bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractEnhanced 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

Abstract
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

AbstractSquiggle 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

Abstract
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

Abstract
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

AbstractPostherpetic 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

Abstract
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.