bluuebunny/crossref_metadata_2025_split huggingface dataset:
A-55 Neuropsychological Findings Associated with Progressive Lesion Development in Cerebral Cavernous Malformation Secondary to PDCD10 Mutation
Authors: Phillips Matthew , Wisinger Amanda , Fink Joseph 
Published: August 2021

Abstract

Objective
A rare mutation in the PDCD10 gene causes cerebral cavernous malformations, which can result in multiple brain hemorrhages and hundreds of lesions. Up to 50% of individuals with the PDCD10 mutation remain symptom-free throughout their lives; however, others can suffer from seizures or focal neurologic deficits. Participant: A 67-year-old Caucasian male presented for a neuropsychological re-evaluation (2020) following a progressive decline in his memory and attention dating back 20 years. A baseline neuropsychological evaluation was obtained 7 years ago. Relevant medical history included a 5 mm left falcine meningioma, epilepsy, obstructive sleep apnea, hypertension, and type II diabetes. Neuroimaging revealed over 250 scattered lesions that had advanced over the past 7 years, particularly in the paramedian pontine reticular formation, left inferior cerebellum, and right middle frontal gyrus.

Results
His neurocognitive profile was marked by mild impairments in immediate verbal memory. The remainder of his cognitive profile was average. Compared to his 2013 evaluation, he showed only a minimal decline in verbal memory, but he showed slight improvements in the domains of executive functioning, visuospatial abilities, and language.

Conclusion
Despite the marked progression of lesions documented on current neuroimaging, aside from immediate verbal memory problems the patient’s neurocognitive functioning was relatively well-preserved. He even exhibited minor improvements within several domains. Given the patient’s current neurocognitive status, this case illustrates the importance of comprehensive neuropsychological testing in cases that would appear more severe based on neuroimaging data alone. Relatedly, progression of neuropathological disease burden on neuroimaging is not necessarily accompanied by consistent progression of neuropsychological dysfunction.
A-58 Unusual Presentation of Anti-NMDAR Encephalitis in a Young Adult Male: A Case Study
Authors: Smetana Racheal , Broshek Donna 
Published: August 2021

Abstract

Objective
To illustrate an unusual presentation of anti-n-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis in a young adult male. Anti-NMDAR encephalitis is an autoimmune-mediated disorder with psychiatric and neurological features that can have lasting impact on cognition. Unique presentation, diagnosis, and assessment are presented.

Method
Patient is a 28-year-old, Caucasian male with a history of bipolar disorder. Initial hospital presentation was characterized by headache, tremor, and acute altered mental status. Imaging revealed chronic meningitis with diffuse leptomeningeal enhancement/multiple cranial nerve enhancement, hydrocephalus, and Chiari I malformation. He underwent external ventricular drain (EVD) placement and was discharged upon stabilization. He presented 1 month later with symptom recurrence and interval development of hydrocephalus. CSF studies were positive for NMDAR antibody. He was treated with immunotherapy. His 3-month long hospitalization was complicated by acute respiratory failure and intracerebral and intraventricular hemorrhages. He was discharged to 1 month of inpatient rehabilitation.

Results
Neuropsychological assessment was completed 4 months following discharge from rehabilitation. Visual deficits due to grade 1 papilledema complicated testing. Results revealed frontal deficits (focused attention, processing, and executive functions), with intact verbal learning/memory. This deviates from previous literature that specify verbal memory dysfunction as a core long-term outcome of anti-NMDAR encephalitis.

Conclusions
This case highlights an unusual presentation and neuropsychological assessment of anti-NMDAR encephalitis. Rare presentations of anti-NMDAR encephalitis can preclude clinical diagnosis and compromise long-term cognitive outcomes if not rapidly and effectively treated. Additionally, mood symptoms may have been early manifestation of the patient’s disease process. Despite acute complications, he demonstrated remarkable functional and cognitive recovery.
A-61 Predictors of Subjective and Objective Everyday Functioning in Middle-Aged and Older Adults with HIV
Authors: Jacob Alexandra E , Crowe Michael , Fazeli Pariya L , Vance David E 
Published: August 2021

Abstract

Objective
Older adults with HIV are at increased risk for difficulties with instrumental activities of daily living (IADLs). Awareness of their functional capacity has emerged as an important area for research, but it is not well studied in PWH. The purpose of this study is: (1) to identify factors associated with subjective and objective IADL difficulty in PWH and (2) to identify factors associated with under- or over-reporting of IADL difficulties.

Methods
This cross-sectional study included 261 adults with HIV. Participants completed a neuropsychological battery, self-report and performance-based measures of IADLs. Self-report measures included the Patient’s Assessment of Own Functioning Inventory (PAOFI) and the Lawton and Brody IADL Questionnaire. The Timed Instrumental Activities of Daily Living (TIADL) task was used as an objective measure. Hierarchical multiple regressions were performed to identify factors associated with subjective and objective assessment of everyday functioning as well as factors associated with discrepancy between self-report and actual performance of IADLS.

Results
On the PAOFI, higher depression (p = 0.001), lower conscientiousness (p &gt; 0.001), and better processing speed (p = 0.017) predicted worse functioning. On the Lawton and Brody, higher depression (p = 0.049) predicted of worse functioning. On the TIADL, older age (p = 0.1), lower WRAT-4 score (p &gt; 0.001), worse processing speed (p &gt; 0.001), and worse motor function (p = 0.1) were associated with worse performance. Processing speed predicted discrepancy between subjective and objective performance of IADLs (p = 0.1).

Conclusions
Several demographic, cognitive, and personality variables are associated with worse subjective and objective everyday functioning, as well as an individual’s ability to accurately self-appraise their functional capacity.
A-64 Neuropsychological Assessment in Bilateral Perisylvian Polymicrogyria: A Tool for Data-Driven Intervention
Authors: Grow Melissa , Culotta Stephanie 
Published: August 2021

Abstract

Objective
This case study examined neurocognitive features associated with a rare genetic/neurological disorder impacting the cerebral cortex. Bilateral perisylvian polymicrogyria (BPP) is characterized by abnormal embryonic growth affecting both sides of the brain near the Sylvian fissure. BPP occurs randomly though researchers suspect an underlying genetic abnormality that may have autosomal recessive inheritance. Neurodevelopmental manifestations include neurocognition marked by EEG abnormalities, impaired motor function, and deficits in speech articulation, language development, learning and memory, and adaptive skills.

Method
A 13-year 7-month-old male with BPP, detected at 24 months by MRI, was seen for neuropsychological assessment to guide habilitative, academic and adaptive interventions. Relevant medical history includes stimulant medication and pharyngeal flap surgery. Parental concerns include the provision of appropriate special education services and withdrawal behaviors.

Results
Assessment revealed a complex neuropsychological profile characterized by nonverbal versus verbal intellectual strengths, receptive-expressive language impairment, underlying deficits in phonemic awareness, diminished fine motor speed, and diminished verbal fluency. Verbal list learning, semantic memory, and attention were intact. Mild elevations were evident for anxiety symptoms.

Conclusion
BPP, a rare genetic disorder, represents significant challenges for affected children. In this case study, a 13-year 7-month-old youngster’s assessment revealed underlying neurocognitive and neuromotor deficits most pronounced in aspects of language, speech articulation, select domains of executive functioning and academic skills. Areas of strength, including verbal memory and semantic recall, were indicated and merit consideration in developing appropriate interventions. This case study illustrates the value of neuropsychological assessment in guiding therapeutic interventions, pharmacotherapy, and appropriate educational services in this rare neurological disorder.
A-69 Baseline Predictors of Longitudinal SDMT Performance in Individuals with Multiple Sclerosis
Authors: Cadden Margaret , Barker Lindsay , Healy Brian , Chitnis Tanuja , Weiner Howard , Glanz Bonnie 
Published: August 2021

Abstract

Objective
More than half of persons with MS (PwMS) experience cognitive difficulties during the course of their illness. However, not everyone develops cognitive problems suggesting a role for important moderating factors. The object of the current study was to identify baseline predictors of cognitive trajectories in PwMS.

Methods
680 PwMS completed the Symbol Digit Modalities Test (SDMT) and a battery of patient-reported outcome (PRO) measures as part their participation in The Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB). Each participant had at least 2 SDMT measurements as well as demographic (age, sex), clinical (EDSS, disease duration, course type), and PRO (fatigue, depression, and quality of life) data. Participants had a concurrent brain MRI scan at the time of the baseline SDMT measurement; intracranial cavity (ICC) was calculated for each participant as a proxy of brain reserve. The association between each baseline measure and the longitudinal change in the SDMT over the course of the follow-up period was calculated using a linear mixed effects model.

Results
Increased baseline age (95% CI: −0.29, −0.06; p = 0.002), increased baseline EDSS (95% CI: −0.24, −0.01; p = 0.037), and decreased baseline ICC (95% CI: 0.02, 0.25; p = 0.023) were each associated with a greater decline in the SDMT score longitudinally. Although most PRO measures were cross-sectionally correlated with SDMT performance, none were associated with longitudinal change.

Discussion
Older individuals and those with more clinical disability are likely to experience declines in SDMT performance over time. Individuals with high baseline brain reserve tend to have more favorable SDMT trajectories.
A-71 Subjective Employment Concerns: Correlates and Impact on Employment Status One Year Later in Women with Multiple Sclerosis
Authors: Cohen Jenna N , Stimmel Marnina , Foley Frederick 
Published: August 2021

Abstract

Objective
Loss of employment is common in multiple sclerosis (MS) and is associated with fatigue, depression, and cognitive dysfunction. This study looked at a “low-risk” group of women, with subclinical levels of these factors, to evaluate whether subjective concerns about employment would relate to decreased employment status over time. Secondarily, fatigue, depressive symptoms, and cognition were also examined in relation to employment concerns at baseline, to determine whether subjective concerns might indicate prodromal psychiatric and cognitive dysfunction.

Methods
Our sample includes 52 employed women with MS who participated in a larger quasi-experimental employment study. Screening included open-ended questions about employment concerns and measures of fatigue (Fatigue Severity Scale), depression (Patient Health Questionnaire), and cognitive functioning (Symbol-Digit Modalities Test). Because this subset of women were considered “low-risk,” they were followed over time (1 year) with no active intervention.

Results
Overall, 16/52 women (44%) voiced employment concerns. A chi-square analysis revealed that 5 (31.3%) of those women had decreased employment status at one year, while only 3 (8.3%) women without employment concerns had decreased employment status (p = 0.049, Fisher’s exact). Comparison of women with and without employment concerns (independent t-tests), indicated that those with concerns had higher depressive symptoms (p = 0.017); groups did not differ in cognitive functioning or fatigue at baseline.

Conclusions
Findings suggest that women with MS who were previously thought to be “low-risk” may still experience negative functional outcomes such as decreased employment status, when they voice subjective employment concerns. Employment concerns may also indicate prodromal depressive symptoms.
Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization
Authors: Balbach Melanie , Ghanem Lubna , Rossetti Thomas , Kaur Navpreet , Ritagliati Carla , Ferreira Jacob , Krapf Dario , Puga Molina Lis C , Santi Celia Maria , Hansen Jan Niklas , Wachten Dagmar , Fushimi Makoto , Meinke Peter T , Buck Jochen , Levin Lonny R 
Published: August 2021

Abstract
Soluble adenylyl cyclase (sAC: ADCY10) has been genetically confirmed to be essential for male fertility in mice and humans. In mice, ex vivo studies of dormant, caudal epididymal sperm demonstrated that sAC is required for initiating capacitation and activating motility. We now use an improved sAC inhibitor, TDI-10229, for a comprehensive analysis of sAC function in mouse and human sperm. In contrast to caudal epididymal mouse sperm, human sperm are collected post-ejaculation, after sAC activity has already been stimulated. In addition to preventing the capacitation-induced stimulation of sAC and protein kinase A activities, tyrosine phosphorylation, alkalinization, beat frequency and acrosome reaction in dormant mouse sperm, sAC inhibitors interrupt each of these capacitation-induced changes in ejaculated human sperm. Furthermore, we show for the first time that sAC is required during acrosomal exocytosis in mouse and human sperm. These data define sAC inhibitors as candidates for non-hormonal, on-demand contraceptives suitable for delivery via intravaginal devices in women.
Intragenic tRNA-promoted R-loops orchestrate transcription interference for plant oxidative stress responses
Authors: Liu Kunpeng , Sun Qianwen 
Published: August 2021

Abstract
Eukaryotic genomes are transcribed by at least three RNA polymerases, RNAPI, II, and III. Co-transcriptional R-loops play diverse roles in genome regulation and maintenance. However, little is known about how R-loops regulate transcription interference, the transcriptional event that is caused by different RNA polymerases transcribing the same genomic templates. Here, we established that the intragenic transfer RNA (tRNA) genes can promote sense R-loop enrichment (named intra-tR-loops) in Arabidopsis thaliana, and found that intra-tR-loops are decreased in an RNAPIII mutant, NUCLEAR RNA POLYMERASE C, SUBUNIT 7(nrpc7-1). NRPC7 is co-localized with RNAPIIS2P at intragenic tRNA genes and interferes with RNAPIIS2P elongation. Conversely, the binding of NRPC7 at intragenic tRNA genes is increased following inhibition of RNAPII elongation. The transcription of specific tRNA host genes is inhibited by RNAPIII, and the inhibition of tRNA host genes is intra-tR-loop dependent. Moreover, alleviating the inhibition of tRNAPro-induced intra-tR-loops on its host gene AtNUDX1 promotes oxidative stress tolerance in A. thaliana. Our work suggests intra-tR-loops regulate host gene expression by modulating RNA polymerases interference.
Identifying and tackling racial disparities in healthcare
Authors: Butler Anisa , Covington Kyla , Parsh Bridget 
Published: August 2021

Abstract:
The US healthcare system is plagued with inequities that disproportionately impact people of color and other marginalized communities. This article discusses some of the key reasons behind these historic and current health disparities, identifies key terms, and discusses strategies for nurses who are interested in allying with efforts to tackle inequity and racism in American healthcare.
Hybrid immunity versus vaccine-induced immunity against SARS CoV2 in Patients with Autoimmune Rheumatic Diseases
Authors: Shenoy Padmanabha , Ahmed Sakir , Paul Aby , Cherian Somy , Umesh Rashwith , shenoy Veena , Vijayan Anuroopa , Babu Sageer , Nivin S , Thambi Arya 
Published: August 2021

AbstractIntroductionSingle-dose COVID-19 vaccines in healthy individuals with past COVID-19 infections seem to provide better immunity than double doses in COVID-19 unexposed individuals. However, it is not known whether the same is true for patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressants.MethodsWe identified 30 patients with AIRD who took a single dose of the ChAdOx1 vaccine post-COVID-19 infection. Age, sex and disease similar patients were enrolled in to three groups of 30 each who had (1) past infection with COVID-19 but no vaccine, (2) a single dose of ChAdOx1 and (3) double doses of ChAdOx1. Sera were collected from each patient approximately 30 days after last vaccine dose or since the onset of COVID19 symptoms (in the unvaccinated group). Antibodies to spike protein were estimated and virus neutralization potential of sera was tested.ResultsBaseline characteristics including drug usage was similar betweenthe groups. Seroconversion occurred in 25(83%), 23(77%), 27(90%), and 30(100%) in natural infection, single-dose vaccine, double dose vaccine, and infection +single dose vaccine groups respectively. Mean antibody titres (10076.8±8998) in the last group were at least 6-100x higher than in the other 3 groups. Also, the infection +vaccine group had the highest neutralization potential of 83.37 % as compared to 45.4% in the fully vaccinated group.ConclusionThe hybrid immunity with a single dose of the vector-based vaccine post-infection seems to be superior to double dosage of the vaccine in patients with AIRD. A universal vaccination strategy involving a single dose of vaccine for all individuals with previous COVID-19 infection seems to be effective in these patients also.What is already known about this subject?A single dose of an RNA based COVID-19 vaccine after COVID-19 natural infection provides superior immune protection as compared to double doses of vaccines in infection naïve personsA second dose of vaccine in healthy people who had infection previously does not increase the immune protection but may paradoxically induce toleranceVaccine responses in patients with autoimmune rheumatic diseases(AIRD) may be suboptimal due to underlying disease or the use of immunosuppressants.What does this study add?Hybrid-induced immunity (single vaccine post COVID-19 infection) produces adequate vaccine responses in patients with AIRD, non-inferior to double dose of vaccineBesides mRNA vaccines, the adenoviral vector vaccine AZD1222 also demonstrates this hybrid phenomenon.How might this impact on clinical practice?Vaccination policies can consider providing only a single vaccine in those who had previous COVID-19 infection. This strategy has been shown not to be harmful for patients with AIRD. This will help reduce vaccine shortages.
May a Strain Chlamydia Isolated From SARS Patient’s Autopsy Issues Inhibit the Proliferation of SARS-CoV? An Early Observation in Vitro
Authors: Quan Xing , Liu Weifei 
Published: August 2021

AbstractWe found that a strain chlamydia isolated from SARS patient’s autopsy issues could decrease the proliferation of SARS-CoV in vitro; The inhibitory factors distribute both in the extracellular and intracellular cultures.
S-acylation stabilizes ligand-induced receptor kinase complex formation during plant pattern-triggered immune signalling
Authors: Hurst Charlotte H. , Turnbull Dionne , Xhelilaj Kaltra , Myles Sally , Pflughaupt Robin L. , Kopischke Michaela , Davies Paul , Jones Susan , Robatzek Silke , Zipfel Cyril , Gronnier Julien , Hemsley Piers A. 
Published: August 2021

SummaryPlant receptor kinases are key transducers of extracellular stimuli, such as the presence of beneficial or pathogenic microbes or secreted signalling molecules. Receptor kinases are regulated by numerous post-translational modifications. Here, using the immune receptor kinases FLS2 and EFR, we show that S-acylation at a cysteine conserved in all plant receptor kinases is crucial for function. S-acylation involves the addition of long-chain fatty acids to cysteine residues within proteins, altering their biophysical properties and behaviour within the membrane environment. We observe S-acylation of FLS2 at C-terminal kinase domain cysteine residues within minutes following perception of its ligand flg22, in a BAK1 co-receptor dependent manner. We demonstrate that S-acylation is essential for FLS2-mediated immune signalling and resistance to bacterial infection. Similarly, mutating the corresponding conserved cysteine residue in EFR supressed elf18 triggered signalling. Analysis of unstimulated and activated FLS2-containing complexes using microscopy, detergents and native membrane DIBMA nanodiscs indicates that S-acylation stabilises and promotes retention of activated receptor kinase complexes at the plasma membrane to increase signalling efficiency.
Flanking sequences regulate the toxicity, non-ATG translation, and aggregation of RNA with tandem CAG Repeats
Authors: Das Michael R. , Chang Yeonji , Saunders Reuben , Zhang Nan , Tomberlin Colson , Vale Ronald D. , Jain Ankur 
Published: August 2021

SummaryNucleotide repeat-expansions cause several neurodegenerative disorders, including Huntington’s disease and spinocerebellar ataxia. The expanded repeat-containing RNA transcribed from the affected loci agglomerate in the nucleus as pathogenic foci. Here we demonstrate that depending on their surrounding sequence context, RNAs with expanded CAG repeats can also undergo nuclear export and aggregate in the cytoplasm. Cytoplasmic aggregation of repeat-containing RNA coincides with several disease hallmarks, including repeat-associated non-AUG (RAN) translation, mislocalization of RNA binding proteins, and cell toxicity. Interestingly, the repeat-containing RNA co-aggregate with RAN translation products. Inhibition of RAN translation prevents cytoplasmic RNA aggregation and also alleviates cell toxicity. Our findings provide a cogent explanation for aberrant cytoplasmic localization of RNA binding proteins and implicate cis-acting flanking sequences in mediating RAN translation and disease.
Elevation of major constitutive heat shock proteins is heat shock factor independent and essential for establishment and growth of Lgl loss and Yorkie gain mediated tumors in Drosophila
Authors: Singh Gunjan , Chakraborty Saptomee , Lakhotia Subhash C. 
Published: August 2021

AbstractCancer cells generally overexpress heat shock proteins (Hsps), the major components of cellular stress response, to overcome and survive the diverse stresses. However, the specific roles of Hsps in initiation and establishment of cancers remain unclear. Using loss of Lgl-mediated epithelial tumorigenesis in Drosophila, we induced tumorigenic somatic clones of different genetic backgrounds to examine the temporal and spatial expression and roles of major heat shock proteins in tumor growth. The constitutively expressed Hsp83, Hsc70 (heat shock cognate), Hsp60 and Hsp27 show elevated levels in all cells of the tumorigenic clone since early stages, which persists till their transformation. However, the stress-inducible Hsp70 is expressd only in a few cells at later stage of established tumorous clones that show high F-actin aggregation. Intriguingly, levels of heat shock factor (HSF), the master regulator of Hsps, remain unaltered in these tumorous cells and its down-regulation does not affect tumorigenic growth of lgl− clones overexpressing Yorkie, although down-regulation of Hsp83 prevents their survival and growth. Interestingly, overexpression of HSF or Hsp83 in lgl− cells makes them competitively successfully in establishing tumorous clones. These results show that the major constitutively expressed Hsps, but not the stress-inducible Hsp70, are involved in early as well as late stages of epithelial tumors and their elevated expression in lgl− clones co-overexpressing Yorkie is independent of HSF.