bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDL-cholesterol concentration and its association with coronary artery calcification: a systematic review and meta-analysis
Authors: Abedi Farshad , Sadeghi Masoumeh , Omidkhoda Navid , Kelesidis Theodoros , Ramezani Javad , Samadi Sara , Mohammadpour Amir Hooshang 
Published: May 2023

Abstract
Background
Coronary artery calcification (CAC) is a potential risk marker of coronary atherosclerosis that has high specificity and sensitivity. However, the association between high-density lipoprotein cholesterol (HDL-C) concentration and CAC incidence and progression is controversial.

Methods
PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies up to March 2023 and assessed the methodological quality using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratios (OR) and 95% confidence interval considering heterogeneity across studies.

Results
Of the 2,411 records, 25 cross-sectional (n = 71,190) and 13 cohort (n = 25,442) studies were included in the systematic review. Ten cross-sectional and eight cohort studies were not eligible and were omitted from the meta-analysis. A total of 15 eligible cross-sectional studies (n = 33,913) were included in the meta-analysis and pooled results revealed no significant association between HDL-C and CAC > 0, CAC > 10, or CAC > 100 [pooled OR: 0.99 (0.97, 1.01)]. Meta-analysis of the 5 eligible prospective cohort studies (n = 10,721) revealed no significant protective effect of high HDL-C against CAC > 0 [pooled OR: 1.02 (0.93, 1.13)].

Conclusions
According to this analysis of observational studies, high HDL-C levels were not found to predict protection against CAC. These results suggest HDL quality rather than HDL quantity is important for certain aspects of atherogenesis and CAC.

Registration number
CRD42021292077.
Purification and proteomic analysis of potent fibrinolytic enzymes extracted from Lumbricus rubellus
Authors: Stephani Laurentia , Rahayu Puji , Retnoningrum Debbie , Suhartono Maggy Thenawidjaja , Rachmawati Heni , Tjandrawinata Raymond R. 
Published: May 2023

Abstract
Background
Lumbrokinase derived from earthworms, Lumbricus rubellus is known to have fibrinolytic enzymes that have potential as therapeutic drugs due to its ability to dissolve fibrin. The current study is aimed to purify the Lumbrokinase from L. rubellus and identify its protein component.

Methods
Water extract of local earthworm Lumbricus rubellus revealed several proteins. Therefore, to identify its protein component, purification through HiPrep DEAE fast flow and proteomic analysis were conducted prior to identifications. A combination of two-dimension gel electrophoresis (2DE) and electrospray ionization mass spectrometry analysis was used to identify the purified fractions.

Results
The purified fractions contain five protein bands, namely F25-1, F25-2, F85-1, F85-2, and F85-3, which displayed strong fibrinogenolytic activity. F25 fractions showed fibrinogenolytic activity of 974.85 U/mg, while F85 fractions showed higher activity of 1,484.11 U/mg. Fractions F85-1, F85-2, and F85-3 showed molecular weights of 42.6 kDa, 27.03 kDa, and 14 kDa, respectively and were identified as Lumbrokinase iso-enzymes.

Conclusion
This preliminary study indicates that the F25 and F85 fractions are similar to published fibrinolytic protease-1 and lumbrokinase, respectively, in terms of their amino acid sequence.
Feasibility and acceptability of inserts promoting virtual overdose monitoring services (VOMS) in naloxone kits: a qualitative study
Authors: Safi Fahad , Rioux William , Rider Nathan , Fornssler Barbara , Jones Stephanie , Ghosh S. Monty 
Published: May 2023

AbstractBackgroundIn response to the ongoing opioid epidemic, there have been efforts to develop novel harm reduction strategies alongside scaling of currently implemented programs. Virtual overdose monitoring services (VOMS) are a novel intervention which aims to reduce substance-related mortality through technology for those who are out of reach of current supervised consumption sites. Scaling of naloxone programs presents a unique opportunity to promote VOMS to people at risk of substance-related mortality. This study aims to explore the feasibility and acceptability of naloxone kit inserts in promoting awareness of VOMS.MethodWe used purposive and snowball sampling to recruit 52 key informants, including people who use drugs (PWUD) with experience using VOMS (n = 16), PWUD with no prior experience using VOMS (n = 9), family members of PWUD (n = 5), healthcare and emergency services professionals (n = 10), community-based harm reduction organizations (n = 6), and VOMS administrators/peer support workers (n = 6). Two evaluators completed semi-structured interviews. Interview transcripts were analyzed using thematic analysis informed to identify key themes.ResultsFour key interrelated themes emerged, including the acceptability of naloxone kit inserts to promote VOMS, best practices for implementation, key messaging to include within promotional materials and facilitators to dissemination of harm reduction material. Participants highlighted that messaging should be promoted both inside and outside the kits, should be concise, provide basic information about VOMS and can be facilitated through current distribution streams. Messaging could further be used to draw attention to local harm reduction services and could be promoted on other supplies, including lighters and safer consumption supplies.ConclusionFindings demonstrate that it is acceptable to promote VOMS within naloxone kits and highlight interviewees preferred ways to do so. Key themes that emerged from interviewees can be used to inform the dissemination of harm reduction information, including VOMS and bolster current strategies for reducing illicit drug overdose.
Targeting ER stress/PKA/GSK-3β/β-catenin pathway as a potential novel strategy for hepatitis C virus-infected patients
Authors: Lin Dong , Chen Yijia , Koksal Ali Riza , Dash Srikanta , Aydin Yucel 
Published: May 2023

Abstract
Background
Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). The HCC risk, while decreased compared with active HCV infection, persists in HCV-cured patients by direct-acting antiviral agents (DAA). We previously demonstrated that Wnt/β-catenin signaling remained activated after DAA-mediated HCV eradication. Developing therapeutic strategies to both eradicate HCV and reverse Wnt/β-catenin signaling is needed.

Methods
Cell-based HCV long term infection was established. Chronically HCV infected cells were treated with DAA, protein kinase A (PKA) inhibitor H89 and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Western blotting analysis and fluorescence microscopy were performed to determine HCV levels and component levels involved in ER stress/PKA/glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway. Meanwhile, the effects of H89 and TUDCA were determined on HCV infection.

Results
Both chronic HCV infection and replicon-induced Wnt/β-catenin signaling remained activated after HCV and replicon eradication by DAA. HCV infection activated PKA activity and PKA/GSK-3β-mediated Wnt/β-catenin signaling. Inhibition of PKA with H89 both repressed HCV and replicon replication and reversed PKA/GSK-3β-mediated Wnt/β-catenin signaling in both chronic HCV infection and replicon. Both chronic HCV infection and replicon induced ER stress. Inhibition of ER stress with TUDCA both repressed HCV and replicon replication and reversed ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling. Inhibition of either PKA or ER stress both inhibited extracellular HCV infection.

Conclusion
Targeting ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling with PKA inhibitor could be a novel therapeutic strategy for HCV-infected patients to overcomes the issue of remaining activated Wnt/β-catenin signaling by DAA treatment.
Inflammatory panel cytokines are elevated in the neocortex of late-stage Alzheimer’s disease but not Lewy body dementias
Authors: Chai Yuek Ling , Lee Jasinda H. , Chong Joyce R. , Ballard Clive , Francis Paul T. , Kennedy Brian K. , Arumugam Thiruma V. , Chen Christopher P. , Aarsland Dag , Lai Mitchell K. P. 
Published: May 2023

Abstract
Background
Chronically dysregulated neuroinflammation has been implicated in neurodegenerative dementias, with separate studies reporting increased brain levels of inflammatory mediators and gliosis in Alzheimer’s disease (AD) as well as in Lewy body dementias (LBD). However, it is unclear whether the nature and extent of neuroinflammatory responses in LBD are comparable to those in AD. In this study, we performed head-to-head measurements of a panel of cytokines in the post-mortem neocortex of AD versus the two major clinical subtypes of LBD, namely, dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).

Methods
Post-mortem tissues from the mid-temporal cortex (Brodmann area 21) of a cohort of neuropathologically well-defined AD, PDD and DLB patients were processed and measured for a comprehensive range of cytokines (IL-1α, IL-1Ra, IL-8, IL-10, IL-12p70, IL-13, IFN-γ, GM-CSF and FGF-2) using a multiplex immunoassay platform. Associations between inflammation markers and neuropathological measures of neuritic plaques, neurofibrillary tangles as well as Lewy bodies were also performed.

Results
We found IL-1α, IFN-γ, GM-CSF and IL-13 to be elevated in the mid-temporal cortex of AD patients. In contrast, none of the measured cytokines were significantly altered in either DLB or PDD. Similar cytokine changes were observed in two other neocortical areas of AD patients. Furthermore, increases of IL-1α, IFN-γ, GM-CSF, IL-10 and IL-13 associated with moderate-to-severe neurofibrillary tangle burden, but not with neuritic plaques or Lewy bodies. Our findings of elevated neocortical pro- and anti-inflammatory cytokines in AD, but not in DLB or PDD, suggest that neuroinflammatory responses are strongly linked to neurofibrillary tangle burden, which is higher in AD compared to LBD. In conclusion, neuroinflammation may not play a prominent role in the pathophysiology of late-stage LBD.
Programmed death ligand 1 expression in diffuse large B cell lymphoma: correlation with clinicopathological prognostic factors
Authors: Ibrahim Eman Mohamad , Refat Sherine , El-Ashwah Shaimaa , Fahmi Maryan Waheeb , Ibrahiem Afaf Taha 
Published: May 2023

Abstract
Background
The prognostic value of the level of programmed death ligand 1 (PD-L1) expression in non-Hodgkin lymphoma (NHL) is still debatable. This study examined the effect of the level of PD-L1 expression on the clinicopathological characteristics and prognosis of diffuse large B cell lymphoma (DLBCL).

Methods
A retrospective study was conducted on formalin-fixed paraffin-embedded tissue blocks of one hundred de novo DLBCL patients diagnosed from 2013 to 2016. PD-L1 expression was defined by a modified Combined-Positive Score (CPS) and their medical records were reviewed to collect their clinical, laboratory and radiological data, treatment, and outcome.

Results
The included patients were aged from 23 to 85 years and treated by rituximab- cyclophosphamide, doxorubicin, oncovin, prednisone (R-CHOP); 49% were males; 85% of the cases were presented at Ann Arbor stages III, IV; 33% of patients were seropositive for HCV and 87% of cases were presented with intermediate and high IPI. All included cases expressed PD-L1 using modified CPS. 27% of patients showed low PD-L1 expression (≥ 5% to < 50% of total tumor cellularity) while 73% of patients showed high PD-L1expression (≥ 50% of total tumor cellularity). High PD-L1 expression is statistically correlated with advanced stage (p 0.01), high IPI score (p 0.017), high incidence of stationary and progressive disease (p 0.002) and high incidence of relapse (p value 0.01). Five-year disease-free survival (DFS) was 29% for patients with high PD-L1 expression compared with 84.8% for patients with low PD-L1 expression (p 0.001).

Conclusions
This study suggests that high PD-L1 expression in DLBCL is associated with aggressive clinicopathological features and a decreased response to R-CHOP. The level of PD-L1 expression could be an independent predictor of DFS of DLBCL. More research is mandatory to standardize the cutoff value and scoring methods.
The terpene synthase (TPS) gene family in kiwifruit shows high functional redundancy and a subset of TPS likely fulfil overlapping functions in fruit flavour, floral bouquet and defence
Authors: Wang Wu , Wang Mindy Y. , Zeng Yunliu , Chen Xiuyin , Wang Xiaoyao , Barrington Anne M. , Tao Jianmin , Atkinson Ross G. , Nieuwenhuizen Niels J. 
Published: May 2023

AbstractVolatile terpenes are important compounds that influence fruit flavour and aroma of kiwifruit. Terpenes in plants also impact on the floral bouquet and defence against pests and pathogens in leaves and fruit. To better understand the overlapping roles that terpenes may fulfil in plants, a systematic gene, chemical and biochemical analysis of terpenes and terpene synthases (TPS) was undertaken in Red5 kiwifruit (Actinidia spp.). Analysis of the Red5 genome shows it contains only 22 TPS gene models, of which fifteen encode full-length TPS. Thirteen TPS can account for the major terpene volatiles produced in different tissues of Red5 kiwifruit and in response to different stimuli. The small Red5 TPS family displays surprisingly high functional redundancy with five TPS producing linalool/nerolidol. Treatment of leaves and fruit with methyl jasmonate enhanced expression of a subset of defence-related TPS genes and stimulated the release of terpenes. Six TPS genes were induced upon herbivory of leaves by the economically important insect pest Ctenopseustis obliquana (brown-headed leaf roller) and emission, but not accumulation, of (E)- and (Z)-nerolidol was strongly linked to herbivory. Our results provide a framework to understand the overlapping biological and ecological roles of terpenes in Actinidia and other horticultural crops.
Stranger Things: New Roles and Opportunities for Androgen Receptor in Oncology Beyond Prostate Cancer
Authors: Leo Javier , Dondossola Eleonora , Basham Kaitlin J , Wilson Nathaniel R , Alhalabi Omar , Gao Jianjun , Kurnit Katherine C , White Michael G , McQuade Jennifer L , Westin Shannon N , Wellberg Elizabeth A , Frigo Daniel E 
Published: May 2023

AbstractThe androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer. In this mini-review, new roles for AR in other cancer types are discussed as well as their potential for treatment with AR-targeted agents. Our understanding of these additional functions for AR in oncology expand this receptor's potential as a therapeutic target and will help guide the development of new treatment approaches.
The Hemoglobin Wayne Variant and Association With Falsely Elevated HbA1c
Authors: Mulpuri Neha , Bryant Ananda , Shahin Daryoush , Soe Kyaw 
Published: May 2023

Abstract
The objective of this work is to explain the effect of the clinically silent hemoglobinopathy hemoglobin Wayne (Hb Wayne) variant on glycated hemoglobin A1c (HbA1c) assay. This variant can result in falsely high HbA1c values among euglycemic individuals without diabetes mellitus (DM). We discuss 3 patients who were diagnosed with type 2 DM based on spuriously high HbA1c values due to the presence of Hb Wayne. All 3 patients were found to have elevated HbA1c values that did not correlate with other glycemic parameters such as capillary blood sugar, 2-hour oral glucose tolerance test, and fructosamine levels. Hemoglobin electrophoresis revealed that each patient had a rare hemoglobinopathy called Hb Wayne variant. These patients were reassured that they did not have DM and were able to avoid unnecessary treatment. These cases emphasize the importance of clinical judgment in recognizing the limitations and caveats of the HbA1c test. It is always necessary to investigate further any discordance between HbA1c values and the clinical picture or other glycemic parameters.
Two Girls With Adrenal Insufficiency and Failing Gonads
Authors: Poon Sarah Wing-Yiu , Li Raymond Hang-Wun , Tung Joanna Yuet-Ling 
Published: May 2023

Abstract
Congenital lipoid adrenal hyperplasia (CLAH) is a rare cause of adrenal insufficiency caused by mutations in the steroidogenic acute regulatory (StAR) gene. Patients classically present with adrenal crisis in early infancy and female external genitalia irrespective of chromosomal sex. We report 2 Chinese patients with normal female external genitalia presenting with salt wasting in the neonatal period. However, the diagnosis of CLAH was made only during pubertal years when they developed hypergonadotropic hypogonadism. One of them was subsequently found to have a 46XY karyotype and gonadectomy was performed at age 15 years. The other patient developed gonadal insufficiency and polycystic ovaries after menarche with hemorrhage into ovarian cysts requiring cystectomy. These 2 cases illustrate the importance of recognizing atypical features in neonates presenting with adrenal crisis. In managing the newborn with adrenal insufficiency and female-appearing external genitalia, the possibility of sex reversal and diagnosis of CLAH should be considered. Accurate delineation of internal pelvic organs using reliable imaging modalities or even laparoscopy, together with careful interpretation of clinical and laboratory findings, are crucial to accurate diagnosis and subsequent management.
New-Onset Type 1 Diabetes in a Child With Diabetic Ketoacidosis and Severe Hypertriglyceridemia Without Pancreatitis
Authors: Vitale Rebecca J , Laffel Lori M B 
Published: May 2023

Abstract
Hypertriglyceridemia is a complication of diabetic ketoacidosis (DKA) secondary to insulin deficiency inhibiting lipoprotein lipase and increasing lipolysis, but it is rare in children. A 7-year-old boy with history of autism spectrum disorder (ASD) presented with abdominal pain, vomiting, and “heavy breathing.” Initial laboratory tests revealed pH 6.87 and glucose 385 mg/dL (21.4 mmol/L), consistent with new-onset diabetes and DKA. His blood appeared lipemic; triglycerides were 17 675 mg/dL (199.6 mmol/L) with normal lipase (10 units/L). He received intravenous insulin and DKA resolved within 24 hours. Insulin infusion continued through day 6 for management of hypertriglyceridemia; triglycerides decreased to 1290 mg/dL (14.6 mmol/L) during this period. He never developed pancreatitis (lipase peaked at 68 units/L) or required plasmapheresis. With his ASD history, he had a restrictive diet high in saturated fat, which included up to 30 breakfast sausages daily. His triglycerides normalized after discharge. Severe hypertriglyceridemia can complicate DKA in newly diagnosed type 1 diabetes (T1D). Hypertriglyceridemia can be safely managed with insulin infusion in the absence of end-organ dysfunction. This complication should be considered in patients with DKA at diagnosis of T1D.
Understanding Potentially Preventable Mortality Following Oesophago-Gastric Cancer Surgery: Analysis of a National Audit of Surgical Mortality
Authors: Liu David S. , Fayed Aly , Evans Penelope , Bright Tim , Aly Ahmad , Duong Cuong , Spillane John , Weinberg Laurence , Watson David I. 
Published: May 2023

Abstract
Introduction
At a national level, understanding preventable mortality after oesophago-gastric cancer surgery can direct quality-improvement efforts. Accordingly, utilizing the Australian and New Zealand Audit of Surgical Mortality (ANZASM), we aimed to: (1) determine the causes of death following oesophago-gastric cancer resections in Australia, (2) quantify the proportion of potentially preventable deaths, and (3) identify clinical management issues contributing to preventable mortality.

Methods
All in-hospital mortalities following oesophago-gastric cancer surgery from 1 January 2010 to 31 December 2020 were analysed using ANZASM data. Potentially preventable and non-preventable cases were compared. Thematic analysis with a data-driven approach was used to classify clinical management issues.

Results
Overall, 636 complications and 123 clinical management issues were identified in 105 mortalities. The most common causes of death were cardio-respiratory in aetiology. Forty-nine (46.7%) deaths were potentially preventable. These cases were characterized by higher rates of sepsis (59.2% vs 33.9%, p = 0.011), multiorgan dysfunction syndrome (40.8% vs 25.0%, p = 0.042), re-operation (63.3% vs 41.1%, p = 0.031) and other complications compared with non-preventable mortality. Potentially preventable mortalities also had more clinical management issues per patient [median (IQR): 2 (1–3) vs 0 (0–1), p < 0.001), which adversely impacted preoperative (30.6% vs 7.1%, p = 0.002), intraoperative (18.4% vs 5.4%, p = 0.037) and postoperative (51.0% vs 17.9%, p < 0.001) care. Thematic analysis highlighted recurrent areas of deficiency with preoperative, intraoperative and postoperative patient management.

Conclusions
Almost 50% of deaths following oesophago-gastric cancer resections were potentially preventable. These were characterized by higher complication rates and clinical management issues. We highlight recurrent themes in patient management to improve future quality of care.
A study of proton-induced reactions on natural Silicon targets
Authors: Nicolis Nikolaos George , Zafeiri Georgia 
Published: May 2023

Experimental excitation functions of isotopes produced in reactions p + natSi are compared with the results of nuclear reaction program TALYS 1.95 and semi-empirical cross section formulas. We consider excitation functions of 7 isotopes (28Mg, 26Al, 24,22Na, 18F and 10,7Be) produced in reactions at bombarding energies of 20-144 MeV. They are compared with the predictions of the code TALYS 1.95, the semi-empirical formulas of Silberberg-Tsao (code yieldx) and SPACS. Comparisons of the results of the code TALYS 1.95 and previously published results of code ALICE are made. The predictive power of code TALYS 1.95 may be questioned for reaction products with mass number very much smaller than the target and of semi-empirical formulas at lower energies.