bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiating antiretroviral treatment for newly diagnosed HIV patients in sexual health clinics greatly improves timeliness of viral suppression
Authors: Pathela Preeti , Jamison Kelly , Braunstein Sarah L. , Borges Christine M. , Lazar Rachael , Mikati Tarek , Daskalakis Demetre , Blank Susan 
Published: May 2021

Objective:
The ‘JumpstART’ program in New York City (NYC) public Sexual Health Clinics (SHC) provides patients newly diagnosed with human immunodeficiency virus (HIV) with antiretroviral medication (ART) (1-month supply) on day of diagnosis and active linkage to HIV care (LTC). We examined viral suppression (VS) among patients who did and did not receive JumpstART services.

Design:
Retrospective cohort.

Methods:
Among newly diagnosed SHC patients (23 November 2016–30 September 2018) who were matched to the NYC HIV surveillance registry to obtain HIV laboratory test results through 30 June 2019, we compared 230 JumpstART and 73 non-JumpstART patients regarding timely LTC (≤30 days), probability of VS (viral load < 200 copies/ml) by 3 months post-diagnosis, and time to and factors associated with achieving VS within the follow-up period.

Results:
Of 303 patients, 76% (230/303) were JumpstART and the remaining were non-JumpstART patients; 36 (11%) had acute HIV infections. LTC ≤30 days was observed for 63% of JumpstART and 73% of non-JumpstART patients. By 3 months post-diagnosis, 83% of JumpstART versus 45% of non-JumpstART patients achieved VS (log-rank, P < .0001). Median times to VS among virally suppressed JumpstART and non-JumpstART patients were 31 (interquartile range [IQR]: 24–51) and 95 days (IQR: 52–153), respectively. For groups with and without timely LTC, JumpstART was associated with viral suppression within 3 months post-diagnosis, after adjusting for age and baseline viral load.

Conclusions:
Prompt ART initiation among SHC patients, some with acute HIV infections, resulted in markedly shortened intervals to VS. Immediate ART provision and active LTC can be key contributors to improved HIV treatment outcomes and the treatment-as-prevention paradigm, with potential for downstream, population-level benefit.
Everyday Abilities Scale for India in Screening for Poststroke Dementia Among Young Stroke Survivors
Authors: Done Indira P. , Aghoram Rajeswari , Narayan Sunil K. 
Published: May 2021

Introduction:
Cognitive dysfunction after stroke is an important concern. We explored the utility of everyday abilities scale for India (EASI) for screening for dementia among young stroke survivors.

Methods:
We interviewed 150 young stroke survivors and caregivers. Vascular dementia was diagnosed according to American Heart Association-American Stroke Association (ASA-AHA) criteria. EASI was administered to all caregivers. Receiver operating characteristic curve analysis was used to determine the area under the curve and optimum cut-points for EASI for the identification of dementia.

Results:
Median EASI scores among subjects with dementia (n=35; 23.3%) was 2 (interquartile range: 0-4) and significantly different from those without (median: 0; interquartile range: 0-1; P<0.001). The area under the curve was 0.768 (95% confidence interval: 0.674-0.863), and at the optimum cut-point of 2 on EASI, a sensitivity of 60% and specificity of 91.3% was achieved for the identification of dementia.

Conclusion:
EASI appears to be a promising tool to screen for dementia among young stroke survivors.
Bone Mineral Density Measurements and Association With Brain Structure and Cognitive Function
Authors: Stefanidou Maria , O’Donnell Adrienne , Himali Jayandra J. , DeCarli Charles , Satizabal Claudia , Beiser Alexa S. , Seshadri Sudha , Zaldy Tan 
Published: May 2021

Background:
Bone mineral density (BMD) is a potential surrogate marker of lifetime estrogen exposure previously linked to increased risk of Alzheimer dementia among elderly women. We examine the association between BMD in the “young old” with imaging biomarkers of brain aging and cognitive performance.

Methods:
Offspring participants (N=1905, mean age 66) of a population-based cohort who had BMD, brain imaging and detailed cognitive assessment were included in the study. Sex-stratified, linear, and logistic regression models were used for analysis.

Results:
Higher femoral neck BMD was associated with lower white matter hyperintensity burden and better performance on Trails B-A in both sexes, even after adjustment for cerebrovascular risk factors. Among women, the positive association with Trails B-A performance was seen only in APOE4 allele carriers. Higher BMD measurements were linked to better visual reproductions test performance in men. Finally, among women, higher femoral trochanter BMD was associated with better logical memory and Hooper visual organization test performance.

Conclusion:
Among the “young old,” higher BMD is associated with less white matter hyperintensity burden and better, domain-specific, cognitive performance. This suggests that lifetime estrogen exposure may modulate the degree of cumulative vascular brain injury independent of cerebrovascular risk factors.
Corynebacterium lizhenjunii sp. nov., isolated from the respiratory tract of Marmota himalayana, and Corynebacterium qintianiae sp. nov., isolated from the lung tissue of Pseudois nayaur
Authors: Zhou Juan , Xu Mingchao , Guo Wentao , Yang Jing , Pu Ji , Lai Xin-He , Jin Dong , Lu Shan , Zhang Sihui , Huang Yuyuan , Zhu Wentao , Huang Ying , Zheng Han , Xu Jianguo 
Published: May 2021

Four Gram-stain-positive, non-motile and asporous bacilli (strains ZJ-599T, ZJ-621, MC1420T and MC1482), isolated from animal tissue and environmental samples collected on the Qinghai-Tibet Plateau, PR China, were taxonomically characterized. Based on the results of 16S rRNA gene sequence analyses, the closest relatives of strains ZJ-599T and ZJ-621 were

Corynebacterium endometrii

LMM-1653T (97.5 %),

Corynebacterium phocae

M408/89/1T (96.5 %) and

Corynebacterium flavescens

OJ8T (96.3 %), whereas strains MC1420T and MC1482 were closest to

Corynebacterium sanguinis

CCUG 58655T (98.9 %),

Corynebacterium mycetoides

DSM 20632T (98.4 %) and

Corynebacterium lipophiloflavum

DSM 44291T (97.9 %). The results of rpoB gene sequence similarity analysis indicated that

C. phocae

M408/89/1T and

C. sanguinis

CCUG 58655T were closest to strains ZJ-599T/ZJ-621 (83.5 %) and MC1420T/MC1482 (91.8 %), respectively. The two novel type strains shared a similarity of 95.2 % in 16S rRNA and 81.3 % in rpoB gene sequences. The TAP-PCR DNA fingerprint and MALDI-TOF MS spectrum patterns clearly differentiated the novel isolates within and between each pair of strains. Strain ZJ-599T had 21.9–22.4 % digital DNA–DNA hybridization (dDDH) scores with

C. endometrii

LMM-1653T,

C. phocae

M408/89/1T and

C. flavescens

OJ8T, and 72.3–72.9 % of average nucleotide identity (ANI) with them. Similarly, strain MC1420T had 22.9–23.7 % dDDH values with

C. sanguinis

CCUG 58655T,

C. mycetoides

DSM 20632T and

C. lipophiloflavum

DSM 44291T, and 80.4–81.3 % ANI scores with them. Strain ZJ-599T had a 23.1 % dDDH value and 70.5 % ANI score with strain MC1420T, both below the corresponding thresholds for species delineation. Strains ZJ-599T and MC1420T both contain mycolic acids and have MK-8(H2) and MK-9(H2) as the predominant respiratory quinones, meso-diaminopimelic acid as the diagnostic diamino acid, and C18 : 1
ω9c as the main fatty acid. C17 : 1
ω8c and C15 : 1
ω8c were predominant in strain ZJ-599T in contrast to C17 : 1
ω7c being predominant in strain MC1420T. The main polar lipids in strain ZJ-599T were diphosphatidylglycerol, phosphatidylinositol and one unidentified glycolipid, while strain MC1420T had diphosphatidylglycerol, phosphatidylglycerol and one unidentified lipid as the major components. Since the two pairs of novel strains (ZJ-599T/ZJ-621, MC1420T/MC1482) distinctly differ from each other and from their nearest relatives, two novel species of the genus

Corynebacterium

are proposed, namely Corynebacterium lizhenjunii (type strain ZJ-599T=GDMCC 1.1779T=JCM 34341T) and Corynebacterium qintianiae (type strain MC1420T=GDMCC 1.1783T=JCM 34340T), respectively.
Cerebral venous thrombosis and portal vein thrombosis: a retrospective cohort study of 537,913 COVID-19 cases
Authors: Taquet Maxime , Husain Masud , Geddes John R , Luciano Sierra , Harrison Paul J 
Published: May 2021

AbstractObjectivesTo estimate the absolute risk of cerebral venous thrombosis (CVT) and portal vein thrombosis (PVT) in the two weeks following a diagnosis of COVID-19, and to assess the relative risks (RR) compared to influenza or the administration of an mRNA vaccine against COVID-19.DesignRetrospective cohort study based on an electronic health records networkSettingLinked records between primary and secondary care centres within 59 healthcare organisations, primarily in the USAParticipantsAll patients with a confirmed diagnosis of COVID-19 between January 20, 2020 and March 25, 2021 were included (N=537,913, mean [SD] age: 46.2 [21.4] years; 54.9% females). Cohorts (matched for age, sex, and race) of participants diagnosed with influenza (N=392,424) or receiving the BNT162b2 or mRNA-1273 vaccine (N=366,869) were used for comparison.Main outcome measuresDiagnosis of CVT (ICD-10 code I67.6) or PVT (ICD-10 code I81) within 2 weeks after a diagnosis of COVID-19.ResultsThe incidence of CVT after COVID-19 diagnosis was 42.8 per million people (95% CI 28.5–64.2) including 35.3 per million (95% CI 22.6–55.2) first diagnoses. This was significantly higher than the CVT incidence in a matched cohort of patients with influenza (RR=3.83, 95% CI 1.56–9.41, P<0.001) and people who received an mRNA vaccine (RR=6.67, 95% CI 1.98–22.43, P<0.001). The incidence of PVT after COVID-19 diagnosis was 392.3 per million people (95% CI 342.8–448.9) including 175.0 per million (95% CI 143.0–214.1) first diagnoses. This was significantly higher than the PVT incidence in a matched cohort of patients with influenza (RR=1.39, 95% CI 1.06–1.83, P=0.02) and people who received an mRNA vaccine (RR=7.40, 95% CI 4.87–11.24, P<0.001). Mortality after CVT and PVT was 17.4% and 19.9% respectively.ConclusionsThe incidence of CVT and PVT is significantly increased after COVID-19. The data highlight the risk of serious thrombotic events in COVID-19 and can help contextualize the risks and benefits of vaccination in this regard.What is known‐A systematic review of cohort studies suggested an incidence of CVT among hospitalised patients with COVID-19 to be about 800 per million patients. There was evidence of selection, ascertainment, and reporting bias in all included studies.‐The incidence of CVT and PVT among both hospitalised and non-hospitalised patients with COVID-19 is unknown.‐It is unknown if COVID-19 increases the risk of CVT and PVT.What this study addsOur study estimates that the absolute risk of CVT and PVT are respectively 42.8 and 392.3 per million patients (both hospitalised and non-hospitalised) in the 2 weeks after a diagnosis of COVID-19. COVID-19 increases the risk of CVT and PVT compared to patients diagnosed with influenza, and to people who have received a COVID-19 mRNA vaccine.
SARS-CoV-2 infection induces autoimmune antibody secretion more in lean than in obese COVID-19 patients
Authors: Frasca Daniela , Reidy Lisa , Romero Maria , Diaz Alain , Cray Carolyn , Kahl Kristin , Blomberg Bonnie B. 
Published: May 2021

AbstractBackground/ObjectivesObesity decreases the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. How obesity impacts the secretion of autoimmune antibodies in COVID-19 patients, however, is not understood. The serum of adult COVID-19 patients contains autoimmune antibodies generated in response to virus-induced tissue damage and cell death leading to the release of intracellular antigens not known to be immunogenic autoantigens. The objective of this study is to evaluate the presence of autoimmune antibodies in COVID-19 patients with obesity.Subjects/MethodsThirty serum samples from individuals who tested positive for SARS-CoV-2 infection by RT-PCR were collected from inpatient and outpatient settings. Of these, 15 were lean (BMI<25), and 15 were obese (BMI ≥30). Control serum samples were from 30 uninfected individuals, age-gender- and BMI-matched, recruited before the current pandemic. Serum IgG antibodies against two autoimmune specificities, as well as against SARS-CoV-2 Spike protein, were measured by ELISA. IgG autoimmune antibodies were specific for malondialdehyde (MDA), a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens (AD), markers of virus-induced cell death in the obese AT.ResultsOur results show that SARS-CoV-2 infection induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese versus lean COVID-19 patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 patients have been correlated with serum levels of C-reactive protein (CRP), a general marker of inflammation, we also evaluated the association of anti-MDA and anti-AT antibodies with serum CRP and found a significant association between CRP and autoimmune antibodies in our cohort of lean and obese COVID-19 patients.ConclusionsOur results highlight the importance of evaluating the quality of the antibody response in COVID-19 patients with obesity, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population that is at higher risk of responding poorly to infection with SARS-CoV-2 compared to lean controls.
Design of the SARS-CoV-2 RBD vaccine antigen improves neutralizing antibody response
Authors: Dickey Thayne H. , Tang Wai Kwan , Butler Brandi , Ouahes Tarik , Orr-Gonzalez Sachy , Salinas Nichole D. , Lambert Lynn E. , Tolia Niraj H. 
Published: May 2021

AbstractThe receptor binding domain (RBD) of the SARS-CoV-2 spike protein is the primary target of neutralizing antibodies and is a component of almost all vaccine candidates. Here, RBD immunogens were created with stabilizing amino acid changes that improve the neutralizing antibody response, as well as characteristics for production, storage, and distribution. A computational design andin vitroscreening platform identified three improved immunogens, each with approximately nine amino acid changes relative to the native RBD sequence and four key changes conserved between immunogens. The changes are adaptable to all vaccine platforms, are compatible with established changes in SARS-CoV-2 vaccines, and are compatible with mutations in emerging variants of concern. The immunogens elicit higher levels of neutralizing antibodies than native RBD, focus the immune response to structured neutralizing epitopes, and have increased production yields and thermostability. Incorporating these variant-independent amino acid changes in next-generation vaccines may enhance the neutralizing antibody response and lead to pan-SARS-CoV-2 protection.
Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy
Authors: Walti Carla S. , Loes Andrea N. , Shuey Kiel , Krantz Elizabeth M. , Boonyaratanakornkit Jim , Keane-Candib Jacob , Loeffelholz Tillie , Wolf Caitlin R. , Taylor Justin J. , Gardner Rebecca A. , Green Damian J. , Cowan Andrew J. , Maloney David G. , Turtle Cameron J. , Pergam Steven A. , Chu Helen Y. , Bloom Jesse D. , Hill Joshua A. 
Published: May 2021

ABSTRACTRecipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B-cell malignancies are immunocompromised and at risk for serious infections. Vaccine immunogenicity is unknown in this population. We conducted a prospective observational study of the humoral immunogenicity of 2019-2020 inactivated influenza vaccines (IIV) in children and adults immediately prior to (n=7) or 13-57 months after (n=15) CD19-, CD20-, or BCMA-targeted CAR-T-cell therapy, as well as controls (n=8). Individuals post-CAR-T-cell therapy were in remission. We tested for antibodies to 4 vaccine strains at baseline and ≥1 time point after IIV using neutralization and hemagglutination inhibition assays. An antibody response was defined as a ≥4-fold titer increase from baseline at the first post-vaccine time point. Baseline A(H1N1) titers in the CAR-T cohorts were significantly lower compared to controls. Antibody responses to ≥1 vaccine strain occurred in 2 (29%) individuals before CAR-T-cell therapy; one individual maintained a response for >3 months post-CAR-T-cell therapy. Antibody responses to ≥1 vaccine strain occurred in 6 (40%) individuals vaccinated after CAR-T-cell therapy. An additional 2 (29%) and 6 (40%) individuals had ≥2-fold increases (at any time) in the pre- and post-CAR-T cohorts, respectively. There were no identified clinical or immunologic predictors of antibody responses. Neither severe hypogammaglobulinemia nor B-cell aplasia precluded antibody responses. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B-cell aplasia. Larger studies are needed to determine correlates of vaccine immunogenicity and durability in CAR-T-cell therapy recipients.Key PointsInfluenza vaccination was immunogenic pre- and post-CAR-T-cell therapy, despite hypogammaglobulinemia and B-cell aplasia.Vaccination with inactivated vaccines can be considered before CAR-T-cell therapy and in individuals with remission after therapy.
Autoantibody screening in Guillain-Barré Syndrome
Authors: Lleixà Cinta , Martín-Aguilar Lorena , Pascual-Goñi Elba , Franco Teresa , Caballero Marta , Diaz-Manera Jordi , Rojas-García Ricard , de Luna Noemí , Gallardo Eduard , Cortés-Vicente Elena , Turón Joana , Suárez-Calvet Xavier , Casasnovas Carlos , Homedes Christian , Gutiérrez-Gutiérrez Gerardo , Jimeno-Montero María Concepción , Berciano José , Sedano Tous Maria José , Garcia-Sobrino Tania , Pardo-Fernandez Julio , Márquez-Infante Celedonio , Rojas-Marcos Iñigo , Jericó-Pascual Ivonne , Martínez-Hernández Eugenia , Morís de la Tassa Germán , Domínguez-González Cristina , Martínez-Martínez Laura , Juárez Cándido , Illa Isabel , Querol Luis 
Published: May 2021

AbstractGuillain-Barré Syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation and pathogenesis. Serum antibodies against various gangliosides can be found in less than half of all patients in the acute phase of GBS but the target antigens remain unknown for the remaining half. Our work describes a comprehensive screening for serum autoantibodies targeting peripheral nerve tissue, cells, and purified antigens in a prospective GBS cohort including 100 patients. Our study confirms that (1) GBS patients display a very heterogeneous repertoire of autoantibodies targeting nerve cells and structures, (2) gangliosides are the most frequent antigens in GBS patients and have prognostic value, (3) a small subset of patients display antibodies targeting the myelin sheath, and (4) further antigen-discovery experiments are needed to elucidate other potential disease-specific autoantibodies in GBS.
Multi-omics characterization of mesenchymal stem/stromal cells for the identification of putative critical quality attributes
Authors: Maughon Ty S. , Shen Xunan , Huang Danning , Michael Adeola O Adebayo , Shockey William A. , Andrews Seth H. , McRae Jon M. , Platt Manu O , Fernández Facundo M. , Edison Arthur S. , Stice Steven L. , Marklein Ross A. 
Published: May 2021

AbstractBackgroundMesenchymal stromal cells (MSCs) have shown great promise in the field of regenerative medicine as many studies have shown that MSCs possess immunomodulatory function. Despite this promise, no MSC therapies have been granted licensure from the FDA. This lack of successful clinical translation is due in part to MSC heterogeneity and a lack of critical quality attributes (CQAs). While MSC Indoleamine 2,3-dioxygnease (IDO) activity has been shown to correlate with MSC function, multiple CQAs may be needed to better predict MSC function.MethodsThree MSC lines (two bone marrow, one iPSC) were expanded to three passages. At the time of harvest for each passage, cell pellets were collected for nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography mass spectrometry (UPLC-MS), and media was collected for cytokine profiling. Harvested cells were also cryopreserved for assessing function using T cell proliferation and IDO activity assays. Linear regression was performed on functional and multiomics data to reduce the number of important features, and partial least squares regression (PLSR) was used to obtain putative CQAs based on variable importance in projection (VIP) scores.ResultsSignificant functional heterogeneity (in terms of T cell suppression and IDO activity) was observed between the three MSC lines, as well as donor-dependent differences based on passage. Omics characterization revealed distinct differences between cell lines using principal component analysis (PCA). Cell lines separated along principal component 1 based on tissue source (bone marrow vs. iPSC-derived) for NMR, MS, and cytokine profiles. PLSR modeling of important features predicts MSC functional capacity with NMR (R2=0.86), MS (R2=0.83), cytokines (R2=0.70), and a combination of all features (R2=0.88).DiscussionThe work described here provides a platform for identifying putative CQAs for predicting MSC functional capacity using PLSR modeling that could be used as release criteria and guide future manufacturing strategies for MSCs and other cell therapies.
Rab35 and glucocorticoids regulate APP and BACE1 trafficking to modulate Aβ production
Authors: Zhuravleva Viktoriya , Vaz-Silva João , Zhu Mei , Gomes Patricia , Silva Joana M. , Sousa Nuno , Sotiropoulos Ioannis , Waites Clarissa L. 
Published: May 2021

AbstractChronic stress and elevated glucocorticoids (GCs), the major stress hormones, are risk factors for Alzheimer’s disease (AD) and promote AD pathomechanisms, including overproduction of toxic amyloid-β (Aβ) peptides and intraneuronal accumulation of hyperphosphorylated Tau protein. The latter is linked to downregulation of the small GTPase Rab35, which mediates Tau degradation via the endolysosomal pathway. Whether Rab35 is also involved in Aβ overproduction remains an open question. Here, we find that hippocampal Rab35 levels are decreased not only by stress/GC but also by aging, another AD risk factor. Moreover, Rab35 negatively regulates Aβ production by sorting amyloid precursor protein (APP) and β-secretase (BACE1) out of the endosomal network, where they interact to produce Aβ. Interestingly, Rab35 coordinates distinct intracellular trafficking events for BACE1 and APP, mediated by its effectors OCRL and ACAP2, respectively. Finally, we show that Rab35 overexpression prevents the amyloidogenic trafficking of APP and BACE1 induced by high GC levels. These studies identify Rab35 as a key regulator of APP processing and suggest that its downregulation may contribute to stress- and AD-related amyloidogenesis.