bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of therapy-induced myelosuppression in newly diagnosed glioblastoma
Authors: Le Rhun Emilie , Oppong Felix Boakye , Vanlancker Maureen , Stupp Roger , Nabors Burt , Chinot Olivier , Wick Wolfgang , Preusser Matthias , Gorlia Thierry , Weller Michael 
Published: March 2022

Abstract

Background
Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma.

Methods
We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, and lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progression-free survival (PFS) or overall survival (OS) in 2073 patients with newly diagnosed glioblastoma enrolled into five clinical trials: CENTRIC, CORE, EORTC 26082, AVAglio, and EORTC 26981. A landmark Cox model was used. For each primary association analysis, a significance level of 1.7% was used.

Results
Lower neutrophil counts at baseline were associated with better PFS (P = .011) and OS (P &lt; .001), independently of steroid intake. Females experienced uniformly more myelotoxicity than males. Lymphopenia during concomitant chemoradiotherapy was associated with OS (P = .009): low-grade (1-2) lymphopenia might be associated with superior OS (HR 0.78, 98.3% CI 0.58–1.06), whereas high-grade (3-4) lymphopenia might be associated with inferior OS (HR 1.08, 98.3% CI 0.75–1.54). There were no associations of altered hematological parameters during concomitant chemoradiotherapy with PFS. During maintenance chemoradiotherapy, no significant association was found between any parameter of myelosuppression and PFS or OS, although exploratory analysis at 5% significance level indicated that either mild-to-moderate (HR 0.76, 95% CI 0.62–0.93) or high-grade lymphopenia (HR 0.65, 95% CI 0.46–0.92) was associated with superior OS (P = .013), but not PFS.

Conclusions
The association of higher neutrophil counts at baseline with inferior PFS and OS requires further prospective evaluation. The link of therapy-induced lymphopenia to better outcome may guide the design for immunotherapy trials in newly diagnosed glioblastoma.
Sphingolipids with 2-hydroxy fatty acids aid in plasma membrane nanodomain organization and oxidative burst
Authors: Ukawa Tomomi , Banno Fumihiko , Ishikawa Toshiki , Kasahara Kota , Nishina Yuuta , Inoue Rika , Tsujii Keigo , Yamaguchi Masatoshi , Takahashi Takuya , Fukao Yoichiro , Kawai-Yamada Maki , Nagano Minoru 
Published: March 2022

Abstract
Plant sphingolipids mostly possess 2-hydroxy fatty acids (HFA), the synthesis of which is catalyzed by FA 2-hydroxylases (FAHs). In Arabidopsis (Arabidopsis thaliana), two FAHs (FAH1 and FAH2) have been identified. However, the functions of FAHs and sphingolipids with HFAs (2-hydroxy sphingolipids) are still unknown because of the lack of Arabidopsis lines with the complete deletion of FAH1. In this study, we generated a FAH1 mutant (fah1c) using CRISPR/Cas9-based genome editing. Sphingolipid analysis of fah1c, fah2, and fah1cfah2 mutants revealed that FAH1 hydroxylates very long-chain FAs (VLCFAs), whereas the substrates of FAH2 are VLCFAs and palmitic acid. However, 2-hydroxy sphingolipids are not completely lost in the fah1cfah2 double mutant, suggesting the existence of other enzymes catalyzing the hydroxylation of sphingolipid FAs. Plasma membrane (PM) analysis and molecular dynamics simulations revealed that hydroxyl groups of sphingolipid acyl chains play a crucial role in the organization of nanodomains, which are nanoscale liquid-ordered domains mainly formed by sphingolipids and sterols in the PM, through hydrogen bonds. In the PM of the fah1cfah2 mutant, the expression levels of 26.7% of the proteins, including defense-related proteins such as the pattern recognition receptors (PRRs) brassinosteroid insensitive 1-associated receptor kinase 1 and chitin elicitor receptor kinase 1, NADPH oxidase respiratory burst oxidase homolog D (RBOHD), and heterotrimeric G proteins, were lower than that in the wild-type. In addition, reactive oxygen species (ROS) burst was suppressed in the fah1cfah2 mutant after treatment with the pathogen-associated molecular patterns flg22 and chitin. These results indicated that 2-hydroxy sphingolipids are necessary for the organization of PM nanodomains and ROS burst through RBOHD and PRRs during pattern-triggered immunity.
Self-Leadership Is Critical for All Physical Therapists
Authors: Green-Wilson Jennifer , Tschoepe Barbara A , Zeigler Stacey L , Sebelski Chris A , Clark Diane 
Published: March 2022

AbstractEvidence that supports the explicit need to develop leadership skills at all levels of clinical practice is prevalent,1–8 yet intentional development of “self-leadership” within health care, and particularly within physical therapy, remains slow, fragmented, and inconsistent. Delineation and standardization of the definition of leadership, and the approach to developing leadership skills in individuals practicing within health care continues to be debated, producing several key dilemmas. Moreover, there is a lingering misperception that developing leadership capacity is reserved for physical therapists who assume positional or formal roles as “leaders” within communities, health care organizations, practices, or teams. This misperception focuses leadership development on “leading others” rather than “leading self.” Similarly, challenges exist between balancing the leadership development needs of the leader as a positional role and the act of “leading” as physical therapists practice and engage within all levels of care and within different communities—as individuals and within teams. This tension further complicates when and how best to prepare physical therapists to meet this essential skill set in clinical practice. The purpose of this perspective is to describe nonpositional self-leadership and its importance to physical therapy practice, to propose common or contemporary leadership-related terminology, and to suggest a framework for leadership development. Through accomplishing these purposes, readers may be encouraged to change and adopt recommendations.
Variation in Racial and Ethnic Representation of Heart Transplant Recipients, Waitlists, and Local Census Demographics Across Transplant Centers in the US
Authors: Thomas Edward 
Published: March 2022

AbstractAs the uses and needs for heart transplants around the world continue to rise, it’s vital to investigate how the recent boom in demand comparative to availability affects racial and ethnic groups, especially in the representation in heart transplant waitlists and recipients. Here, comparisons between the racial/ethnic representation in heart transplant waitlists and recipients at heart transplant centers through the Scientific Registry for Transplant Recipients (SRTR) are drawn, comparative to the racial/ethnic representation in the location that these centers are located. Findings point towards the overrepresentation of White individuals in both waitlists and recipients, and underrepresentation in all other ethnic minorities --except African Americans-- in waitlists and recipients comparative to their demographic representation in the location of the centers. This difference in representation is largest for Hispanics/Latinos and those that the SRTR classify as “Other”. Though just a snapshot of representation between 07/01/2019 and 06/30/2020, this may point to various systemic issues in the accessibility of care of minorities, especially during the COVID-19 pandemic, that need to be addressed as the general populous ages and heart transplants are increasingly relied upon as a treatment for cardiovascular conditions and failure.
An observational study of uptake and adoption of the NHS App in England
Authors: Tewolde Salina , Costelloe Céire , PowelI John , Papoutsi Chrysanthi , Reidy Claire , Gudgin Bernard , Shenton Craig , Greaves Felix 
Published: March 2022

AbstractObjectivesThis study aimed to evaluate patterns of uptake and adoption of the NHS App. Data metrics from the NHS App were used to assess acceptability by looking at total app downloads, registrations, appointment bookings, GP health records viewed, and prescriptions ordered. The impact of the UK COVID-19 lockdown and introduction of the COVID Pass were also explored to assess App usage and uptake.MethodsDescriptive statistics and an interrupted time series analysis were used to look at monthly NHS App metrics at a GP practice level from January 2019-May 2021 in the population of England. Interrupted time series models were used to identify changes in level and trend among App usage and the different functionalities before and after the first COVID-19 lockdown. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used for reporting and analysis.ResultsBetween January 2019 and May 2021, there were a total of 8,524,882 NHS App downloads and 4,449,869 registrations. There was a 4-fold increase in app downloads from April 2021 (650,558 downloads) to May 2021 (2,668,535 downloads) when the COVID Pass feature was introduced. Areas with the highest number of App registrations proportional to the GP patient population occurred in Hampshire, Southampton and Isle of Wight CCG, and the lowest in Blackburn with Darwen CCG. After the announcement of the first lockdown (March 2020), a positive and significant trend in the number of login sessions was observed at 602,124 (p=0.004)** logins a month. National NHS App appointment bookings ranged from 298 to 42,664 bookings per month during the study period. The number of GP health records viewed increased by an average of 371,656 (p=0.001)** views per month and the number of prescriptions ordered increased by an average of 19934 (p<0.001)*** prescriptions per month following the first lockdown.ConclusionThis analysis has shown that uptake and adoption of the NHS App was positive post lockdown, and increased significantly due to the COVID Pass feature being introduced, but further research is needed to measure the extent to which it improves patient experience and influences health service access and care outcomes.
Meta-analysis fine-mapping is often miscalibrated at single-variant resolution
Authors: Kanai Masahiro , Elzur Roy , Zhou Wei ,   Global Biobank Meta-analysis Initiative, Daly Mark J , Finucane Hilary K 
Published: March 2022

AbstractMeta-analysis is pervasively used to combine multiple genome-wide association studies (GWAS) into a more powerful whole. To resolve causal variants, meta-analysis studies typically apply summary statistics-based fine-mapping methods as they are applied to single-cohort studies. However, it is unclear whether heterogeneous characteristics of each cohort (e.g., ancestry, sample size, phenotyping, genotyping, or imputation) affect fine-mapping calibration and recall. Here, we first demonstrate that meta-analysis fine-mapping is substantially miscalibrated in simulations when different genotyping arrays or imputation panels are included. To mitigate these issues, we propose a summary statistics-based QC method, SLALOM, that identifies suspicious loci for meta-analysis fine-mapping by detecting outliers in association statistics based on ancestry-matched local LD structure. Having validated SLALOM performance in simulations and the GWAS Catalog, we applied it to 14 disease endpoints from the Global Biobank Meta-analysis Initiative and found that 67% of loci showed suspicious patterns that call into question fine-mapping accuracy. These predicted suspicious loci were significantly depleted for having likely causal variants, such as nonsynonymous variants, as a lead variant (2.7x; Fisher’s exact P = 7.3 × 10−4). Compared to fine-mapping results in individual biobanks, we found limited evidence of fine-mapping improvement in the GBMI meta-analyses. Although a full solution requires complete synchronization across cohorts, our approach identifies likely spurious results in meta-analysis fine-mapping. We urge extreme caution when interpreting fine-mapping results from meta-analysis.
Identification of novel genetic variants in the malaria vaccine candidate PfRh5: structure-guided insights into potential function
Authors: Mangou Khadidiatou , Moore Adam J. , Thiam Laty Gaye , Ba Aboubacar , Orfanó Alessandra , Desamours Ife , Ndegwa Duncan Ndungu , Goodwin Justin , Guo Yicheng , Sheng Zizhang , Patel Saurabh D. , Diallo Fatoumata , Sene Seynabou D. , Pouye Mariama N. , Faye Awa Thioub , Nunez Vanessa , Diagne Cheikh Tidiane , Sadio Bacary Djilocalisse , Shapiro Lawrence , Faye Ousmane , Mbengue Alassane , Bei Amy K. 
Published: March 2022

ABSTRACTThe recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive diversity of Plasmodium falciparum antigens. While genetic diversity plays a major role in immune evasion and is a barrier to the development of both natural and vaccine-induced protective immunity, it has been under-prioritized in the evaluation of malaria vaccine candidates. This study uses genomic approaches to evaluate genetic diversity in next generation malaria vaccine candidate PfRh5. We used targeted deep amplicon sequencing to identify non-synonymous Single Nucleotide Polymorphisms (SNPs) in PfRH5 (Reticulocyte-Binding Protein Homologue 5) in 189 P. falciparum positive samples from Southern Senegal and identified 74 novel SNPs. We evaluated the population prevalence of these SNPs as well as the frequency in individual samples and found that only a single SNP, C203Y, was present at every site. Many SNPs were unique to the individual sampled, with over 90% of SNPs being found in just one infected individual. In addition to population prevalence, we assessed individual level SNP frequencies which revealed that some SNPs were dominant (frequency of greater than 25% in a polygenomic sample) whereas most were rare, present at 2% or less of total reads mapped to the reference at the given position. Structural modeling uncovered 3 novel SNPs occurring under epitopes bound by inhibitory monoclonal antibodies, potentially impacting immune evasion, while other SNPs were predicted to impact PfRh5 structure or interactions with the receptor or binding partners. Our data demonstrate that PfRh5 exhibits greater genetic diversity than previously described, with the caveat that most of the uncovered SNPs are at a low overall frequency in the individual and prevalence in the population. The structural studies reveal that novel SNPs could have functional implications on PfRh5 receptor binding, complex formation, or immune evasion, supporting continued efforts to validate PfRh5 as an effective malaria vaccine target and development of a PfRh5 vaccine.
A SARS-CoV-2 negative antigen rapid diagnostic in RT-qPCR positive samples correlates with a low likelihood of infectious viruses in the nasopharynx
Authors: Corrêa Isadora Alonso , Faffe Débora Souza , Galliez Rafael Mello , Gonçalves Cássia Cristina Alves , Araújo Maia Richard , da Silva Gustavo Peixoto , Rebello Moreira Filipe Romero , Mariani Diana , Campos Mariana Freire , de Carvalho Leitão Isabela , de Souza Marcos Romário , Cunha Marcela Sabino , dos Santos Nascimento Érica Ramos , de Jesus Ribeiro Liane , da Cruz Thais Felix Cordeiro , Policarpo Cintia , Gonzales Luis , Rodgers Mary A , Berg Michael , Vijesurier Roy , Cloherty Gavin A , Hackett John , da Costa Ferreira Orlando , Castiñeiras Terezinha Marta Pereira Pinto , Tanuri Amilcar , da Costa Luciana Jesus 
Published: March 2022

AbstractSARS-CoV-2 transmission occurs even among fully vaccinated individuals; thus, prompt identification of infected patients is central to control viral circulation. Antigen rapid diagnostic tests (Ag-RDT) are highly specific, but sensitivity is variable.Discordant RT-qPCR vs Ag-RDT results are reported, raising the question of whether negative Ag-RDT in positive RT-qPCR samples could imply the absence of infectious viruses. To study the relationship between a negative Ag-RDT results with virological, molecular, and serological parameters, we selected a cross sectional and a follow-up dataset and analyzed virus culture, subgenomic RNA quantification, and sequencing to determine infectious viruses and mutations. We demonstrated that a positive SARS-CoV-2 Ag-RDT result correlates with the presence of infectious virus in nasopharyngeal samples. A decrease in sgRNA detection together with an expected increase in detectable anti-S and anti-N IgGs was verified in negative Ag-RDT / positive RT-qPCR samples. The data clearly demonstrates the less likelihood of a negative Ag-RDT sample to harbor infectious SARS-CoV-2 and consequently with a lower transmissible potential.
A Meta-Analytic Investigation of Grey Matter Differences in Anorexia Nervosa and Autism Spectrum Disorder
Authors: Sader Michelle , Williams Justin H. G. , Waiter Gordon D. 
Published: March 2022

ABSTRACTRecent research reports Anorexia Nervosa (AN) to be highly dependent upon neurobiological function. Some behaviours, particularly concerning food selectivity are found in populations with both Autism Spectrum Disorder (ASD) and AN, and there is a proportionally elevated number of anorexic patients exhibiting symptoms of ASD. We performed a systematic review of structural MRI literature with the aim of identifying common structural neural correlates common to both AN and ASD. Across 46 ASD publications, a meta-analysis of volumetric differences between ASD and healthy controls revealed no consistently affected brain regions. Meta-analysis of 23 AN publications revealed increased volume within the orbitofrontal cortex and medial temporal lobe, and adult-only AN literature revealed differences within the genu of the anterior cingulate cortex. The changes are consistent with alterations in flexible reward-related learning and episodic memory reported in neuropsychological studies. There was no structural overlap between ASD and AN. Findings suggest no consistent neuroanatomical abnormality associated with ASD, and evidence is lacking to suggest that reported behavioural similarities between those with AN and ASD are due to neuroanatomical structural similarities.
TUNNEL WIDENING OF ACL RECONSTRUCTION AUGMENTED BY AN PLATELET RICH OSTEOCONDUCTIVE-OSTEOINDUCTIVE ALLOGRAFT COMPOUND: A RANDOMIZED BLIND-ANALYSIS PILOT STUDY
Authors: Solomon Ruth , Hommen Jan Pieter , Travascio Francesco 
Published: March 2022

ABSTRACTBackgroundThe anterior cruciate ligament (ACL) is a commonly injured ligament in the knee. Bone tunnel widening is a known phenomenon after soft-tissue ACL reconstruction and etiology and clinical relevance have not been fully elucidated. Osteoconductive compounds are biomaterials providing an appropriate scaffold for bone formation such as demineralized bone matrix. Osteoinductive materials contain growth factors stimulating bone lineage cells and bone growth. A possible application of osteoinductive/osteoconductive (OIC) material is in ACL surgery.Questions/PurposesWe hypothesized that OIC placed in ACL bone tunnels: 1) reduces tunnel widening, 2) improves graft maturation and 3) reduces tunnel ganglion cyst formation. To test this hypothesis, this study evaluated the osteogenic effects of demineralized bone matrix (DBM) and platelet rich plasma (PRP) on tunnel widening, graft maturation, and ganglion cyst formation.Study DesignRandomized controlled clinical trial pilot study.MethodsA total of 26 patients electing ACL reconstruction surgery were randomized between OIC and control group. Measurements of tunnel expansion and graft-tunnel incorporation were conducted via quantitative image analysis of MRI scans performed at six months after surgery for both groups.ResultsNo patients had adverse post-operative reactions or infections. The use of OIC significantly reduced tunnel widening (p < 0.05) and improved graft maturation (p < 0.05). Patients treated with OIC presented with a significantly lower prevalence of ganglion cyst compared to the control group (p < 0.05).ConclusionThe use of OIC has measurable effects on the reduction of tunnel widening, improved graft maturation and decreased size of ganglion cyst after ACL reconstruction.Clinical RelevanceThis study explored the utilization of biologics to minimize bone tunnel widening in ACL reconstruction surgery.
SARS-CoV-2 infections in infants in Haiti 2020-2021; evidence from a serological cohort
Authors: Louis Rigan , Pu Ruiyu , Logan Tracey D , Trimmer-Smith Luke , Chamblain Richard , Gallagher Adriana , De Rochars Valery Madsen Beau , Nelson Eric , Cummings Derek AT , Long Maureen T , Morris J. Glenn 
Published: March 2022

SummaryBetween February 2019 and March 2021, 388 dried blood spot samples were obtained from 257 children <30 months of age who were part of a longitudinal maternal/infant cohort in Haiti. Among the children followed, 16.7% became seropositive; sampling date was the only covariate associated with the hazard of seroconversion.
Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy
Authors: Otero Sebastian , Miller Emily S. , Sunderraj Ashwin , Shanes Elisheva D. , Sakowicz Allison , Goldstein Jeffery A. , Mithal Leena B. 
Published: March 2022

AbstractBackgroundPregnant persons are at increased risk of severe COVID-19 and adverse obstetric outcomes. Understanding maternal antibody response and transplacental transfer after SARS-CoV-2 infection and COVID-19 vaccination is important to inform public health recommendations.MethodsThis prospective observational cohort study included 351 birthing individuals who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. IgG and IgM to SARS-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across 1) disease severity for those with SARS-CoV-2 infection and 2) infection versus vaccination.FindingsThere were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection category had higher maternal and cord blood IgG levels (p=0.0001, p=0.0001). Median IgG transfer ratio was 0.87-1.2. Maternal and cord blood IgG were higher after vaccination than infection (p=0.001, p=0.001). Transfer ratio was higher after 90 days in the vaccinated group (p<0.001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (p<0.0001). There were no significant differences by fetal sex.InterpretationCOVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG levels, higher cord blood IgG, and higher transfer ratio after 90 days compared to SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.