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Intrathecal synthesis of central nervous system (CNS)-reactive autoantibodies is observed across patients with autoimmune encephalitis (AE), who show multiple residual neurobehavioral deficits and relapses despite immunotherapies. We leveraged two common forms of AE, mediated by leucine-rich glioma inactivated-1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies, as human models to comprehensively reconstruct and profile cerebrospinal fluid (CSF) B cell receptor (BCR) characteristics. We hypothesized that the resultant observations would both inform the observed therapeutic gap and determine the contribution of intrathecal maturation to pathogenic B cell lineages. From the CSF of three patients, 381 cognate-paired IgG BCRs were isolated by cell sorting and scRNA-seq, and 166 expressed as monoclonal antibodies (mAbs). Sixty-two percent of mAbs from singleton BCRs reacted with either LGI1 or CASPR2 and, strikingly, this rose to 100% of cells in clonal groups with ≥4 members. These autoantigen-reactivities were more concentrated within antibody-secreting cells (ASCs) versus B cells (P < 0.0001), and both these cell types were more differentiated than LGI1- and CASPR2-unreactive counterparts. Despite greater differentiation, autoantigen-reactive cells had acquired few mutations intrathecally and showed minimal variation in autoantigen affinities within clonal expansions. Also, limited CSF T cell receptor clonality was observed. In contrast, a comparison of germline-encoded BCRs versus the founder intrathecal clone revealed marked gains in both affinity and mutational distances (P = 0.004 and P < 0.0001, respectively). Taken together, in patients with LGI1 and CASPR2 antibody encephalitis, our results identify CSF as a compartment with a remarkably high frequency of clonally expanded autoantigen-reactive ASCs whose BCR maturity appears dominantly acquired outside the CNS. [ABSTRACT FROM AUTHOR]

A subset S of an integral domain is called a semidomain if the pairs (S, +) and (S∖{0},⋅) are commutative and cancellative semigroups with identities. The multiplication of S extends to the group of differences 풢(S), turning 풢(S) into an integral domain. In this paper, we study the arithmetic of semisubtractive semidomains (i.e. semidomains S for which either s ∈ S or − s ∈ S for every s ∈풢(S)). Specifically, we provide necessary and sufficient conditions for a semisubtractive semidomain to be atomic, to satisfy the ascending chain condition on principals ideals, to be a bounded factorization semidomain, and to be a finite factorization semidomain, which are subsequent relaxations of the property of having unique factorizations. In addition, we present a characterization of factorial and half-factorial semisubtractive semidomains. Throughout the paper, we present examples to provide insight into the arithmetic aspects of semisubtractive semidomains. [ABSTRACT FROM AUTHOR]

Introduction: To report the long‐term oncological and functional outcomes of en bloc TORS lateral oropharyngectomy to address the close/involved margin following diagnostic tonsillectomy in HPV‐related SCC of unknown primary. Material and methods: A single tertiary center observational cohort over a 4‐year period. Primary outcome measures were disease‐specific survival (DSS), overall survival (OS), and PSS NOD (Performance Status Scale‐Normalcy of Diet) scores. Results: TORS specimens did not evidence residual carcinoma in 93% of patients. Of 14 patients, 50% received surgery alone (median follow‐up 57 months; range 46–96), the remainder surgery and adjuvant therapy (median follow‐up of 58 months; range 51–69) with 100% DSS, OS and no deterioration of PSS NOD scores. Conclusions: Long‐term oncological outcomes confirm TORS lateral oropharyngectomy alone is an oncologically safe treatment. Due consideration of this approach is warranted to mitigate against the morbidity of adjuvant radiotherapy treatment in this group of patients. [ABSTRACT FROM AUTHOR]

Background: As of the end of 2019, at least 79.5 million people worldwide have been forced to flee their homes. Those seeking asylum face adversity before, during and after arrival in the UK, resulting in complex health and social needs. The study setting was a nurse-led asylum seeker service in a dispersal city, commissioned to provide an initial health assessment, immunisations and support to register with a general practitioner. Aims: The aim was to quantify the health needs of migrants in vulnerable circumstances registered with a nurse-led primary care service by clinical audit. Methods: In June 2018, 80 electronic records were reviewed by seven auditors to analyse documentation of demographics, asylum status, service use, barriers to care, physical and mental health. Results: Where data were available, 86% migrated due to persecution or trafficking, 59% had a chronic physical illness, 51% had a mental health condition and 49% experienced barriers to accessing a mainstream general practitioner. Conclusions: Although a small sample, this survey demonstrated high physical and mental health needs that are often unmet in mainstream services. There was a high level of unknown need, for example of torture rates. These findings informed quality improvement in documentation and health assessments, and further research. [ABSTRACT FROM AUTHOR]

This correction notice updates the list of authors for an article in Nature Communications about brain injury in COVID-19 patients. The article discusses how brain injury can persist in these patients despite reduced immune responses. The document is a list of authors who have contributed to a report on the neurological and neuropsychiatric complications of COVID-19. The report covers a wide range of topics and includes diverse perspectives to ensure a comprehensive understanding of the effects of the virus on the nervous system. [Extracted from the article]

Objectives: To analyse the oncological outcomes following primary Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). Design: Observational case series. Setting: Tertiary centre; first TORS practice to commence in the UK. Participants: All consecutive patients undergoing primary TORS with curative intent, with or without adjuvant treatment. Main outcome measures: Descriptive analysis of patient and tumour pathology variables. Survival outcomes: Overall, Disease‐Specific, Progression‐Free and Locoregional control. Results: The cohort comprised of 120 patients undergoing TORS with minimum 12‐month follow‐up data and the following characteristics: mean age 58 years, 91 males (76%), 78 tonsil (65%) and 34 base of tongue primaries (28%), 89% HPV‐related OPSCC. The surgical pathology revealed 14 (12%) with positive margins, 19 (16%) had close margins <2mm and 31% with extranodal extension. The treatment was as follows: 39 (33%) treated with TORS alone, 50 (42%) received adjuvant radiotherapy and 31 (26%) received adjuvant radiotherapy with chemotherapy. There were 15 recurrences. Estimated survival for all patients at 3 years (95% CI): overall 85% (78‐92), disease‐specific 90% (85‐96), progression‐free 86% (79‐92) and locoregional control 90% (84‐96). The equivalent survival figures for the HPV‐related cases alone were as follows: overall 88% (82‐94), disease‐specific 93% (87‐98), progression‐free 88% (81‐95) and locoregional control 92% (87‐98). Conclusions: Whilst TORS has become a common practice in the management of OPSCC in the UK, these are the first reported oncological outcomes. For selected patients, TORS with or without adjuvant therapy is an appropriate treatment modality. [ABSTRACT FROM AUTHOR]

The purpose of this observational study was to assess the impact of COVID-19 on the presentation, stage and management pattern on newly presented HNC patients during the pandemic era. The data on all newly diagnosed HNC patients at our centre during April-December 2020 (COVID-19 cohort) were collected, and it was compared against the baseline pre-COVID-19 cohort (all new HNC patients diagnosed between April and December 2019). During the COVID-19 pandemic, it was postulated that there might be a delay in cancer patients' presentation, stage migration and changes in management leading to excess cancer mortality.1 However, there is a paucity of real-time objective data to support this, particularly in HNC. [Extracted from the article]

The article focuses on why maintaining and protecting teaching professionalism is integral to effective teacher development. Topics discussed include continuing professional development (CPD) is a crucial part of any educator's life in the Grate Britain; and understood as practices to develop a teacher's expertise and professional standards beyond their initial education, with a focus on improving the quality of teaching and learning (DfE, 2016).

An adaptive immune response in less than 1% of people who develop cancer produces antibodies against neuronal proteins. These antibodies can be associated with paraneoplastic syndromes, and their accurate detection should instigate a search for a specific cancer. Over the years, multiple systems, from indirect immunofluorescence to live cell-based assays, have been developed to identify these antibodies. As the specific antigens were identified, high throughput, multi-antigen substrates such as line blots and ELISAs were developed for clinical laboratories. However, the evolution of assays required to identify antibodies to membrane targets has shone a light on the importance of antigen conformation for antibody detection. This chapter discusses the early antibody assays used to detect antibodies to nuclear and cytosolic targets and how new approaches are required to detect antibodies to membrane targets. The chapter presents recent data that support international recommendations against the sole use of line blots for antibody detection and highlights a new antigen-specific approach that appears promising for the detection of submembrane targets., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction Sexually transmitted infections (STIs) are frequently tested for and treated in the emergency department (ED). Age, race, and number of sexual partners are known risk factors for STIs. The objective of the current study was to examine marital status as it relates to testing and treating for STIs in the ED. Methods A database of 75,000 ED patient encounters from a single healthcare system in northeast Ohio between April 18, 2014, and March 7, 2017, was examined. All patients in the dataset underwent a urinalysis and urine culture or received STI testing in the ED. We performed Chi-square and multivariable regression analysis to examine the relationships between the patient's marital status and testing and treatment for STIs performed in the ED. Results There were 20,965 patient encounters where STI testing was performed and was analyzed. Patients were 9.1% (N=1,912) married, 86.6% (N=18,149) single, 4.0% (N=837) were neither married nor single, and 0.3% (N=67) with an unknown marital status. There were 7.1% (19/267) and 4.9% (12/267) of tested married men who were infected with gonorrhea and chlamydia, respectively, whereas only 0.4% (6/1,583) and 2.2% (35/1,588) of tested married women were infected with gonorrhea and chlamydia, respectively. Single men and women were both significantly more likely to have a positive test for gonorrhea and chlamydia compared to married men and women, respectively (P<0.001). Married men and women, compared to single men and women, respectively, were more likely to be given antibiotics for gonorrhea and chlamydia in the ED when the infection was present and not be given antibiotics for the infections when testing was negative (P<0.001). Single women (9.1%; 1,291/14,258) were more likely than married women (4.9%; 75/1,534) to have a positive test for trichomonas, but there were no significant differences between married (1.0%; 1/100) and single men (0.7%; 6/893). Conclusion Even when accounting for age and race, marital status can help predict infection with gonorrhea and chlamydia in the ED. The marital status could be considered by clinicians when risk stratifying patients regarding testing and treating for the diseases in the ED. Gonorrhea and chlamydia are much more common in single men and women and much less common in married persons. However, married men tested for gonorrhea and chlamydia were more than twice as likely to test positive for infection than married women. Married men and women were both more likely to be appropriately treated with antibiotics for gonorrhea and chlamydia in the ED (i.e., testing negative for infection and not receiving antibiotics or testing positive and receiving antibiotics) compared to non-married men and women. While trichomonas was more common in single women than married women, the infection was less common in men, and both married men and single men had similar rates of testing positive for the infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Fox et al.)