bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of BA.1- and BA.4/BA.5-containing bivalent COVID-19 mRNA vaccines against symptomatic SARS-CoV-2 infection during the BA.5-dominant period in Japan
Authors: Arashiro Takeshi , Arima Yuzo , Kuramochi Jin , Muraoka Hirokazu , Sato Akihiro , Chubachi Kumi , Yanai Atsushi , Arioka Hiroko , Uehara Yuki , Ihara Genei , Kato Yasuyuki , Yanagisawa Naoki , Ueda Akihiro , Kato Hideaki , Oka Hideaki , Nishida Yusuke , Nidaira Yuki , Asami Takahiro , Jinta Torahiko , Nakamura Akira , Oba Kunihiro , Taniyama Daisuke , Yamamoto Kei , Tanaka Katsushi , Ueshima Kankuro , Fuwa Tetsuji , Stucky Ashley , Suzuki Tadaki , Smith Chris , Hibberd Martin , Ariyoshi Koya , Suzuki Motoi 
Published: May 2023

Abstract
In this multi-center prospective test-negative case-control study in Japan, the effectiveness of both BA.1-containing and BA.4/BA.5-containing bivalent COVID-19 mRNA vaccines against symptomatic infection during the BA.5-dominant period was high compared to no vaccination (65% and 76%) and moderate compared to monovalent vaccines administered over half a year before (46% combined).
Prevalence of Cardiometabolic Disease Risk Factors in People with HIV Initiating Anti-retroviral Therapy at a High-Volume HIV Clinic in Kampala, Uganda
Authors: Amutuhaire Willington , Mulindwa Frank , Castelnuovo Barbara , Brusselaers Nele , Schwarz Jean-Marc , Edrisa Mutebi , Dujanga Simon , Salata Robert A , Yendewa George A 
Published: May 2023

Abstract

Background
Cardiometabolic diseases are a leading cause of HIV-related morbidity and mortality, yet routine screening is not undertaken in high burden countries. We aimed to assess the prevalence and risk factors of the metabolic syndrome (MetS) and its components in adult Ugandan people living with HIV (PWH) initiating dolutegravir-based antiretroviral therapy (ART).

Methods
We conducted a cross-sectional study using baseline sociodemographic and clinical data of PWH aged ≥ 18 years enrolled in the GLUMED (Glucose metabolism changes in Ugandan HIV patients on Dolutegravir) Study from January to October 2021. MetS was defined as having ≥ 3 of the following: abdominal obesity, hypertension (HTN), hyperglycemia, elevated triglycerides and low high-density lipoprotein cholesterol. Multiple logistic regression was used to assess associations between potential risk factors and MetS and its components.

Results
309 PWH were analyzed (100% ART-naive, 59.2% female, median age 31 years and median CD4 count 318 cells/mm3). The prevalence of MetS was 13.9%. The most common cardiometabolic condition was dyslipidemia (93.6%), followed by abdominal obesity (34.0%), hyperglycemia (18.4%), and HTN (8.1%). In adjusted analysis, MetS was associated with age &gt; 40 years (adjusted odds ratio 3.33, 95% confidence interval 1.45-7.67) and CD4 count &gt; 200 cells/mm3 (3.79, 1.23-11.63). HTN was associated with age &gt; 40 years (2.96, 1.32-6.64), and dyslipidemia was associated with urban residence (4.99, 1.35-18.53).

Conclusion
Cardiometabolic risk factors were common in this young Ugandan cohort of PWH initiating dolutegravir-based ART, underscoring the need for programmatic implementation of surveillance and management of comorbidities in Uganda and similar settings.
Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer
Authors: Madan Ravi A , Bilusic Marijo , Stein Mark N , Donahue Renee N , Arlen Philip M , Karzai Fatima , Plimack Elizabeth , Wong Yu-Ning , Geynisman Daniel M , Zibelman Matthew , Mayer Tina , Strauss Julius , Chen Gang , Rauckhorst Myrna , McMahon Sheri , Couvillon Anna , Steinberg Seth , Figg William D , Dahut William L , Schlom Jeffrey , Gulley James L 
Published: May 2023

Abstract

Background
Before 2018, there was no standard of care for non-metastatic (M0) castration resistant prostate cancer nmCRPC. Androgen receptor antagonists (ARAs) were commonly used sequentially nmCRPC.

Methods
This was a multicenter, randomized clinical trial comparing the ARA flutamide+/−PROSTVAC, a pox viral vaccine targeting PSA that includes T-cell co-stimulatory molecules. Eligible men had negative CT and Tc99 bone scans, and rising PSA on ADT. Previous treatment with ARA was a stratification factor. Patients were also evaluated for antigen-specific immune responses using intracellular cytokine staining.

Results
Thirty-three patients randomized to flutamide and 31 to flutamide+vaccine. The median age was 71.8 and 69.8 years, respectively. The median time to treatment failure after a median potential follow-up of 46.7 months was, 4.5 months (range 2-70) for flutamide alone vs. 6.9 months (2.5-40; P = .38) with flutamide+vaccine. Seven patients in each arm had a &gt;50% PSA response. Antigen-specific responses were similar in both arms (58% of patients in flutamide alone and 56% in flutamide+vaccine). The treatments were well tolerated. The most common side effect &gt; grade 2 was injection site reaction seen in 29/31 vaccine patients which were self-limiting.

Conclusion
The combination of flutamide+PROSTVAC did not improve outcomes in men with nmCRPC compared with flutamide alone. (ClinicalTrials.gov Identifier: NCT00450463)
Stramenopile-Type Lipid Droplet Protein Functions as a Lipid Droplet Scaffold Protein in the Marine Diatom Phaeodactylum tricornutum
Authors: Yoneda Kohei , Oishi Reika , Yoshida Masaki , Matsuda Yusuke , Suzuki Iwane 
Published: May 2023

Abstract
Oleaginous microalgae are gaining great attention as feedstock for biofuels because of their substantial accumulation capacity for neutral lipids in the cytosolic compartment called the lipid droplet (LD). Understanding the regulatory mechanism of neutral lipid accumulation and degradation, which is mediated by LD-associated proteins, is an important issue in improving lipid productivity. However, LD-associated proteins vary among species and are waiting to be characterized in many microalgae. Stramenopile-type LD protein (StLDP) was previously identified as a primary LD protein in the marine diatom Phaeodactylum tricornutum. We produced a knockout mutant of StLDP by clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing. Also, we tried to complement this mutant by expressing recognition site–modified StLDP (RSM-StLDP), which is designed to avoid an attack by Cas9 nuclease expressing in the mutant. The RSM-StLDP:enhanced green fluorescent protein was localized to both LDs and the outer chloroplast-endoplasmic reticulum. The decrease in the LD number per cell, increase in LD size and no alteration of neutral lipid content in the mutant under nitrogen deficiency clearly indicate that StLDP acts as an LD scaffold protein. The number of LDs per cell increased in the complemented strain compared to wild-type (WT) cells. The LD morphology in the mutant is probably over-rescued in the complemented strain by the strong function of the nitrate reductase promoter, which is also supported by high neutral lipid content in the complemented strain. The growth of stldp mutant showed a long lag phase relative to WT cells, suggesting that the low surface-to-volume ratio of fused LD decreased the efficiency of LD hydrolysis during the initial growth phase.
Ethylene enhances MdMAPK3-mediated phosphorylation of MdNAC72 to promote apple fruit softening
Authors: Wei Yun , Liu Zhi , Lv Tianxing , Xu Yaxiu , Wei Yajing , Liu Weiting , Liu Li , Wang Aide , Li Tong 
Published: May 2023

Abstract
The phytohormone ethylene plays an important role in promoting the softening of climacteric fruits, such as apples (Malus domestica); however, important aspects of the underlying regulatory mechanisms are not well understood. In this study, we identified apple MITOGEN-ACTIVATED PROTEIN KINASE 3 (MdMAPK3) as an important positive regulator of ethylene-induced apple fruit softening during storage. Specifically, we show that MdMAPK3 interacts with and phosphorylates the transcription factor NAM-ATAF1/2-CUC2 72 (MdNAC72), which functions as a transcriptional repressor of the cell wall degradation-related gene POLYGALACTURONASE1 (MdPG1). The increase in MdMAPK3 kinase activity was induced by ethylene, which promoted the phosphorylation of MdNAC72 by MdMAPK3. Additionally, MdPUB24 functions as an E3 ubiquitin ligase to ubiquitinate MdNAC72, resulting in its degradation via the 26S proteasome pathway, which was enhanced by ethylene-induced phosphorylation of MdNAC72 by MdMAPK3. The degradation of MdNAC72 increased the expression of MdPG1, which in turn promoted apple fruit softening. Notably, using variants of MdNAC72 that were mutated at specific phosphorylation sites, we observed that the phosphorylation state of MdNAC72 affected apple fruit softening during storage. This study thus reveals that the ethylene–MdMAPK3–MdNAC72–MdPUB24 module is involved in ethylene-induced apple fruit softening, providing insights into climacteric fruit softening.
Long Covid: conceptualizing the challenges for public health
Authors: Prashar Jai 
Published: May 2023

Abstract

Background
Long Covid has caused significant disruption to public services, economies and population health worldwide, but no single public health approach has proven effective in its management. This essay was the winning entry for the Faculty of Public Health’s Sir John Brotherston Prize 2022.

Methods
In this essay, I synthesize existing literature on public health policy in long Covid, and discuss the challenges and opportunities posed by long Covid for the public health profession. The utility of specialist clinics and community care, in the UK and internationally, is examined, as well as key outstanding issues relating to evidence generation, health inequality and defining long Covid. I then use this information to inform a simple conceptual model.

Results
The generated conceptual model integrates community- and population-level interventions; key areas of identified policy need at both levels include ensuring equitable access to long Covid care, developing screening programmes for high-risk populations, co-production of research and clinical services with patients, and using interventions to generate evidence.

Conclusions
Significant challenges remain in the management of long Covid from a public health policy perspective. Multidisciplinary community-level and population-level interventions should be employed with a view to achieving an equitable and scalable model of care.
Earning the Role: Father Role Institutionalization and the Achievement of Contemporary Fatherhood
Authors: Brown-Weinstock Rachel , Gold Sarah , Edin Kathryn , Nelson Timothy 
Published: May 2023

Abstract
Fatherhood has become an achieved status among complex, disadvantaged families. Stepfathers may have an advantage over nonresident biological fathers in earning the father role; in-depth interview studies reveal that nonresident fathers are often stripped of the father label while stepfathers commonly achieve it instead. This stepfather advantage is surprising given extant institutionalization theory, which suggests that the stronger institutionalization of the biological father role should benefit nonresident fathers over stepfathers. Drawing on 55 in-depth interviews with adolescents and their primary caregivers, we recenter youth agency in family theory by exploring how some men and not others earn the father role from the perspective of their adolescent children. We find that the strongly institutionalized role obligations of biological fathers impeded rather than aided nonresident father-child engagement. When nonresident fathers did not meet institutionalized expectations, adolescents experienced psychological trauma and usually resisted their attempts to become more involved. In contrast, the incomplete institutionalization of the stepparent role benefited stepfather-stepchild relations by allowing stepfathers to flexibly adapt to complex family dynamics. Further, stepfathers more easily met, and even exceeded, their stepchildren’s limited expectations of them. Thus, stepfathers may face a lower cultural bar for and gain greater satisfaction from fulfilling the father role than nonresident biological fathers.
Perioperative Complications and Health-related Quality of Life Outcomes in Severe Pediatric Spinal Deformity
Authors: Gupta Munish C. , Lenke Lawrence G. , Gupta Sachin , Farooqi Ali S. , Asghar Jahangir K. , Boachie-Adjei Oheneba , Cahill Patrick J. , Erickson Mark A. , Garg Sumeet , Newton Peter O. , Samdani Amer F. , Shah Suken A. , Shufflebarger Harry L. , Sponseller Paul D. , Sucato Daniel J. , Bumpass David B. , McCarthy Richard E. , Yaszay Burt , Pahys Joshua M. , Ye Jichao ,   The Fox Pediatric Spinal Deformity Study Group, Kelly Michael P. 
Published: May 2023

Study Design.
Prospective multicenter cohort study.

Objective.
To evaluate perioperative complications and mid-term outcomes for severe pediatric spinal deformity.

Summary of Background Data.
Few studies have evaluated the impact of complications on health-related quality of life (HRQoL) outcomes in severe pediatric spinal deformity.

Methods.
Patients from a prospective, multicenter database with severe pediatric spinal deformity (minimum of 100 degree curve in any plane or planned vertebral column resection (VCR)) with a minimum of 2-years follow-up were evaluated (n=231). SRS-22r scores were collected preoperatively and at 2-years postoperatively. Complications were categorized as intraoperative, early postoperative (within 90-days of surgery), major, or minor. Perioperative complication rate was evaluated between patients with and without VCR. Additionally, SRS-22r scores were compared between patients with and without complications.

Results.
Perioperative complications occurred in 135 (58%) patients, and major complications occurred in 53 (23%) patients. Patients that underwent VCR had a higher incidence of early postoperative complications than patients without VCR (28.9% vs. 16.2%, P=0.02). Complications resolved in 126/135 (93.3%) patients with a mean time to resolution of 91.63 days. Unresolved major complications included motor deficit (n=4), spinal cord deficit (n=1), nerve root deficit (n=1), compartment syndrome (n=1), and motor weakness due to recurrent intradural tumor (n=1). Patients with complications, major complications, or multiple complications had equivalent postoperative SRS-22r scores. Patients with motor deficits had lower postoperative satisfaction subscore (4.32 vs. 4.51, P=0.03), but patients with resolved motor deficits had equivalent postoperative scores in all domains. Patients with unresolved complications had lower postoperative satisfaction subscore (3.94 vs. 4.47, P=0.03) and less postoperative improvement in self-image subscore (0.64 vs. 1.42, P=0.03) as compared to patients with resolved complications.

Conclusion.
Most perioperative complications for severe pediatric spinal deformity resolve within 2-years postoperatively and do not result in adverse HRQoL outcomes. However, patients with unresolved complications have decreased HRQoL outcomes.
Regulatory mucosa-associated invariant T cells controlled by β1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression
Authors: Fu Sicheng , Liu Muziying , Zhu Chenwen , Zhang Huimin , Zhao Changfeng , Xie Yaping , Chen Guanghou , Sheng Daping , Pan Jun , He Ziqing , Dai Ying , Gao Yufeng , Li Xiaomei , Chen Lijian , Qian Yeben , Jin Tengchuan , Sun Cheng , Tian Zhigang , Wang Hua , Bai Li 
Published: May 2023

Background and Aims:
The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored.

Approach and Results:
Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3+ CXCR3+ MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3− CXCR3+ MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by β1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes.

Conclusions:
Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.
Paradoxical Associations of Occupational and Nonoccupational Sedentary Behavior With Cardiovascular Disease Risk Measures in Desk Workers
Authors: Alansare Abdullah B. , Paley Joshua L. , Quinn Tyler D. , Gibbs Bethany B. 
Published: May 2023

Objectives
We assessed sedentary behavior (SB) patterns and examined its associations, by domain, with cardiovascular disease (CVD) risk measures in desk workers (N = 273).

Methods
Sedentary behavior was measured by activPAL3 and partitioned into occupational and nonoccupational SB. Cardiovascular disease risk measures included blood pressure, pulse wave velocity, heart rate, and heart rate variability. Paired t tests evaluated patterns of SB across domains. Linear regressions estimated associations of occupational and nonoccupational SB with CVD risk measures.

Results
Participants spent 69% of their time in SB; higher proportions were accumulated during occupational versus nonoccupational time. Higher all-domain SB was only associated with higher pulse wave velocity. Paradoxically, greater nonoccupational SB unfavorably associated with CVD risk measures, while higher occupational SB favorably correlated to CVD risk measures.

Conclusions
Observed paradoxical associations suggest that domain should be considered in efforts to improve cardiovascular health by reducing SB.
The impact of surgery and survival prediction in patients with gastroenteropancreatic neuroendocrine tumors: a population-based cohort study
Authors: Wu Zenghong , Wang Weijun , Zhang Kun , Fan Mengke , Lin Rong 
Published: May 2023

Objective:
This study aimed at assessing the impact of surgical treatments in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods:
A propensity score-matched analysis based on data in the Surveillance, Epidemiology, and End Results database was used to assess the efficacy of surgical treatment in patients with GEP-NETs.

Results:
A total of 7515 patients diagnosed with GEP-NETs from 2004 to 2015 were evaluated from the Surveillance, Epidemiology, and End Results database. There were 1483 patients in the surgery group and 6032 patients in the nonsurgery group. Compared with patients in the surgery group, patients in the nonsurgery group were inclined to receive chemotherapy (50.8 vs. 16.7%) and radiation (12.9 vs. 3.7%) as treatment options. Multivariate Cox regression analysis revealed higher rates of overall survival (OS) outcomes for GEP-NETs patients who had been subjected to surgery (hazard ratio=0.483, 95% CI=0.439–0.533, P<0.001). Then, to reduce the impact of bias, a 1 : 1 propensity score-matched analysis was performed for the two groups of patients. A total of 1760 patients were assessed and each subgroup included 880 patients. In the matched population, the patients exhibited the ability to significantly benefit from surgery (hazard ratio=0.455, 95% CI=0.439–0.533, P<0.001). The OS outcomes for radiation or chemotherapy patients who had been treated with surgery were better than those of patients who had not been treated with surgery (P<0.001). In addition, it was found that the OS of patients was not significant after rectum and small intestine surgery, whereas there was a significant difference in OS after colon, pancreas, and stomach surgery on the patients. Patients who had been subjected to surgery in the rectum and small intestines exhibited better therapeutic benefits.

Conclusion:
Patients with GEP-NETs who are treated with surgery have better OS outcomes. Therefore, surgery is recommended for specified selected patients with metastatic GEP-NETs.
External validation of 18F-FDG PET-based radiomic models on identification of residual oesophageal cancer after neoadjuvant chemoradiotherapy
Authors: Valkema Maria J. , Beukinga Roelof J. , Chatterjee Avishek , Woodruff Henry C. , van Klaveren David , Noordzij Walter , Valkema Roelf , Bennink Roel J. , Roef Mark J. , Schreurs Wendy , Doukas Michail , Lagarde Sjoerd M. , Wijnhoven Bas P.L. , Lambin Philippe , Plukker John T.M. , van Lanschot J. Jan B. 
Published: May 2023

Objectives
Detection of residual oesophageal cancer after neoadjuvant chemoradiotherapy (nCRT) is important to guide treatment decisions regarding standard oesophagectomy or active surveillance. The aim was to validate previously developed 18F-FDG PET-based radiomic models to detect residual local tumour and to repeat model development (i.e. ‘model extension’) in case of poor generalisability.

Methods
This was a retrospective cohort study in patients collected from a prospective multicentre study in four Dutch institutes. Patients underwent nCRT followed by oesophagectomy between 2013 and 2019. Outcome was tumour regression grade (TRG) 1 (0% tumour) versus TRG 2-3-4 (≥1% tumour). Scans were acquired according to standardised protocols. Discrimination and calibration were assessed for the published models with optimism-corrected AUCs >0.77. For model extension, the development and external validation cohorts were combined.

Results
Baseline characteristics of the 189 patients included [median age 66 years (interquartile range 60–71), 158/189 male (84%), 40/189 TRG 1 (21%) and 149/189 (79%) TRG 2-3-4] were comparable to the development cohort. The model including cT stage plus the feature ‘sum entropy’ had best discriminative performance in external validation (AUC 0.64, 95% confidence interval 0.55–0.73), with a calibration slope and intercept of 0.16 and 0.48 respectively. An extended bootstrapped LASSO model yielded an AUC of 0.65 for TRG 2-3-4 detection.

Conclusion
The high predictive performance of the published radiomic models could not be replicated. The extended model had moderate discriminative ability. The investigated radiomic models appeared inaccurate to detect local residual oesophageal tumour and cannot be used as an adjunct tool for clinical decision-making in patients.