bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses than that of the Partially Effective gB/MF59 Vaccine
Authors: Hu Xintao , Karthigeyan Krithika P. , Herbek Savannah , Valencia Sarah M. , Jenks Jennifer A. , Webster Helen , Miller Itzayana G. , Connors Megan , Pollara Justin , Andy Caroline , Gerber Linda M. , Walter Emmanuel B. , Edwards Kathryn M. , Bernstein David I. , Hou Jacob , Koch Matthew , Panther Lori , Carfi Andrea , Wu Kai , Permar Sallie R. 
Published: August 2023

ABSTRACTBackgroundThe MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated ~50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting efforts to improve this vaccine design might yield a vaccine suitable for licensure. A vaccine candidate employing nucleoside-modified mRNAs encoding HCMV gB and pentameric complex (PC) encapsulated in lipid nanoparticle, mRNA-1647, is currently in late-stage efficacy trials. Yet, its immunogenicity has not been compared to the partially-effective gB/MF59 vaccine.MethodsWe assessed neutralizing and Fc-mediated IgG effector antibody responses induced by mRNA-1647, a vaccine comprising an equal mass of 6 mRNAs encoding gB and PC antigens, in both HCMV seropositive and seronegative vaccinees from a first-in-human clinical trial through 1-year following 3rdvaccination using a systems serology approach. Further, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative female adolescent gB/MF59 vaccine recipients.ResultsmRNA-1647 vaccination boosted pre-existing HCMV-specific IgG responses in seropositive vaccinees, including neutralizing and Fc-mediated effector antibody responses. In seronegative vaccinees, mRNA-1647 induced durable and functional HCMV-specific IgG responses. Elicited gB-specific IgG responses were lower than the PC-specific IgG responses. Additionally, gB-specific IgG and antibody-dependent cellular phagocytosis (ADCP) responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited robust neutralization and high antibody-dependent cellular cytotoxicity (ADCC) responses.ConclusionsmRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses. mRNA-1647-elicited gB-specific IgG responses were lower than PC-specific IgG responses and lower than those elicited by the partially effective gB/MF59. However, higher neutralization and ADCC responses were elicited by mRNA-1647 than gB/MF59.Clinical Trials RegistrationClinicalTrials.gov(NCT03382405, mRNA-1647) and (NCT00133497, gB/MF59).SummarymRNA-1647 HCMV vaccine elicited polyfunctional and durable antibody responses in humans. While the mRNA-1647-elicited glycoprotein B (gB)-specific IgG responses were lower than that of the moderately-effective gB/MF59 vaccine, the pentameric complex (PC)-specific IgG responses were strong.
COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records
Authors: Rison Stuart CG , Redfern Oliver , Mathur Rohini , Dostal Isabel , Carvalho Chris , Raisi-Estabragh Zahra , Robson John P 
Published: August 2023

ABSTRACTBackgroundThe COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities.Method and findingsIn 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (<80 years old, BP ≤140/90mmHg; 80 or more years old: ≤150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using ‘blood pressure control’ (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively.The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control.Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value<0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value<0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value<0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value<0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study.ConclusionThe COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.
Resident memory T cell precursors in tumor draining lymph nodes require type-1 IFN for optimal differentiation
Authors: Khatwani Nikhil , Searles Tyler , Han Jichang , Messier Cameron , Mittal Neeti , Hawkes Aaron , Molodstov Aleksey K. , Ramirez Delaney E. , Wilkins Owen , Huang Yina H. , Kolling Fred W. , Rosato Pamela C , Turk Mary Jo 
Published: August 2023

AbstractResident memory (Trm) cells play an essential role in anti-tumor immunity. However, little is known about the precursors that differentiate into protective Trm populations against cancer. Here we employed an established model of B16 melanoma neoadjuvant anti-CD4 therapy, to track tumor antigen-specific CD8+ T cells through tissues and across time; from their priming as effectors to their differentiation into Trm. We show that tumor-draining lymph nodes (TDLNs) contain Teff cells that begin to express canonical Trm markers CD103 and CD69. These tumor-specific Teff cells seeded skin and tumor during the effector phase of the response, although egress from these tissues was not required Trm development in LNs. Paired scRNAseq/scTCRseq was used to identify Teff clonotypes in TDLNs and trace their differentiation, in real-time, into Trm populations. We found that expanded clonotypes favored the Trm fate and were unlikely to co-differentiate into other lineages. Precursors of Trm (pre-Trm) clonotypes that subsequently seeded populations throughout tumors, LNs, and skin, were characterized by early expression of tissue residency, stemness, and type-1 IFN sensing genes. These multipotent pre-Trm cells sensed plasmacytoid dendritic cell-derived type-1 interferons in TDLNs, and their expression of interferon alpha receptor was required for their formation of Trm populations in LNs but not in skin. These findings reveal the defining features of pre-Trm cells in response to tumor antigens, and reveal a previously unappreciated role for type-1 IFNs in programming regional Trm immunity to cancer.One Sentence SummaryAnti-tumor effector CD8 T cells adopt early characteristics of tissue residency and stemness, and rely on the sensing of type-1 interferons for their local differentiation into resident memory T cells.
Exome sequencing in Asian populations identifies rare deficientSMPD1alleles that increase risk of Parkinson’s disease
Authors: Chew Elaine GY , Liu Zhehao , Li Zheng , Chung Sun Ju , Lian Michelle M , Tandiono Moses , Ng Ebonne Y , Tan Louis CS , Chng Wee Ling , Tan Tiak Ju , Peh Esther KL , Ho Ying Swan , Chen Xiao Yin , Lim Erin YT , Chang Chu Hua , Leong Jonavan J , Heng Yue Jing , Peh Ting Xuan , Chan Ling-Ling , Chao Yinxia , Au Wing-Lok , Prakash Kumar M , Lim Jia Lun , Tay Yi Wen , Mok Vincent , Chan Anne YY , Lin Juei-Jueng , Jeon Beom S , Song Kyuyoung , Tham Clement CY , Pang Chi Pui , Ahn Jeeyun , Park Kyu Hyung , Wiggs Janey L , Aung Tin , Tan Ai-Huey , Annuar Azlina Ahmad , Makarious Mary B. , Blauwendraat Cornelis , Nalls Mike A , Robak Laurie A. , Alcalay Roy N. , Gan-Or Ziv , Lim Shen-Yang , Khor Chiea Chuen , Tan Eng-King , Wang Zhenxun , Foo Jia Nee 
Published: August 2023

AbstractParkinson’s disease is an incurable and progressive disease that adversely affects balance, muscle control, and movement. We hypothesized that the landscape of rare, protein-altering genetic variants could provide further mechanistic insights into disease pathogenesis. We performed whole-exome sequencing on 4,298 persons with Parkinson’s disease and 5,512 unaffected controls from Singapore, Malaysia, Hong Kong, South Korea, and Taiwan. We tested for association between gene-based burden of rare, predicted damaging variants and risk of Parkinson’s disease. Genes surpassing exome-wide significance (P<2.5×10-6) were tested for replication in sequencing data from a further 5,585 Parkinson’s disease patients and 5,642 controls of Asian and European ancestry. We observed that carriage of rare, protein-altering variants that were predicted to impair protein function atSMPD1(a gene encoding for acid sphingomyelinase) were significantly associated with increased risk of Parkinson’s disease. Refinement of variant classification using functional acid sphingomyelinase assays suggest that individuals carryingSMPD1variants with less than 44 percent of normal enzymatic activity show the strongest association with Parkinson’s disease risk in both the discovery (odds ratio (OR) = 2.37, 95% CI = 1.68 - 3.35,P= 4.35 × 10-7) and replication collections (OR = 2.18, 95% CI = 1.69 - 2.81,P= 4.80 × 10-10), leading to a significant observation when all data were meta-analyzed (OR = 2.24, 95% CI = 1.83 - 2.76,P= 1.25 × 10-15). Our findings affirm the importance of sphingomyelin metabolism in the pathobiology of neurodegenerative diseases and highlights the utility of functional genomic assays in large-scale exome sequencing studies.
A placebo-controlled clinical study to assess the impact of variable complex weak magnetic fields (VCMF’s) generated by the BeCurie™ (Evolv28) device on the subjects with perceived stress and anxiety
Authors: Jonnalagadda Mohan Krishna , Palle Lalitha , Pasumarthi Shyam Sunder , Gali Chaitanya Chakravarthi 
Published: August 2023

ABSTRACTBackgroundExposure to variable weak magnetic fields, reported to have shown beneficial effects on several neurological illnesses. However, existing therapies are costly, complex, and lack subject ease for frequent follow ups. In the current study, the novel BeCurie™ (Evolv28) wearable neck device that emits variable complex weak magnetic fields (VCMF’s) is evaluated for its positive impact on subjects with perceived stress and anxiety.MethodsEighteen participants were enrolled in this study. The primary outcomes of the study were to assess the improvements in perceived stress and anxiety symptoms in the BeCurie™ treated group. Stress and anxiety scores were assessed using DASS-21, HAM-A, and PSS. Quality of life was assessed using the MQoL-R questionnaire. Serum Cortisol and complete blood profile were assessed to understand the safety profile of BeCurie™ treatment.ResultsParticipants in the BeCurie™ group showed a significant reduction in stress and anxiety scores compared to the placebo group on Day 30. Furthermore, open label study assessments on Days 60 and 90 revealed improvements in self-reported stress and anxiety scores, significant time dependent improvements in all major domains of quality of life, including physical, psychological, existential, and support-based aspects of life. No adverse events were reported during the study. Comprehensive blood profile assessment showed no significant changes in either the placebo or BeCurie™ groups.ConclusionsThe findings indicate that VCMF’s emitted by the BeCurie™ device can be a supporting non-invasive alternative therapy for managing stress and anxiety. Nonetheless, the limitations of the study, including the small sample size and the lack of a follow-up assessment beyond 90 days, suggest that further investigations are needed to establish the long-term efficacy of BeCurie™ in managing stress and anxiety symptoms.
Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England
Authors: Mountain Rachael , Knight Jo , Heys Kelly , Giorgi Emanuele , Gatheral Timothy 
Published: August 2023

AbstractBackgroundPromoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.MethodsData on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.ResultsThe first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate, respectively.ConclusionsRoutinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.
Identification of patients at risk for pancreatic cancer in a 3-year timeframe based on machine learning algorithms
Authors: Zhu Weicheng , Aphinyanaphongs Yindalon , Kastrinos Fay , Simeone Diane M. , Pochapin Mark , Razavian Narges , Gonda Tamas 
Published: August 2023

AbstractImportanceEarly detection of pancreatic cancer (PC) remains challenging largely due to the low population incidence and few known risk factors. However, screening in at-risk populations and detection of early cancer has the potential to significantly alter survival.ObjectiveIn this study, we aim to develop a predictive model to identify patients at risk for developing new-onset PC at two and a half to three year time frameData SourcesWe used the Electronic Health Records (EHR) of a large medical system from 2000 to 2021 (N=537,410). The EHR data analyzed in this work consists of patients’ demographic information, diagnosis records, and lab values, which are used to identify patients who were diagnosed with pancreatic cancer and the risk factors used in the machine learning algorithm for prediction.ResultsWe identified 73 risk factors of pancreatic cancer with the Phenome-wide Association Study (PheWAS) on a matched case-control cohort. Based on them, we built a large-scale machine learning algorithm based on EHR. A temporally stratified validation based on patients not included in any stage of the training of the model was performed. This model showed an AUROC at 0.742 [0.727, 0.757] which was similar in both the general population and in a subset of the population who has had prior cross-sectional imaging. The prevalence of pancreatic cancer in those in the top 5 percentile of the risk score was 6 folds higher than the general population.ConclusionOur model leverages data extracted from a 6-month window of time in the electronic health record to identify patients at nearly 6-fold higher than baseline risk of developing pancreatic cancer 2.5 to 3 years from evaluation. This approach offers an opportunity to define an enriched population entirely based on static data, where current screening may be recommended.
Evidence-Based Practice Competencies among Nutrition Professionals and Students: A Systematic Review
Authors: Ghosh Nirjhar R. , Esmaeilinezhad Zahra , Zając Joanna , Creasy Rebecca A. , Lorenz Saundra G. , Crews Molly , Beathard Karen M. , Bala Malgorzata M. , Klatt Kevin C. , Johnston Bradley C. 
Published: August 2023

ABSTRACTBackgroundEvidence-based practice (EBP) promotes shared decision-making between clinicians and patients and has been widely adopted by various health professions including nutrition & dietetics, medicine and nursing.ObjectiveTo determine evidence-based practice (EBP) competencies among nutrition professionals and students reported in the literature.DesignSystematic review.Data sourcesMedline, Embase, CINAHL, ERIC, CENTRAL, ProQuest Dissertations and Theses Global, BIOSIS Citation Index, andClinicalTrials.govup to March 2023.Eligibility criteria for study selectionEligible primary studies had to objectively or subjectively document the assessment of at least one of six predefined core EBP competencies, including formulating structured clinical questions, searching the literature for best evidence, and assessing studies for methodological quality, magnitude (size) of effects, certainty of evidence for effects, and determining the clinical applicability of study results based on patient values and preferences.Data extraction and synthesisTwo reviewers independently screened articles and extracted data, including the reporting quality for eligible studies. Results were not amenable to meta-analysis and were thus summarized for each EBP competency.ResultsWe identified 12 eligible cross-sectional survey studies, comprised of 1065 participants, primarily registered dietitians, across six countries, with the majority assessed in the United States (n=470). The reporting quality of the survey studies was poor overall, with 43% of items not reported and 22% of items partially reported. Only one study (8%) explicitly used an objective questionnaire to assess EBP competencies. The proportion of studies reporting on each competency were: 17% on the formulation of clinical questions, 83% on searching the literature, 75% on methodological quality or critical appraisal, 58% on interpreting statistical results, and 75% on applying study results. In general, the six competencies were incompletely defined or reported (e.g., it was unclear what ‘applicability’ and ‘critical appraisal’ referred to, and what study designs were appraised by the participants). Two core competencies, the magnitude (size) of effects and the certainty of evidence for effects, were not assessed.ConclusionsAmong 12 included articles the overall quality of study reports was poor, and when EBP competencies were reported they were predominantly self-perceived assessments as opposed to objective assessments. No studies reported on competencies in assessing magnitude of effect or certainty of evidence, skills that are essential for optimizing clinical nutrition decision-making.Systematic review registrationPROSPERO CRD42022311916.
Machine learning based prediction of recurrence after curative resection for rectal cancer
Authors: Jeon Youngbae , Kim Young-Jae , Jeon Jisoo , Nam Kug-Hyun , Hwang Tae-Sik , Kim Kwang-Gi , Baek Jeong-Heum 
Published: August 2023

ABSTRACTPurposePatients with rectal cancer without distant metastases are typically treated with radical surgery. Post curative resection, several factors can affect tumor recurrence. This study aimed to analyze factors related to rectal cancer recurrence after curative resection using different machine learning techniques.MethodsConsecutive patients who underwent curative surgery for rectal cancer between 2004 and 2018 at Gil Medical Center were included. Patients with stage IV disease, colon cancer, anal cancer, other recurrent cancer, emergency surgery, or hereditary malignancies were excluded from the study. The SMOTETomek technique was used to compensate for data imbalance between recurrent and no-recurrent groups. Four machine learning methods, logistic regression (LR), support vector machine (SVM), random forest (RF), and XGBoost (XGB), were used to identify significant factors. To overfit and improve the model performance, feature importance was calculated using the permutation importance technique.ResultsA total of 3320 patients were included in the study. However, after exclusion, the total sample size of the study was 961 patients. The median follow-up period was 60.8 months (range:1.2-192.4). The recurrence rate during follow-up was 13.2% (n=127). After applying the SMOTETomek method, the number of patients in both groups, recurrent and non-recurrent group were equalized to 667 patients. After analyzing for 16 variables, the top eight ranked variables (pT, sex, concurrent chemoradiotherapy, pN, age, postoperative chemotherapy, pTNM, and perineural invasion) were selected based on the order of permutational importance. The highest area under the curve (AUC) was for the SVM method (0.831). The sensitivity, specificity, and accuracy were found to be 0.692, 0.814, and 0.798, respectively. The lowest AUC was obtained for the XGBloost method (0.804), with a sensitivity, specificity, and accuracy of 0.308, 0.928, and 0.845, respectively. The variable with highest importance was pT as assessed through SVM, RF, and XGBoost (0.06, 0.12, and 0.13, respectively), whereas pTNM had the highest importance when assessed by LR (0.05).ConclusionsIn the current study, SVM showed the best AUC, and the most influential factor across all machine learning methods except LR was found to be pT. Clinicians should be more alert if patients have a high pT stage during postoperative follow-up in rectal cancer patients.