bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic barrier to resistance: a critical parameter for efficacy of neutralizing monoclonal antibodies against SARS-CoV-2 in a nonhuman primate model
Authors: Stahl-Hennig Christiane , Peter Antonia Sophia , Cordsmeier Arne , Stolte-Leeb Nicole , Vestweber Ramona , Socher Eileen , Merida Samuel Alberto , Sauermann Ulrike , Bleyer Martina , Fraedrich Kirsten , Grunwald Thomas , Winkler Thomas H. , Ensser Armin , Jäck Hans-Martin , Überla Klaus 
Published: June 2024

ABSTRACT

The potency of antibody neutralization in cell culture has been used as the key criterion for selection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for clinical development. As other aspects may also influence the degree of protection
in vivo
, we compared the efficacy of two neutralizing monoclonal antibodies (TRES6 and 4C12) targeting different epitopes of the receptor binding domain (RBD) of SARS-CoV-2 in a prophylactic setting in rhesus monkeys. All four animals treated with TRES6 had reduced viral loads in the upper respiratory tract 2 days after naso-oropharyngeal challenge with the Alpha SARS-CoV-2 variant. Starting 2 days after challenge, mutations conferring resistance to TRES6 were dominant in two of the rhesus monkeys, with both animals failing to maintain reduced viral loads. Consistent with its lower serum neutralization titer at the day of challenge, prophylaxis with 4C12 tended to suppress viral load at day 2 less efficiently than TRES6. However, a week after challenge, mean viral loads in the lower respiratory tract in 4C12-treated animals were lower than in the TRES6 group and no mutations conferring resistance to 4C12 could be detected in viral isolates from nasal or throat swabs. Thus, genetic barrier to resistance seems to be a critical parameter for the efficacy of prophylaxis with monoclonal antibodies against SARS-CoV-2. Furthermore, comparison of antibody concentrations in respiratory secretions to those in serum shows reduced distribution of the 4C12 antibody into respiratory secretions and a delay in the appearance of antibodies in bronchoalveolar lavage fluid compared to their appearance in secretions of the upper respiratory tract.

IMPORTANCE
Monoclonal antibodies are a powerful tool for the prophylaxis and treatment of acute viral infections. Hence, they were one of the first therapeutic agents licensed for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oftentimes, the main criterion for the selection of antibodies for clinical development is their potency of neutralization in cell culture. By comparing two antibodies targeting the Spike protein of SARS-CoV-2, we now observed that the antibody that neutralized SARS-CoV-2 more efficiently in cell culture suppressed viral load in challenged rhesus monkeys to a lesser extent. Extraordinary rapid emergence of mutants of the challenge virus, which had lost their sensitivity to the antibody, was identified as the major reason for the reduced efficacy of the antibody in rhesus monkeys. Therefore, the viral genetic barrier to resistance to antibodies also affects their efficacy.
Broadly protective bispecific antibodies that simultaneously target influenza virus hemagglutinin and neuraminidase
Authors: Ramos Kevin E. , Okba Nisreen M. A. , Tan Jessica , Bandawane Pooja , Meade Philip S. , Loganathan Madhumathi , Francis Benjamin , Shulenin Sergey , Holtsberg Frederick W. , Aman M. Javad , McMahon Meagan , Krammer Florian , Lai Jonathan R. 
Published: June 2024

ABSTRACT

Monoclonal antibodies (mAbs) are an attractive therapeutic platform for the prevention and treatment of influenza virus infection. There are two major glycoproteins on the influenza virion surface: hemagglutinin (HA), which is responsible for viral attachment and entry, and neuraminidase (NA), which mediates viral egress by enzymatically cleaving sialic acid to release budding particles from the host cell surface. Broadly neutralizing antibodies (bNAbs) that target the conserved HA central stalk region, such as CR9114, can inhibit both viral entry and egress. More recently, broadly binding mAbs that engage and inhibit the NA active site, such as 1G01, have been described to prevent viral egress. Here, we engineered bispecific antibodies (bsAbs) that combine the variable domains of CR9114 and 1G01 into a single molecule and evaluated if simultaneous targeting of two different glycoproteins improved antiviral properties
in vitro
and
in vivo
. Several CR9114/1G01 bsAbs were generated with various configurations of the two sets of the variable domains (“bsAb formats”). We found that combinations employing the addition of a single-chain variable fragment in the hinge region of an IgG scaffold had the best properties in terms of expression, stability, and binding. Further characterization of selected bsAbs showed potent neutralizing and egress-inhibiting activity. One such bsAb (“hSC_CR9114_1G01”) provided higher levels of prophylactic protection from mortality and morbidity upon challenge with H1N1 than either of the parental mAbs at low dosing (1 mg/kg). These results highlight the potential use of bsAbs that simultaneously target HA and NA as new influenza immunotherapeutics.

IMPORTANCE
Infection by the influenza virus remains a global health burden. The approaches utilized here to augment the activity of broadly protective influenza virus antibodies may lead to a new class of immunotherapies with enhanced activity.
IL-9 plays a critical role in helminth-induced protection against COVID-19-related cytokine storms
Authors: Xiang ChunXiao , Zhong Gang , Wang Huiqing 
Published: June 2024

ABSTRACT

A recent study published in
mBio
by Cao et al. demonstrated that the helminth
Trichinella sprialis
(Ts) alleviates COVID-19-related cytokine storms in an IL-9-dependent way (Z. Cao, J. Wang, X. Liu, Y. Liu, et al., mBio 15:e00905-24, 2024,
https://doi.org/10.1128/mbio.00905-24
). A cytokine storm is a severe immune response characterized by the overproduction of proinflammatory cytokines, such as TNF-α and IFN-γ, leading to tissue damage and mortality in COVID-19 patients. This study indicated that IL-9 is crucial in protecting against cytokine storm syndromes associated with SARS-CoV-2 infection and proposed that anti-inflammatory molecules from Ts excretory/secretory (TsES) products could be a novel source for treating such illnesses.
Whole-genome sequence of
Mucor velutinosus
NIH1002, a strain associated with disseminated disease
Authors: Conlan Sean , Subramanian Poorani , Plata Barril Beatriz , Youn Jung-Ho , Thomas Pamela J. , Koren Sergey , Dotson Gabrielle A. , Park Morgan , Rhie Arang , Segre Julie A. , Dekker John P. , Zelazny Adrian M. 
Published: June 2024

ABSTRACT

The draft genome of
Mucor velutinosus
NIH1002, a 2011 isolate from a case of disseminated disease, was sequenced using PacBio long-read and HiSeq short-read technologies. The genome has 43 contigs, an N50 of 2.65 Mb, and 13,295 protein-coding genes. It is the most complete
M. velutinosus
genome to date.
Association between semen microbiome disorder and sperm DNA damage
Authors: He Junxian , Ma Menghui , Xu Zhenhan , Guo Jintao , Chen Haicheng , Yang Xing , Chen Peigen , Liu Guihua 
Published: June 2024

ABSTRACT

DNA fragmentation index (DFI), a new biomarker to diagnose male infertility, is closely associated with poor reproductive outcomes. Previous research reported that seminal microbiome correlated with sperm DNA integrity, suggesting that the microbiome may be one of the causes of DNA damage in sperm. However, it has not been elucidated how the microbiota exerts their effects. Here, we used a combination of 16S rRNA sequencing and untargeted metabolomics techniques to investigate the role of microbiota in high sperm DNA fragmentation index (HDFI). We report that increased specific microbial profiles contribute to high sperm DNA fragmentation, thus implicating the seminal microbiome as a new therapeutic target for HDFI patients. Additionally, we found that the amount of
Lactobacillus
species was altered:
Lactobacillus iners
was enriched in HDFI patients, shedding light on the potential influence of
L. iners
on male reproductive health. Finally, we also identified enrichment of the acetyl-CoA fermentation to butanoate II and purine nucleobase degradation I in the high sperm DNA fragmentation samples, suggesting that butanoate may be the target metabolite of sperm DNA damage. These findings provide valuable insights into the complex interplay between microbiota and sperm quality in HDFI patients, laying the foundation for further research and potential clinical interventions.

IMPORTANCE

The DNA fragmentation index (DFI) is a measure of sperm DNA fragmentation. Because high sperm DNA fragmentation index (HDFI) has been strongly associated with adverse reproductive outcomes, this has been linked to the seminal microbiome. Because the number of current treatments for HDFI is limited and most of them have no clear efficacy, it is critical to understand how semen microbiome exerts their effects on sperm DNA. Here, we evaluated the semen microbiome and its metabolites in patients with high and low sperm DNA fragmentation. We found that increased specific microbial profiles contribute to high sperm DNA fragmentation. In particular,
Lactobacillus iners
was uniquely correlated with high sperm DNA fragmentation. Additionally, butanoate may be the target metabolite produced by the microbiome to damage sperm DNA. Our findings support the interaction between semen microbiome and sperm DNA damage and suggest that seminal microbiome should be a new therapeutic target for HDFI patients.
Pros and cons of internal limiting membrane peeling during epiretinal membrane surgery: a randomised clinical trial with microperimetry (PEELING)
Authors: Ducloyer Jean-Baptiste , Eude Yannick , Volteau Christelle , Lebreton Olivier , Bonissent Alexandre , Fossum Paul , Tadayoni Ramin , Creuzot-Garcher Catherine P , Le Mer Yannick , Perol Julien , Fortin June , Jobert Alexandra , Billaud Fanny , Ivan Catherine , Poinas Alexandra , Weber Michel 
Published: June 2024

Background
After idiopathic epiretinal membrane (iERM) removal, it is unclear whether the internal limiting membrane (ILM) should be removed. The objective was to assess if active ILM peeling after iERM removal could induce microscotomas.

Methods
The PEELING study is a national randomised clinical trial. When no spontaneous ILM peeling occurred, patients were randomised either to the ILM peeling or no ILM peeling group. Groups were compared at the month 1 (M1), M6 and M12 visits in terms of microperimetry, best-corrected visual acuity (BCVA) and optical coherence tomography findings. The primary outcome was the difference in microscotoma number between baseline and M6.

Results
213 patients were included, 101 experienced spontaneous ILM peeling and 100 were randomised to the ILM peeling (n=51) or no ILM peeling group (n=49). The difference in microscotoma number between both groups was significant at M1 (3.9 more microscotomas in ILM peeling group, (0.8;7.0) p=0.0155) but not at M6 (2.1 more microscotomas in ILM peeling group (−0.5;4.7) p=0.1155). Only in the no ILM peeling group, the number of microscotomas significantly decreased and the mean retinal sensitivity significantly improved. The ERM recurred in nine patients in the no ILM peeling group (19.6%) versus zero in the ILM peeling group (p=0.0008): two of them underwent revision surgery. There was no difference in mean BCVA and microperimetry between patients experiencing or not a recurrence at M12.

Conclusion
Spontaneous ILM peeling is very common. Active ILM peeling prevents anatomical ERM recurrence but may induce retinal impairments and delay visual recovery.

Trial Registration

NCT02146144
.
Codesigned standardised referral form: simplifying the complexity
Authors: Laing Scott , Jarmain Sarah , Elliott Jacobi , Dang Janet , Gylfadottir Vala , Wierts Kayla , Nair Vineet 
Published: June 2024

BackgroundReferring providers are often critiqued for writing poor-quality referrals. This study characterised clinical referral guidelines and forms to understand which data consultant providers require. These data were then used to codesign an evidence-based, high-quality referral form.MethodsThis study used both observational and quality improvement approaches. Canadian referral guidelines were reviewed and summarised. Referral data fields from 150 randomly selected Ontario referral forms were categorised and counted. The referral guideline summary and referral data were then used by referring providers, consultant providers and administrators to codesign a referral form.ResultsReferral guidelines recommended 42 types of referral data be included in referrals. Referral data were categorised as patient demographics, provider demographics, reason for referral, clinical information and administrative information. The percentage of referral guidelines recommending inclusion of each type of referral data varied from 8% to 77%. Ontario referral forms requested 264 different types of referral data. Digital referral forms requested more referral data types than paper-based referral forms (55.0±10.6 vs 30.5±8.1; 95% CI p<0.01). A codesigned referral form was created across two sessions with 29 and 21 participants in each.DiscussionReferral guidelines lack consistency and specificity, which makes writing high-quality referrals challenging. Digital referral forms tend to request more referral data than paper-based referrals, which creates administrative burdens for referring and consultant providers. We created the first codesigned referral form with referring providers, consultant providers and administrators. We recommend clinical adoption of this form to improve referral quality and minimise administrative burdens.
Screening for adverse social conditions in child healthcare settings: protocol for a systematic review
Authors: Schwenker Rosemarie , Alayli Adrienne , Rasch Lena , Ballmeyer Christian , Maguire Jonathon L , Cohen-Silver Justine , De Bock Freia 
Published: June 2024

IntroductionAdverse social conditions affect children’s development and health outcomes from preconception throughout their life course. Early identification of adverse conditions is essential for early support of children and their families. Healthcare contacts with children provide a unique opportunity to screen for adverse social conditions and to take preventive action to identify and address emerging, potentially harmful or accumulating social problems. The aim of our study is to identify and describe available screening tools in outpatient and inpatient healthcare settings that capture social conditions that may affect children’s development, health or well-being.Methods and analysisWe will conduct a systematic review and will report the results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. A systematic search of three databases (PubMed (Ovid), PsycInfo (EBSCOhost) and Web of Science Core Collection (Clarivate)) for English-language and German-language articles from 2014 to date will be conducted. We will include peer-reviewed articles that develop, describe, test or use an instrument to screen children for multiple social conditions in paediatric clinics or other outpatient or inpatient child healthcare settings. Key study characteristics and information on screening tools will be extracted and presented in structured tables to summarise the available evidence. We will assess the methodological quality of the instruments with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist.Ethics and disseminationEthical approval is not required for this study as we will not be collecting any personal data. Dissemination will consist of publications, presentations, and other knowledge translation activities.
Identifying the needs of people with long COVID: a qualitative study in the UK
Authors: Miller Amy , Song Ning , Sivan Manoj , Chowdhury Rumana , Burke Melanie Rose 
Published: June 2024

ObjectivesTo identify the needs of people with long COVID (LC) in the UK.DesignQualitative study using the Framework Analysis to analyse focus group discussions.Participants25 adults with LC aged 19–76 years including 17 men and 8 women. Average disease duration was 80.1 weeks.SettingEight focus groups were conducted in April 2023 online and in-person at the University of Leeds (UoL), UK. Recruitment routes included advertisement via Leeds Community Healthcare services, the English National Opera Breathe Programme and within the UoL.ResultsThree key themes/needs were identified. (Theme 1) Support systems including community groups, disability benefits, clinical services and employment support should be accessible and tailored to the needs of people with LC. (Theme 2) Research should investigate the physiology of symptoms, new clinical tests and treatment interventions to improve clinical understanding of the condition and symptom management. (Theme 3) Societal awareness should be promoted via local and national initiatives to educate the public about the condition and reduce stigma.ConclusionsParticipants experienced varied and individual challenges to daily life due to LC. There is a need for government acknowledgement of LC as a disability to ensure people with LC have access to disability support and legal protection. Policy development should be patient-driven and acknowledge the individual needs of people with LC in order to improve their quality of life.
Association of social support before ICU admission with postdischarge mental health symptoms in ICU patients: a single-centre prospective cohort study in Japan
Authors: Yoshino Yasuyo , Unoki Takeshi , Hata Kimiko , Ito Kiyoe 
Published: June 2024

ObjectivesMental health problems after discharge from the intensive care unit (ICU) interfere with physical recovery and seriously affect daily life. Social support has been suggested to be associated with mental health but has not been sufficiently characterised. This study aimed to evaluate the association of social support before ICU admission with mental health after ICU discharge.DesignProspective cohort study.SettingMedical–surgical ICU of a hospital in Japan.ParticipantsPatients admitted to the ICU for more than 48 hours were surveyed on social support prior to ICU admission, and 3 months after discharge from the ICU, mental health questionnaires were mailed to the patient.Primary outcome measuresPost-traumatic stress disorder (PTSD)-related symptoms were measured using the Impact of Event Scale-Revised, and anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale.ResultsA total of 153 patients were enrolled; the prevalence of PTSD-related symptoms, anxiety and depressive symptoms 3 months after discharge from the ICU was 11.3%, 14.0% and 24.6%, respectively. Multivariate analysis using linear regression models adjusted for age, sex and years of education for PTSD-related symptoms, anxiety and depressive symptoms revealed that social support (β=−0.018, 95% CI: −0.029 to 0.006, p=0.002) and female sex (β=0.268, 95% CI: 0.005 to 0.531, p=0.046) were independent factors associated with the severity of depressive symptoms. In addition, sex differences were observed in the association between depressive symptoms and social support (p for interaction=0.056).ConclusionsHigher social support before ICU admission was not associated with PTSD symptoms after ICU discharge, although it may be associated with a lower prevalence depressive symptoms after ICU discharge. Therefore, it is important to provide necessary social support when needed.
Assessing the feasibility and acceptability of a diabetes-specific nurse-led multicomponent smoking cessation intervention in diabetes education: study protocol for an open-label pragmatic randomised controlled trial
Authors: Grech Joseph , Norman Ian , Azzopardi Catherine , Grixti Moira , Sammut Roberta 
Published: June 2024

IntroductionSmoking cessation is an essential, but often overlooked aspect of diabetes management. Despite the need for tailored smoking cessation support for individuals with diabetes, evidence of effective interventions for this cohort is limited. Additionally, individuals with diabetes do not easily adopt such interventions, resulting in low uptake and abstinence rates. This protocol describes a study that aims to assess the feasibility and acceptability of a unique smoking cessation intervention, based on the best evidence, theory and the needs of individuals with diabetes, among patients and service providers, the diabetes nurse educators.Methods and analysisThis is an open-label pragmatic randomised controlled trial. Between 80 and 100 individuals with type 1 or type 2 diabetes who smoke will be recruited from the diabetes outpatients at the main acute public hospital in Malta, starting in August 2023. Participants will be randomly assigned (1:1 ratio) to the intervention or control arm for 12 weeks. The experimental intervention will consist of three to four smoking cessation behavioural support sessions based on the 5As (Ask, Advise, Assess, Assist and Arrange) algorithm, and a 6-week supply of nicotine replacement therapy. The control intervention will consist of an active referral to the Maltese National Health Service’s one-to-one smoking cessation support service, which is based on motivational interviewing. The primary feasibility and acceptability outcomes include the recruitment and participation rates, resources used, problems identified by the nurses, the nurses’ perceived challenges and facilitators to implementation and the nurses’ and patients’ acceptability of the study intervention. Data analyses will be descriptive, with quantitative feasibility and acceptability outcomes reported with 95% confidence intervals.Ethics and disseminationEthical clearance was obtained from the Faculty of Health Sciences Research Ethics Committee, University of Malta. The study results will be disseminated through conference presentations and a publication in a peer-reviewed journal.Trial registration numberNCT05920096.