bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing staff attitudes to COVID-19 vaccination in care homes in England: a qualitative study
Authors: Friedrich Bettina , Forbes Gillian , Jhass Arnoupe , Lorencatto Fabiana , Shallcross Laura , Antonopoulou Vivi
Published: October 2023

Background

The COVID-19 pandemic disproportionately affected people living and working in UK care homes causing high mortality rates. Vaccinating staff members and residents is considered the most effective intervention to reduce infection and its transmission rates. However, uptake of the first dose of the COVID-19 vaccine in care homes was variable. We sought to investigate factors influencing uptake of COVID-19 vaccination in care home staff to inform strategies to increase vaccination uptake and inform future preparedness.

Methods

Twenty care home staff including managerial and administrative staff, nurses, healthcare practitioners and support staff from nine care homes across England participated in semi-structured telephone interviews (March-June 2021) exploring attitudes towards the COVID-19 vaccine and factors influencing uptake. We used thematic analysis to generate themes which were subsequently deductively mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. The Behavioural Change Wheel (BCW) was used to identify potential intervention strategies to address identified influences.

Results

Enablers to vaccine uptake included the willingness to protect care home residents, staff and family/friends from infection and the belief that vaccination provided a way back to normality (reflective motivation); convenience of vaccination and access to accurate information (physical opportunity); and a supporting social environment around them favouring vaccination (social opportunity). Barriers included fears about side-effects (automatic motivation); a lack of trust due to the quick release of the vaccine (reflective motivation); and feeling pressurised to accept vaccination if mandatory (automatic motivation).

Conclusions

We identified influences on COVID-19 vaccine uptake by care home staff that can inform the implementation of future vaccination programmes. Strategies likely to support uptake include information campaigns and facilitating communication between staff and managers to openly discuss concerns regarding possible vaccination side effects. Freedom of choice played an important role in the decision to be vaccinated suggesting that the decision to mandate vaccination may have unintended behavioural consequences.
Cost minimization analysis of a hexavalent vaccine in Argentina
Authors: Olivera Ignacio , Pérez Carlos Grau , Lazarov Luis , Lopez Eduardo , Oddo Cristian , Dibarboure Hugo
Published: October 2023

Background

Argentina currently uses a pentavalent vaccine containing diphtheria, tetanus, pertussis (whole cell), Haemophilus influenza type b and hepatitis B antigens, administered concomitantly with the inactivated polio vaccine (IPV) (DTwP-Hib-HB plus IPV) in its childhood vaccination schedule. However, hexavalent vaccines containing acellular pertussis antigens (DTaP-Hib-HB-IPV) and providing protection against the same diseases are also licensed, but are only available with a private prescription or for high-risk pre-term infants in the public health program. We analyzed the cost of switching from the current schedule to the alternative schedule with the hexavalent vaccine in Argentina, assuming similar levels of effectiveness.

Methods

The study population was infants ≤ 1 year of age born in Argentina from 2015 to 2019. The analysis considered adverse events, programmatic, logistic, and vaccine costs of both schemes from the societal perspective. The societal costs were disaggregated to summarize costs incurred in the public sector and with vaccination pre-term infants in the public sector. Costs were expressed in 2021 US Dollars (US$).

Results

Although the cost of vaccines with the alternative scheme would be US$39.8 million (M) more than with the current scheme, these additional costs are in large part offset by fewer adverse event-associated costs and lower programmatic costs such that the overall cost of the alternative scheme would only be an additional US$3.6 M from the societal perspective. The additional cost associated with switching to the alternative scheme in the public sector and with the vaccination of pre-term infants in the public sector would be US$2.1 M and US$84,023, respectively.

Conclusions

The switch to an alternative scheme with the hexavalent vaccine in Argentina would result in marginally higher vaccine costs, which are mostly offset by the lower costs associated with improved logistics, fewer separate vaccines, and a reduction in adverse events.
Changing patterns in the burden of paediatric injuries during the COVID-19 pandemic: a study in Mozambique’s central hospitals
Authors: Amado Vanda , Trott Sebastien , Möller Jette , Couto Maria Tereza , Wallis Lee , Laflamme Lucie
Published: October 2023

Introduction

There is a substantial body of knowledge on the effects of the COVID-19 pandemic on injuries showing frequent but inconsistent reductions in both volume and pattern. Yet, studies specifically addressing children are less common, not least from low- and middle-income countries. This study investigated whether changes in the pattern and outcome of paediatric injury admissions to Mozambique’s four regional referral hospitals during 2020.

Methods

Clinical charts of paediatric patients presenting to the targeted hospitals with acute injuries were reviewed using a set of child, injury, and outcome characteristics during each of two consecutive restriction periods in 2020 using as a comparator the same periods in 2019, the year before the pandemic. Differences between 2020 and 2019 proportions for any characteristic were examined using the t-test (significance level 0.05).

Results

During both restriction periods, compared with the previous year, reductions in the number of injuries were noticed in nearly all aspects investigated, albeit more remarkably during the first restriction period, in particular, greater proportions of injuries in the home setting and from burns (7.2% and 11.5% respectively) and a reduced one of discharged patients (by 2.5%).

Conclusion

During the restrictions implemented to contend the pandemic in Mozambique in 2020, although each restriction period saw a drop in the volume of injury admissions at central hospitals, the pattern of child, injury and outcome characteristics did not change much, except for an excess of home and burn injuries in the first, more restrictive period. Whether this reflects the nature of the restrictions only or, rather, other mechanisms that came into play, individual or health systems related, remains to be determined.
ERK mediates interferon gamma-induced melanoma cell death
Authors: Champhekar Ameya , Heymans Rachel , Saco Justin , Turon Font Guillem , Gonzalez Cynthia , Gao Anne , Pham John , Lee June , Maryoung Ryan , Medina Egmidio , Campbell Katie M. , Karin Daniel , Austin David , Damioseaux Robert , Ribas Antoni
Published: October 2023

Background

Interferon-gamma (IFNγ) exerts potent growth inhibitory effects on a wide range of cancer cells through unknown signaling pathways. We pursued complementary screening approaches to characterize the growth inhibition pathway.

Methods

We performed chemical genomics and whole genome targeting CRISPR/Cas9 screens using patient-derived melanoma lines to uncover essential nodes in the IFNγ-mediated growth inhibition pathway. We used transcriptomic profiling to identify cell death pathways activated upon IFNγ exposure. Live imaging experiments coupled with apoptosis assays confirmed the involvement of these pathways in IFNγ-mediated cell death.

Results

We show that IFNγ signaling activated ERK. Blocking ERK activation rescued IFNγ-mediated apoptosis in 17 of 23 (~ 74%) cell lines representing BRAF, NRAS, NF1 mutant, and triple wild type subtypes of cutaneous melanoma. ERK signaling induced a stress response, ultimately leading to apoptosis through the activity of DR5 and NOXA proteins.

Conclusions

Our results provide a new understanding of the IFNγ growth inhibition pathway, which will be crucial in defining mechanisms of immunotherapy response and resistance.
Anakinra and hepatotoxicity in pediatric rheumatology: a case series
Authors: Martins Frederico Rajão , Azevedo André Costa , Ganhão Sara , Aguiar Francisca , Rodrigues Mariana , Brito Iva
Published: October 2023

Background

Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist used in systemic juvenile idiopathic arthritis (sJIA), refractory Kawasaki disease (KD) and cryopyrin-associated autoinflammatory syndrome (CAPS). Anakinra associated hepatotoxicity, while rare, has been described in several cases in daily practice. ​In this case series the authors describe three pediatric patients with this side effect in the setting of severe macrophage activation syndrome (MAS) in KD and sJIA.

Case presentation

The first patient was a 12-year-old boy who presented with fever, maculo-papular exanthema and polyarthralgia. Tonsillitis, distal limb induration and tender cervical lymph nodes were observed. Erythrocyte-sedimentation rate (ESR), C-reactive protein (CRP), ferritin (11,975 ng/mL), D-dimers (5,98 mg/L FEU) and soluble CD25 (3645 pg/mL) levels were elevated. Exclusion of sepsis / toxic shock syndrome warranted introduction of IV methylprednisolone and immunoglobulin (IG IV), with partial response. A MAS secondary to KD was assumed, and anakinra 2 mg/kg/day was introduced. Twenty days later he developed new-onset nausea and severe cyto-cholestasis, normalizing after 2 months of drug discontinuation. Posterior onset of polyarthritis and evanescent lead to a final diagnosis of sJIA. The second patient was a 2-year-old boy with a 10-day history of fevers, generalized rash, hepatosplenomegaly and strawberry tongue. Leucocytosis with neutrophilia and elevated CRP were observed. Initial treatment with IVIG in the setting of incomplete KD was ineffective. Mild anaemia, leukopenia and very high serum ferritin (maximum 26,128 ng/mL) ensued. Presumptive sJIA associated MAS was treated with IV methylprednisolone and anakinra 2 mg/kg/day, with prompt response. Four weeks later transaminitis was detected, and temporary anakinra suspension led to normalisation of laboratorial values. The third case related to a 4-year-old boy presenting with fever, maculopapular rash and cervical lymphadenopathy. CRP and ESR were elevated, and KD was diagnosed. IVIG and methylprednisolone were initiated with clinical worsening, warranting for anakinra introduction at 2 mg/kg/day. After three weeks, liver enzymes progressively elevated, resolving on 2 weeks of anakinra discontinuation.

Conclusions

To the best of our knowledge, this is the first case series describing anakinra associated hepatotoxicity in pediatric patients with rheumatic diseases other than sJIA, bringing additional insight to therapeutic monitoring in patients undergoing this treatment.
‘The current mental health status of children and young people with JIA, and their wider family’: a charity partner collaboration survey
Authors: Livermore Polly , Ainsworth S. , Beesley R. , Douglas S. , Earle E. , Wilson D. , Woolley L. , Clinch J.
Published: October 2023

Background

This paper presents insight into the scale of mental health concerns for families who have a child or young person with a diagnosis of Juvenile Idiopathic Arthritis (JIA) living in any of the four nations of the United Kingdom (UK). The study’s objective is to share the current experiences of those that responded to a charity survey and consider future work to improve mental health support.

Methods

This work was initiated and led by five UK charity partner organisations working with families affected by JIA. Parents/carers of a child or young person with JIA, and young people with JIA, submitted self-completion online questionnaires. The questionnaire asked 19 core questions, with a focus on the mental health impact of having and living with a JIA diagnosis. Questionnaires were delivered via charity partner UK-wide mailing lists and social media.

Results

Questionnaire were completed by 291 participants over a 3-week period in February 2022. The majority of respondents were parents (229, 79%), 103 children had been diagnosed for over six years (35%), and 131 (45%) received shared care between paediatric rheumatology centres. In total, 168 (59%) children and young people with JIA had received, were currently receiving or were waiting for mental health support. Parents reported that their child’s diagnosis impacted their own mental health (218, 82%). Children and young people reported never being offered mental health support during appointments for JIA (157, 54%), and 71 (50%) of these had never received support.

Conclusion

Children and young people with JIA have significant mental health sequelae from their diagnosis. Our findings found that nearly 60% of our respondents have had or are requiring mental health support, with significant numbers of parents/carers reporting difficulties in accessing care for their child’s mental health or their own mental health, due to their child’s diagnosis. This unique collaborative charity-led study, illustrates the importance of timely and accessible mental health support. Further work is needed to understand why best practice guidance for mental health support is not being met consistently and to identify how to embed it into standard rheumatology care.
Safety and effectiveness of oral medium to high dose blonanserin in patients with schizophrenia: subgroup analysis from a prospective, multicenter, post-marketing surveillance study in mainland China
Authors: Yang Yuan , Ge Hongmin , Wang Xijin , Liu Xuejun , Li Keqing , Wang Gang , Yang Xiaodong , Deng Huaili , Sun Meijuan , Zhang Ruiling , Chen Jindong , Cai Duanfang , Sang Hong , Liu Xianglai , Zhan Guilai , Zhao Guijun , Li Haiyun , Xun Zhiyuan
Published: October 2023

Background

Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ).

Methods

A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions.

Results

364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild.

Conclusions

BNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ.

Trial registration number: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered).
Enhanced perioperative care in emergency general surgery: the WSES position paper
Authors: Ceresoli Marco , Braga Marco , Zanini Nicola , Abu-Zidan Fikri M. , Parini Dario , Langer Thomas , Sartelli Massimo , Damaskos Dimitrios , Biffl Walter L. , Amico Francesco , Ansaloni Luca , Balogh Zsolt J. , Bonavina Luigi , Civil Ian , Cicuttin Enrico , Chirica Mircea , Cui Yunfeng , De Simone Belinda , Di Carlo Isidoro , Fette Andreas , Foti Giuseppe , Fogliata Michele , Fraga Gustavo P. , Fugazzola Paola , Galante Joseph M. , Beka Solomon Gurmu , Hecker Andreas , Jeekel Johannes , Kirkpatrick Andrew W. , Koike Kaoru , Leppäniemi Ari , Marzi Ingo , Moore Ernest E. , Picetti Edoardo , Pikoulis Emmanouil , Pisano Michele , Podda Mauro , Sakakushev Boris E. , Shelat Vishal G. , Tan Edward , Tebala Giovanni D. , Velmahos George , Weber Dieter G. , Agnoletti Vanni , Kluger Yoram , Baiocchi Gianluca , Catena Fausto , Coccolini Federico
Published: October 2023

Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients’ outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.
Burden of care and a sense of loneliness in caregivers of children with type 1 diabetes. a cross-sectional study
Authors: Kobos Ewa , Rojkowska Sylwia , Szewczyk Alicja , Dziedzic Beata
Published: October 2023

Background

Treatment of type 1 diabetes is a process involving not only sick children, but also their caregivers.

Aim

To assess the burden of care and sense of loneliness in caregivers of children with type 1 diabetes. Also, an analysis was conducted of the connection between sociodemographic factors characterizing caregivers and the clinical factors characterizing sick children and between the burden of care and the sense of loneliness.

Materials and methods

The study included 125 caregivers of children with type 1 diabetes. In order to collect the research data, the Caregiver Burden Scale and the Revised UCLA Loneliness Scale were used.

Results

In the research group, the total result in the caregiving burden scale was 2.14, which remains within the average burden level. Caregivers showed the highest burden level in the General Strain Subscale. The analysis showed that mothers experience a greater burden of care than fathers in the General Strain Subscale and that caregivers of younger children are more burdened with care within the Isolation and Disappointment Subscales. Moderate high degree of loneliness was shown in 4.8% of caregivers. A higher burden of care for caregivers of children with type 1 diabetes is accompanied by a higher sense of loneliness.

Conclusions

The results of this study may help healthcare professionals plan a holistic, family-centered care program that will take into account factors that increase the burden of care: younger age of the affected child, motherhood, caregiver unemployment, feelings of loneliness, lower education, caregiver unemployment, blood glucose meter measurements, and frequent night-time blood glucose measurements.
Quantum analysis of squiggle data
Authors: Nagy Naya , Stuart-Edwards Matthew , Nagy Marius , Mitchell Liam , Zovoilis Athanasios
Published: October 2023

Squiggle data is the numerical output of DNA and RNA sequencing by the Nanopore next generation sequencing platform. Nanopore sequencing offers expanded applications compared to previous sequencing techniques but produces a large amount of data in the form of current measurements over time. The analysis of these segments of current measurements require more complex and computationally intensive algorithms than previous sequencing technologies. The purpose of this study is to investigate in principle the potential of using quantum computers to speed up Nanopore data analysis. Quantum circuits are designed to extract major features of squiggle current measurements. The circuits are analyzed theoretically in terms of size and performance. Practical experiments on IBM QX show the limitations of the state of the art quantum computer to tackle real life squiggle data problems. Nevertheless, pre-processing of the squiggle data using the inverse wavelet transform, as experimented and analyzed in this paper as well, reduces the dimensionality of the problem in order to fit a reasonable size quantum computer in the hopefully near future.
Granulocytic anaplasmosis in cats from central Europe and molecular characterization of feline Anaplasma phagocytophilum strains by ankA gene, groEL gene and multilocus sequence typing
Authors: Kruppenbacher Anna-Sophia , Müller Elisabeth , Aardema Matthew L. , Schäfer Ingo , von Loewenich Friederike D.
Published: October 2023

Background

Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes. It is transmitted by ticks of the Ixodes ricinus complex and causes febrile illness called granulocytic anaplasmosis primarily in humans, horses, dogs, sheep, cattle and goats. In comparison, clinically apparent disease has been described rarely in cats especially compared to dogs and horses. It is currently unknown whether cats are less susceptible to A. phagocytophilum or whether granulocytic anaplasmosis might be underdiagnosed in cats.

Methods

To address this question, we examined clinical signs and laboratory findings in seven A. phagocytophilum infected cats from Germany and Switzerland. We then genetically characterized feline A. phagocytophilum strains and compared them to those from other hosts showing clinically apparent disease. For this purpose, ankA-based, groEL-based and multilocus sequence typing (MLST) were applied. Furthermore, the concordance between these typing methods was assessed.

Results

Fever, lethargy and anorexia were the most common clinical signs in cats suffering from granulocytic anaplasmosis. The most frequent laboratory finding was thrombocytopenia. All three typing methods consistently indicated that the A. phagocytophilum strains found infecting cats are the same as those that cause disease in humans, dogs and horses. In general, the three typing methods applied exhibited high concordance.

Conclusions

The genetic characterization of the feline A. phagocytophilum strains indicates that strain divergence is not the explanation for the fact that granulocytic anaplasmosis is much less frequently diagnosed in cats than in dogs and horses. Otherwise, it may be possible that cats are less susceptible to the same strains than dogs and horse are. However, due to the unspecific clinical signs, it should be considered that granulocytic anaplasmosis may be under-diagnosed in cats.

Graphical Abstract
Small extrachromosomal circular DNA harboring targeted tumor suppressor gene mutations supports intratumor heterogeneity in mouse liver cancer induced by multiplexed CRISPR/Cas9
Authors: Guo Tao , Chen Guo-Qiao , Li Xu-Fan , Wang Meng , Liu Kun-Ming , Yang Xiao-Ying , Liu Si-Cheng , Feng Yi-Li , Liu Peng-Yuan , Lin Hui , Xie An-Yong
Published: October 2023

Background

Primary liver cancer has significant intratumor genetic heterogeneity (IGH), which drives cancer evolution and prevents effective cancer treatment. CRISPR/Cas9-induced mouse liver cancer models can be used to elucidate how IGH is developed. However, as CRISPR/Cas9 could induce chromothripsis and extrachromosomal DNA in cells in addition to targeted mutations, we wondered whether this effect contributes to the development of IGH in CRISPR/Cas9-induced mouse liver cancer.

Methods

CRISPR/Cas9-based targeted somatic multiplex-mutagenesis was used to target 34 tumor suppressor genes (TSGs) for induction of primary liver tumors in mice. Target site mutations in tumor cells were analyzed and compared between single-cell clones and their subclones, between different time points of cell proliferation, and between parental clones and single-cell clones derived from mouse subcutaneous allografts. Genomic instability and generation of extrachromosomal circular DNA (eccDNA) was explored as a potential mechanism underlying the oscillation of target site mutations in these liver tumor cells.

Results

After efficiently inducing autochthonous liver tumors in mice within 30–60 days, analyses of CRISPR/Cas9-induced tumors and single-cell clones derived from tumor nodules revealed multiplexed and heterogeneous mutations at target sites. Many target sites frequently displayed more than two types of allelic variations with varying frequencies in single-cell clones, indicating increased copy number of these target sites. The types and frequencies of targeted TSG mutations continued to change at some target sites between single-cell clones and their subclones. Even the proliferation of a subclone in cell culture and in mouse subcutaneous graft altered the types and frequencies of targeted TSG mutations in the absence of continuing CRISPR/Cas9 genome editing, indicating a new source outside primary chromosomes for the development of IGH in these liver tumors. Karyotyping of tumor cells revealed genomic instability in these cells manifested by high levels of micronuclei and chromosomal aberrations including chromosomal fragments and chromosomal breaks. Sequencing analysis further demonstrated the generation of eccDNA harboring targeted TSG mutations in these tumor cells.

Conclusions

Small eccDNAs carrying TSG mutations may serve as an important source supporting intratumor heterogeneity and tumor evolution in mouse liver cancer induced by multiplexed CRISPR/Cas9.
Alterations of the gut microbiota in patients with postherpetic neuralgia
Authors: Jiao Bo , Cao Xueqin , Zhang Caixia , Zhang Wencui , Yu Shangchen , Zhang Mi , Zhang Xianwei
Published: October 2023

Postherpetic neuralgia (PHN) is a prevalent, intricate, and intractable form of neuropathic pain. The available evidence indicates that alterations in the gut microbiota are significant environmental determinants in the development of chronic neuropathic pain. Nevertheless, the correlation between the gut microbiota and PHN remains elusive. A cross-sectional study was performed on a cohort of 27 patients diagnosed with PHN and 27 matched healthy controls. Fecal samples were collected and subjected to microbiota analysis using 16S ribosomal RNA gene sequencing. Comparable levels of bacterial richness and diversity were observed in the gut microbiota of PHN patients and healthy controls. A significant difference was observed in 37 genera between the two groups. Furthermore, the LEfSe method revealed that the abundance levels of Escherichia-Shigella, Streptococcus, Ligilactobacillus, and Clostridia_UCG-014_unclassified were elevated in PHN patients, while Eubacterium_hallii_group, Butyricicoccus, Tyzzerella, Dorea, Parasutterella, Romboutsia, Megamonas, and Agathobacter genera were reduced in comparison to healthy controls. Significantly, the discriminant model utilizing the predominant microbiota exhibited efficacy in distinguishing PHN patients from healthy controls, with an area under the curve value of 0.824. Moreover, Spearman correlation analysis demonstrated noteworthy correlations between various gut microbiota and clinical symptoms, including disease course, anxiety state, sleep quality, heat pain, pain intensity, and itching intensity. Gut microbiota dysbiosis exists in PHN patients, microbiome differences could be used to distinguish PHN patients from normal healthy individuals with high sensitivity and specificity, and altered gut microbiota are related to clinical manifestations, suggesting potentially novel prevention and therapeutic directions of PHN.
COVID-19 among undocumented migrants admitted to French intensive care units during the 2020–2021 period: a retrospective nationwide study
Authors: Hraiech Sami , Pauly Vanessa , Orleans Véronica , Auquier Pascal , Azoulay Elie , Roch Antoine , Boyer Laurent , Papazian Laurent
Published: October 2023

Background

Before the Coronavirus Disease 2019 (COVID-19) pandemic in France, undocumented migrants had a higher risk than general population for being admitted to the intensive care unit (ICU) because of acute respiratory failure or severe infection. Specific data concerning the impact of COVID-19 on undocumented migrants in France are lacking. We aimed to analyze the mortality and respiratory severity of COVID-19 in this specific population.

We retrospectively included all undocumented adult migrants admitted in French ICUs from March 2020 through April 2021 using the French nationwide hospital information system (Programme de Médicalisation des Systèmes d’Information). We focused on admissions related to COVID-19. Undocumented migrants were compared to the general population, first in crude analysis, then after matching on age, severity and main comorbidities. The primary outcome was the ICU mortality from COVID-19. Secondary objectives were the incidence of acute respiratory distress syndrome (ARDS), the need for mechanical ventilation (MV), the duration of MV, ICU and hospital stay.

Results

During the study period, the rate of ICU admission among patients hospitalized for COVID-19 was higher for undocumented migrants than for general population (463/1627 (28.5%) vs. 81 813/344 001 (23.8%); p < 0.001). Although ICU mortality was comparable after matching (14.3% for general population vs. 13.3% for undocumented migrants; p = 0.50), the incidence of ARDS was higher among undocumented migrants (odds ratio, confidence interval (OR (CI)) 1.25 (1.06–1.48); p = 0.01). Undocumented migrants needed more frequently invasive MV (OR (CI) 1.2 (1.01–1.42); p = 0.04 than general population. There were no differences between groups concerning duration of MV, ICU and hospital length of stay.

Conclusion

During the first waves of COVID-19 in France, undocumented migrants had a mortality similar to the general population but a higher risk for ICU admission and for developing an ARDS. These results highlight the need for reinforcing prevention and improving primary healthcare access for people in irregular situation.
Evaluation of a prototype machine learning tool to semi-automate data extraction for systematic literature reviews
Authors: Panayi Antonia , Ward Katherine , Benhadji-Schaff Amir , Ibanez-Lopez A Santiago , Xia Andrew , Barzilay Regina
Published: October 2023

Background

Evidence-based medicine requires synthesis of research through rigorous and time-intensive systematic literature reviews (SLRs), with significant resource expenditure for data extraction from scientific publications. Machine learning may enable the timely completion of SLRs and reduce errors by automating data identification and extraction.

Methods

We evaluated the use of machine learning to extract data from publications related to SLRs in oncology (SLR 1) and Fabry disease (SLR 2). SLR 1 predominantly contained interventional studies and SLR 2 observational studies.

Predefined key terms and data were manually annotated to train and test bidirectional encoder representations from transformers (BERT) and bidirectional long-short-term memory machine learning models. Using human annotation as a reference, we assessed the ability of the models to identify biomedical terms of interest (entities) and their relations. We also pretrained BERT on a corpus of 100,000 open access clinical publications and/or enhanced context-dependent entity classification with a conditional random field (CRF) model.

Performance was measured using the F1 score, a metric that combines precision and recall. We defined successful matches as partial overlap of entities of the same type.

Results

For entity recognition, the pretrained BERT+CRF model had the best performance, with an F1 score of 73% in SLR 1 and 70% in SLR 2. Entity types identified with the highest accuracy were metrics for progression-free survival (SLR 1, F1 score 88%) or for patient age (SLR 2, F1 score 82%). Treatment arm dosage was identified less successfully (F1 scores 60% [SLR 1] and 49% [SLR 2]). The best-performing model for relation extraction, pretrained BERT relation classification, exhibited F1 scores higher than 90% in cases with at least 80 relation examples for a pair of related entity types.

Conclusions

The performance of BERT is enhanced by pretraining with biomedical literature and by combining with a CRF model. With refinement, machine learning may assist with manual data extraction for SLRs.
Epigenomic signature of major congenital heart defects in newborns with Down syndrome
Authors: Mouat Julia S. , Li Shaobo , Myint Swe Swe , Laufer Benjamin I. , Lupo Philip J. , Schraw Jeremy M. , Woodhouse John P. , de Smith Adam J. , LaSalle Janine M.
Published: October 2023

Background

Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs.

Methods

We used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the California Biobank Program: (1) 45 DS-CHD (27 female, 18 male) and (2) 41 DS non-CHD (27 female, 14 male). We analyzed global CpG methylation and identified differentially methylated regions (DMRs) in DS-CHD versus DS non-CHD comparisons (both sex-combined and sex-stratified) corrected for sex, age of blood collection, and cell-type proportions. CHD DMRs were analyzed for enrichment in CpG and genic contexts, chromatin states, and histone modifications by genomic coordinates and for gene ontology enrichment by gene mapping. DMRs were also tested in a replication dataset and compared to methylation levels in DS versus typical development (TD) WGBS NDBS samples.

Results

We found global CpG hypomethylation in DS-CHD males compared to DS non-CHD males, which was attributable to elevated levels of nucleated red blood cells and not seen in females. At a regional level, we identified 58, 341, and 3938 CHD-associated DMRs in the Sex Combined, Females Only, and Males Only groups, respectively, and used machine learning algorithms to select 19 Males Only loci that could distinguish CHD from non-CHD. DMRs in all comparisons were enriched for gene exons, CpG islands, and bivalent chromatin and mapped to genes enriched for terms related to cardiac and immune functions. Lastly, a greater percentage of CHD-associated DMRs than background regions were differentially methylated in DS versus TD samples.

Conclusions

A sex-specific signature of DNA methylation was detected in NDBS of DS-CHD compared to DS non-CHD individuals. This supports the hypothesis that epigenetics can reflect the variability of phenotypes in DS, particularly CHDs.
Assessment of the mind-body connection: preliminary psychometric evidence for a new self-report questionnaire
Authors: Van Bael Kristen , Ball Michelle , Scarfo Jessica , Suleyman Emra
Published: October 2023

Objectives

While interoceptive self-report scales provide a foundation for measuring the mind-body connection, they variably consider other important factors that could influence interpretations of internal bodily sensations and perceptions related to mind-body integration. The proposed Body-Mind Connection Questionnaire (BMCQ) aimed to operationalise the notion that this construct involves three major components: (a) Interoceptive Attention, (b) Sensation-Emotion Articulation, and (c) Body-Mind Values.

Methods

Following panel review and piloting with the target population, the developed BMCQ was evaluated in 316 participants (189 identifying as female) aged 18-50 (MAge=30.78), alongside established self-report measures of interoceptive sensibility, body awareness, sensory processing sensitivity, and alexithymia. We examined the BMCQ factor structure through exploratory factor analysis and analysed convergent and discriminant validity.

Results

Exploratory factor analysis supported three scales of the BMCQ, which explained 54.03% of variance. Factor loadings (>0.44) and reliability indices (0.74 to 0.85) were acceptable. Inter-scale correlations suggested that the scales are distinct but related (rs=0.38 to 0.59). BMCQ scales were supported by convergent (r=0.33 to 0.67) and discriminant evidence (rs=0.01 to 0.39, p range n.s. to <.05).

Conclusions

Preliminary psychometric properties indicate that the BMCQ is multidimensional and consists of three constructs that differentially relate to theoretically associated measures. Interoceptive Attention, Sensation-Emotion Articulation, and Body-Mind Values may serve as a basis for efficiently assessing the mind-body connection more holistically, which could be useful for developing interventions aimed at enhancing mind-body integration.
De novo synthesis of nervonic acid and optimization of metabolic regulation by Yarrowia lipolytica
Authors: Zhao Xin-Ru , Chen Xin-Liang , Yang Jing-Lin , Gao Qi , Shi Jiang-Ting , Hua Qiang , Wei Liu-Jing
Published: October 2023

Nervonic acid, a natural fatty acid compound and also a core component of nerve fibers and nerve cells, has been widely used to prevent and treat related diseases of the brain nervous system. At present, fatty acids and their derivatives are mainly obtained by natural extraction or chemical synthesis which are limited by natural resources and production costs. In this study, the de novo synthetic pathway of nervonic acid was constructed in Yarrowia lipolytica by means of synthetic biology, and the yield of nervonic acid was further improved by metabolic engineering and fermentation optimization. Specially, heterologous elongases and desaturases derived from different organism were successfully expressed and evaluated for their potential for the production of nervonic acid in Y. lipolytica. Meanwhile, we overexpressed the genes involved in the lipid metabolism to increase the nervonic acid titer to 111.6 mg/L. In addition, the potential of adding oil as auxiliary carbon sources for nervonic acid production by the engineered Y. lipolytica was analyzed. The results indicated that supplementation with colleseed oil as an auxiliary carbon source can be beneficial for the nervonic acid productivity, which led to the highest concentration of 185.0 mg/L in this work. To summarize, this study describes that the Y. lipolytica can be used as a promising platform for the production of nervonic acid and other very long-chain fatty acids.

Graphical Abstract
Identification of fragmented cranial remains excavated from a site adjoining Ajnala well: a forensic anthropological case report
Authors: Sehrawat J. S. , Rai Niraj
Published: October 2023

Background

Mankind have suffered several unexpected disasters, heinous crimes, and brutalities, resulting into large number of unknown skeletal remains to be identified and repatriated to their relatives.

Case presentation

One such incident of mass killing of 282 Indian-origin soldiers by the colonial rulers in 1857 was reported from Ajnala (India) in early 2014. The damaged cranial fragments belonging to two individuals were retrieved from the vicinity of Ajnala mass-burial site later in 2014. In present study, the retrieved cranial elements were examined forensic anthropologically to assess whether their affinity is akin to the slain Ajnala sepoys or to the deceased who were buried prior to or later than it. The morphological and molecular analyses of these remains affirmed their affiliation to the mutiny sepoys of 1857 killed at Ajnala.

Conclusions

The forensic anthropological and molecular examinations of cranial fragments found that these remains belonged to the individuals killed in the Ajnala incident. The multidisciplinary approach applied for identification of the badly damaged, fragmented, and commingled human remains helped in their presumptive identification.
Aparecium: understanding and detecting scam behaviors on Ethereum via biased random walk
Authors: Yan Chuyi , Zhang Chen , Shen Meng , Li Ning , Liu Jinhao , Qi Yinhao , Lu Zhigang , Liu Yuling
Published: October 2023

Ethereum’s high attention, rich business, certain anonymity, and untraceability have attracted a group of attackers. Cybercrime on it has become increasingly rampant, among which scam behavior is convenient, cryptic, antagonistic and resulting in large economic losses. So we consider the scam behavior on Ethereum and investigate it at the node interaction level. Based on the life cycle and risk identification points we found, we propose an automatic detection model named Aparecium. First, a graph generation method which focus on the scam life cycle is adopted to mitigate the sparsity of the scam behaviors. Second, the life cycle patterns are delicate modeled because of the crypticity and antagonism of Ethereum scam behaviors. Conducting experiments in the wild Ethereum datasets, we prove Aparecium is effective which the precision, recall and F1-score achieve at 0.977, 0.957 and 0.967 respectively.
The role of miRNA-29b1, MMP-2, MMP-9 mRNAs, and proteins in early diagnosis of HCC
Authors: Abdel-Tawab Marwa Sayed , Fouad Hanan , Khalil Doaa Mahmoud , Shaaban Saeed , Nafady Shaymaa , Moawad Hanan Hosni , Mostafa Heba Ahmed , Abdel-Salam Soha Mahmoud , Elazeem Naglaa Adly Abd , Mohamed Alaa A.
Published: October 2023

Background

Hepatocellular carcinoma (HCC) is a common, serious malignancy with a dismal prognosis. As HCC is frequently missed in its early stages, non-invasive early detection is urgently needed. The purpose of this study was to evaluate the possible utility of circulating miRNA-29b1, matrix metalloproteinases (MMPs)-2 and -9 mRNAs, and proteins as diagnostic and predictive biomarkers for HCC.

Subjects and methods

This study included 92 subjects, including 52 patients with HCC at various stages and grades and 40 healthy subjects as controls. RT-PCR was used to detect circulating miRNA-29b1, MMPs-2, and 9 mRNAs, while ELISA was used to detect AFP, MMPs-2, and 9 proteins in the participants’ blood.

Results

When HCC patients were compared to controls, there were significant increases in the levels of MMPs-2, 9 mRNAs, and proteins, and a significant drop in the levels of miRNA-29b1. There were no significant variations in the levels of miRNA-29b1, mRNAs, and MMP-2 and -9 proteins in advanced HCC. There were negative associations between miRNA-29b1 and MMPs-2, 9 mRNAs, and proteins, implying overlapping molecular microRNA-mediated mechanisms that control MMPs that should be investigated further in the future. The levels of miRNA-29b1, MMPs-2, 9 mRNAs, and proteins indicated significant sensitivity and specificity in the early identification of HCC.

Conclusion

MMP-2, 9 mRNAs, and proteins may be employed as diagnostic but not prognostic biomarkers in HCC. miRNA-29b1 may play a protective role in HCC. An overlapping molecular microRNA-29b1-mediated pathway that may control MMPs-2 and 9 requires further experimental investigation in the future.
Stem cell therapy in sensorineural hearing loss: a systematic review
Authors: Mady Ossama Mustafa , Ezzat Waleed Farag , Askoura Anas Mohamed , Elbadawy Gamal Mohamed Gamal
Published: October 2023

Background

Damage to the inner ear or cochlear nerve results in sensorineural hearing loss (SNHL), which is typically persistent deafness. SNHL can range in severity from mild to profound. The shape of the audiogram is used to categorise it as high-frequency hearing loss, low-frequency, flat, peaked, or notched. Pure tone audiometry can be used to diagnose SNHL.

Objective

To summarise the recent updates in the usage of stem cells in sensory neural hearing loss (SNHL).

Methods

Published studies about using stem cell therapy in ENT practice through comprehensive PubMed, EKG, and Google Scholar search (from 2010 to 2022). Including studies in English, experimental studies, and studies that discuss the application of regenerative medicine in SNHL.

Results

Progenitor stem cells may be employed to repair damaged cells and restore sensorineural hearing function, according to 36 of the publications. The majority of these articles—about 90%—discussed animal model-based experimental investigations; the remaining 10% were clinical trials.

Conclusion

The application of stem cells in the treatment of SNHL will be a significant step in the future since it will change the way that patients are now treated in the hopes of regaining their hearing. The application to the clinical setting is still in its early stage, although a number of encouraging researches illustrate how progenitor stem cells differentiate into sensorineural cells.
FRI042 Worsening Shortness Of Breath After A Mild Case Of Covid-19
Authors: Qureshi Khurrum , Krause Terry S , Vidlock Kathryn
Published: October 2023

Disclosure: K. Qureshi: None. T.S. Krause: None. K. Vidlock: None.

This case demonstrates a complication of COVID 19 that may be more common than we know and overlooked. A 34-year-old female presents to the Emergency Department with worsening shortness of breath and tachycardia for 3 days. Her symptoms are worse with ambulation. She feels dizzy and lightheaded. The patient had COVID-19 about two weeks ago and received monoclonal antibodies. The patient has a history of “drenching” night sweats and unintentional weight loss. She denies fever and cough. The patient is eating and drinking normally with no abdominal pain, nausea, or rash. No changes in bowel movements. The patient’s past medical history consists of ADHD, Anxiety, Neuropathy, and Insomnia. The patient takes Adderall, amitriptyline (ELAVIL), fluocinonide (LIDEX). The patient’s family history consists of an aunt who has autoimmune disease and a maternal grandfather who has Non-Hodgkin's Lymphoma. She works as a medical assistant in a family medicine clinic. Patient underwent a CTA which displayed a new anterior mediastinal mass measuring 4.6 x 2.6 x 3.2 cm which was not shown on a previous CT scan 11 months prior. She was referred to a thoracic surgeon for mediastinoscopy, which couldn’t be performed due to location not adjacent to trachea. A PET scan showed mildly FDG-avid soft tissue density in the anterior mediastinum. Four months later, the patient had a CT scan which showed a modest decrease in size measuring 2.1 x 2.5 cm. The thymus is important in maturation of T cells and is replaced with fat through aging. The thymus plays an important immunological role in defending against pathogens and cancer by maturing and releasing T cells. Thymic hyperplasia is a response that has been displayed in autoimmune diseases such as Myasthenia Gravis. Thymic rebound hyperplasia is seen more often in children, typically after chemotherapy treatment but not seen in adults. Rebound hyperplasia occurs less often with viral illness. There have been a limited number of cases seen with COVID-19. An observational study of 87 participants suggested that rebound thymic hyperplasia may be a positive predictive factor due to the benefit of T-cell lymphocyte production. The presence of thymic hyperplasia on CT scan in COVID patients correlated with a better prognosis in a retrospective study of 325 COVID patients that had a CT scan. This patient will require repeated imaging and follow up. The long-term consequences of this finding are unknown and this patient has a history of night sweats which preceded the COVID course.

Presentation: Friday, June 16, 2023