bluuebunny/crossref_metadata_2025 huggingface dataset:
TMPRSS4 is a novel biomarker and correlated with immune infiltration in thyroid carcinoma
Authors: Xu Xiaoqin , Sun Ting , Jing Jiexian
Published: November 2022

Transmembrane protease serine 4 (TMPRSS4) is a cancer-associated protease associated with prognosis in various types of cancer. Mechanistically, TMPRSS4 mainly regulates malignant phenotypes, such as tumor invasion and metastasis, by either the epithelial to mesenchymal transition (EMT) program or promoting the proliferation of cancer cells. To date, TMPRSS4 and immune infiltration in thyroid carcinoma (TC) are largely unknown. Thus, this paper evaluated the expression of TMPRSS4 in tumor tissue through the Tumor Immune Estimation Resource (TIMER) database, and Oncomine, and its correlation with clinical parameters by UALCAN databases. Furthermore, we analyzed its prognostic value from Kaplan-Meier Plotter database, and the relationship between TMPRSS4 and the abundance of tumor-infiltrating lymphocytes (TILs) in TC in TISIDB, screening potential immune targets to explore novel mechanisms for the clinical management of TC. Finally, we assessed the correlation between TMPRSS4 and some immune markers to uncover a potential immune-related biomarker in TC patients by TIMER2.0. The results revealed that TMPRSS4 was highly expressed in TC and was also associated with lymphatic metastasis, advanced stage, histological subtype, and favorable clinical outcome. The stratified analysis based on immune cell content showed that decreased TMPRSS4 had worse prognosis in CD8+ T cell-enriched TC patients. TMPRSS4 was positively correlated with tumor immune infiltration and the expression of gene markers of immune cells. Notably, its expression was lower in the lymphocyte-depleted subtype than in other immunosubtypes in TC. Moreover, TMPRSS4 was closely related to chemokines as well as their receptors and the immunosuppressive checkpoints CTLA-4, PD-1, and HLA-G. In conclusion, TMPRSS4 may act as a novel biomarker predicting prognosis and immune infiltration in TC.
Assessment of reliability and information quality of YouTube videos about root canal treatment after 2016
Authors: Jung Myoung-jun , Seo Min-Seock
Published: November 2022

Background

This study aimed to assess and update the content, reliability, and information quality of content related to root canal treatment (RCTx) on YouTube and evaluate the correlation between each evaluation index.

Methods

YouTube was searched using two terms related to RCTx (“root canal and endodontic treatment”). A total of 240 videos (120 for each search term) were screened. Exclusion criteria were as follows: no sound or visuals, non-English, irrelevant to the search term, longer than 15 min, duplicate, or old (uploaded before 2016). After exclusion, 50 videos of “root canal treatment” and 45 videos of “endodontic treatment” were analyzed. Video length, total number of views, likes, dislikes, comments, and days since upload were recorded using descriptive video data. Viewers’ interaction, reliability and information quality of the video, and quality of video content were measured using nondescriptive video data. The interaction index and video power index were used for viewer interactions, and the modified DISCERN index, JAMA criteria, and Global Quality Score were used to assess the reliability and information quality of the video. The quality of the video content was measured using the completeness score.

Results

The videos of the “root canal treatment” group had a significantly higher completeness score for the etiology and symptoms (p < 0.05), and videos of the “endodontic treatment” group showed a higher interaction index, completeness score for the procedure (p < 0.05). Videos for dentists had significantly higher completeness scores for the procedure, while videos for laypersons had higher completeness scores for etiology, anatomy, symptoms, and prognosis (p < 0.05). Furthermore, the total completeness score and the interaction index of the videos for laypersons were significantly higher (p < 0.05). The videos uploaded by the university had a significantly higher modified DISCERN index (p = 0.044), and the JAMA score was significantly higher in the commercial group (p = 0.001).

Conclusions

Although the accuracy of videos related to RCTx was higher in videos by universities and professionals, the total completeness of YouTube videos was low regardless of the video source. Therefore, professionals should be responsible for providing more accurate and reliable videos.
Assessment of the informed consent process in the provision of dental care in Mulago hospital, Uganda
Authors: Nono David , Mapley Edward , Rwenyonyi Charles Mugisha , Okullo Isaac
Published: November 2022

Background

Informed consent is grounded in the principle of autonomy and represents patients’ right to participate in clinical decisions regarding their treatment. It is equally an ethical and legal requirement in dental care. The dental practitioner must offer appropriate information about all aspects of the treatment and ensure that a patient understands and makes an informed decision. There is limited literature on informed consent for dental care in Uganda. This study assessed patients’ comprehension of the informed consent process and dental practitioners’ practices in obtaining informed consent.

Methods

This was a cross-sectional descriptive study conducted in the Dental Outpatient Department of Mulago Hospital. Two separate questionnaires were employed to collect data from dental patients and dental practitioners, respectively. Data were entered into Epi-data, coded, and imported into STATA 14 for statistical analysis.

Results

Overall, the level of patients’ comprehension of the informed consent process was 91.1%, with 96.3% who felt the dental practitioners satisfactorily explained to them the treatment received and, 65.1% understood very well the information given to them. About 93.5% of the patients confessed that they were given other options of treatment while 98.5% consented before the dental practitioners started treatment.

Most dental practitioners 94.7% followed good clinical practices in obtaining informed consent and 98.7% gave information before initiation of treatment while 85.3% obtained consent from patients before starting any procedures. However, only 5.3% of the dental practitioners obtained written informed consent from patients.

Conclusion

There is a need to devise ways of improving patients’ understanding of the treatment information given to them to support them make better and informed decisions regarding their care. Dental practitioners need to put more emphasis on the use of written consent in dental care because documentation helps in providing accountability and protects dentists from medical litigation in case the patients were to sue them for any treatment-related complications.
“I don’t think people are ready to trust these algorithms at face value”: trust and the use of machine learning algorithms in the diagnosis of rare disease
Authors: Hallowell Nina , Badger Shirlene , Sauerbrei Aurelia , Nellåker Christoffer , Kerasidou Angeliki
Published: November 2022

Background

As the use of AI becomes more pervasive, and computerised systems are used in clinical decision-making, the role of trust in, and the trustworthiness of, AI tools will need to be addressed. Using the case of computational phenotyping to support the diagnosis of rare disease in dysmorphology, this paper explores under what conditions we could place trust in medical AI tools, which employ machine learning.

Methods

Semi-structured qualitative interviews (n = 20) with stakeholders (clinical geneticists, data scientists, bioinformaticians, industry and patient support group spokespersons) who design and/or work with computational phenotyping (CP) systems. The method of constant comparison was used to analyse the interview data.

Results

Interviewees emphasized the importance of establishing trust in the use of CP technology in identifying rare diseases. Trust was formulated in two interrelated ways in these data. First, interviewees talked about the importance of using CP tools within the context of a trust relationship; arguing that patients will need to trust clinicians who use AI tools and that clinicians will need to trust AI developers, if they are to adopt this technology. Second, they described a need to establish trust in the technology itself, or in the knowledge it provides—epistemic trust. Interviewees suggested CP tools used for the diagnosis of rare diseases might be perceived as more trustworthy if the user is able to vouchsafe for the technology’s reliability and accuracy and the person using/developing them is trusted.

Conclusion

This study suggests we need to take deliberate and meticulous steps to design reliable or confidence-worthy AI systems for use in healthcare. In addition, we need to devise reliable or confidence-worthy processes that would give rise to reliable systems; these could take the form of RCTs and/or systems of accountability transparency and responsibility that would signify the epistemic trustworthiness of these tools. words 294.
Italian law n. 219/2017 on consent and advance directives: survey among Ethics Committees on their involvement and possible role
Authors: Porteri Corinna , Ienco Giulia , Turla Edda Mariaelisa , Petrini Carlo , Pasqualetti Patrizio
Published: November 2022

Background

On December 2017 the Italian Parliament approved law n. 219/2017 “Provisions for informed consent and advance directives” regarding challenging legal and bioethical issues related to healthcare decisions and end-of-life choices. The law does not contain an explicit reference to Ethics Committees (ECs), but they could still play a role in implementing the law.

Methods

A questionnaire-based survey was performed among the ECs of the Italian Institute for Research and Care belonging to the Network of neuroscience and neurorehabilitation, with the aim of (1) knowing whether the ECs participated and, if so, how in the process of implementation of law n. 219/2017 in the referring institutes; (2) investigating the point of view of the ECs regarding their possible involvement in the process; (3) exploring the contribution ECs can provide to give effective implementation to the law principles and provisions.

Results

Seventeen ECs out of thirty took part in the survey; the characteristics of the responding and non-responding committees are similar, so the responding ECs can be regarded as representative of all ECs in the Network. Nine ECs did not discuss the law in anyway: the main reason for this is that the referring institutions (6) and the health care professionals (3) did not ask for an EC intervention. Nevertheless, the large majority of the ECs believe that their involvement in the implementation of the law as a whole is appropriate (8) or absolutely appropriate (6), while 3 of them are neutral. No EC believes that the involvement is inappropriate. The aspect of the law on which the 14 ECs converge in considering the EC involvement appropriate/absolutely appropriate is the one related to the health facilities obligation to guarantee the full and proper implementation of the principles of the law.

Conclusions

Our survey confirms that ECs believe they can play a role in the implementation of law n. 219/2017, although this does not entirely correspond to what the committees have actually done in reality. This role could be better exercised by ECs specifically established for clinical practice, which would have a composition, functioning and a mandate better suited to the purpose. This supports the call for a national regulation of ECs for clinical practice.
From nanoparticles to crystals: one-pot programmable biosynthesis of photothermal gold structures and their use for biomedical applications
Authors: Nudelman Roman , Alhmoud Hashim , Delalat Bahman , Kaur Ishdeep , Vitkin Anastasia , Bourgeois Laure , Goldfarb Ilan , Cifuentes-Rius Anna , Voelcker Nicolas H. , Richter Shachar
Published: November 2022

Inspired by nature, green chemistry uses various biomolecules, such as proteins, as reducing agents to synthesize metallic nanostructures. This methodology provides an alternative route to conventional harsh synthetic processes, which include polluting chemicals. Tuning the resulting nanostructure properties, such as their size and shape, is challenging as the exact mechanism involved in their formation is still not well understood. This work reports a well-controlled method to program gold nanostructures' shape, size, and aggregation state using only one protein type, mucin, as a reduction and capping material in a one-pot bio-assisted reaction. Using mucin as a gold reduction template while varying its tertiary structure via the pH of the synthesis, we demonstrate that spherical, coral-shaped, and hexagonal gold crystals can be obtained and that the size can be tuned over three orders of magnitude. This is achieved by leveraging the protein's intrinsic reducing properties and pH-induced conformational changes. The systematic study of the reaction kinetics and growth steps developed here provides an understanding of the mechanism behind this phenomenon. We further show that the prepared gold nanostructures exhibit tunable photothermal properties that can be optimized for various hyperthermia-induced antibacterial applications.
Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia
Authors: Bae Ki Hyun , Lai Fritz , Mong Jamie , Niibori-Nambu Akiko , Chan Kiat Hwa , Her Zhisheng , Osato Motomi , Tan Min-Han , Chen Qingfeng , Kurisawa Motoichi
Published: November 2022

Background

Currently available anti-leukemia drugs have shown limited success in the treatment of acute myeloid leukemia (AML) due to their poor access to bone marrow niche supporting leukemic cell proliferation.

Results

Herein, we report a bone marrow-targetable green tea catechin-based micellar nanocomplex for synergistic AML therapy. The nanocomplex was found to synergistically amplify the anti-leukemic potency of sorafenib via selective disruption of pro-survival mTOR signaling. In vivo biodistribution study demonstrated about 11-fold greater bone marrow accumulation of the nanocomplex compared to free sorafenib. In AML patient-derived xenograft (AML-PDX) mouse model, administration of the nanocomplex effectively eradicated bone marrow-residing leukemic blasts and improved survival rates without noticeable off-target toxicity.

Conclusion

This study may provide insights into the rational design of nanomedicine platforms enabling bone marrow-targeted delivery of therapeutic agents for the treatment of AML and other bone marrow diseases.

Graphical Abstract
Economic evaluation of infliximab, synthetic triple therapy and methotrexate in the treatment of newly diagnosed juvenile idiopathic arthritis
Authors: Tarkiainen Maarit , Tynjälä Pirjo , Vähäsalo Paula , Aalto Kristiina , Kröger Liisa , Rebane Katariina , Lahdenne Pekka , Martikainen Janne
Published: November 2022

Background

Evaluation of costs and short-term cost-effectiveness of infliximab plus methotrexate (IFX + MTX); triple therapy of hydroxychloquine, sulphasalazine, and methotrexate (TRIPLE); or methotrexate monotherapy (MTX) in patients with new-onset polyarticular juvenile idiopathic arthritis (JIA).

Methods

In a prospective multicenter study (ACUTE-JIA), costs and health outcomes of 60 randomized patients with new-onset disease-modifying anti-rheumatic drug (DMARD)-naïve polyarticular JIA were analyzed during the first year. A mapping algorithm was used to obtain utility values from Child Health Assessment Questionnaire (CHAQ). Wallace criteriae were used to assess clinically inactive disease (CID). Linear regression with non-parametric bootstrapping was used to adjust imbalances at baseline.

Results

Using prices for IFX biosimilar, adjusted annual mean (SD) costs of treatment (€) were 21,164 (4158), 12,136 (5286), and 18,300 (8635) on IFX + MTX, TRIPLE, and MTX, respectively. Incremental cost-effectiveness ratio (ICER) for IFX + MTX as compared with TRIPLE or MTX were 3442 € or 678 € per additional month spent in CID. Mean (SD) quality-adjusted life years (QALYs) for IFX + MTX, TRIPLE and MTX were 0.755 (0.065), 0.725 (0.062), and 0.686 (0.124). ICER for IFX + MTX vs TRIPLE was 294,433 €, and for IFX + MTX vs MTX 31,435 € per QALY gained.

Conclusions

In short-term, biosimilar IFX + MTX can be considered cost-effective when compared with MTX alone. TRIPLE was cost-effective when compared with MTX and showed cost advantage when compared with IFX + MTX. Cost per time spent in CID showed similar results than ICER evaluations.

Trial registration

This trial was primarily registered with the Ethical Board of Helsinki District University Hospital (https://www.hus.fi), clinical trial number 211864, and later with ClinicalTrials.gov, number NCT01015547.
Pulmonary manifestations of childhood-onset primary Sjogren’s syndrome (SS) masquerading as reactive airways disease in a male patient and review of interstitial lung disease associated with SS
Authors: Bartholomeo Adam , Aujla Shean , Eklund Meryle , Kerrigan Cheryl , Riemer Ellen , Gilbert Mileka
Published: November 2022

Background

Sjogren’s syndrome (SS) is a rare chronic autoimmune disease involving exocrine glands presenting with sicca syndrome, recurrent parotitis and other extraglandular stigmata. SS is well characterized in the adult population with classification criteria; however, primary SS presenting in childhood is poorly defined and rare in males. Recurrent parotitis is the most common presenting symptom in children with primary SS; however, clinical phenotype in children appears more variable than in adults. The lungs are a common extraglandular location for manifestations of primary SS. However, interstitial lung disease (ILD) is rare in children with primary SS. There are only four published reports of ILD associated with primary SS in female children. Here, we present a very rare case of primary SS in a pediatric male with pulmonary manifestations and review of the literature on ILD in childhood-onset primary SS.

Case presentation

A 14-year-old White male with a history of chronic severe asthma, recurrent parotitis and idiopathic intracranial hypertension was referred to pediatric rheumatology for evaluation of a positive ANA. In early childhood, he was diagnosed with persistent asthma recalcitrant to therapy. At age 8, he developed recurrent episodes of bilateral parotitis despite multiple treatments with sialoendoscopy. At age 14, respiratory symptoms significantly worsened prompting reevaluation. Lab workup was notable for positive ANA and Sjogren’s Syndrome A and B antibodies. Pulmonary function tests showed only a mild obstructive process. Computed tomography of chest was significant for small airway disease, and lung biopsy was positive for mild interstitial lymphocytic inflammation presenting a conflicting picture for ILD. The constellation of findings led to the diagnosis of primary SS with associated pulmonary manifestations. He was treated with hydroxychloroquine, mycophenolate mofetil and oral corticosteroids with resolution of symptoms.

Conclusions

Primary SS is a rare disease in the pediatric population that is poorly characterized. This case is the very rare presentation of childhood-onset primary SS with pulmonary manifestations in a male patient. ILD associated with primary SS is also very rare with only four pediatric patients reported in the literature. Collaborative effort is needed to develop pediatric specific diagnostic and treatment guidelines in this rare condition.
Viral load testing among pregnant women living with HIV in Mutare district of Manicaland province, Zimbabwe
Authors: Musanhu Christine Chiedza Chakanyuka , Takarinda Kudakwashe C. , Shea Jawaya , Chitsike Inam , Eley Brian
Published: November 2022

Background

Viral load (VL) monitoring of pregnant women living with HIV (PWLHIV) and antiretroviral therapy (ART) may contribute to lowering the risk of vertical transmission of HIV. The aims of this study were to assess the uptake of HIV VL testing among PWLHIV at entry to the prevention-of-mother-to-child transmission (PMTCT) services and identify facilitatory factors and barriers to HIV VL access.

Methods

A retrospective, cross-sectional study was conducted at 15 health facilities in Mutare district, Manicaland Province, Zimbabwe from January to December 2018. This analysis was complemented by prospective interviews with PWLHIV and health care providers between October 2019 and March 2020. Quantitative data were analysed using descriptive and inferential statistical methods. Risk factors were evaluated using multivariate logistic regression. Open-ended questions were analysed and recurring and shared experiences and perceptions of PWLHIV and health care providers identified.

Results

Among 383 PWLHIV, enrolled in antenatal care (ANC) and receiving ART, only 121 (31.6%) had a VL sample collected and 106 (88%) received their results.Among these 106 women, 93 (87.7%) had a VL < 1000 copies/mL and 77 (73%) a VL < 50 copies/mL. The overall median duration from ANC booking to VL sample collection was 87 (IQR, 7–215) days. The median time interval for the return of VL results from date of sample collection was 14 days (IQR, 7–30). There was no significant difference when this variable was stratified by time of ART initiation. VL samples were significantly less likely to be collected at local authority compared to government facilities (aOR = 0.28; 95% CI 0.16–0.48). Barriers to VL testing included staff shortages, non-availability of consumables and sub-optimal sample transportation. Turnaround time was prolonged by the manual results feedback system.

Conclusions and recommendation

The low rate of HIV VL testing among PWLHIV in Mutare district is a cause for concern. To reverse this situation, the Ministry of Health should consider interventions such as disseminating antiretroviral guidelines and policies electronically, conducting regular PMTCT mentorship for clinical staff members, and utilising point of care testing and telecommunication devices like mHealth to increase uptake of VL testing and improve results turnaround time.
Application of C2 subfacetal screws for the management of atlantoaxial dislocation in patients with Klippel-Feil syndrome characterized by a narrow C2 pedicle and high-riding vertebral artery
Authors: Hou Zhe , Jian Qiang , Fan Wayne , Zhao Xingang , Wang Yinqian , Fan Tao
Published: November 2022

Objective

This study aims to investigate the clinical application and feasibility of C2 subfacetal screws in patients with Klippel-Feil syndrome (KFS), narrow C2 pedicles, and high-riding vertebral arteries (HRVAs).

Methods

The clinical data of seven patients with KFS, atlantoaxial dislocation, narrow C2 pedicles, and HRVAs treated with C2 subfacetal screws were analyzed in this retrospective study. The internal height, isthmus height, and pedicle width of C2 vertebra were measured using preoperative computed tomography (CT). Subfacetal screws were inserted for 7 patients (12 sides). The position and length of the screws were observed using postoperative CT. Intraoperative dura mater and vertebral artery (VA) injuries were recorded. Bone fusion was observed using follow-up CT.

Results

The internal height was 10.5 ± 3.2 mm, the isthmus height was 3.7 ± 1.8 mm, the pedicle width was 3.0 ± 1.4 mm, and the screw length was 19.7 ± 1.5 mm. All patients had HRVAs and narrow pedicles. No injury to the dura mater and vertebral artery (VA) occurred in this group of patients. Bone fusion was achieved in all patients during follow-up.

Conclusions

In patients with KFS, HRVA, and a narrow C2 pedicle, there is sufficient space below the C2 articular surface for screw insertion. When the pedicle is narrow and the C2 pedicle screw is not suitable for placement due to possible injury to the VA, subfacetal screws are a feasible alternative.
Malaria vector bionomics in Taita-Taveta County, coastal Kenya
Authors: Karisa Jonathan , Ominde Kelly , Muriu Simon , Munyao Vanessa , Mwikali Kioko , Babu Lawrence , Ondieki Zedekiah , Bartilol Brian , Tuwei Mercy , Wanjiku Caroline , Maia Marta , Midega Janet , Rono Martin , Peshu Norbert , Mbogo Charles , Mwangangi Joseph M.
Published: November 2022

Background

Estimation of the composition and densities of mosquito species populations is crucial for monitoring the epidemiology of mosquito-borne diseases and provide information on local vectors to public health officials and policy-makers. The aim of this study was to evaluate malaria vector bionomics in ecologically distinct sites in Taita-Taveta County, Kenya.

Methods

Adult mosquitoes were collected using backpack aspirators and paired indoor/outdoor CDC light traps in 10 randomly selected households in six villages with distinct ecologies over a study period of 3 years. All Anopheles mosquitoes were morphotyped, and sibling species of Anopheles gambiae sensu lato (An. gambiae s.l.) were identified and separated by PCR analysis of extracted ribosomal DNA. All female anophelines were tested for sporozoite infectivity, with engorged females screened for blood-meal sources using the enzyme-linked immunosorbent assay technique. A subsample of those testing positive and those testing negative for Plasmodium in the ELISA were subjected to PCR assay.

Results

A total of eight different Anopheles species were collected both indoors and outdoors. Anopheles gambiae s.l. (82.6%, n = 5252) was the predominant species sensu lato, followed by Anopheles coustani sensu lato (An. coustani s.l.; (10.5%, n = 666) and Anopheles funestus sensu lato (An. funestus s.l.; 5.6%, n = 357). A subset of 683 mosquito samples representing An. gambiae s.l. (n = 580, approx. 11.0%) and An. funestus s.l. (n = 103, approx. 28.9%) were identified by molecular diagnostic assays into sibling species. The An. gambiae s.l. complex was composed of Anopheles arabiensis (62.5%, n = 363/580), An. gambiae sensu stricto (An. gambiae s.s.; 0.7%, n = 4/580), Anopheles merus (0.7%, n = 4/580) and Anopheles quadriannulatus (0.2%, n = 1/580), with the remaining samples (35.5%, n = 206/580) unamplified. Anopheles funestus s.l. was composed of An. rivulorum (14.6%, n = 15/103) and An. leesoni (11.6%, n = 12/103); the remaining samples were unamplified (73.8%, n = 76/103). A total of 981 samples were subjected to PCR analysis for malaria parasite detection; of these 16 (1.6%) were confirmed to be positive for Plasmodium falciparum. The overall human blood index was 0.13 (32/238).

Conclusions

Anopheles gambiae, An. funestus and An. coustani are key malaria vectors in the Taveta region of Kenya, showing concurrent indoor and outdoor transmission. All of the vectors tested showed a higher propensity for bovine and goat blood than for human blood.

Graphical Abstract
Miller–Fisher syndrome after first dose of Oxford/AstraZeneca coronavirus disease 2019 vaccine: a case report
Authors: Pirola Fernanda Junqueira Cesar , Santos Bruno Antônio Müzel , Sapienza Gabriela Feres , Cetrangolo Lucas Yuri , Geranutti Caio Henrique Wthen Gambacorta , de Aguiar Paulo Henrique Pires
Published: November 2022

Introduction

Miller-Fisher Syndrome (MFS) is a variant of Guillain–Barré syndrome (GBS), an acute immune-mediated neuropathy, which manifests as a rapidly evolving areflex motor paralysis. This syndrome presents as a classic triad: ophthalmoplegia, areflexia, and ataxia. MFS is usually benign and self-limited.

Case report

A Caucasian patient was admitted to our hospital with the flu, loss of bilateral strength in the lower limbs and upper limbs and sudden-onset ataxia 7 days after receiving a first dose of the Oxford/AstraZeneca COVID-19 vaccine. On neurological examination, the patient had Glasgow Coma Scale score of 15, with absence of meningeal signs; negative Babinski sign; grade 2 strength in the lower limbs and grade 4 strength in the upper limbs; axial and appendicular cerebellar ataxia; and peripheral facial diparesis predominantly on the right, without conjugate gaze deviation. Cerebrospinal fluid (CSF) was collected on admission, and analysis revealed albuminocytological dissociation with CSF protein of 148.9 mg/dL; leukocytes, 1; chlorine, 122; glucose, 65 mg/mL; red cells, 2; and non-reactive venereal disease research laboratory test result. The COVID-19 IgG/IgM rapid immunological test was negative. Electroneuromyography revealed a recent moderate-grade and primarily sensory and motor demyelinating polyneuropathy with associated proximal motor block.

Discussion and conclusion

Miller-Fisher Syndrome may be related to events other than infections prior to neuropathy, as in the case reported here. The patient presented strong correlations with findings for MFS reported in the literature, such as the clinical condition, the results of electroneuromyography, and results of the CSF analysis typical for MFS. When treatment was provided as proposed in the literature, the disease evolved with improvement. Ultimately, the diagnosis of incomplete MFS was made, including acute ataxic neuropathy (without ophthalmoplegia).
The role of neutrophil extracellular traps in cancer progression, metastasis and therapy
Authors: Chen Yue , Hu Haoyue , Tan Songtao , Dong Qionglan , Fan Xue , Wang Yi , Zhang Huan , He Jun
Published: November 2022

Neutrophil extracellular traps (NETs) released by activated neutrophils typically consist of DNA-histone complexes and granule proteins. NETs were originally identified as a host defense system against foreign pathogens and are strongly associated with autoimmune diseases. However, a novel and predominant role of NETs in cancer is emerging. Increasing evidence has confirmed that many stimuli can facilitate NET formation in an NADPH oxidase (NOX)-dependent/NOX-independent manner. In cancer, NETs have been linked to cancer progression, metastasis, and cancer-associated thrombosis. In this review, we aimed to summarize the current available knowledge regarding NET formation and focused on the role of NETs in cancer biological behaviors. The potential target for cancer therapy will be further discussed.
Development of a risk assessment tool for deep geothermal projects: example of application in the Paris Basin and Upper Rhine graben
Authors: Maury Julie , Hamm Virginie , Loschetter Annick , Le Guenan Thomas
Published: November 2022

This paper presents the development of a tool to perform risk assessment for deep geothermal projects. The tool is aimed at project developers to help them present their project to local authority, decision-makers and financers so they can highlight how they take into account risks and consider mitigation measures to minimize them. The main criteria for this tool are the simplicity of use, the quality of presentation and flexibility. It is based on results from the H2020 GEORISK project that identified risks that apply to geothermal projects and proposed insurance schemes all over Europe. A characteristic of this tool is that it considers all the categories of risks that a project may face, including geological, technical, environmental risks as well as risks related to the social, economic and political contexts. The tool can be customized: selection of risks in a list that can be completed, adaptable rating scheme for risk analysis, possibility to choose the best display for results depending on the user needs. Two case applications are presented, one in the Paris Basin considering a doublet targeting the Upper Trias, a geological layer that presents some technical challenges; and one in the Upper Rhine graben targeting a fault zone, where the risk of induced seismicity must be carefully considered. A posteriori risk assessment highlights the main issues with these types of projects, and the comparison between the two cases emphasizes the flexibility of the tool, as well as, the different ways to present the results depending on the objective of the analyses.
Reliability of the TUDS test for children with cerebral palsy
Authors: Ayed Amr E. , Hanna Silvia , Abdelazeim Faten H.
Published: November 2022

Background

The timed up and down stairs (TUDS) test is widely used to assess the time required by a patient to climb up and down stairs as a measure of functional mobility.

Aim

This cross-sectional study was conducted to examine test-retest, intra-rater, and inter-rater reliability of TUDS test in children with cerebral palsy (CP).

Subjects

Forty children (22 boys and 18 girls) with unilateral and bilateral spastic CP were selected from the Cairo University Hospitals to participate in this study. The age range was 3–9 years. Subjects classified according to Gross Motor Function Classification System-Expanded and Revised (GMFCS-E&R) in categories 1 or 2 only were included. All subjects with muscle tone above normal (spasticity) were included.

Methods

The TUDS test was performed at two testing sessions on the same day to determine test-retest reliability; the main investigator scored all children at real time using a stopwatch and then rescored them later from video recording to determine intra-rater reliability. Another research team member scored all children from video recording to determine inter-rater reliability. Scoring was carried out at real time and from video recordings of the trials. Reliability was estimated using intra-class correlation coefficients (ICC).

Results

The TUDS test showed excellent reliability for all measured types of reliability. ICC score for test-retest reliability was 0.978, ICC score for intra-rater reliability was 0.999, while ICC score for inter-rater reliability was 0.998 and 0.999.

Conclusion

The TUDS test is a reliable outcome measure for children with spastic CP. It can be measured at real time or later from video recording of the performance trials. The TUDS test is an important tool in the re-evaluation process of children with CP.
Risk Management Activities in a Lung Cancer Multidisciplinary Team at a Comprehensive Cancer Center: Results of a Prospective Analysis
Authors: Morabito Alessandro , Mercadante Edoardo , Muto Paolo , Palumbo Giuliano , Manzo Anna , Montanino Agnese , Sandomenico Claudia , Sforza Vincenzo , Costanzo Raffaele , Damiano Simona , La Manna Carmine , Martucci Nicola , La Rocca Antonello , De Luca Giuseppe , Totaro Giuseppe , De Cecio Rossella , Picone Carmine , Piccirillo Maria Carmela , De Feo Gianfranco , Tracey Maura , D'Auria Stefania , Normanno Nicola , Capasso Arturo , Pascarella Giacomo
Published: November 2022

PURPOSE:

The objective of the study was to highlight sources of harm that could negatively affect the lung cancer multidisciplinary team (MDT) activities to reduce the level of risk of each factor.

METHODS:

A modified Delphi approach was used by a board of multi–health care professionals of the lung cancer MDT to identify the main processes, subprocesses, and risk factors of the multidisciplinary pathway of patients with lung cancer. A semiquantitative matrix was built with a five-point scale for probability of harm (likelihood) and severity of harm (consequences) according to the international risk management standards (ISO 31000-2018). The risk level was calculated by multiplying likelihood × consequences. Mitigation strategies have been identified and applied by the MDT to reduce risks to acceptable levels.

RESULTS:

Three main processes (outpatient specialist visit, MDT discussion, and MDT program implementation), eight related subprocesses, and 16 risk factors were identified. Four risk factors (25%) were related to outpatient specialist visit, seven (43.75%) to case discussion, and five (31.25%) to program implementation. Overall, two risk factors were assigned a low-risk level (12.5%), 11 a moderate-risk level (68.75%), one (6.25%) a high-risk level, and two (12.5%) a very high-risk level. After the implementation of mitigation measures, the new semiquantitative risk analysis showed a reduction in almost all hazardous situations: two risk factors (12.5%) were given a very low level, six (37.5%) a low level, seven (43.75%) a moderate level, and one (6.25%) a very high level.

CONCLUSION:

An interdisciplinary risk assessment analysis is applicable to MDT activities by using an ad hoc risk matrix: if the hazard is identified and monitored, the risk could be reduced and managed in a short time.
Efficacy and Safety of Tyrosine Kinase Inhibitors in Patients with Metastatic Pheochromocytomas/Paragangliomas
Authors: Zhou Yue , Cui Yunying , Zhang Dingding , Tong Anli
Published: November 2022

Context

Tyrosine kinase inhibitors (TKIs) can be used to treat locally unresectable or distantly metastatic pheochromocytomas/paragangliomas (PPGLs), such as sunitinib, according to the National Comprehensive Cancer Network guidelines in 2022. However, the precise effect of different TKIs in metastatic PPGLs is still unclear.

Objective

The aim of this meta-analysis is to assess the efficacy and safety of TKIs in metastatic PPGLs.

Methods

The PubMed, Cochrane Library, Scopus, Clinical Trial, and Embase databases were searched by synonyms of 48 TKIs and metastatic PPGLs from inception up to August 2022. Outcomes were tumor response or survival data and the incidence of adverse events (AEs) after treatment. The MIONRS scale and the JBI's tools for case series were used for interventional and observational studies to assess risk of bias, respectively. The combined effects with fixed- or random-effect models, the combined median with the weighted median of medians method and their 95% CIs were reported.

Results

A total of 7 studies with 160 patients were included. Tumor responses in metastatic PPGLs in 5 studies with available data showed the pooled proportion of partial response (PR), stable disease, and disease control rate (DCR) of, respectively, 0.320 (95% CI 0.155-0.486), 0.520 (95% CI 0.409-0.630), and 0.856 (95% CI 0.734-0.979). The combined median progressive-free survival in 6 studies was 8.9 months (95% CI 4.1-13.5) and the proportion of those who discontinued due to AEs in 5 studies was 0.143 (95% CI 0.077-0.209).

Conclusion

This meta-analysis suggests that patients with metastatic PPGLs can benefit from TKI therapy with PR and DCR up to more than 30% and 80%. However, because of restricted studies, larger clinical trials should be performed in the future.
Completion of an Enhanced Recovery Program in a Pediatric Ambulatory Surgery Center: A Quality Improvement Initiative
Authors: Martin Lynn D. , Chiem Jennifer L. , Hansen Elizabeth E. , Low Daniel K. , Reece Kayla , Casey Corrie , Wingate Christina S. , Bezzo Leah K. , Merguerian Paul A. , Parikh Sanjay R. , Susarla Srinivas M. , O’Reilly-Shah Vikas N.
Published: November 2022

BACKGROUND:

Enhanced Recovery After Surgery (ERAS) was first established in 2001 focusing on recovery from complex surgical procedures in adults and recently expanded to ambulatory surgery. The evidence for ERAS in children is limited. In 2018, recognized experts began developing needed pediatric evidence. Center-wide efforts involving all ambulatory surgical patients and procedures have not previously been described.

METHODS:

A comprehensive assessment and gap analysis of ERAS elements in our ambulatory center identified 11 of 19 existing elements. The leadership committed to implementing an Enhanced Recovery Program (ERP) to improve existing elements and close as many remaining gaps as possible. A quality improvement (QI) team was launched to improve 5 existing ERP elements and to introduce 6 new elements (target 17/19 ERP elements). The project plan was broken into 1 preparation phase to collect baseline data and 3 implementation phases to enhance existing and implement new elements. Statistical process control methodology was used. Team countermeasures were based on available evidence. A consensus process was used to resolve disagreement. Monthly meetings were held to share real-time data, gather new feedback, and modify countermeasure plans as needed. The primary outcome measure selected was mean postanesthesia care unit (PACU) length of stay (LOS). Secondary outcomes measures were mean maximum pain score in PACU and patient/family satisfaction scores.

RESULTS:

The team had expanded the pool of active ERP elements from 11 to 16 of 19. The mean PACU LOS demonstrated significant reduction (early in phase 1 and again in phase 3). No change was seen for the mean maximum pain score in PACU or surgical complication rates. Patient/family satisfaction scores were high and sustained throughout the period of study (91.1% ± 5.7%). Patient/family and provider engagement/compliance were high.

CONCLUSIONS:

This QI project demonstrated the feasibility of pediatric ERP in an ambulatory surgical setting. Furthermore, a center-wide approach was shown to be possible. Additional studies are needed to determine the relevance of this project to other institutions.
Age reprogramming: cell rejuvenation by partial reprogramming
Authors: Singh Prim B. , Zhakupova Assem
Published: November 2022

‘Age reprogramming’ refers to the process by which the molecular and cellular pathways of a cell that are subject to age-related decline are rejuvenated without passage through an embryonic stage. This process differs from the rejuvenation observed in differentiated derivatives of induced pluripotent stem cells, which involves passage through an embryonic stage and loss of cellular identity. Accordingly, the study of age reprogramming can provide an understanding of how ageing can be reversed while retaining cellular identity and the specialised function(s) of a cell, which will be of benefit to regenerative medicine. Here, we highlight recent work that has provided a more nuanced understanding of age reprogramming and point to some open questions in the field that might be explored in the future.
Distinct Gag interaction properties of HIV-1 RNA 5′ leader conformers reveal a mechanism for dimeric genome selection
Authors: Yang Xin , Liu Yong , Cui Wen , Liu Mengmeng , Wang Wei
Published: November 2022

During HIV-1 assembly, two copies of viral genomic RNAs (gRNAs) are selectively packaged into new viral particles. This process is mediated by specific interactions between HIV-1 Gag and the packaging signals at the 5′ leader (5′L) of viral gRNA. 5′L is able to adopt different conformations, which promotes either gRNA dimerization and packaging or Gag translation. Dimerization and packaging are coupled. Whether the selective packaging of the gRNA dimer is due to favorable interactions between Gag and 5′L in the packaging conformation is not known. Here, using RNAs mimicking the two 5′L conformers, we show that the 5′L conformation dramatically affects Gag–RNA interactions. Compared to the RNA in the translation conformation (5′LT), the RNA in the packaging conformation (5′LP) can bind more Gag molecules. Gag associates with 5′LPfaster than it binds to 5′LT, whereas Gag dissociates from 5′LPmore slowly. The Gag–5′LPcomplex is more stable at high salt concentrations. The NC–SP2–p6 region of Gag likely accounts for the faster association and slower dissociation kinetics for the Gag–5′LPinteraction and for the higher stability. In summary, our data suggest that conformational changes play an important role in the selection of dimeric genomes, probably by affecting the binding kinetics and stability of the Gag–5′L complex.
Laser-induced chemical liquid-phase deposition of copper on transparent substrates
Authors: Zehnder S. , Schwaller P. , Von Arx U. , Neuenschwander B.
Published: November 2022

Laser-induced chemical liquid phase deposition allows maskless manufacturing of metallic structures on the surface of dielectrics and is prospected to be a promising tool in the field of microelectronics and microfluidics. The aim of the work presented here is to combine this deposition method with a related micro-structuring method known as laser-induced backside wet etching. Fabricating both, microstructured surface structures and subsequent deposition of conducting patterns within the same setup would be an interesting tool for rapid prototyping.To demonstrate the functional principle of this combined approach conductive copper lines were deposited at the backside of both polished and structured soda lime glass substrates by using a focused, scanning ns-pulsed Ytterbium fiber laser at 532nm wavelength. The deposition process is initiated by a photo induced reaction of a CuSO4-based liquid precursor in contact with the backside of the substrate. The obtained metallic copper deposits are crystalline, stable under ambient conditions and have a conductivity in the same order of magnitude as bulk copper.
Microsurgery of Cell Membrane with Femtosecond Laser Pulses for Cell Fusion and Optical Injection
Authors: Ilina I.V. , Ovchinnikov A.V. , Sitnikov D.S. , Chefonov O.V. , Agranat M.B. , Khramova Yu.V. , Semenova M.L.
Published: November 2022

We report on results of using femtosecond laserscalpel for microsurgery of plasma membrane ofliving cells. Femtosecond laser pulses were appliedto initiate cell fusion as well as to performreversible permeabilization of cell membranerequired for efficient injection of extrinsicsubstances into the target cells. Laser-based cellfusion of mammalian embryo blastomeres as wellas fusion of cell bodies of neurons of molluskLymnaea stagnalis were successfully carried out byapplying single femtosecond laser pulses (secondharmonic of a Cr:Forsterite laser system) 620 nm,100 fs with the fluences of 0.42-0.71 J/cm2. It wasshown that the fusion of cells was completed within5-60 minutes depending on the cell type. Successfulpermeabilization of a cell membrane andoptoinjection of a membrane impermeable dye wasperformed with the help of a compact laser systemfor cell microsurgery DissCell-F (ytterbium laser,1050 nm, 75 MHz, ~115 fs). In both cases the laserirradiation parameters were thoroughly optimized toachieve high viability of treated cells and highefficiency of the procedures of cell fusion andoptical injection.
Introduction to Linguistics
Authors: Blinov Aleksandr , Rozhdestvenskiy Yuriy , Marchuk Yuriy , Romashko Sergey
Published: November 2022

The textbook is based on the lecture course "Fundamentals of Linguistics", taught at the Faculty of Philology of Lomonosov Moscow State University. The book introduces students to the system of concepts and terms used by any philological discipline. The purpose of the textbook is to provide theoretical training for students to learn languages and help them master languages practically. The text of the textbook introduces students to the range of problems that are further generalized in the courses "General Linguistics", "Theory of Language", "History of linguistic teachings".
Meets the requirements of the federal state educational standards of higher education of the latest generation.
For students of philological faculties of higher educational institutions studying in the direction of training 45.03.01 "Philology" (bachelor's degree).
Comparing Calculi for First-Order Infinite-Valued Łukasiewicz Logic and First-Order Rational Pavelka Logic
Authors: Gerasimov Alexander S.
Published: November 2022

We consider first-order infinite-valued Łukasiewicz logic and its expansion, first-order rational Pavelka logic RPL∀. From the viewpoint of provability, we compare several Gentzen-type hypersequent calculi for these logics with each other and with Hájek’s Hilbert-type calculi for the same logics. To facilitate comparing previously known calculi for the logics, we define two new analytic calculi for RPL∀ and include them in our comparison. The key part of the comparison is a density elimination proof that introduces no cuts for one of the hypersequent calculi considered.