bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent pregnancy loss in a patient with anti‐Rh17
Authors: Moiz Bushra , Salman Muhammed , Rasheed Seher , Qudus Ruhul , Millard Glenda , Hyland Catherine A. , Flower Robert L. , Wilson Brett , Turner Robyn , Lopez Genghis H. , Liew Yew‐Wah
Published: November 2023

Background

Rh is one of the most important blood group systems in transfusion medicine. The two homologous genesRHDandRHCEare located on chromosome 1p36.11 and encode for RhD and RhCE proteins, respectively. Complex genetic polymorphisms result in a variety of antigenic expression of D, C, E, c, and e. Here, we describe a case of a young female with D−− who developed anti‐Rh17 secondary to blood transfusion and had signs of haemolytic disease of the fetus and fetal death in five consecutive pregnancies.

Case Description

EDTA‐whole blood samples were collected from the patient, husband and eight siblings for blood grouping, phenotyping, and red cell antibody screening. Extracted DNA was genotyped by SNP‐microarray and massively parallel sequencing (MPS) with targeted blood group exome sequencing. Copy number variation analysis was performed to identify structural variants in theRHDandRHCE. Routine phenotyping showed all family members were D+. The patient's red blood cells were C−E−c−e−, Rh17− and Rh46− and had anti‐Rh17 and anti‐e antibodies. MPS showed the patient carried a wildtypeRHDsequence and homozygous forRHCE(1)–D(2–9)–CE(10) hybrid gene predicted to express a D−− phenotype.

Conclusions

Our patient had a rare D−− phenotype and confirmed to haveRHCE/RHDhybrid gene with replacement of 2–9 exons ofRHCEbyRHDsequences. Unfortunately, our patient developed anti‐Rh17 and anti‐e antibodies due to blood transfusion and suffered fetal demise in her very first pregnancy. The adverse outcomes could have been prevented by active prenatal management.
Evaluation of SaTo pans as a new latrine technology in Kisumu County healthcare facilities, Kenya
Authors: Prentice‐Mott Graeme , Odhiambo Aloyce , Conners Erin E. , Mwaki Alex , Blackstock Anna J. , Oremo Jared , Akelo Oscar , Eleveld Alie , Quick Robert , Murphy Jennifer , Berendes David M.
Published: November 2023

Objectives

Innovations to improve public sanitation facilities, especially in healthcare facilities (HCFs) in low‐income countries, are limited. SaTo pans represent novel, largely untested, modifications to reduce odour and flies and improve acceptability of HCF sanitation facilities. We conducted a pilot project to evaluate acceptability, cleanliness, flies and odour within latrines in 37 HCFs in Kisumu, Kenya, randomised into intervention (SaTo pan modifications) and control arms by sub‐county and HCF level.

Methods

At baseline (pre‐intervention) and endline (>3 months after completion of SaTo pan installations in latrines in intervention HCFs), we surveyed users, cleaners and in‐charges, observed odour and cleanliness, and assessed flies using fly tape. Unadjusted difference‐in‐difference analysis compared changes from baseline to endline in patient‐reported acceptability and observed latrine conditions between intervention and control HCFs. A secondary assessment compared patient‐reported acceptability following use of SaTo pan versus non‐SaTo pan latrines within intervention HCFs.

Results

Patient‐reported acceptability of latrines was higher following the intervention (baseline: 87%, endline: 96%, p = 0.05). However, patient‐reported acceptability was also high in the control arm (79%, 86%, p = 0.34), and the between‐arm difference‐in‐difference was not significant. Enumerator‐observed odour declined in intervention latrines (32%–14%) compared with controls (36%–51%, difference‐in‐difference ratio: 0.32, 95% confidence interval: 0.12–0.84), but changes in flies, puddling of urine and visible faeces did not differ between arms. In the secondary assessment, fewer intervention than control latrines had patient‐reported flies (0% vs. 26%) and odour (18% vs. 50%), and reported satisfaction was greater. Most cleaners reported dropholes and floors were easier to clean in intervention versus controls; limited challenges with water for flushing were reported.

Conclusions

Our results suggest SaTo pans may be acceptable by cleaners and users and reduce odour in HCF sanitation facilities, though challenges exist and further evaluation with larger sample sizes is needed.
Hepatic abscessation in dogs: A multicenter study of 56 cases (2010–2019)
Authors: Burke Jasper E. , Hess Rebecka S. , McEntee Elisa P. , Griffin Maureen A. , Harmon Selimah M. , Silverstein Deborah C.
Published: November 2023

Objective

To investigate the clinical findings, treatment strategies, and outcomes in dogs with confirmed hepatic abscessation.

Design

Retrospective cohort study from 2010 to 2019.

Setting

Multicenter study.

Animals

Fifty‐six client‐owned dogs with hepatic abscessation confirmed by culture, cytology, or histopathology.

Measurements and Main Results

Dogs were presented for lethargy (39/56), hyporexia (31/56), and vomiting (26/56). Abnormal physical examination findings included increased temperature (41/56) and abdominal pain (22/54). CBCs revealed neutrophilia (31/49), toxic changes (25/49), anemia (28/49), and thrombocytopenia (23/49). Biochemical analyses revealed increased alkaline phosphatase (45/50), increased alanine aminotransferase (40/50), hypoalbuminemia (25/48), and hyperbilirubinemia (19/49). Hypoglycemia was found in 13 of 49 dogs. Hepatic abscesses ranging from 0.5 to 15 cm in diameter were identified ultrasonographically in 37 of 48 dogs; 19 of 37 had solitary abscesses, and 18 of 37 had multifocal abscessation. Escherichia coli was the most commonly cultured organism, isolated in 18 of 42 cases. Histopathology revealed underlying hepatic neoplasia in 10 of 47 dogs. Surgical management was performed in 41 of 49 dogs, and 35 of 41 survived to discharge. Medical management was performed in 8 of 49 dogs, and 5 of 8 survived to discharge. With univariate analysis, hypoglycemia and multifocal abscessation were associated with decreased odds of survival (odds ratio [OR]: 0.2, 95% confidence interval [CI]: 0.03–0.9,P = 0.04; OR: 0.07, 95% CI: 0.01–0.6,P = 0.02, respectively). With multivariate analysis, only multifocal abscessation was associated with decreased odds of survival (OR: 0.09, 95% CI: 0.01–0.87,P = 0.04).

Conclusions

Hepatic abscessation, although rare, should remain a differential diagnosis for dogs presenting with nonspecific clinical signs and increase liver enzyme activities, especially with concurrent increased temperature and neutrophilia. Rate of survival to discharge for dogs in this study was consistent with previously reported survival rates, with 40 of 56 (71%) of the total population surviving to discharge. No variables assessed were able to predict survival to discharge; however, hypoglycemia and multifocal abscessation should be assessed in larger populations to determine prognostic significance.
Usefulness of an auditory aid to improve chest compression rate accuracy during cardiopulmonary resuscitation
Authors: Genetti Ashley , Llewellyn Efa A.
Published: November 2023

Objective

To assess compression rate accuracy among veterinarians and registered veterinary nurses (RVNs) without and with an audible aid.

Design

Prospective study with use of a canine CPR manikin.

Setting

Small animal teaching hospital.

Subjects

Thirty‐six participants (20 veterinarians and 16 RVNs).

Interventions

Each participant completed the first 2‐minute cycle of chest compressions without an auditory aid on a canine CPR manikin. Each participant was then randomized to 1 of 3 auditory aid groups (Group B: Bee Gees “Stayin’ Alive”; Group Q: Queen “Another One Bites the Dust”; or Group M: traditional metronome) and then completed a second 2‐minute cycle of chest compressions with the instruction to synchronize their compression rate with the beat of the auditory aid. An accurate chest compression rate was defined as obtaining a rate between 100 and 120 compressions per minute (cpm).

Measurements and Main Results

Median number of compressions administered by participants during Cycle 1 for the first minute was 111 (range 88–140) and for the second minute was 107 (range 80–151), with 25 of 36 (69%) participants obtaining an accurate chest compression rate. Median number of compressions administered during Cycle 2 for the first minute was 110 (range 76–125) and for the second minute was 110 (range 72–125), with 34 of 36 participants (94%) obtaining an accurate chest compression rate. Participants were more likely to obtain an accurate chest compression rate when an auditory aid was present compared to without (McNemar's test; P = 0.013). Subgroup analysis suggested the auditory aid was beneficial in Groups Q and M but not Group B (Kruskal–Wallis with Dunn's post hoc testing; P = 0.014, P = 0.0455, and P = 0.5637, respectively).

Conclusions

An auditory aid was associated with improved chest compression rate accuracy. However, as the auditory aid was not beneficial for Group B participants, our findings suggest that some auditory aids are more helpful than others.
Rebound hyperkalemia in a dog with albuterol toxicosis after cessation of potassium supplementation
Authors: Guida Samantha J. , Bazzle Lisa
Published: November 2023

Objective

To describe the presentation of rebound hyperkalemia as a delayed side effect of albuterol toxicity in a dog.

Case Summary

A 3‐year‐old female neutered mixed‐breed dog was presented for albuterol toxicosis that led to a severe hypokalemia, hyperlactatemia, and hyperglycemia. The dog also experienced sinus tachycardia and generalized weakness. Treatment was instituted with intravenous fluid therapy and potassium supplementation, and the dog was monitored with a continuous electrocardiogram. Resolution of hypokalemia was documented 12 hours after initial presentation, at which time fluid therapy and potassium supplementation were discontinued. There were no further periods of sinus tachycardia, but instead the dog developed ventricular ectopy with rapid couplets (instantaneous rates of 300/min). An echocardiogram revealed normal cardiac size and function. Twenty‐four hours after presentation, the patient developed severe hyperkalemia, despite discontinuation of fluids and potassium supplementation for 12 hours. Serial venous and urinary electrolytes were performed for determination of the fractional excretion of electrolytes. These data confirmed rebound hyperkalemia (7.0 mmol/L), consistent with a markedly increased fractional excretion of potassium, and secondary to the release of potassium from inside the cells. Fluid therapy with dextrose supplementation was provided until 36 hours postpresentation. The hyperkalemia resolved, and the dog was discharged after 44 hours of hospitalization.

New or Unique Information Provided

This case documents rebound hyperkalemia following treatment of albuterol toxicosis in a dog. This case highlights the importance of understanding the distribution of total body potassium when treating serum hypokalemia. Transcellular shifts of potassium, as in the case of albuterol toxicosis, can lead to rebound hyperkalemia even after discontinuation of potassium supplementation. This case further explores the utility of fractional excretion of electrolytes in elucidating the etiology and management of electrolyte disturbances.
Evaluation of subchondral bone cysts in canine elbows with radiographic osteoarthritis secondary to elbow dysplasia
Authors: Jones Gareth M. C. , Gosby Madelaine R. , May Eleanore M. , Meeson Richard L.
Published: November 2023

Objective

To investigate whether subchondral bone cysts (SBCs) were present in dogs with radiographic elbow osteoarthritis (OA) and to investigate their relationship with radiographic OA severity.

Study design

Retrospective cross‐sectional study.

Sample population

Thirty‐eight Labrador retrievers (total of 76 elbows).

Methods

Elbow computed tomography (CT) images of 18 young (≤2 years old) and 20 old (>2 years old) Labrador retrievers, which presented for elbow‐associated lameness, were reviewed. Radiographic elbow OA was graded into four groups based on the largest osteophyte size on CT. The presence, number, and maximum diameter of SBCs were determined.

Results

Subchondral bone cysts were only identified in elbows with osteophytic new bone formation. The number and size of SBCs were associated with radiographic OA severity (p < .001 and p = .041 respectively). Specifically, the rate at which SBCs were present increased for both moderate and severe OA in comparison with the mild OA (moderate OA RR = 2.46, 95% CI 2.08–2.92, p < .001; severe OA RR = 5.60, 95% CI 4.79–6.55, p < .001). For dogs with severe OA, there was an increased likelihood that their SBCs were larger than SBCs from dogs with mild OA (OR = 1.056, 95% CI 1.012–1.101, p = .012). No SBCs were observed in elbows without radiographic evidence of OA.

Conclusion

Subchondral bone cysts were identified as a feature of radiographic elbow osteoarthritis in Labrador retrievers, and their number and size were indicative of the presence and severity of radiographic elbow OA.

Clinical significance

Subchondral bone cysts are a potential imaging biomarker for quantitative assessment for canine OA.
The Effect of an Increasing Subglottal Stenosis Constriction That Extends From the Vocal Folds to the Inferior Border of the Cricoid Cartilage
Authors: Michaud-Dorko Jacob , Sundström Elias , de Luzan Charles Farbos , Gutmark Ephraim , Oren Liran
Published: November 2023

Acquired subglottal stenosis is an unpredicted complication that can occur in some patients who have undergone prolonged endotracheal intubation. It is a narrowing of the airway at the level of the cricoid cartilage that can restrict airflow and cause breathing difficulty. Stenosis is typically treated with endoscopic airway dilation, with some patients experiencing multiple recurrences. The study highlights the potential of computational fluid dynamics as a noninvasive method for monitoring subglottic stenosis, which can aid in early diagnosis and surgical planning. An anatomically accurate human laryngeal airway model was constructed from computerized tomography (CT) scans. The subglottis cross-sectional area was narrowed systematically using ≈10% decrements. A quadratic profile was used to interpolate the transformation of the airway geometry from its modified shape to the baseline geometry. The numerical results were validated by static pressure measurements conducted in a physical model. The results show that airway resistance follows a squared ratio that is inversely proportional to the size of the subglottal opening (R∝A−2). The study found that critical constriction occurs in the subglottal region at 70% stenosis (upper end of grade 2). Moreover, removing airway tissue below 40% stenosis during surgical intervention does not significantly decrease airway resistance.
Meta Data Analysis of Sex Distribution of Study Samples Reported in Summer Biomechanics, Bioengineering, and Biotransport Annual Conference Abstracts
Authors: Sebastian Frederick , Vargas Ana I. , Clarin Julia , Hurgoi Anthony , Amini Rouzbeh
Published: November 2023

The biased use of male subjects in biomedical research has created limitations, underscoring the importance of including women to enhance the outcomes of evidence-based medicine and to promote human health. While federal policies (e.g., the 1993 Revitalization Act and the 2016 Sex as a Biological Variable Act) have aimed to improve sex balance in studies funded by the National Institutes of Health (NIH), data on sex inclusivity in non-NIH funded research remain limited. The objective of this study was to analyze the trend of sex inclusion in abstracts submitted to the Summer Biomechanics, Bioengineering, & Biotransport Conference (SB3C) over 7 years. We scored every abstract accepted to SB3C, and the findings revealed that approximately 20% of total abstracts included sex-related information, and this trend remained stable. Surprisingly, there was no significant increase in abstracts, including both sexes and those with balanced female and male samples. The proportion of abstracts with balanced sexes was notably lower than those including both sexes. Additionally, we examined whether the exclusion of one sex from the corresponding studies was justified by the research questions. Female-only studies had a 50% justification rate, while male-only studies had only 2% justification. Disparity in sex inclusion in SB3C abstracts was apparent, prompting us to encourage scientists to be more mindful of the sex of the research samples. Addressing sex inclusivity in biomechanics and mechanobiology research is essential for advancing medical knowledge and for promoting better healthcare outcomes for everyone.
Influence of Buoyancy and Inter-Surface Radiation on Confined Jet Impingement Cooling of a Semi-Cylindrical Concave Plate
Authors: Sarper Bugra
Published: November 2023

In this article, the confined jet impingement cooling of a semicylindrical concave plate is analyzed numerically. The finite volume approach is applied to two-dimensional numerical simulations in the transient regime. Air is employed as the working fluid and is regarded as nonparticipant for radiation. The investigation is done for different jet Reynolds numbers (Rej) ranging from 100 to 1000, as the Richardson number (Ri) corresponding to this interval ranges between 0.1 and 10. For any Richardson number, the modified Grashof number (Gr*) is fixed at 105. When analyzing the impact of intersurface radiation between the target plate and confined surfaces on the overall cooling performance, three emissivity values (ε= 0.05, 0.5, and 0.95) are taken into consideration. Additionally, simulations are done for the pure convective heat transfer, ignoring intersurface radiation (ε= 0.0). The influence of surface emissivity and the Richardson number on velocity, temperature, and pressure distribution in the flow domain, local dimensionless temperature (θ) alterations on the target plate and confined walls, alterations in convective (Nuc), radiative (Nur), overall Nusselt numbers (Nuovr), pressure coefficient (Cp), and ratio of radiative Nusselt number to overall Nusselt number (Nur/Nuovr) on the target plate are highlighted. The findings demonstrate that surface emissivity has a significant influence on thermal and hydrodynamic boundary layer formation, buoyancy induced flow and heat transfer, and the proportion of intersurface radiation in overall heat transfer rises as the Richardson number and surface emissivity increase. At low Richardson numbers, the pressure in the stagnation region is greater than the atmospheric pressure. However, as the buoyancy effect increases, the pressure in the stagnation region falls below the atmospheric pressure and rises toward the exit.
A Re-Evaluation of Rupture Data for CF8C-Plus Austenitic Stainless Steel
Authors: Bolton J.
Published: November 2023

Models of creep rupture data for CF8C-Plus Austenitic steel are presented and compared to recently published models of the same data. Metrics for the accuracy of these models are compared and the reliability of extrapolations to times of practical interest is discussed. Significant differences are reported between previous predictions of long-term rupture strength and the results of re-evaluation.
Miniature battery-free bioelectronics
Authors: Nair Vishnu , Dalrymple Ashley N. , Yu Zhanghao , Balakrishnan Gaurav , Bettinger Christopher J. , Weber Douglas J. , Yang Kaiyuan , Robinson Jacob T.
Published: November 2023

Miniature wireless bioelectronic implants that can operate for extended periods of time can transform how we treat disorders by acting rapidly on precise nerves and organs in a way that drugs cannot. To reach this goal, materials and methods are needed to wirelessly transfer energy through the body or harvest energy from the body itself. We review some of the capabilities of emerging energy transfer methods to identify the performance envelope for existing technology and discover where opportunities lie to improve how much—and how efficiently—we can deliver energy to the tiny bioelectronic implants that can support emerging medical technologies.
Adapting to growing wildfire property risk
Authors: Boomhower Judson
Published: November 2023

Cost-effective and equitable physical and financial protections are needed
Circling back to magnetism
Authors: Kaindl Robert A.
Published: November 2023

Ultrafast experiments unveil control of magnetization with atomic rotations
How domestic cats wiped out the Scottish wildcat
Authors: Grimm David
Published: November 2023

After millennia of isolation, a few decades of interbreeding have rendered the animal “genomically extinct”
The effect of hydrostatic pressure on the activity and community composition of hydrocarbon-degrading bacteria in Arctic seawater
Authors: Marietou Angeliki , Schmidt Jennie Spicker , Rasmussen Martin R. , Scoma Alberto , Rysgaard Søren , Vergeynst Leendert
Published: November 2023

There is a renewed interest in hydrocarbon biodegradation in Arctic seawaters due to increasing ship traffic and risk for oil spills. Most studies, however, fail to address the effect of increasing pressure as an environmental parameter. Here, we conducted a series of pressurized enrichments (0.1–30 MPa, 4°C) inoculated with a 100-day-old hydrocarbon-degrading biofilm collected from 615 m deep in Arctic seawater. Cell-specific CO
2
production rates provided a clear summary of the observed microbial activity: a bloom of a hydrocarbon degrading-biofilm generating 0.82–0.90 fmol CO
2
⋅bacterial gene
−1
⋅day
−1
at 0.1–8 MPa, but undetectable activity at 30 MPa until day 6. At 30 MPa, the microbial activity increased between days 6 and 34 with an average rate of 0.36 ± 0.08 fmol CO
2
⋅bacterial gene
−1
⋅day
−1
. Amplicon sequencing revealed no differences in the microbial community composition at 0.1–12 MPa. While the typical Arctic alkane degraders
Oleispira
and
Shewanella
were abundant across all hydrostatic pressures and over time,
Colwellia, Neptunomonas
,
and Kiloniella
were significantly enriched solely at 30 MPa. Our results suggest that the physiological adaptations of psychrophilic bacteria to thrive at sub-zero temperature make Arctic oil degraders tolerant to mild hydrostatic pressures of up to 12 MPa, whereas temperate climate communities have shown hydrostatic pressure-induced inhibition at 10–15 MPa in comparable studies. The activity of hydrocarbon degraders in sinking marine oil snow in the Arctic may remain unaffected down to depths of about 1,200 m, after which hydrostatic pressure can significantly affect hydrocarbon degradation at increasing depths down to 3,000 m.

IMPORTANCE

Increased ship traffic in the Arctic region raises the risk of oil spills. With an average sea depth of 1,000 m, there is a growing concern over the potential release of oil sinking in the form of marine oil snow into deep Arctic waters. At increasing depth, the oil-degrading community is exposed to increasing hydrostatic pressure, which can reduce microbial activity. However, microbes thriving in polar regions may adapt to low temperature by modulation of membrane fluidity, which is also a well-known adaptation to high hydrostatic pressure. At mild hydrostatic pressures up to 8–12 MPa, we did not observe an altered microbial activity or community composition, whereas comparable studies using deep-sea or sub-Arctic microbial communities with
in situ
temperatures of 4–5°C showed pressure-induced effects at 10–15 MPa. Our results suggest that the psychrophilic nature of the underwater microbial communities in the Arctic may be featured by specific traits that enhance their fitness at increasing hydrostatic pressure.
Regulation of the pleiotropic transcriptional regulator CodY on the conversion of branched-chain amino acids into branched-chain aldehydes in
Lactococcus lactis
Authors: Chen Chen , Huang Zhiyang , Ge Chang , Yu Haiyan , Yuan Haibin , Tian Huaixiang
Published: November 2023

Lactococcus lactis
is a key strain in the production of branched-chain aldehydes that contribute to the nutty flavor in cheese. It has been hypothesized that the conversion of branched-chain amino acids (BCAAs) into branched-chain aldehydes is under the regulation of a global transcriptional regulator, CodY; however, the functions remain unclear. This study aimed to elucidate the regulatory effect of CodY on the key genes for the BCAAs conversion into branched-chain aldehydes in
L. lactis
, namely branched-chain aminotransferase (encoded by
bcaT
) α-keto acid decarboxylase (encoded by
kdc
A) and α-keto acid dehydrogenase (encoded by
pdh
ABCD). The deletion of
codY
was associated with a significant increase in the production of 3-methylbutanal and 2-methylbutanal, indicating the inhibitory effect of CodY on the BCAAs conversion into branched-chain aldehydes. Real-time quantitative reverse transcription-PCR demonstrated the negative regulatory effect of CodY on
bcaT
and
kdc
A, whereas
pdh
ABCD was activated by CodY. Potential CodY binding sites in the promoter regions of
bcaT
,
kdc
A, and
pdh
ABCD were predicted, and four CodY-boxes within the regulatory regions were verified by electrophoretic mobility shift assay and DNase I footprinting assay. The sites located within the promoter of
bcaT
and
kdc
A led to repression by CodY. When one site was located upstream and the other was located within the promoter of
pdh
ABCD, the ultimate effect was activation. Overall, the study revealed that CodY, together with isoleucine, acts as a pleiotropic transcriptional regulator of the conversion of BCAAs into branched-chain aldehydes in
L. lactis
via binding to various regulatory regions of key genes.

IMPORTANCE

Branched-chain aldehydes are the primary compounds that contribute to the nutty flavor in cheddar cheese.
Lactococcus lactis
, which is often applied as primary starter culture, is a significant contributor to the nutty flavor of cheddar cheese due to its ability of conversion of BCAAs into branched-chain aldehydes. In the present study, we found that the regulatory role of CodY is crucial for the conversion. CodY acts as a pleiotropic transcriptional regulator via binding to various regulatory regions of key genes. The results presented valuable knowledge into the role of CodY on the regulation and biosynthetic pathway of branched-chain amino acids and the related aldehydes. Furthermore, it provided new insight for increasing the nutty flavor produced during the manufacture and ripening of cheese.
The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies
Authors: Kikawa Caroline , Cartwright-Acar Catiana H. , Stuart Jackson B. , Contreras Maya , Levoir Lisa M. , Evans Matthew J. , Bloom Jesse D. , Goo Leslie
Published: November 2023

Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.

IMPORTANCE

The wide endemic range of mosquito-vectored flaviviruses—such as Zika virus and dengue virus serotypes 1–4—places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue toward development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies.
Draft genome sequences of
Neurospora crassa
clade B, isolated from burned
Cytisus
sp. plants in France
Authors: Bonometti Lucas , De Bellis Fabien , Cros-Arteil Sandrine , Gueret Elise , Gladieux Pierre
Published: November 2023

Neurospora crassa
clade A is a model system for genetics, biochemistry, molecular biology, and experimental evolution. Here, we present the draft genome sequences of four isolates of
N. crassa
clade B. These data represent a valuable resource to investigate the population biology and evolutionary history of
N. crassa sensu lato
.
Colistin plasma concentrations are not associated with better clinical outcomes in patients with pneumonia caused by extremely drug-resistant
Pseudomonas aeruginosa
Authors: Sorlí Luisa , Luque Sonia , Li Jian , Benítez-Cano Adela , Fernández Xenia , Prim Nuria , Vega Victoria , Gómez-Junyent Joan , López-Montesinos Inmaculada , Gómez-Zorrilla Silvia , Montero M. Milagro , Grau Santiago , Horcajada Juan Pablo
Published: November 2023

The objective of this study was to examine the relationship between colistin plasma concentrations and clinical outcomes in patients with hospital-acquired pneumonia (HAP) caused by extensively drug-resistant
Pseudomonas aeruginosa
(XDR-PA). A prospective observational cohort study was conducted at a tertiary care hospital. Patients diagnosed with HAP caused by XDR-PA between January 2010 and September 2018 were included. Steady-state plasma concentrations (
C
ss,avg
) of colistin were measured by high performance liquid chromatography (HPLC). Based on the pharmacokinetic/pharmacodynamic data of colistin in animal models, previous clinical data, and the minimum inhibitory concentration (MIC) of the most prevalent strain in our center, an area under the ROC curve (AUC)/MIC
24h
between 30 and 60 mg·h/L was considered optimal. The primary outcome was 30-day mortality, and the secondary outcomes were clinical cure and colistin-associated nephrotoxicity. Seventy-five patients were included. The median
C
ss,avg
was 1.1 (0.56–1.75) mg/L and only 23 (30.7%) patients achieved an AUC/MIC
24h
of 30–60 mg·h/L and the 30-day mortality was 30.7%. In multivariate analysis, sequential organ failure assessment score [adjusted hazard ratio (95% confidence interval, CI) 1.19 (1.07–1.32)] and high AUC/MIC
24h
(hazard ratio 1.55, 95% CI 1.17–2.04,
P
= 0.002) were associated with increased risk of death and clinical failure. Based on the maximally selected standardized log-rank statistic, the
C
ss,avg
cutoff point that best predicted mortality was 1.5 mg/L. Nephrotoxicity at the end of treatment was 38.7%. High colistin exposure was not associated with improved clinical outcomes in the setting of HAP caused by XDR-PA. These data suggest that caution is required with intravenous colistin for the treatment of HAP caused by XDR-PA.

IMPORTANCE

In some cases, colistin is the only treatment option for infections caused by the very drug-resistant
Pseudomonas aeruginosa
. However, in the past decade, there have been questions concerning its pharmacokinetics and concentration at the site of infection. In this scenario, its use in a difficult-to-treat infection like pneumonia is currently debatable. This is a clinical pharmacokinetic study of colistin in patients with multidrug-resistant P. aeruginosa pneumonia. Our findings demonstrate that colistin exposure is associated with worse clinical outcomes rather than better clinical outcomes, implying that other therapeutic options should be explored in this clinical setting.
A new measure of exercise adherence: the ATEMPT (Adherence To Exercise for Musculoskeletal Pain Tool)
Authors: Bailey Daniel Leslie , Bishop Annette , McCray Gareth , Foster Nadine E , Holden Melanie A
Published: November 2023

Objectives

This study aimed to (1) develop a new measure of adherence to exercise for musculoskeletal (MSK) pain (Adherence To Exercise for Musculoskeletal Pain Tool: ATEMPT) based on previously conceptualised domains of exercise adherence, (2) report the content and structural validity, internal consistency, test–retest reliability, and measurement error for the ATEMPT outcome measure in patients managed with exercise for MSK pain.

Methods

ATEMPT was created using statements describing adherence generated by patients, physiotherapists and researchers, with content validity established. Baseline and retest questionnaires were distributed to patients recommended exercise for MSK pain in 11 National Health Service physiotherapy clinics. Items demonstrating low response variation were removed and the following measurement properties assessed: structural validity, internal consistency, test–retest reliability and measurement error.

Results

Baseline and retest data were collected from 382 and 112 patients with MSK pain, respectively. Confirmatory factor analysis established that a single factor solution was the best fit according to Bayesian Information Criterion. The 6-item version of the measure (scored 6–30) demonstrated optimal internal consistency (Cronbach’s Alpha 0.86, 95% CI 0.83 to 0.88) with acceptable levels of test–retest reliability (intraclass correlation coefficient 0.84, 95% CI 0.78 to 0.88) and measurement error (smallest detectable change 3.77, 95% CI 3.27 to 4.42) (SE of measurement 2.67, 95% CI 2.31 to 3.16).

Conclusion

The 6-item ATEMPT was developed from the six domains of exercise adherence. It has adequate content and structural validity, internal consistency, test–retest reliability and measurement error in patients with MSK pain, but should undergo additional testing to establish the construct validity and responsiveness.
Correlation between right-to-left shunt and sudden sensorineural hearing loss: protocol for a case–control study
Authors: Zheng Jianrong , Zhan Ying , Cheng Yajing , Liu Cong , Lu Bihua , Yang Weiqiang , Hu Jun
Published: November 2023

Background and purpose

Sudden sensorineural hearing loss (SSNHL) is a neurological and otolaryngological emergency during which rapid diagnosis and early treatment are of great importance. Clinical experience indicates that a considerable number of patients with SSNHL have concurrent right-to-left shunt (RLS). With limited reports, the association between SSNHL and RLS is yet unclear and there is a need for large observational studies to explore their latent relationship.

Methods and analysis

This proposed study is a prospective, observational case–control study. A total of 194 eligible participants matched in age and sex will be divided equally into two groups: 97 patients with SSNHL included in the case group and 97 individuals without SSNHL in the control group. Medical evaluations, including clinical characteristics, laboratory examination, audiological examination and ultrasonography examination, will be performed in all subjects. The primary outcome of the study is the difference in RLS rates between the groups. Differences in patent foramen ovale rates and other measured variables will be further assessed. A conditional logistic regression as a correlation analysis will be used to evaluate the relationship between RLS and SSNHL.

Discussion

This study may provide evidence on the correlation between RLS and SSNHL in order to enrich the aetiology of SSNHL.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee of Peking University Shenzhen Hospital. A written informed consent form will be signed and dated by the participants and the researchers before the study begins. The results will be disseminated in peer-reviewed publications.

Trial registration number

ChiCTR2200064067.
Infographic summaries for clinical practice guidelines: results from user testing of the BMJ Rapid Recommendations in primary care
Authors: Van Bostraeten Pieter , Aertgeerts Bert , Bekkering Geertruida E , Delvaux Nicolas , Dijckmans Charlotte , Ostyn Elise , Soontjens Willem , Matthysen Wout , Haers Anna , Vanheeswyck Matisse , Vandekendelaere Alexander , Van der Auwera Niels , Schenk Noémie , Stahl-Timmins Will , Agoritsas Thomas , Vermandere Mieke
Published: November 2023

Objectives

Infographics have the potential to enhance knowledge translation and implementation of clinical practice guidelines at the point of care. They can provide a synoptic view of recommendations, their rationale and supporting evidence. They should be understandable and easy to use. Little evaluation of these infographics regarding user experience has taken place. We explored general practitioners’ experiences with five selected BMJ Rapid Recommendation infographics suited for primary care.

Methods

An iterative, qualitative user testing design was applied on two consecutive groups of 10 general practitioners for five selected infographics. The physicians used the infographics before clinical encounters and we performed hybrid think-aloud interviews afterwards. 20 interviews were analysed using the Qualitative Analysis Guide of Leuven.

Results

Many clinicians reported that the infographics were simple and rewarding to use, time-efficient and easy to understand. They were perceived as innovative and their knowledge basis as trustworthy and supportive for decision-making. The interactive, expandable format was preferred over a static version as general practitioners focused mainly on the core message. Rapid access through the electronic health record was highly desirable. The main issues were about the use of complex scales and terminology. Understanding terminology related to evidence appraisal as well as the interpretation of statistics and unfamiliar scales remained difficult, despite the infographics.

Conclusions

General practitioners perceive infographics as useful tools for guideline translation and implementation in primary care. They offer information in an enjoyable and user friendly format and are used mainly for rapid, tailored and just in time information retrieval. We recommend future infographic producers to provide information as concise as possible, carefully define the core message and explore ways to enhance the understandability of statistics and difficult concepts related to evidence appraisal.

Trial registration number

MP011977.
Implementing paediatric patient-reported outcome measures in outpatient asthma clinics: a feasibility assessment study
Authors: Bele Sumedh , Paolucci Elizabeth Oddone , Johnson David W , Quan Hude , Santana Maria-Jose
Published: November 2023

Objective

Implementation of patient-reported outcome measures (PROMs) is limited in paediatric routine clinical care. The KidsPRO programme has been codesigned to facilitate the implementation of PROMs in paediatric healthcare settings. Therefore, this study (1) describes the development of innovative KidsPRO programme and (2) reports on the feasibility of implementing PedsQL (Pediatric Quality of Life Inventory) PROM in asthma clinics using the KidsPRO programme.

Design

Feasibility assessment study.

Setting

Outpatient paediatric asthma clinics in the city of Calgary, Canada.

Participants

Five paediatric patients, four family caregivers and three healthcare providers were recruited to pilot the implementation of PedsQL PROM using KidsPRO. Then, a survey was used to assess its feasibility among these study participants.

Main outcome measures

Participants’ understanding of using PROMs, the adequacy of support provided to them, the utility of using PROMs as part of their appointment, and their satisfaction with using PROMs.

Analyses

The quantitative data generated through closed-ended questions was analysed and represented in the form of bar charts for each category of study participants (ie, patients, their family caregivers and healthcare providers). The qualitative data generated through the open-ended questions were content analysed and categorised into themes.

Results

The experience of using PROMs was overwhelmingly positive among patients and their family caregivers, results were mixed among healthcare providers. Qualitative data collected through open-ended questions also complemented the quantitative findings.

Conclusion

The evidence from this study reveals that the implementation of PROMs in routine paediatric clinical care asthma clinics in Alberta is seems to be feasible.
First contact with the health system: a survey study in northern Portugal
Authors: Granja Mónica , Alves Luís , Correia Sofia
Published: November 2023

Objective

The objective of this study is to characterise the self-reported first contact with the health system and the reasons stated for each choice, testing associations with population characteristics.

Design

Cross-sectional survey.

Setting

Primary care department of a local health unit in northern Portugal.

Participants

Random sample of 4286 persons, retrieved from all registered adults.

Outcomes

Participants who stated they usually see the same doctor when a health problem arises were considered to adopt first-contact care and were asked to identify their regular doctor. Participants were asked why they adopt first-contact care or why they choose to do otherwise. Associations between personal characteristics and the adoption of first-contact care were tested using logistic regression.

Results

There were 808 valid questionnaires received (19% response rate). The mean age of respondents was 53 years, 58% were women and 60% had a high school or higher degree. Most (71%) stated always seeing the same doctor when facing a health problem. This was a general practitioner (GP) in 84%. The main reasons were previous knowledge and trust in the doctor. When this doctor was not a GP, the main reason was the need to obtain an appointment quickly. Participants who chose first-contact care were less likely to have university degrees than those who did not (OR 0.31; 95% CI 0.13 to 0.76). Being registered with the same GP for over 1 year increased the odds of adopting first-contact care: twice as likely for those registered for 1–4 years with the same GP (2.07; 95% CI 1.04 to 4.11), and three times more likely for those registered for over 10 years (3.21; 95% CI 1.70 to 6.08).

Conclusions

The high adoption of first-contact care and the reasons given for this suggest a strong belief in primary care in this population. The longer patients experience continuity, the more they adopt first-contact care. The preferences of higher-educated patients regarding first-contact care deserve reflection.
Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis
Authors: Chen Lanlan , Qiu Wei , Sun Xiaodong , Gao Menghan , Zhao Yuexuan , Li Mingyue , Fan Zhongqi , Lv Guoyue
Published: November 2023

Objective

Different serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question.

Design

We prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets’ effects on cholelithiasis, includingHMGCR,NPC1L1,PCSK9,APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARDandPPARG.

Results

We found that serum levels of LDL-C and HDL-C were inversely associated with cholelithiasis risk and such associations were linear. However, the serum level of TC was non-linearly associated with cholelithiasis risk where lower TC was associated with higher risk of cholelithiasis, and the serum TG should be in an inverted ‘U-shaped’ relationship with it. The MR analyses supported that lower TC and higher TG levels were two independent causal risk factors. The drug-target MR analysis suggested thatHMGCRinhibition should reduce the risk of cholelithiasis, which was corroborated by colocalisation analysis.

Conclusion

Lower serum TC can causally increase the risk of cholelithiasis. The cholelithiasis risk would increase with the elevation of serum TG but would decrease when exceeding 2.57 mmol/L. The use ofHMGCRinhibitors should prevent its risk.
Lymphoma triage from H&E using AI for improved clinical management
Authors: Tsakiroglou Anna Maria , Bacon Chris M , Shingleton Daniel , Slavin Gabrielle , Vogiatzis Prokopios , Byers Richard , Carey Christopher , Fergie Martin
Published: November 2023

Aims

In routine diagnosis of lymphoma, initial non-specialist triage is carried out when the sample is biopsied to determine if referral to specialised haematopathology services is needed. This places a heavy burden on pathology services, causes delays and often results in over-referral of benign cases. We aimed to develop an automated triage system using artificial intelligence (AI) to enable more accurate and rapid referral of cases, thereby addressing these issues.

Methods

A retrospective dataset of H&E-stained whole slide images (WSI) of lymph nodes was taken from Newcastle University Hospital (302 cases) and Manchester Royal Infirmary Hospital (339 cases) with approximately equal representation of the 3 most prevalent lymphoma subtypes: follicular lymphoma, diffuse large B-cell and classic Hodgkin’s lymphoma, as well as reactive controls. A subset (80%) of the data was used for training, a further validation subset (10%) for model selection and a final non-overlapping test subset (10%) for clinical evaluation.

Results

AI triage achieved multiclass accuracy of 0.828±0.041 and overall accuracy of 0.932±0.024 when discriminating between reactive and malignant cases. Its ability to detect lymphoma was equivalent to that of two haematopathologists (0.925, 0.950) and higher than a non-specialist pathologist (0.75) repeating the same task. To aid explainability, the AI tool also provides uncertainty estimation and attention heatmaps.

Conclusions

Automated triage using AI holds great promise in contributing to the accurate and timely diagnosis of lymphoma, ultimately benefiting patient care and outcomes.
Hospital space interpreted according to Heidegger’s concepts of care and dwelling
Authors: Park Hye Youn
Published: November 2023

Modern hospitals have succeeded in saving humans from numerous diseases owing to the rapid development of medical technology. However, modern medical science, combined with advanced technology, has developed a strong tendency to view human beings as mere targets of restoration and repair, with modern hospitals characterised as spaces centred on technology-focused treatment. This results in a situation where human beings are reduced to objects and alienated. This study, integrating Heidegger’s concepts ofdwellingandcare,contends that ‘care’ is a vital concept in terms of the fundamental spatiality of hospitals and needs to be restored as the key guiding principle affecting hospital space. The loss of the caring spirit in the development of modern hospitals affects how hospitals are conceived, built and managed, as well as how human experiences within hospitals are dealt with or allowed for appropriately. This study offers critical reflection on how future planning of hospital spaces can be better conducted to ensure that human experiences, and the care needed to appropriately value such experiences, are adequately expressed, and the complexity of human existence is suitably considered.