytoplankton-derived N and P (DONp, DOPp). We address these questions by exudate addition experiments from the ubiquitous pico-cyanobacteriumProchlorococcusto contrasting ecosystems in the Eastern Mediterranean – a coastal and an open-ocean, oligotrophic station. Nutrient addition did not lower the incorporation of exudate DONp, nor did it reduce alkaline phosphatase activity, suggesting that bacterial communities are able to exclusively cover their nitrogen and phosphorus demands with organic forms provided by phytoplankton exudates. Approximately half of the cells in each ecosystem took up detectable amounts ofProchlorococcus-derived C and N, yet based on 16S rRNA sequencing different bacterial genera were responsible for the observed exudate utilization patterns. In the coastal community, several phylotypes ofAureimarina,PsychrosphaeraandGlaciecolaresponded positively to the addition of phytoplankton exudates, whereas phylotypes ofPseudoalteromonasincreased and dominated the open ocean communities. Together, our results strongly indicate that phytoplankton exudates provide coastal and open-ocean bacterial communities with organic carbon, nitrogen and phosphorus, and that phytoplankton exudate serve a full-fledged meal for specific members of the accompanying bacterial community in the nutrient-poor eastern Mediterranean.
Anti-arthralgic activity of the n-hexane extract (HTp) of yellow oleander seeds; Thevetia peruviana (Pers.) K. Schum
Authors: Odimegwu Joy Ifunanya , Olabisi Fatiha Oyebola
Published: July 2021

Thevetia peruviana (Pers.) K.Schum. (Apocynaceae) seeds are known to possess cardioactive glycosides such as thevetin A, thevetin B, nerifolin etc. They are also used locally for general pain relief for which there is no scientific evidence to our knowledge. Arthralgia is regarded generally as pain without inflammation. It is endemic in the society and sufferers continue to imbibe pain relieving drugs in their tons all over the world. Analgesic activity test was carried out using the formalin-induced pain models, at 0.1g, 0.2g and 0.3g/kg doses of n-hexane extracts of Thevetia peruviana seeds (HTp) in Wistar mice. Diclofenac was used as positive control. Acute toxicity test was carried out at doses of 1000, 2500 and 5000 mg/kg weight of test subject. It was observed that HTp at concentrations of 0.1g, 0.2g and 0.3g/kg showed significant analgesic effect at compared to the control. The percentage inhibition observed was 29.60%, 44.80% and 50.72% for the early pain phase and 100% for the late pain phase respectively, indicating HTp’s NSAID-like property. HTp showed the highest percentage inhibition at 300 mg/kg (50.72 %) and significant (P<0.005) pain reduction. HTp did not produce any toxicity up to a dose of 5000 mg/kg weight which is very interesting as the seeds are known for their toxicity due to the cardiac glycoside presence. The results of the study suggest that HTp does indeed relieve pain significantly in a dose dependent manner, thus justifying its use in management of arthralgia.