bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Prevalence of Rare Copy Number Variants in Treatment-Resistant Psychosis
Authors: Farrell Martilias , Dietterich Tyler E , Harner Matthew K , Bruno Lisa M , Filmyer Dawn M , Shaughnessy Rita A , Lichtenstein Maya L , Xavier Rose Mary , Britt Allison M , Biondi Tamara F , Crowley James J , Lázaro-Muñoz Gabriel , Forsingdal Annika E , Nielsen Jacob , Didriksen Michael , Berg Jonathan S , Wen Jia , Szatkiewicz Jin , Sullivan Patrick F , Josiassen Richard C 
Published: May 2022

AbstractBackgroundIt remains unknown why ∼30% of patients with psychotic disorders fail to respond to treatment. Previous genomic investigations into treatment-resistant psychosis have been inconclusive, but some evidence suggests a possible link between rare disease-associated copy number variants (CNVs) and worse clinical outcomes in schizophrenia. Here, we test whether schizophrenia-associated CNVs are more prevalent in patients with treatment-resistant psychotic symptoms compared to previously published schizophrenia cases not selected for treatment-resistance.MethodsCNVs were identified using chromosomal microarrays and exome sequencing in 509 patients with treatment-resistant psychosis (a lack of clinical response to ≥ 3 adequate antipsychotic medication trials over at least five years of psychiatric hospitalization). Prevalence of schizophrenia-associated CNVs in this sample was compared against a previous large schizophrenia cohort study.ResultsIn total, 47 cases (9.2%) carried at least one CNV with known or possible neuropsychiatric risk. The prevalence of schizophrenia-associated CNVs (n=21; 4.1%) was significantly increased compared to a previous schizophrenia cohort study (p = 0.005322; OR = 1.93). This increase in prevalence was primarily due to duplications at 15q11.2-q13.1 and 16p11.2, which were independently associated with treatment-resistance in pairwise loci-based analysis.ConclusionsThese findings suggest that rare schizophrenia-associated CNVs, particularly duplications of 15q11.2-q13.1 and 16p11.2, may serve as biological entry points for studying treatment resistance. Further investigation will be necessary to elucidate the spectrum of phenotypic characteristics observed in adult psychiatric patients with disease-associated CNVs.
Longitudinal analysis reveals elevation then sustained higher expression of autoantibodies for six months after SARS-CoV-2 infection
Authors: Bhadelia Nahid , Olson Alex , Smith Erika , Riefler Katherine , Cabrejas Jacob , Ayuso Maria-Jose , Clarke Katherine , Yuen Rachel R. , Lin Nina H. , Manickas-Hill Zachary J. , Rifkin Ian , Bujor Andreea , Sagar Manish , Belkina Anna C. , Snyder-Cappione Jennifer E. 
Published: May 2022

AbstractHigh autoantibody levels are found in individuals hospitalized for COVID-19. The temporal trajectories and levels of these autoantibodies months into convalescence after SARS-CoV-2 infection are unclear. It is also unknown if the composite autoantibody signatures of convalescent SARS-CoV-2-infected individuals resemble those with diagnosed autoimmune diseases. We measured the circulating levels of 17 autoantibodies associated with autoimmune connective tissue diseases from SARS-CoV-2 hospitalized and outpatient participants, as well as from individuals with scleroderma (SSc), systemic lupus erythematosus (SLE), and uninfected pre-pandemic controls. Seven of the 17 autoantibodies measured were higher in hospitalized and/or outpatient SARS-CoV-2 individuals an average of six months after symptom onset compared with controls, with multivariate analyses revealing links between SARS-CoV-2 infection and positivity of SSB-La, Sm, Proteinase 3, Myleoperoxidase, Jo-1, and Ku reactive IgG six months post-symptom onset. Autoantibody levels from SARS-CoV-2 infected individuals were followed over time from initial symptom onset for an average of six months, and different temporal autoantibody trajectories were classified. A ‘negative, then positive’ expression pattern was found for at least one autoantibody in 18% of the outpatient and 53% of the hospitalized participants, indicating initiation and durable expression of self-reactive immune responses post-infection, particularly with severe acute illness. Analysis of individual participant autoantibody expression patterns revealed similar patterns between pre-pandemic and convalescent SARS-CoV-2 infected groups that are distinct from participants with both the SSc and SLE. As autoantibody positivity can occur years prior to autoimmune disease onset, the possibility that SARS-CoV-2-associated autoantibodies are a herald of future autoimmune disorders requires further investigation.One Sentence SummaryAutoantibody levels rise after acute SARS-CoV-2 infection and remain elevated for at least six months after symptom onset in participants with mild or severe COVID-19.
Managing COVID-19 in an Australian designated isolation facility: Implications for current and future healthcare crises
Authors: Achat Helen M , Mittal Rakhi , Stubbs Joanne M , Gilroy Nicky , Schindeler Suzanne K , Shaban Ramon Z , Solano Thomas 
Published: May 2022

AbstractHealth care workers’ (HCWs) lived experiences and perceptions of the pandemic can prove to be a valuable resource in the face of a seemingly persistent Novel coronavirus disease 2019 (COVID-19) – to inform ongoing efforts, as well as identify components essential to a crisis preparedness plan and the issues pertinent to supporting relevant, immediate change. We employed a phenomenological approach and, using purposive sampling, conducted 39 semi-structured interviews with senior healthcare professionals who were employed at a designated COVID-19 facility in New South Wales (NSW), Australia during the height of the pandemic in 2020. Participants comprised administrators, heads of department and senior clinicians. We obtained these HCWs’ (i) perspectives of their lived experience on what was done well and what could have been done differently and (ii) recommendations on actions for current and future crisis response. Four themes encapsulated respondents’ insights that should inform our capacity to meet current needs, direct meaningful and in situ change, and prepare us for future crises. Respondents’ observations and recommendations are informative for decision-makers tasked with mobilising an efficacious approach to the next health crisis and, in the interim, would aid the governance of a more robust workforce to effect high quality patient care in a safe environment.
Grey matter morphometric biomarkers for classifying early schizophrenia and PD psychosis: a multicentre study
Authors: Knolle Franziska , Arumugham Shyam S. , Barker Roger A. , Chee Michael W.L. , Justicia Azucena , Kamble Nitish , Lee Jimmy , Liu Siwei , Lenka Abhishek , Lewis Simon J.G. , Murray Graham K. , Pal Pramod Kumar , Saini Jitender , Szeto Jennifer , Yadav Ravi , Zhou Juan H. , Koch Kathrin 
Published: May 2022

AbstractPsychotic symptoms occur in a majority of schizophrenia patients, and in approximately 50% of all Parkinson’s disease (PD) patients. Altered grey matter (GM) structure within several brain areas and networks may contribute to their pathogenesis. Little, however, is known about transdiagnostic similarities when psychotic symptoms occur in different disorders, such as schizophrenia and PD.The present study investigated a large, multicenter sample containing 722 participants: 146 patients with first episode psychosis, FEP; 106 individuals at-risk mental state for developing psychosis, ARMS; 145 healthy controls matching FEP and ARMS, Con-Psy; 92 PD patients with psychotic symptoms, PDP; 145 PD patients without psychotic symptoms, PDN; 88 healthy controls matching PDN and PDP, Con-PD. We applied source-based morphometry in association with receiver operating curves (ROC) analyses to identify common GM structural covariance networks (SCN) and investigated their accuracy in identifying the different patient groups. We assessed group-specific homogeneity and variability across the different networks and potential associations with clinical symptoms.SCN-extracted GM values differed significantly between FEP and Con-Psy, PDP and Con-PD as well as PDN and Con-PD, indicating significant overall grey matter reductions in PD and early schizophrenia. ROC analyses showed that SCN-based classification algorithms allow good classification (AUC∼0.80) of FEP and Con-Psy, and fair performance (AUC∼0.72) when differentiating PDP from Con-PD. Importantly, best performance was found in partly the same networks including the precuneus. Finally, reduced GM volume in SCN with increased variability was linked to increased psychotic symptoms in both FEP and PDP.Alterations within selected SCNs may be related to the presence of psychotic symptoms in both early schizophrenia and PD psychosis, indicating some commonality of underlying mechanisms. Furthermore, results provide first evidence that GM volume within specific SCNs may serve as a biomarker for identifying FEP and PDP.
Accuracy and Glycemic Efficacy of Continuous Glucose Monitors in Critically Ill COVID-19 Patients: a Retrospective Study
Authors: Boeder Schafer , Kobayashi Emily , Ramesh Gautam , Serences Brittany , Kulasa Kristen , Majithia Amit R. 
Published: May 2022

AbstractBackgroundContinuous Glucose Monitoring (CGM) is approved for insulin dosing decisions in the ambulatory setting, but not currently for inpatients. CGM has the capacity to reduce patient-provider contact in inpatients with coronavirus disease 2019 (COVID-19), thus potentially reducing in hospital virus transmission. However, there are sparse data on the accuracy and efficacy of CGM to titrate insulin doses in inpatients.MethodsUnder an emergency use protocol, CGM (Dexcom G6) was used alongside standard point-of-care (POC) glucose measurements in patients critically ill from complications of COVID-19 requiring intravenous (IV) insulin. Glycemic control during IV insulin therapy was retrospectively assessed comparing periods with and without adjunctive CGM use. Accuracy metrics were computed and Clarke Error Grid analysis performed comparing CGM glucose values with POC measurements.Results24 critically ill patients who met criteria for emergency use of CGM resulted in 47333 CGM and 5677 POC glucose values. During IV insulin therapy, individuals’ glycemic control improved when CGM was used (mean difference -30.2 mg/dL). Among 2194 matched CGM:POC glucose pairs a high degree of concordance was observed with a MARD of 14.8% and 99.5% of CGM:POC pairs falling in Zones A and B of the Clarke Error Grid.ConclusionsCGM use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. CGM glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient-provider contact and mitigating infection transmission.
Automated Prioritization of Sick Newborns for Whole Genome Sequencing Using Clinical Natural Language Processing and Machine Learning
Authors: Peterson Bennet , Hernandez Javier , Hobbs Charlotte , Jenkins Sabrina Malone , Moore Barry , Juarez Edwin , Zoucha Samuel , Kobayashi Erica Sanford , Bainbridge Matthew N. , Oriol Albert , Brunelli Luca , Kingsmore Stephen , Yandell Mark 
Published: May 2022

AbstractBackgroundRapidly and efficiently identifying critically ill infants for WGS is a costly and challenging task currently performed by scarce, highly trained experts, and is a major bottleneck for application of WGS in the NICU. Automated means to prioritize patients for WGS are thus badly needed.MethodsInstitutional databases of Electronic Health Records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for Rapid and Whole Genome Sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a Clinical Natural Language Processing (CNLP) workflow with a machine learning-based prioritization tool we call the Mendelian Phenotype Search Engine (MPSE).ResultsMPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children’s Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients.ConclusionsOur results indicate that an entirely automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel.
Phase I study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B
Authors: Orozco Natalia Martin , Vale Noah , Mihic Alan , Amor Talya , Reiter Lawrence , Arita Yuko , Samson Reuben , Hu Queenie , Gingras Anne-Claude , Sorenson Brad , Marcusson Eric G. , Patel Piyush 
Published: May 2022

ABSTRACTPTX-COVID19-B mRNA vaccine encodes for SARS-CoV-2 Spike protein G614 variant and lacks the proline-proline (986-987 position) mutation present in other COVID-19 vaccines. This Phase 1 observer-blinded, randomized, placebo-controlled, ascending dose study evaluated the safety, tolerability, and immunogenicity of two doses of PTX-COVID19-B vaccine in healthy seronegative adults. Participants received two intramuscular doses, 4 weeks apart, of 16-μg, 40-μg, or 100-μg PTX-COVID19-B. Adverse events were generally mild to moderate, self-resolving, and transient. The most common solicited local and systemic adverse event was pain at the injection site and headache, respectively. After the first immunization, all participants seroconverted, producing high titers of anti-receptor-binding-domain, anti-Spike, and neutralizing antibodies, including neutralizing antibodies against the ancestral viral strain and the Alpha, Beta, and Delta variants of concern, in a dose-dependent way, further increasing over 10-20 times after the second dose. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-μg dose showed fewer adverse reactions than the 100-μg dose, supporting further investigation of the 40-μg dose.Clinical Trial RegistrationClinicalTrials.gov identifier: NCT04765436 (https://clinicaltrials.gov/ct2/show/NCT04765436)
Factors influencing the sustainability of homestead vegetable production intervention in Rufiji, Tanzania: A cross-sectional mixed methods study
Authors: Mlalama Killian N , Matemu Athanasia , Kosia Ephraim , Canavan Chelsey R , Bellows Alexandra L , Blakstad Mia , Noor Ramadhani A , Kinabo Joyce , Fawzi Wafaie W , Masanja Honorati , Mosha Dominic 
Published: May 2022

AbstractBackgroundThere is growing evidence that home vegetable gardening interventions improve food security and nutrition outcomes at the family level. This study assessed factors influencing the sustainability of homestead vegetable production intervention in Rufiji district, Tanzania, one year after the cessation of external support.MethodsThis was a cross-sectional study using both quantitative and qualitative data collection methods. A total of 247 randomly selected women from households who participated in the homestead vegetable intervention were interviewed using a structured questionnaire. The study held four focus group discussions with women from households that participated in the intervention, and four In-Depth interviews with two extension workers, one community health worker, and one agriculture district officer. Multiple logistic regression for quantitative data and thematic analysis for qualitative data was conducted.ResultsAbout 20.24% (50/247) of households sustained homestead vegetable production for one year after the intervention phased out. Lack of seeds (adjusted OR=1.26: CI=0.39-0.89) and either manure or fertilizers (adjusted OR=1.69: CI =1.08-2.63) were significant factors influencing the sustainability of homesteads vegetable production. In the Focus Group discussions (FGDs) and In-Depth Interview (IDIs), all participating women and extension workers reported high cost of water, destruction from free-grazing animals, agriculture pests and diseases, poor soil fertility, shortage of seeds, and lack of capital affected homestead vegetable production sustainability.ConclusionExisting individual, community, and system challenges influence the sustainability of external-funded agriculture and nutrition interventions. The study findings underscore the importance of community authorities, scientists, and policymakers in having a well-thought sustainability plan in all promising external-funded interventions.
PCSK6 and Survival in Idiopathic Pulmonary Fibrosis
Authors: Oldham Justin M. , Allen Richard J. , Lorenzo-Salazar Jose M. , Molyneaux Philip L. , Ma Shwu-Fan , Joseph Chitra , Kim John S. , Guillen-Guio Beatriz , Hernández-Beeftink Tamara , Kropski Jonathan A. , Huang Yong , Lee Cathryn T. , Adegunsoye Ayodeji , Pugashetti Janelle Vu , Linderholm Angela L. , Vo Vivian , Strek Mary E. , Jou Jonathan , Muñoz-Barrera Adrian , Rubio-Rodriguez Luis A. , Hubbard Richard , Hirani Nik , Whyte Moira K.B. , Hart Simon , Nicholson Andrew G. , Lancaster Lisa , Parfrey Helen , Rassl Doris , Wallace William , Valenzi Eleanor , Zhang Yingze , Mychaleckyj Josyf , Stockwell Amy , Kaminski Naftali , Wolters Paul J. , Molina-Molina Maria , Fahy William A. , Martinez Fernando J. , Hall Ian P. , Tobin Martin D. , Maher Toby M. , Blackwell Timothy S. , Yaspan Brian L. , Jenkins R Gisli , Flores Carlos , Wain Louise V , Noth Imre 
Published: May 2022

AbstractRationaleIdiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. Novel therapies and prognostic biomarkers are needed.ObjectiveTo identify and validate molecular determinants of IPF survival.MethodsA staged genome-wide association study (GWAS) was performed using paired genomic and survival data. Stage I cases were drawn from centers across the US and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplant-free survival (TFS). Stage I variants with nominal significance (p<5×10−5) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance (p<5×10−8). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance.Main ResultsAfter quality controls, 1481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of proprotein convertase subtilisin/kexin type 6 (PCSK6) reaching genome-wide significance (HR 4.11; 95%CI 2.54-6.67; p=9.45×10−9). PCSK6 protein was highly expressed in IPF lung parenchyma and negatively correlated with survival. Peripheral blood PCSK6 gene expression and plasma concentration were associated with reduced transplant-free survival.ConclusionsWe identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein may serve as prognostic biomarker in IPF and potential therapeutic target.
HOXA Amplification Defines a Genetically Distinct Subset of Angiosarcomas
Authors: Xie Hongbo Michael , Bernt Kathrin M. 
Published: May 2022

AbstractAngiosarcoma is a rare, devastating malignancy with few curative options for disseminated disease. We analyzed a recently published genomic data set of 48 angiosarcomas and noticed recurrent amplifications of HOXA cluster genes in 33% of patients. HOXA genes are master regulators of embryonic vascular development and adult neovascularization, which provides a molecular rationale to suspect that amplified HOXA genes act as oncogenes in angiosarcoma. HOXA amplifications typically affected multiple pro-angiogenic HOXA genes and co-occurred with amplifications of CD36 and KDR, whereas the overall mutation rate in these tumors was relatively low. HOXA amplifications were found most commonly in angiosarcomas located in the breast, and were rare in angiosarcomas arising in sun-exposed areas on the head, neck, face and scalp. Our data suggest that HOXA amplified angiosarcoma is a distinct molecular subgroup. Efforts to develop therapies targeting oncogenic HOX gene expression in AML and other sarcomas may have relevance for HOXA amplified angiosarcoma.
Time-specific effects of a multifaceted intervention on accelerometer-measured physical activity in primary school children: A cluster-randomized controlled trial
Authors: Liu Zheng , Yue Zhi-Han , Wen Li-Ming , Zhao Jinfeng , Zhou Shuang , Gao Ai-Yu , Zhang Fang , Wang Hai-Jun 
Published: May 2022

AbstractBackgroundIt is unclear whether intervention effects on school-aged children’s physical activity differ across specific periods of the week or day. This study aimed to assess the time-specific intervention effects on accelerometer-measured physical activity in primary school children.MethodsThis was a nested study in a cluster-randomized controlled trial conducted from September 2018 to June 2019 in China. The intervention group included 4 schools (119 children) and the control group included 4 schools (99 children) in Beijing. The obesity prevention intervention engaged schools and families to improve children’s physical activity. Outcome measures included accelerometer-assessed intensity and amounts of physical activity within specific periods of a week (weekday/weekend day) or a day (in-school/out-of-school periods). Linear mixed models were used to estimate intervention effects. Subgroup analyses were also conducted to examine potential moderators including sex, age, body mass index, physical activity, and accelerometer compliance.ResultsThe intervention lead to an increase in time engaged in moderate-to-vigorous physical activity (MVPA) within in-school periods of a day (adjusted mean difference: 0.54 minutes/hour; 95% confidence interval: 0.13, 0.94, P = 0.012) but it did not improve physical activity within out-of-school periods (P > 0.05) compared with the control group. There was no difference in the effect size across most of the moderators except for age, as younger children appeared to benefit more from the intervention in the improvement of in-school MVPA (Pinteraction = 0.035). No between-group differences were observed in physical activity within the whole weekday or weekend day (P > 0.05).ConclusionThe intervention effectively increased MVPA within in-school periods but did not improve out-of-school physical activity. Findings support the tailoring of intervention components to specific periods of a day to improve school-aged children’s whole pattern of physical activity.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT03665857