bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose Metabolism and Human Immunodeficiency Virus Type 1 Infection
Authors: Chen Zhonghe , Wang Tiantian , Deng Kai 
Published: February 2023

Abstract
Acquired immune deficiency syndrome is still one of the most severe global infectious diseases that pose a significant threat to human health. With the successful application of antiretroviral therapy, productive replication of human immunodeficiency virus type 1 (HIV-1) can be effectively blocked; however, antiretroviral therapy alone cannot cure the infection because of the presence of a stable and reactivatable viral latent reservoir. Thus, it is of great importance to have a better comprehension of the mechanisms driving HIV-1 pathogenesis and long-term persistence in infected individuals, based on which to further discover novel targets for therapeutic applications to treat or even cure the infection. Various studies have revealed that cellular metabolism is a critical factor impacting the fate and intracellular activities of immune cells. Emerging evidence implies that the alternations of cellular metabolism induced by HIV-1 infection play an important role in HIV-1 pathogenesis. Consequently, a promising approach of “metabolism as a therapeutic target” raised the possibility of using metabolic reprogramming as a treatment option for chronic HIV-1 infection. In this review, we summarize the latest studies about the interplay of the hosts' reprogramming of glucose metabolism and HIV-1 infection and introduce potential applications of searching for hallmarks and therapeutic targets of metabolic interventions for HIV-1 infection.
Lipid-Based Poly(I:C) Adjuvants Strongly Enhance the Immunogenicity of SARS-CoV-2 Receptor-Binding Domain Vaccine
Authors: Wu Yixin , Meng Liuxian , Zhang Huicong , Hu Shun , Li Fusheng , Yu Yingjie 
Published: February 2023

Abstract

Background
The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly threatened public health. Recent studies have revealed that the spike receptor-binding domain (RBD) of SARS-CoV-2 is a potent target for vaccine development. However, adjuvants are usually required to strengthen the immunogenicity of recombinant antigens. Different types of adjuvants can elicit different immune responses.

Methods
We developed an RBD recombinant protein vaccine with a polyriboinosinic acid–polyribocytidylic acid [poly(I:C)] adjuvant to evoke a strong immune response. The delivery of poly(I:C) was optimized in two steps. First, poly(I:C) was complexed with a cationic polymer, poly-l-lysine (PLL), to form poly(I:C)–PLL, a polyplex core. Thereafter, it was loaded into five different lipid shells (group II, III-1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC], III-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine [DOPE], IV-DOPE, and IV-DSPC). We performed an enzyme-linked immunosorbent assay and enzyme-linked immunosorbent spot assay to compare the ability of the five lipopolyplex adjuvants to enhance the immunogenicity of the SARS-CoV-2 RBD protein, including humoral and cellular immune responses. Finally, the adjuvant with the highest immunogenicity was selected to verify the protective immunity of the vaccine through animal challenge experiments.

Results
Recombinant RBD protein has low immunogenicity. The different adjuvants we developed enhanced the immunogenicity of the RBD protein in different ways. Among the lipopolyplexes, those containing DOPE (III-DOPE and IV-DOPE) elicited RBD-specific immunoglobulin G antibody responses, and adjuvants with four components elicited better RBD-specific immunoglobulin G antibody responses than those containing three components (P < 0.05). The IC50 and IC90 titers indicated that the IV-DOPE lipopolyplex had the greatest neutralization ability, with IC50 titers of 1/117,490. Furthermore, in the challenge study, IV-DOPE lipopolyplex protected mice from SARS-CoV-2 infection. On the fourth day after infection, the average animal body weights were reduced by 18.56% (24.164 ± 0.665 g vs. 19.678 ± 0.455 g) and 0.06% (24.249 ± 0.683 g vs. 24.235 ± 0.681 g) in the MOCK and vaccine groups, respectively. In addition, the relative expression of viral RNA in the vaccinated group was significantly lower than that in the MOCK group (P < 0.05). Interstitial inflammatory cell infiltration was observed in the MOCK group, whereas no obvious damage was observed in the vaccinated group.

Conclusions
The IV-DOPE–adjuvanted SARS-CoV-2 recombinant RBD protein vaccine efficiently protected mice from SARS-CoV-2 in the animal challenge study. Therefore, IV-DOPE is considered an exceptional adjuvant for SARS-CoV-2 recombinant RBD protein-based vaccines and has the potential to be further developed into a SARS-CoV-2 recombinant RBD protein-based vaccine.
Relative efficacy of intracameral moxifloxacin injection methods
Authors: Arshinoff Steve A. , Shi Runjie B. 
Published: February 2023

Purpose:
To determine the amount of moxifloxacin remaining in the anterior chamber (AC), immediately after its injection using 3 current injection methods, assuming mixing and fluid exchange with the AC contents during injection of the drug, and to determine the most desirable injection method.

Setting:
Department of Ophthalmology and Vision Sciences and Institute of Biomedical Engineering, University of Toronto, Toronto, Canada.

Design:
Mathematical modeling.

Methods:
Mathematical modeling using first-order mixing methods were used to assess mixing.

Results:
The Kaiser method of injecting 0.5 mL × 100 μg/0.1 mL does not achieve the desired 500 μg level of moxifloxacin in the AC. The “straight from the bottle” method of injecting 0.1 mL × 500 μg/0.1 mL is fraught with potential error, yielding a relatively unreliable final amount in the AC. Injecting 0.5 to 0.6 mL × 150 μg/0.1 mL yields a result closest to the desired goal.

Conclusions:
Based on the calculation, the most accurate of current methods to deliver 500 μg moxifloxacin intracamerally is the method of 150 μg/0.1 mL × 0.5 to 0.6 mL.
Comparison of blood levels of vitamin B12, folic acid, riboflavin, and homocysteine in keratoconus and healthy subjects
Authors: Sozer Omer , Ozalp Onur , Atalay Eray , Demir Sukru Saygin , Alatas İbrahim Ozkan , Yildirim Nilgun 
Published: February 2023

Purpose:
To evaluate blood levels of vitamin B12, folic acid, riboflavin, and homocysteine in keratoconus (KC) and healthy subjects.

Setting:
Eskişehir Osmangazi University, Eskişehir, Turkey.

Design:
Cross-sectional study.

Methods:
100 KC patients (patient group) between the ages of 18 to 35 years and 200 healthy individuals (control group) in the same age range were included in the Eskişehir Osmangazi University Hospital Eye Clinic between October 2019 and March 2020. In all cases, a complete ophthalmologic examination and corneal tomography evaluation with a Pentacam Scheimpflug camera were performed. In blood samples, vitamin B12 and folic acid levels were measured using an electrochemiluminescence immunoassay analyzer, and homocysteine and riboflavin levels were measured using high-performance liquid chromatography. Chi-square tests were used in the analysis of categorical variables, and Mann-Whitney U and Kruskal-Wallis tests were used in the analysis of numerical variables.

Results:
Homocysteine (13.0 ± 6.6 vs 12.1 ± 5.4 μmol/L, P = .190), vitamin B12 (313.5 ± 119.4 vs 322.9 ± 128.3 pg/mL, P = .619), and folic acid (7.0 ± 2.7 vs 7.4 ± 2.9 ng/mL, P = .230) levels were not different between KC (100 eyes of 100 subjects) and control (200 eyes of 200 subjects) groups. The mean riboflavin level was 84.0 ± 21.8 μg/L in the patient group and 183.6 ± 74.3 μg/L in the control group, with a significant difference between the 2 groups (P < .001). Riboflavin levels were below 180 μg/L in 99% (n = 99) of the cases in the KC group and 53.5% (n = 107) in the control group (P < .001).

Conclusions:
Low blood riboflavin levels in KC patients may be a possible risk factor in the pathogenesis of KC.
Follicular pancreatitis: Case report and literature review
Authors: Lee Wan-Sik , Kim Ki-Hyun , Noh Myung-Giun , Joo Young-Eun 
Published: February 2023

Rationale:
Follicular pancreatitis is a very rare type of focal chronic pancreatitis and is often mistaken for pancreatic neoplasms. It is histologically characterized by extensive lymphoid follicular formation with reactive germinal centers.

Patient concerns:
A 50-year-old man was admitted to our hospital with 1-month history of epigastric pain. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a 4.7 cm sized enhancing pancreatic head mass with anterior mesenteric soft tissue infiltration and superior mesenteric vein invasion. Endoscopic ultrasonography revealed an ill-defined hypoechoic mass in the head of the pancreas.

Diagnoses:
A laparoscopic surgical biopsy was performed. Hematoxylin-eosin staining showed the acini structure destruction within the pancreatic parenchyma and different-sized lymphoid follicles with reactive germinal centers around the duct. Immunohistochemical examination showed that cells were positive for the B-cell marker CD20, T-cell marker CD3, and slightly positive for IgG4. However, cells were negative for the B-cell marker Bcl-2. Follicular pancreatitis was confirmed based on the findings of histology and immunohistochemistry.

Interventions:
The patient was regularly followed without any specific treatment.

Outcomes:
Follow-up computed tomography revealed no change in the lesion 1 year after diagnosis.

Lessons:
To the best of our knowledge, this is the first case of follicular pancreatitis in Korea.
Postpartum Home Blood Pressure Monitoring Program
Authors: Hayden-Robinson Kamilah A. , Deeb Jessica L. 
Published: February 2023

Abstract

Background and Significance:
Hypertensive disorders of pregnancy complicate about 10% of pregnancies and are a leading cause of maternal morbidity and mortality.

Purpose:
The purpose of this quality improvement project was to evaluate a program to provide a home blood pressure monitor to all postpartum patients who had a hypertensive diagnosis and elevated blood pressure.

Methods:
The program includes a blood pressure monitor, instructions for its use, education about hypertension, and a guidance grid with standardized blood pressure parameters reviewed prior to discharge from the hospital. Patients are taught about potential adverse outcomes during postpartum. Patients are instructed to follow-up with their care provider based on the parameters. A retrospective medical record review was used to evaluate clinical outcomes.

Results:
Medical records of 185 patients indicated that 20% (n = 36) who received the home BP monitor reported one or more mild-to-severe range blood pressure(s) during postpartum. Twenty-eight percent (n = 52) had outpatient medication adjustments, including decreasing, increasing, starting, and discontinuing medications. Nine percent (n = 17) of patients returned to the obstetric triage for evaluation. There was patient overlap between those experiencing elevated blood pressures, medication adjustments, and those who returned to hospital for evaluation.

Clinical Implications:
Ongoing monitoring may improve identification and management of postpartum hypertension and potentially prevent progression to hypertensive-related adverse events.
Improving Cardiovascular Follow-Up after Diagnosis of a Hypertensive Disorder of Pregnancy using the Electronic Health Record
Authors: Burgess Adriane , Stover Samantha 
Published: February 2023

Abstract

Background:
Cardiovascular disease is the leading cause of death among women. Sex-specific risk factors for cardiovascular disease include history of a hypertensive disorder of pregnancy.

Problem:
After diagnosis of a hypertensive disorder of pregnancy, professional societies recommend follow-up with a primary care provider for preventative care. There are gaps in patient and health care provider knowledge of the association between a hypertensive disorder of pregnancy and cardiovascular disease. That gap has a negative effect on patients receiving recommended follow-up.

Methods:
An electronic registry was created to identify those who gave birth in our health system and had a diagnosis of hypertensive disorder of pregnancy. From this, information outreach was sent electronically to the patient and their primary care provider.

Interventions:
Communication in the outreach included education on the association between hypertensive disorders of pregnancy and cardiovascular disease, the importance of follow-up, cardiopreventative strategies, and biochemical assessment. Medical records were audited at approximately 6 months postpartum to determine if patients completed a visit with their primary care provider to discuss cardiovascular risks.

Results:
Between May 2021 and June 2022, 15% (n = 1,131) of patients who gave birth in our health system had a diagnosis of hypertensive disorder of pregnancy. Ninety percent of those patients who received outreach communication viewed the letter. At baseline, 16% of patients during postpartum with a hypertensive disorder of pregnancy saw their primary care provider to discuss cardiopreventative strategies. After implementation of our program, 26% of those with a hypertensive disorder of pregnancy saw their primary care provider for follow-up and discussed cardiopreventative strategies.

Clinical Implications:
Nurses should ensure that women during postpartum and their primary care providers are educated about the association of hypertensive disorders of pregnancy and long-term cardiovascular risk. The electronic health record may be an optimal way to ensure education is provided and follow-up scheduled.
Abdominal Imaging Findings on Computed Tomography as a Tool for COVID-19 Mortality Risk Assessment: Comparison With Chest Radiograph Severity Scores
Authors: Balthazar Patricia , Mercaldo Nathaniel , Pisuchpen Nisanard , Mendoza Dexter P. , Little Brent P. , Flores Efren J. , Kambadakone Avinash 
Published: February 2023

Objective
To quantify the association between computed tomography abdomen and pelvis with contrast (CTAP) findings and chest radiograph (CXR) severity score, and the incremental effect of incorporating CTAP findings into predictive models of COVID-19 mortality.

Methods
This retrospective study was performed at a large quaternary care medical center. All adult patients who presented to our institution between March and June 2020 with the diagnosis of COVID-19 and had a CXR up to 48 hours before a CTAP were included. Primary outcomes were the severity of lung disease before CTAP and mortality within 14 and 30 days. Logistic regression models were constructed to quantify the association between CXR score and CTAP findings. Penalized logistic regression models and random forests were constructed to identify key predictors (demographics, CTAP findings, and CXR score) of mortality. The discriminatory performance of these models, with and without CTAP findings, was summarized using area under the characteristic (AUC) curves.

Results
One hundred ninety-five patients (median age, 63 years; 119 men) were included. The odds of having CTAP findings was 3.89 times greater when a CXR score was classified as severe compared with mild (P = 0.002). When CTAP findings were included in the feature set, the AUCs for 14-day mortality were 0.67 (penalized logistic regression) and 0.71 (random forests). Similar values for 30-day mortality were 0.76 and 0.75. When CTAP findings were omitted, all AUC values were attenuated.

Conclusions
The CTAP findings were associated with more severe CXR score and may serve as predictors of COVID-19 mortality.
Bodyweight-adjusted Contrast Media With Shortened Injection Duration for Step-and-Shoot Coronary Computed Tomography Angiography to Acquire Improved Image Quality
Authors: Jin Liang , Wang Kun , Wang Xiaodong , Li Cheng , Sun Yingli , Gao Pan , Xiao Yi , Li Ming 
Published: February 2023

Purpose:
Shortened injection durations are not recommended in step-and-shoot coronary computed tomography angiography (CCTA). We aimed to evaluate the image quality of CCTA performed using bodyweight-adjusted iodinated contrast media (ICM) with different injection durations to generate an optimized ICM administration protocol to acquire convincible image quality in step-and-shoot CCTA.

Materials and Methods:
A total of 200 consecutive patients with suspected coronary artery disease (CAD) were enrolled in group A (N=50, 350 mgI/mL, bodyweight×0.8 mL/kg with a 13-s injection duration), group B (N=50, 350 mgI/mL, bodyweight×0.9 mL/kg with a 13-s injection duration), group C (N=50, 350 mgI/mL, bodyweight×0.8 mL/kg with a 12-s injection duration), and group D (N=50, 320 mgI/mL, bodyweight×0.8 mL/kg with a 13-s injection duration). Patient characteristics, ICM administration protocols, quantitative computed tomography (CT) value measurements, and qualitative image scores were analyzed and compared among the groups.

Results:
Groups A and D achieved the lowest ICM volume, saline volume, injection flow rate, and total iodine and iodine injection rates among the groups. All the CT values of the coronary arteries in all groups were >300 HU. All the observers’ average scores exceeded three points. In group A, the CT values showed significant positive correlation with the iodine injection rate (r=0.226, P<0.001), whereas the signal-to-noise ratio (r=−0.004, P=0.927) and contrast-to-noise ratio (r=−0.006, P=0.893) values were not.

Conclusions:
Bodyweight×0.8 mL/kg with a 13-second injection duration is a comprehensive option for step-and-shoot CCTA with improved image quality, and a 350 mgI/mL iodine concentration is preferred.
Temperature modifies trait-mediated infection outcomes in aDaphnia–fungal parasite system
Authors: Sun Syuan-Jyun , Dziuba Marcin K. , Jaye Riley N. , Duffy Meghan A. 
Published: February 2023

One major concern related to climate change is that elevated temperatures will drive increases in parasite outbreaks. Increasing temperature is known to alter host traits and host–parasite interactions, but we know relatively little about how these are connected mechanistically—that is, about how warmer temperatures impact the relationship between epidemiologically relevant host traits and infection outcomes. Here, we used a zooplankton–fungus (Daphnia dentifera–Metschnikowia bicuspidata) disease system to experimentally investigate how temperature impacted physical barriers to infection and cellular immune responses. We found thatDaphniareared at warmer temperatures had more robust physical barriers to infection but decreased cellular immune responses during the initial infection process. Infected hosts at warmer temperatures also suffered greater reductions in fecundity and lifespan. Furthermore, the relationship between a key trait—gut epithelium thickness, a physical barrier—and the likelihood of terminal infection reversed at warmer temperatures. Together, our results highlight the complex ways that temperatures can modulate host–parasite interactions and show that different defense components can have qualitatively different responses to warmer temperatures, highlighting the importance of considering key host traits when predicting disease dynamics in a warmer world.This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Infection burdens and virulence under heat stress: ecological and evolutionary considerations
Authors: Hector T. E. , Gehman A.-L. M. , King K. C. 
Published: February 2023

As a result of global change, hosts and parasites (including pathogens) are experiencing shifts in their thermal environment. Despite the importance of heat stress tolerance for host population persistence, infection by parasites can impair a host's ability to cope with heat. Host–parasite eco-evolutionary dynamics will be affected if infection reduces host performance during heating. Theory predicts that within-host parasite burden (replication rate or number of infecting parasites per host), a key component of parasite fitness, should correlate positively with virulence—the harm caused to hosts during infection. Surprisingly, however, the relationship between within-host parasite burden and virulence during heating is often weak. Here, we describe the current evidence for the link between within-host parasite burden and host heat stress tolerance. We consider the biology of host–parasite systems that may explain the weak or absent link between these two important host and parasite traits during hot conditions. The processes that mediate the relationship between parasite burden and host fitness will be fundamental in ecological and evolutionary responses of host and parasites in a warming world.This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
A prospective study on tumour response assessment methods after neoadjuvant endocrine therapy in early oestrogen receptor positive breast cancer
Authors: López-Velazco Joanna I. , Manzano Sara , Otaño María , Elorriaga Kepa , Bultó Núria , Herrero Julio , Lahuerta Ainhara , Segur Virginia , Álvarez-López Isabel , Caffarel Maria M. , Urruticoechea Ander 
Published: February 2023

AbstractNeoadjuvant endocrine therapy (NET) in oestrogen receptor-positive/HER2-negative breast cancer (ER+/HER2-BC) allows real-time evaluation of drug efficacy and biological changes upon estrogenic deprivation. Clinical and pathological evaluation after NET may be used to obtain prognostic and predictive information of tumour response. Scales developed to evaluate response after neoadjuvant chemotherapy are not useful and there are not many validated biomarkers to assess response to NET. In this prospective study, we analysed radiological and pathological tumour response of 104 postmenopausal ER+/HER2-BC patients, treated with NET for a mean of 7 months. Our results show that radiological evaluation underestimates pathological tumour size, although it can be used to assess tumour response. In addition, we propose that the tumour cellularity size (TCS), calculated as the product of the residual tumour cellularity in the surgical specimen and the tumour pathological size, could become a new tool to standardize response assessment to NET. It is simple, reproducible and correlates with the existing biomarkers. Our findings shed light on the dynamics of NET response, challenge the paradigm of the ability of NET to decrease surgical volume and point to the utility of the TCS to quantify the scattered tumour response usually produced by endocrine therapy.
A Methylation-Phosphorylation Switch Controls EZH2 Stability and Hematopoiesis
Authors: Guo Pengfei , Rajawasam Keshari , Trinh Tiffany , Sun Hong , Zhang Hui 
Published: February 2023

ABSTRACTThe Polycomb Repressive Complex 2 (PRC2) methylates H3K27 to regulate development and cell fate by transcriptional silencing. Alteration of PRC2 is associated with various cancers. Here, we show that mouseLsd1/Kdm1adeletion causes dramatic reduction of PRC2 proteins, whereas mouse null mutation ofL3mbtl3orDcaf5results in PRC2 accumulation and increased H3K27 trimethylation. The catalytic subunit of PRC2, EZH2, is mono-methylated at lysine 20 (K20), promoting EZH2 proteolysis by L3MBTL3 and the CLR4DCAF5ubiquitin ligase. LSD1 demethylates the methylated K20 to stabilize EZH2. K20 methylation is inhibited by AKT-mediated phosphorylation of serine 21 in EZH2. Mouse K20R mutants develop hepatosplenomegaly associated with high GFI1B expression, and K20R mutant bone marrows expand hematopoietic stem cells and downstream hematopoietic populations. Our studies reveal that EZH2 is regulated by methylation dependent proteolysis, which is negatively controlled by AKT-mediated S21 phosphorylation to establish a methylation-phosphorylation switch to control the PRC2 activity and hematopoiesis.