bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson’s disease
Authors: Galiano-Landeira Jordi , Torra Albert , Vila Miquel , Bové Jordi 
Published: July 2020

AbstractThere is no consensus on the exact role of the adaptive immune system in Parkinson’s disease pathogenesis, although there is increasing evidence that it is somehow involved. Moreover, T cell infiltration in the brain has not been thoroughly studied in Parkinson’s disease and no study has assessed the infiltration in incidental Lewy body diseases cases that are considered to be early presymptomatic stages of the disease. In this study, we performed an immunohistochemistry/immunofluorescence quantitative and phenotypic assessment of T cell infiltration in human substantia nigra pars compacta and analysed the correlations with neuronal death and synucleinopathy throughout different stages of the disease. We included two groups of incidental Lewy disease in the study. One of the groups, which is believed to be the earliest stage of the disease, showed α-synuclein aggregates only in the olfactory bulb. The second group also presented α-synuclein aggregates in the substantia nigra. We also assessed the formation of different α-synuclein aggregates throughout the different stages of the unified staging system for Lewy body disorders (I to IV). We found that CD8 T cells were increased in diagnosed Parkinson’s disease cases compared to the control group and their density positively correlated with neuronal death. Some of the infiltrating CD8 T cells were indeed contacting dopaminergic neurons. No differences were found regarding CD4 T cells. In the earliest stage of the disease, when substantia nigra α-synuclein aggregation is absent, we found a robust CD8 T cell infiltration and no dopaminergic neuronal death yet. Conversely, in the next stage we found neuronal loss and a milder CD8 T cell infiltration. CD8 T cell infiltration paralleled that of α-synuclein accumulation and neuronal death throughout stages II to IV. We also confirmed that CD8 T cells in charge of immune surveillance and involved in the aetiopathogenesis of the disease are equipped with cytolytic enzymes (granzyme A, B and K) and/or proinflammatory cytokines (interferon gamma), and that phenotypic differences were observed between early and late stages of the disease. We also demonstrate that a high proportion of nigral CD8 T cells are tissue resident memory T cells. Our results show that nigral cytotoxic CD8 T cell infiltration is an earlier pathogenic event than α-synuclein aggregation and neuronal death and that it parallels the progression of neuronal death and synucleinopathy in Parkinson’s disease. Overall, our study suggests that CD8 T cell cytotoxic attack may initiate and propagate neuronal death and synucleinopathy in Parkinson’s disease.
Urethral Microbiota in Men: Association of Haemophilus influenzae and Mycoplasma penetrans With Nongonococcal Urethritis
Authors: Srinivasan Sujatha , Chambers Laura C , Tapia Kenneth A , Hoffman Noah G , Munch Matthew M , Morgan Jennifer L , Domogala Daniel , Sylvan Lowens M , Proll Sean , Huang Meei-Li , Soge Olusegun O , Jerome Keith R , Golden Matthew R , Hughes James P , Fredricks David N , Manhart Lisa E 
Published: July 2020

Abstract

Background
Nongonococcal urethritis (NGU) is a common syndrome with no known etiology in ≤50% of cases. We estimated associations between urethral bacteria and NGU in men who have sex with men (MSM) and men who have sex with women (MSW).

Methods
Urine was collected from NGU cases (129 MSM, 121 MSW) and controls (70 MSM, 114 MSW) attending a Seattle STD clinic. Cases had ≥5 polymorphonuclear leukocytes on Gram stain plus symptoms or discharge; controls had &lt;5 PMNs, no symptoms, no discharge. NGU was considered idiopathic when Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenovirus, and herpes simplex virus were absent. The urethral microbiota was characterized using 16S rRNA gene sequencing. Compositional lasso analysis was conducted to identify associations between bacterial taxa and NGU and to select bacteria for targeted qPCR.

Results
Among NGU cases, 45.2% were idiopathic. Based on compositional lasso analysis, we selected Haemophilus influenzae (HI) and Mycoplasma penetrans (MP) for targeted qPCR. Compared with 182 men without NGU, the 249 men with NGU were more likely to have HI (14% vs 2%) and MP (21% vs 1%) (both P ≤ .001). In stratified analyses, detection of HI was associated with NGU among MSM (12% vs 3%, P = .036) and MSW (17% vs 1%, P &lt; .001), but MP was associated with NGU only among MSM (13% vs 1%, P = .004). Associations were stronger in men with idiopathic NGU.

Conclusions
HI and MP are potential causes of male urethritis. MP was more often detected among MSM than MSW with urethritis.
Human Immunodeficiency Virus (HIV) Drug Resistance, Phylogenetic Analysis, and Superinfection Among Men Who Have Sex with Men and Transgender Women in Sub-Saharan Africa: HIV Prevention Trials Network (HPTN) 075 Study
Authors: Sivay Mariya V , Palumbo Philip J , Zhang Yinfeng , Cummings Vanessa , Guo Xu , Hamilton Erica L , McKinstry Laura , Ogendo Arthur , Kayange Noel , Panchia Ravindre , Dominguez Karen , Chen Ying Q , Sandfort Theodorus G M , Eshleman Susan H 
Published: July 2020

Abstract

Background
The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TGW) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075.

Methods
HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads &gt;400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing.

Results
HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2–6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort.

Conclusions
This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TGW in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.
Proadrenomedullin Predicts Severe Disease in Children With Suspected Community-acquired Pneumonia
Authors: Florin Todd A , Ambroggio Lilliam , Brokamp Cole , Zhang Yin , Nylen Eric S , Rattan Mantosh , Crotty Eric , Belsky Michael A , Krueger Sara , Epperson Thomas N , Kachelmeyer Andrea , Ruddy Richard M , Shah Samir S 
Published: July 2020

Abstract

Background
Proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, predicts severe outcomes in adults with community-acquired pneumonia (CAP) to a greater degree than C-reactive protein and procalcitonin. We evaluated the ability of proADM to predict disease severity across a range of clinical outcomes in children with suspected CAP.

Methods
We performed a prospective cohort study of children 3 months to 18 years with CAP in the emergency department. Disease severity was defined as mild (discharged home), mild–moderate (hospitalized but not moderate–severe or severe), moderate–severe (eg, hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (eg, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined using proportional odds logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP.

Results
Among 369 children, median proADM increased with disease severity (mild: median [IQR], 0.53 [0.43–0.73]; mild–moderate: 0.56 [0.45–0.71]; moderate–severe: 0.61 [0.47–0.77]; severe: 0.70 [0.55–1.04] nmol/L) (P = .002). ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP: OR, 1.68; 95% CI, 1.2–2.36; radiographic CAP: OR, 2.11; 95% CI, 1.36–3.38) adjusted for age, fever duration, antibiotic use, and pathogen. ProADM had an AUC of 0.64 (95% CI, .56–.72) in those with suspected CAP and an AUC of 0.77 (95% CI, .68–.87) in radiographic CAP.

Conclusions
ProADM was associated with severe disease and discriminated moderately well children who developed severe disease from those who did not, particularly in radiographic CAP.
Longitudinal Dynamics of the Neutralizing Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection
Authors: Wang Kai , Long Quan-Xin , Deng Hai-Jun , Hu Jie , Gao Qing-Zhu , Zhang Gui-Ji , He Chang-Long , Huang Lu-Yi , Hu Jie-Li , Chen Juan , Tang Ni , Huang Ai-Long 
Published: July 2020

Abstract

Background
Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific neutralizing antibodies (NAbs) in patients with COVID-19.

Methods
Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2–specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines.

Results
SARS-CoV-2–specific NAb titers were low for the first 7–10 days after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 days (interquartile range [IQR], 24–59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6–42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P &lt; .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF).

Conclusions
These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.
Transmission Dynamics in Tuberculosis Patients With Human Immunodeficiency Virus: A Systematic Review and Meta-analysis of 32 Observational Studies
Authors: Martinez Leonardo , Woldu Henok , Chen Cheng , Hallowell Benjamin D , Castellanos Maria Eugenia , Lu Peng , Liu Qiao , Whalen Christopher C , Zhu Limei 
Published: July 2020

Abstract

Background
There are large knowledge gaps on the transmission dynamics of Mycobacterium tuberculosis in settings where both tuberculosis and human immunodeficiency virus (HIV) are endemic. We aimed to assess the infectiousness of tuberculosis patients coinfected with HIV.

Methods
We systematically searched for studies of contacts of both HIV-positive and HIV-negative tuberculosis index cases. Our primary outcome was Mycobacterium tuberculosis infection in contacts. Data on sputum smear and lung cavitation status of index cases were extracted from each study to assess effect modification. Secondary outcomes included prevalent tuberculosis and HIV in contacts of HIV-positive and HIV-negative index cases.

Results
Of 5255 original citations identified, 32 studies met inclusion criteria, including 25 studies investigating M. tuberculosis infection (Nparticipants = 36 893), 13 on tuberculosis (Nparticipants = 18 853), and 12 on HIV positivity (Nparticipants = 18 424). Risk of M. tuberculosis infection was lower in contacts of HIV-positive index cases (odds ratio [OR], 0.67, 95% confidence interval [CI], .58–.77) but was heterogeneous (I2 = 75.1%). Two factors modified this relationship: the lung cavitary status of the index case and immunosuppression (measured through CD4 counts or HIV or acquired immunodeficiency syndrome diagnoses) among index people living with HIV. Rates of HIV were consistently higher in contacts of coinfected index cases (OR, 4.9; 95% CI, 3.0–8.0). This was modified by whether the study was in sub-Saharan Africa (OR, 2.8; 95% CI, 1.6–4.9) or in another global region (OR, 9.8; 95% CI, 5.9–16.3).

Conclusions
Tuberculosis patients coinfected with HIV are less infectious than HIV-uninfected cases when they have severe immunosuppression or paucibacillary disease. Contacts of coinfected index cases are almost 5 times more likely to also have HIV.
Role of Human Bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients
Authors: Ogimi Chikara , Martin Emily T , Xie Hu , Campbell Angela P , Waghmare Alpana , Jerome Keith R , Leisenring Wendy M , Milano Filippo , Englund Janet A , Boeckh Michael 
Published: July 2020

Abstract

Background
Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients.

Methods
In a longitudinal surveillance study among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then at least every 3 months through 1 year post-HCT at the Fred Hutchinson Cancer Research Center (2005–2010). Samples were tested by multiplex semiquantitative polymerase chain reaction (PCR) for 12 viruses. Plasma samples from BoV + subjects were analyzed by PCR. Separately, we conducted a retrospective review of HCT recipients with BoV detected in lower respiratory tract specimens.

Results
Among 51 children and 420 adults in the prospective cohort, 21 distinct BoV respiratory tract infections (RTIs) were observed by 1 year post-HCT in 19 patients. Younger age and exposure to children were risk factors for BoV acquisition. Univariable models among patients with BoV RTI showed higher peak viral load in nasal samples (P = .04) and presence of respiratory copathogens (P = .03) were associated with presence of respiratory symptoms, but BoV plasma detection was not. Only watery eyes and rhinorrhea were associated with BoV RTI in adjusted models. With additional chart review, we identified 6 HCT recipients with BoV detected in lower respiratory tract specimens (incidence rate of 0.4% [9/2509] per sample tested). Although all cases presented with hypoxemia, 4 had respiratory copathogens or concomitant conditions that contributed to respiratory compromise.

Conclusions
BoV RTI is infrequent in transplant recipients and associated with mild symptoms. Our studies did not demonstrate convincing evidence that BoV is a serious respiratory pathogen.
Central Station-Based Demand Prediction for Determining Target Inventory in a Bike-Sharing System
Authors: Huang Jianbin , Sun Heli , Li He , Huang Longji , Li Ao , Wang Xiangyu 
Published: July 2020

Abstract
Predicting the bike demand can help rebalance the bikes and improve the service quality of a bike-sharing system. A lot of works focus on predicting the bike demand for all the stations, which is unnecessary as the travel cost of rebalance operations increases sharply as the number of stations increases. In this paper, we propose a framework for predicting the hourly bike demand based on the central stations we define. Firstly, we propose Two-Stage Station Clustering Algorithm to assign central stations and common stations into each cluster. Secondly, we propose a hierarchical prediction model to predict the hourly bike demand for every cluster and each central station progressively. Thirdly, we use a well-studied queuing model to determine the target initial inventory for each central station. The most innovative contribution of this paper is proposing the concept of central station, the use of a novel algorithm to cluster the central stations and present a hierarchical model, containing the Time and Weather Similarity Weighted K-Nearest Neighbor Algorithm and a linear model to predict the bike demand for central stations. The experimental results on the New York citi bike system demonstrate that our proposed method is more accurate than other methods in solving existing problems.
Maintenance Golimumab Treatment in Pediatric UC Patients With Moderately to Severely Active UC: PURSUIT PEDS PK Long-Term Study Results
Authors: Hyams Jeffrey S , O’Brien Christopher D , Padgett Lakshmi , Rosh Joel R , Turner Dan , Veereman Genevieve , Griffiths Anne M , Heyman Melvin B , Wahbeh Ghassan , Adedokun Omoniyi J , Strauss Richard S , Lynch John P , Chan Daphne 
Published: July 2020

AbstractBackgroundLong-term safety, pharmacokinetics, and efficacy of open-label golimumab therapy in children with moderate–severe ulcerative colitis were evaluated.MethodsWeek-6 golimumab responders (Mayo score decrease of ≥30% and ≥3 points from baseline, rectal bleeding subscore of 0/1 or ≥1 decrease from baseline) entered the long-term extension at week 14 and received maintenance therapy (subcutaneous, q4w). Patients ≥45 kg could receive at-home treatments at week 18. Pharmacokinetic, safety, and efficacy results were summarized through week 126 (2 years).ResultsAmong 35 enrolled children, 21 (60%) responded at week 6 and 20 entered the long-term extension (median age of 14.5 years and median weight of 46.1 kg). Eleven of 20 patients (55%) completed 2 years of treatment. No anaphylactic or serum sickness-like reactions, opportunistic infections, malignancies, tuberculosis, or deaths occurred. The safety profile of golimumab from weeks 14 through 126 and that observed through week 14 was generally consistent. Median trough golimumab concentrations in evaluable patients were consistent from weeks 14 (1.39, interquartile range 0.67–3.60) through 102 (1.18, 0.78–2.16), but higher at week 110 (4.10, 1.30–4.81). The incidence of antigolimumab antibodies increased from 10% (2/20) at week 30 to 25.0% (5/20) at week 126; 1 patient had neutralizing antibodies. At week 110, 50% (10/20) of patients were in remission (ie, Pediatric Ulcerative Colitis Activity Index &lt;10). Among all enrolled patients, 28.6% (10/35) achieved remission at week 110.ConclusionsAmong children with ulcerative colitis who initially responded to golimumab induction and received q4w maintenance treatment in the long-term extension, 50% showed continued clinical benefit through 2 years. No new safety signals were observed.
School Crisis Management Planning
Authors: Elbedour Salman , Alsubie Futiem , Al’Uqdah Shareefah N , Bawalsah Joseph A 
Published: July 2020

Abstract
The fundamental need for safety in schools requires research-based and trauma-informed strategies for implementing crisis management plans (CMPs). Beyond the immediate harm, longer-term potential outcomes of crises are psychological trauma and damage to the reputation for safety of the school, leading to staff attrition. An effective CMP involves (a) planning, (b) communication, (c) protocols for immediate action, and (d) protocols specific to different types of school crises. School crises can occur on the organizational level, such as natural disasters or shootings; community level, such as bullying or community violence; or individual level, such as suicide, pregnancy, or family changes. This article incorporates research from the business sector as well as education, social work, and psychology to describe the vital components of a school CMP and the role of the school mental health staff. School mental health staff must be central to development and implementation of a trauma-informed school CMP that incorporates prevention, communication, and different protocols for the various types of crises.
Practitioners’ Self-Assessment of Family-Centered Practice in Telepractice Versus In-Person Early Intervention
Authors: McCarthy Melissa , Leigh Greg , Arthur-Kelly Michael 
Published: July 2020

Abstract
For infants and young children who are identified as deaf or hard of hearing (DHH), best practice principles indicate the provision of family-centered early intervention (FCEI). However, factors such as geographical inaccessibility and workforce shortages can limit families’ access to FCEI in their local area. One strategy for overcoming these barriers is telepractice—a method of connecting families and practitioners using synchronous, two-way audiovisual technologies. This study compared the self-assessed use of family-centered practices by a group of practitioners delivering FCEI through telepractice with that of a similar group delivering FCEI in-person. A sample of 38 practitioners (15 telepractice and 23 in-person) from two early intervention programs for children who are DHH completed a self-assessment tool: the Measures of Processes of Care for Service Providers. Results indicated that there were no significant differences between telepractice and in-person sessions with regard to practitioners’ self-assessment of their use of family-centered practices.
Case report: Synergetic effect of ischaemia and increased vagal tone inducing ventricular fibrillation in a patient with Brugada syndrome
Authors: Van Malderen Sophie C H , Schultz Carl J , Jordaens Luc 
Published: July 2020

Abstract

Background
Brugada syndrome (BS) is a hereditary channelopathy associated with syncope, malignant ventricular arrhythmia, and sudden cardiac death. Right ventricular ischaemia and BS have similar underlying substrates precipitating ventricular tachycardia or fibrillation (VF).

Case summary
A 72-year-old woman with BS and a stenosis on the proximal right coronary artery received several subsequent implantable cardioverter-defibrillator shocks due to VF during an episode of extreme nausea with vomiting.

Discussion
This case report emphasizes on the synergetic effect of mild ischaemia and increased vagal tone on the substrate responsible for BS to create pathophysiological changes precipitating VF.
Age Differences in Risk and Resilience Factors in COVID-19-Related Stress
Authors: Pearman Ann , Hughes MacKenzie L , Smith Emily L , Neupert Shevaun D 
Published: July 2020

Abstract

Objectives
Older adults are at higher risk for death and infirmity from COVID-19 than younger and middle-aged adults. The current study examines COVID-19-specific anxiety and proactive coping as potential risk and resilience factors that may be differentially important for younger and older adults in understanding stress experienced due to the COVID-19 pandemic.

Methods
Five hundred and fifteen adults aged 20–79 years in the United States reported on their anxiety about developing COVID-19, proactive coping, and stress related to COVID-19 in an online survey.

Results
Although there were no age differences in stress levels, anxiety about developing COVID-19 was associated with more COVID-19 stress for older adults relative to younger adults, but proactive coping was associated with less COVID-19 stress for older adults relative to younger adults.

Discussion
Our results suggest that anxiety might function as a risk factor, whereas proactive coping may function as a resilience factor for older adults’ COVID-19 stress. We encourage future context-dependent investigations into mental health among older adults during this pandemic and beyond.