bluuebunny/crossref_metadata_2025 huggingface dataset:
Framing access to essential medicines in the context of Universal Health Coverage: a critical analysis of health sector strategic plans from eight countries in the WHO African region
Authors: Mhazo Alison T. , Maponga Charles C.
Published: November 2022

Background

Framing affects how issues are understood and portrayed. This profoundly shapes the construction of social problems and how policy options are considered. While access to essential medicines (ATM) in the World Health Organization (WHO) African Region is often framed as a societal problem, there is dominance of medical and technically oriented approaches to analyze and remedy the situation. Hence, the systematic application of social science approaches, such as framing theory, remains under-explored. Through a framing analysis of National Strategic Plans (NSPs) from eight countries, this study explores the applicability and potential usefulness of framing theory to analyze essential medicines policies.

Methods

We inductively coded the relevant NSP textual fragments using the qualitative content analysis software ATLAS.ti.22. Benford and Snow’s conceptualization of framing was used to organize the coded data into three frames: diagnostic (problems), prognostic (solutions) and motivational (values and ideological).

Results

The following five diagnostic frames were dominant or in-frame: medicine unavailability, ineffective regulation, weak supply chain management, proliferation of counterfeit (substandard or falsified) medicines and use of poor quality medicines. Diagnostic frames related to financing, affordability, efficiency and corruption were given limited coverage or out of frame. Prognostic frames corresponded with how these problems were framed. Whilst Universal Health Coverage (UHC) and its guiding principles was the dominant motivational frame, we identified some frame discordance between the global discourse and national level policies.

Conclusions

Social science approaches such as framing analysis are applicable and useful to systematically analyze essential medicine aspects. By applying framing theory, we revealed that ATM aspects in the eight countries we analyzed are more often characterized in relation to availability at the expense of affordability which undermines UHC. We conclude that whilst UHC is a strong motivational frame to guide ATM aspects, it is insufficient to inform a comprehensive approach to address the problems related to ATM at country level. To effectively advance ATM, concerned actors need to realize such limitation and endeavor to gain a deeper understanding of how problems are framed and agendas are set at country level, the processes through which ideas and knowledge become policies, including the political demands, incentives and trade-offs facing decision-makers in selecting policy priorities.
Plasma metabolomic profiling of dietary patterns associated with glucose metabolism status: The Maastricht Study
Authors: Yu Evan Yi-Wen , Ren Zhewen , Mehrkanoon Siamak , Stehouwer Coen D. A. , van Greevenbroek Marleen M. J. , Eussen Simone J. P. M. , Zeegers Maurice P. , Wesselius Anke
Published: November 2022

Background

Glucose metabolism has been reported to be affected by dietary patterns, while the underlying mechanisms involved remain unclear. This study aimed to investigate the potential mediation role of circulating metabolites in relation to dietary patterns for prediabetes and type 2 diabetes.

Methods

Data was derived from The Maastricht Study that comprised of 3441 participants (mean age of 60 years) with 28% type 2 diabetes patients by design. Dietary patterns were assessed using a validated food frequency questionnaire (FFQ), and the glucose metabolism status (GMS) was defined according to WHO guidelines. Both cross-sectional and prospective analyses were performed for the circulating metabolome to investigate their associations and mediations with responses to dietary patterns and GMS.

Results

Among 226 eligible metabolite measures obtained from targeted metabolomics, 14 were identified to be associated and mediated with three dietary patterns (i.e. Mediterranean Diet (MED), Dietary Approaches to Stop Hypertension Diet (DASH), and Dutch Healthy Diet (DHD)) and overall GMS. Of these, the mediation effects of 5 metabolite measures were consistent for all three dietary patterns and GMS. Based on a 7-year follow-up, a decreased risk for apolipoprotein A1 (APOA1) and docosahexaenoic acid (DHA) (RR 0.60, 95% CI 0.55, 0.65; RR 0.89, 95% CI 0.83, 0.97, respectively) but an increased risk for ratio of ω-6 to ω-3 fatty acids (RR 1.29, 95% CI 1.05, 1.43) of type 2 diabetes were observed from prediabetes, while APOA1 showed a decreased risk of type 2 diabetes from normal glucose metabolism (NGM; RR 0.82, 95% CI 0.75, 0.89).

Conclusions

In summary, this study suggests that adherence to a healthy dietary pattern (i.e. MED, DASH, or DHD) could affect the GMS through circulating metabolites, which provides novel insights into understanding the biological mechanisms of diet on glucose metabolism and leads to facilitating prevention strategy for type 2 diabetes.
TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes
Authors: Zhu Ping , Lao Guojuan , Chen Chuping , Luo Lihui , Gu Jing , Ran Jianmin
Published: November 2022

Background

Evidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes.

Methods

This prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39–1.30 mIU/L; medium-normal, 1.30–2.09 mIU/L; high-normal, 2.09–4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality.

Results

During a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07–1.61) and CVD (1.52; 1.08–2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12–1.73) and CVD (1.69; 1.17–2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants.

Conclusion

Low- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.
Is the cholesterol-perfluoroalkyl substance association confounded by dietary fiber intake?: a Bayesian analysis of NHANES data with adjustment for measurement error in fiber intake
Authors: Linakis Matthew W , Gustafson Paul , Allen Bruce C , Bachand Annette M , Van Landingham Cynthia , Keast Debra R , Longnecker Matthew P
Published: November 2022

Background

Serum concentrations of total cholesterol and related lipid measures have been associated with serum concentrations of per- and polyfluoroalkyl substances (PFAS) in humans, even among those with only background-level exposure to PFAS. Fiber is known to decrease serum cholesterol and a recent report based on National Health and Nutrition Examination Survey (NHANES) showed that PFAS and fiber are inversely associated. We hypothesized that confounding by dietary fiber may account for some of the association between cholesterol and PFAS.

Methods

We implemented a Bayesian correction for measurement error in estimated intake of dietary fiber to evaluate whether fiber confounds the cholesterol-PFAS association. The NHANES measure of diet, two 24-h recalls, allowed calculation of an estimate of the “true” long-term fiber intake for each subject. We fit models to the NHANES data on serum cholesterol and serum concentration of perfluorooctanoic acid (PFOA) and two other PFAS for 7,242 participants in NHANES.

Results

The Bayesian model, after adjustment for soluble fiber intake, suggested a decrease in the size of the coefficient for PFOA by 6.4% compared with the fiber-unadjusted model.

Conclusions

The results indicated that the association of serum cholesterol with PFAS was not substantially confounded by fiber intake.
Lipoprotein(a) predicts recurrent cardiovascular events in patients with prior cardiovascular events post-PCI: five-year findings from a large single center cohort study
Authors: Xu Na , Yao Yi , Jiang Lin , Xu Jingjing , Wang Huanhuan , Song Ying , Yang Yuejin , Xu Bo , Gao Runlin , Yuan Jinqing
Published: November 2022

Background

It is well established that lipoprotein(a)[Lp(a)] play a vital role in atherosclerosis. Whether Lp(a) can predict recurrence of cardiovascular events (CVEs) in prior CVEs patients is still unclear. We aim to investigate its association with subsequent long-term adverse events in this high-risk population.

Methods

A total of 4,469 patients with prior CVEs history after PCI were consecutively enrolled and categorized according Lp(a) values of < 10 (low), 10 to 30 (medium), and ≥ 30 mg/dL (high). The primary endpoint was MACCE, a composite of all-cause death, myocardial infarction, stroke and unplanned revascularization.

Results

During an average of 5.0 years of follow-up, 1,078 (24.1%) and 206 (4.6%) patients experienced MACCE and all-cause death with 134 (3.0%) of whom from cardiac death. The incidence of MACCE, all-cause death and cardiac death were significantly higher in the high Lp(a) group (p < 0.05). After adjustment of confounding factors, high Lp(a) level remained an independent risk factor for MACCE (adjusted HR 1.240, 95%CI 1.065–1.443, p = 0.006), all-cause death (adjusted HR 1.445, 95%CI 1.023–2.042, p = 0.037) and cardiac death (adjusted HR 1.724, 95%CI 1.108–2.681, p = 0.016). This correlation remained significant when treated as a natural logarithm-transformed continuous variable. This finding is relatively consistent across subgroups and confirmed again in two sensitivity analyses.

Conclusions

Our present study confirmed that Lp(a) was an independent predictor for recurrent CVEs in patients with established CVEs, illustrating that Lp(a) level might be a valuable biomarker for risk stratification and prognostic assessment in this high-risk population.
Preoperative coagulation biomarkers associate with survival and pulmonary embolism after surgical treatment of non-spinal skeletal metastases
Authors: Matilainen Sanna , Kask Gilber , Nieminen Jyrki , Lassila Riitta , Laitinen Minna
Published: November 2022

Background

Thrombotic complications are synergistic and associated with orthopedic procedures, trauma, and malignancy. Because cancer enhances coagulation activity and vice versa, we assessed preoperative biomarkers for survival and complications after treatment of pathologic fractures in non-spinal skeletal metastases.

Patients/methods

Our study population comprised 113 actual or impending pathologic fractures in 100 patients admitted to two referral centers. Laboratory variables were collected retrospectively from patient records and analyzed related to incidence of pulmonary embolism (PE) and mortality (Kaplan-Meier and Cox regression analyses and biomarker quartiles).

Results

Preoperative coagulation variables were high without exceptions. PE occurred in 12 patients at 36 post-operative days at incidence of 11% in the lower and 13% in the upper extremity fractures. Patients with fibrinogen exceeding 5 g/l (log-rank 0.022) developed PE earlier (5 to 15 days postoperatively) than others. Also, mean patient survival with normal fibrinogen range (2–4 g/l) was 34 months, whereas it halved upon elevated fibrinogen (log-rank p = 0.009). Survival in patients with FVIII levels under 326 IU/dl (Q3) was 22 months, but only 7 months if FVIII exceeded 326 IU/dl (log-rank p = 0.002). Combined elevated fibrinogen and FVIII predicted survival: for patients with levels below threshold limits was 22 months versus only 7 months when both variables exceeded the ranges (log-rank p < 0.001). Multivariate analysis to control confounders supported an independent role of fibrinogen and FVIII for survival.

Conclusions

Our study has established fibrinogen and FVIII as potential preoperative contributors of survival and complications after treatment of metastatic fractures. These results highlight the need for novel anticoagulation and thromboprophylaxis strategies among these patients.
Antiviral role of IFITM3 in prototype foamy virus infection
Authors: Wang Zhaohuan , Tuo Xiaopeng , Zhang Junshi , Chai Keli , Tan Juan , Qiao Wentao
Published: November 2022

Background

Foamy viruses (FVs) are retroviruses with unique replication strategies that cause lifelong latent infections in their hosts. FVs can also produce foam-like cytopathic effects in vitro. However, the effect of host cytokines on FV replication requires further investigation. Although interferon induced transmembrane (IFITMs) proteins have become the focus of antiviral immune response research due to their broad-spectrum antiviral ability, it remains unclear whether IFITMs can affect FV replication.

Method

In this study, the PFV virus titer was characterized by measuring luciferase activity after co-incubation of PFVL cell lines with the cell culture supernatants (cell-free PFV) or the cells transfected with pcPFV plasmid/infected with PFV (cell-associated PFV). The foam-like cytopathic effects of PFV infected cells was observed to reflect the virus replication. The total RNA of PFV infected cells was extracted, and the viral genome was quantified by Quantitative reverse transcription PCR to detect the PFV entry into target cells.

Results

In the present study, we demonstrated that IFITM1-3 overexpression inhibited prototype foamy virus (PFV) replication. In addition, an IFITM3 knockdown by small interfering RNA increased PFV replication. We further demonstrated that IFITM3 inhibited PFV entry into host cells. Moreover, IFITM3 also reduced the number of PFV envelope proteins, which was related to IFITM3 promoted envelope degradation through the lysosomal pathway.

Conclusions

Taken together, these results demonstrate that IFITM3 inhibits PFV replication by inhibiting PFV entry into target cells and reducing the number of PFV envelope.
Forebrain-specific conditional calcineurin deficiency induces dentate gyrus immaturity and hyper-dopaminergic signaling in mice
Authors: Hagihara Hideo , Shoji Hirotaka , Kuroiwa Mahomi , Graef Isabella A. , Crabtree Gerald R. , Nishi Akinori , Miyakawa Tsuyoshi
Published: November 2022

Calcineurin (Cn), a phosphatase important for synaptic plasticity and neuronal development, has been implicated in the etiology and pathophysiology of neuropsychiatric disorders, including schizophrenia, intellectual disability, autism spectrum disorders, epilepsy, and Alzheimer’s disease. Forebrain-specific conditional Cn knockout mice have been known to exhibit multiple behavioral phenotypes related to these disorders. In this study, we investigated whether Cn mutant mice show pseudo-immaturity of the dentate gyrus (iDG) in the hippocampus, which we have proposed as an endophenotype shared by these disorders. Expression of calbindin and GluA1, typical markers for mature DG granule cells (GCs), was decreased and that of doublecortin, calretinin, phospho-CREB, and dopamine D1 receptor (Drd1), markers for immature GC, was increased in Cn mutants. Phosphorylation of cAMP-dependent protein kinase (PKA) substrates (GluA1, ERK2, DARPP-32, PDE4) was increased and showed higher sensitivity to SKF81297, a Drd1-like agonist, in Cn mutants than in controls. While cAMP/PKA signaling is increased in the iDG of Cn mutants, chronic treatment with rolipram, a selective PDE4 inhibitor that increases intracellular cAMP, ameliorated the iDG phenotype significantly and nesting behavior deficits with nominal significance. Chronic rolipram administration also decreased the phosphorylation of CREB, but not the other four PKA substrates examined, in Cn mutants. These results suggest that Cn deficiency induces pseudo-immaturity of GCs and that cAMP signaling increases to compensate for this maturation abnormality. This study further supports the idea that iDG is an endophenotype shared by certain neuropsychiatric disorders.
Early postnatal alterations in follicular stress response and survival in a mouse model of Classic Galactosemia
Authors: Hagen-Lillevik Synneva , Johnson Joshua , Lai Kent
Published: November 2022

Primary ovarian insufficiency is characterized by accelerated loss of primordial follicles, which results in ovarian failure and concomitant menopause before age 40. About 1–3% of females in the general population are diagnosed with POI; however, greater than 80% of females with the inherited disease Classic Galactosemia will develop POI. Classic Galactosemia is caused by mutations in the GALT gene encoding the enzyme galactose-1 phosphate uridylyltransferase. While dietary restriction of galactose is lifesaving in the neonatal period, the development of complications including primary ovarian insufficiency is not mitigated. Additionally, the pattern(s) of follicle loss have not been completely characterized. The chronic accumulation of aberrant metabolites such as galactose-1-phosphate and galactitol are suspected culprits in the development of the sequelae, yet the mechanisms remain elusive.

Our group uses a GalT gene-trapped mouse model to study the pathophysiology of primary ovarian insufficiency in Classic Galactosemia. We recently showed that differences in the Integrated Stress Response pathway occur in mutant ovaries that likely contribute to their primary ovarian insufficiency phenotype. Using immunofluorescent staining of histological sections of ovaries at progressive ages, we saw evidence of altered Integrated Stress Response activity in granulosa cells and primordial oocytes consistent with accelerated primordial follicle growth activation, aberrant DNA damage and/or repair, and increased cellular stress/death. Overall, our findings indicate that abnormal Integrated Stress Response in the Classic Galactosemia model ovary results in accelerated primordial follicle growth activation, sometimes referred to as “burnout.” These aberrant early events help further clarify when/how the primary ovarian insufficiency phenotype arises under galactosemic conditions.
Steroid treatment as anti-inflammatory and neuroprotective agent following out-of-hospital cardiac arrest: a randomized clinical trial
Authors: Obling Laust Emil Roelsgaard , Beske Rasmus Paulin , Wiberg Sebastian , Folke Fredrik , Moeller Jacob Eifer , Kjaergaard Jesper , Hassager Christian
Published: November 2022

Background

Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have a high morbidity and mortality risk and often develop post-cardiac arrest syndrome (PCAS) involving systemic inflammation. The severity of the inflammatory response is associated with adverse outcome, with anoxic irreversible brain injury as the leading cause of death following resuscitated OHCA. The study aimed to investigate the anti-inflammatory and neuroprotective effect of pre-hospital administration of a high-dose glucocorticoid following OHCA.

Methods

The study is an investigator-initiated, randomized, multicenter, single-blinded, placebo-controlled, clinical trial. Inclusion will continue until one hundred twenty unconscious OHCA patients surviving a minimum of 72 h are randomized. Intervention is a 1:1 randomization to an infusion of methylprednisolone 250 mg following a minimum of 5 min of sustained return of spontaneous circulation in the pre-hospital setting. Methylprednisolone will be given as a bolus infusion of 1 × 250 mg (1 × 4 mL) over a period of 5 min. Patients allocated to placebo will receive 4 mL of isotonic saline (NaCl 0.9%). Main eligibility criteria are OHCA of presumed cardiac cause, age ≥ 18 years, Glasgow Coma Scale ≤ 8, and sustained ROSC for at least 5 min. Co-primary endpoint: Reduction of interleukin-6 and neuron-specific-enolase. Secondary endpoints: Markers of inflammation, brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, safety, neurological function at follow-up, and mortality. A research biobank is set up with blood samples taken daily during the first 72 h from hospitalization to evaluate primary and secondary endpoints.

Discussion

We hypothesize that early anti-inflammatory steroid treatment in the pre-hospital setting can mitigate the progression of PCAS following resuscitated OHCA. Primary endpoints will be assessed through analyses of biomarkers for inflammation and neurological damage taken during the first 72 h of admission.

Trial registration

EudraCT number: 2020-000855-11; submitted March 30, 2020

ClinicalTrials.gov Identifier: NCT04624776; submitted October 12, 2020, first posted November 10, 2020
Immediate versus early (24-hours) urinary catheter removal after elective minimally invasive colonic resection: study protocol for a randomized, multicenter, non-inferiority trial
Authors: Pedrazzani Corrado , Montroni Isacco , Conti Cristian , Turri Giulia , Foppa Caterina , Carvello Michele , Taffurelli Giovanni , Ugolini Giampaolo , Spinelli Antonino
Published: November 2022

Background

Enhanced Recovery After Surgery (ERAS) represents the standard of care in colorectal surgery. Among ERAS items, early removal of urinary catheter (UC) is considered a key issue, though adherence to this specific item still varies among centers. UC placement allows for monitoring of post-operative urinary output but relates to an increased risk of urinary tract infection (UTI), reduced mobility, and patient’s discomfort. Several studies investigated the role of early UC removal specifically looking at the rate of acute urinary retention (AUR) but most of them were retrospective, single-center, underpowered, cohort studies. The main purpose of this study is to compare the rate of AUR after immediate (at the end of the surgery) versus early (within 24 h from the completion of surgery) removal of UC in patients undergoing minimally invasive colonic resection (MICR). The secondary outcomes focus on goals that could be positively impacted by the immediate removal of the UC at the end of the surgery. In particular, the rate of UTIs, perception of pain, time-to-return of bowel and physical functions, postoperative complications, and length of hospital stay will be measured.

Methods

This is a prospective, randomized, controlled, two-arm, multi-center, study comparing the rate of AUR after immediate versus early removal of UC in patients undergoing MICR. The investigators hypothesize that immediate UC removal is non-inferior to 24-h UC removal in terms of AUR rate. Randomization is at the patient level and participants are randomized 1:1 to remove their UC either immediately or within 24 h from the completion of surgery. Those eligible for inclusion were patients undergoing any MICR with an anastomosis above the peritoneal reflection. Those patients who need to continue urinary output monitoring after the surgery will be excluded. The number of patients calculated to be enrolled in each group is 108 based on an expected AUR rate of 3% for the 24-h UC removal group and considering acceptable an AUR of 9% for the immediate UC removal group.

Discussion

The demonstration of a non-inferiority of immediate versus 24-h removal of UC would call into question the usefulness of urinary drainage in the setting of MICR.

Trial registration

ClinicalTrials.gov NCT05249192. Prospectively registered on February 21, 2022.
Elimination of probable praziquantel-resistant Dipylidium caninum with nitroscanate in a mixed-breed dog: a case report
Authors: Loftus John P. , Acevedo Andrew , Bowman Dwight D. , Liotta Janice L. , Wu Timothy , Zhu Melinda
Published: November 2022

Background

Praziquantel is the drug of choice for treating the tapeworm Dipylidium caninum in dogs; however, resistance is possible, and regular, non-targeted administration of praziquantel may select for anthelminthic-resistant populations.

Methods

The zinc sulfate fecal floatation procedure was conducted. Gross visualization was used to identify Dipylidium spp. segments, and capsule endoscopy was used to visualize adult tapeworms within the intestinal tract.

Results

An 18-month-old spayed female terrier mix was presented due to diarrhea, hematochezia and weight loss. The dog received appropriate anthelmintic therapy for Giardia spp., Ancylostoma spp. and Dipylidium spp. The dog’s clinical signs resolved, and elimination of Ancylostoma spp. was confirmed by subsequent fecal analysis. However, Dipylidium spp. segments were repeatedly present in the stool. Observation of the segments confirmed the presence of adult Dipylidium spp in feces. Treatment with praziquantel and epsiprantel were unsuccessful in eliminating the organism but was apparently successful in flea prevention. A single dose of nitrosconate was administered and eliminated Dipylidium spp. infection in the dog.

Conclusions

Nitrosconate can be an effective treatment for praziquantel-resistant dipylidiasis in dogs. The novel application of capsule endoscopy confirmed the anthelmintic efficacy of this treatment.

Graphical Abstract
White blood cells and chronic rhinosinusitis: a Mendelian randomization study
Authors: Pongdee Thanai , Bielinski Suzette J. , Decker Paul A. , Kita Hirohito , Larson Nicholas B.
Published: November 2022

Background

Risk factors for the pathogenesis of chronic rhinosinusitis (CRS) remain largely undetermined, which is likely due to the heterogeneity of the disease. White blood cell counts have been largely unexplored as a risk factor for CRS even though different types of white blood cells are involved in the inflammatory process of CRS.

Objective

To investigate causal associations between different types of white blood cells on risk of CRS utilizing a Mendelian randomization (MR) analysis.

Methods

A two-sample MR analysis was performed using respective GWAS summary statistics for the exposure traits (neutrophil count, eosinophil count, basophil count, lymphocyte count, and monocyte count) and outcome trait (CRS). For the exposure traits, the European Bioinformatics Institute database of complete GWAS summary data was used. For the outcome trait, summary statistics for CRS GWAS were obtained from FinnGen. Primary analysis for MR was performed using inverse-variance weighted two-sample MR. Sensitivity analyses included weighted median, MR-Egger, and MR-PRESSO (raw and outlier-corrected).

Results

Eosinophils were associated with CRS (OR = 1.55 [95% CI 1.38, 1.73]; p = 4.3E-14). Eosinophil results were similar across additional MR methods. MR results did not demonstrate significant causal relationships between neutrophils, lymphocytes, monocytes, or basophils with CRS. No significant pleiotropic bias was observed.

Conclusions

In a two-sample MR analysis, a potential causal link between blood eosinophil counts and CRS has been demonstrated. In addition, causal relationships between blood counts among other white blood cell types and CRS were not found. Further studies involving genetic variation in CRS are needed to corroborate genetic causal effects for CRS.
Computed tomography in acute intracerebral hemorrhage: neuroimaging predictors of hematoma expansion and outcome
Authors: Hillal Amir , Ullberg Teresa , Ramgren Birgitta , Wassélius Johan
Published: November 2022

Intracerebral hemorrhage (ICH) accounts for 10–20% of all strokes worldwide and is associated with serious outcomes, including a 30-day mortality rate of up to 40%. Neuroimaging is pivotal in diagnosing ICH as early detection and determination of underlying cause, and risk for expansion/rebleeding is essential in providing the correct treatment. Non-contrast computed tomography (NCCT) is the most used modality for detection of ICH, identification of prognostic markers and measurements of hematoma volume, all of which are of major importance to predict outcome. The strongest predictors of 30-day mortality and functional outcome for ICH patients are baseline hematoma volume and hematoma expansion. Even so, exact hematoma measurement is rare in clinical routine practice, primarily due to a lack of tools available for fast, effective, and reliable volumetric tools. In this educational review, we discuss neuroimaging findings for ICH from NCCT images, and their prognostic value, as well as the use of semi-automatic and fully automated hematoma volumetric methods and assessment of hematoma expansion in prognostic studies.
Value of texture analysis based on dynamic contrast-enhanced magnetic resonance imaging in preoperative assessment of extramural venous invasion in rectal cancer
Authors: Fang Junjie , Sun Wei , Wu Dan , Pang Peipei , Guo Xiuyu , Yu Chunyao , Lu Wei , Tang Guangyu
Published: November 2022

Objective

Accurate preoperative assessment of extramural vascular invasion (EMVI) is critical for the treatment and prognosis of rectal cancer. The aim of our research was to develop an assessment model by texture analysis for preoperative prediction of EMVI.

Materials and methods

This study enrolled 44 rectal patients as train cohort, 7 patients as validation cohort and 18 patients as test cohort. A total of 236 texture features from DCE MR imaging quantitative parameters were extracted for each patient (59 features of Ktrans, Kep, Ve and Vp), and key features were selected by least absolute shrinkage and selection operator regression (LASSO). Finally, clinical independent risk factors, conventional MRI assessment, and T-score were incorporated to construct an assessment model using multivariable logistic regression.

Results

The T-score calculated using the 4 selected key features were significantly correlated with EMVI (p < 0.010). The area under the receiver operating characteristic curve (AUC) was 0.797 for discriminating between EMVI-positive and EMVI-negative patients with a sensitivity of 88.2% and specificity of 70.4%. The conventional MRI assessment of EMVI had a sensitivity of 23.53% and a specificity of 96.30%. The assessment model showed a greatly improved performance with an AUC of 0.954 (sensitivity, 88.2%; specificity, 92.6%) in train cohort, 0.833 (sensitivity, 66.7%; specificity, 100%) in validation cohort and 0.877 in test cohort, respectively.

Conclusions

The assessment model showed an excellent performance in preoperative assessment of EMVI. It demonstrates strong potential for improving the accuracy of EMVI assessment and provide a reliable basis for individualized treatment decisions.
Justification of CT practices across Europe: results of a survey of national competent authorities and radiology societies
Authors: Foley Shane J. , Bly Ritva , Brady Adrian P. , Ebdon-Jackson Steve , Karoussou-Schreiner Alexandra , Hierath Monika , Sosna Jacob ,   ESR EU-JUST-CT Project consortium, Brkljačić Boris
Published: November 2022

Objectives

Published literature on justification of computed tomography (CT) examinations in Europe is sparse but demonstrates consistent sub-optimal application. As part of the EU initiated CT justification project, this work set out to capture CT justification practices across Europe.

Methods

An electronic questionnaire consisting of mostly closed multiple-choice questions was distributed to national competent authorities and to presidents of European radiology societies in EU member states as well as Iceland, Norway, Switzerland, and the UK (n = 31).

Results

Fifty-one results were received from 30 European countries. Just 47% (n = 24) stated that advance justification of individual CT examinations is performed by a medical practitioner. Radiologists alone mostly (n = 27, 53%) perform daily justification of CT referrals although this is a shared responsibility in many countries. Imaging referral guidelines are widely available although just 13% (n = 6) consider them in daily use. Four countries (Cyprus, Ireland, Sweden, UK) reported having them embedded within clinical decision support systems. Justification of new practices with CT is mostly regulated (77%) although three countries (Belgium, Iceland and Portugal) reported not having any national system in place for generic justification. Health screening with CT was reported by seven countries as part of approved screening programmes and by eight countries outside. When performed, CT justification audits were reported to improve CT justification rates.

Conclusions

CT justification practices vary across Europe with less than 50% using advance justification and a minority having clinical decision support systems in place. CT for health screening purposes is not currently widely used in Europe.
Regulatory of miRNAs in tri-lineage differentiation of C3H10T1/2
Authors: Huang Wei , Wu Xiaoyue , Xiang Shuaixi , Qiao Mingxin , Li Hanfei , Zhu Yujie , Zhu Zhou , Zhao Zhihe
Published: November 2022

MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes, which play a vital role in cell generation, metabolism, apoptosis and stem cell differentiation. C3H10T1/2, a mesenchymal cell extracted from mouse embryos, is capable of osteogenic differentiation, adipogenic differentiation and chondrogenic differentiation. Extensive studies have shown that not only miRNAs can directly trigger targeted genes to regulate the tri-lineage differentiation of C3H10T1/2, but it also can indirectly regulate the differentiation by triggering different signaling pathways or various downstream molecules. This paper aims to clarify the regulatory roles of different miRNAs on C3H10T1/2 differentiation, and discussing their balance effect among osteogenic differentiation, adipogenic differentiation and chondrogenic differentiation of C3H10T1/2. We also review the biogenesis of miRNAs, Wnt signaling pathways, MAPK signaling pathways and BMP signaling pathways and provide some specific examples of how these signaling pathways act on C3H10T1/2 tri-lineage differentiation. On this basis, we hope that a deeper understanding of the differentiation and regulation mechanism of miRNAs in C3H10T1/2 can provide a promising therapeutic method for the clinical treatment of bone defects, osteoporosis, osteoarthritis and other diseases.
A Unitary Association-based conodont biozonation of the Smithian–Spathian boundary (Early Triassic) and associated biotic crisis from South China
Authors: Leu Marc , Bucher Hugo , Vennemann Torsten , Bagherpour Borhan , Ji Cheng , Brosse Morgane , Goudemand Nicolas
Published: November 2022

The Smithian–Spathian boundary (SSB) crisis played a prominent role in resetting the evolution and diversity of the nekton (ammonoids and conodonts) during the Early Triassic recovery. The late Smithian nektonic crisis culminated at the SSB, ca. 2.7 Myr after the Permian–Triassic boundary mass extinction. An accurate and high-resolution biochronological frame is needed for establishing patterns of extinction and re-diversification of this crisis. Here, we propose a new biochronological frame for conodonts that is based on the Unitary Associations Method (UAM). In this new time frame, the SSB can thus be placed between the climax of the extinction and the onset of the re-diversification. Based on the study of new and rich conodont collections obtained from five sections (of which four are newly described here) in the Nanpanjiang Basin, South China, we have performed a thorough taxonomical revision and described one new genus and 21 new species. Additionally, we have critically reassessed the published conodont data from 16 other sections from South China, and we have used this new, standardized dataset to construct the most accurate, highly resolved, and laterally reproducible biozonation of the Smithian to early Spathian interval for South China. The resulting 11 Unitary Association Zones (UAZ) are intercalibrated with lithological and chemostratigraphical (δ13Ccarb) markers, as well as with ammonoid zones, thus providing a firm basis for an evolutionary meaningful and laterally consistent definition of the SSB. Our UAZ8, which is characterized by the occurrence of Icriospathodus ex gr. crassatus, Triassospathodus symmetricus and Novispathodus brevissimus, is marked by a new evolutionary radiation of both conodonts and ammonoids and is within a positive peak in the carbon isotope record. Consequently, we propose to place the SSB within the separation interval intercalated between UAZ7 and UAZ8 thus leaving some flexibility for future refinement and updating.

ZooBank LSID: urn:lsid:zoobank.org:pub:12326FE6-79DD-43A8-9421-26C3883FBE2E
The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity
Authors: Li Qianhui , Chen Feng , Wang Fei
Published: November 2022

Acute liver failure caused by drug overdose is a significant clinical problem in developed countries. Acetaminophen (APAP), a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. In addition to APAP-induced direct hepatotoxicity, the intracellular signaling mechanisms of APAP-induced liver injury (AILI) including metabolic activation, mitochondrial oxidant stress and proinflammatory response further affect progression and severity of AILI. Liver inflammation is a result of multiple interactions of cell death molecules, immune cell-derived cytokines and chemokines, as well as damaged cell-released signals which orchestrate hepatic immune cell infiltration. The immunoregulatory interplay of these inflammatory mediators and switching of immune responses during AILI lead to different fate of liver pathology. Thus, better understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression are essential to identify novel therapeutic targets for the treatment of AILI. Here, this present review aims to systematically elaborate on the underlying immunological mechanisms of AILI, its relevance to immune cells and their effector molecules, and briefly discuss great therapeutic potential based on inflammatory mediators.
General decay synchronization stability on the nonautonomous BAM recurrent neural networks with delays
Authors: Halik Azhar , Wumaier Aishan
Published: November 2022

This paper studies the general decay synchronization (GDS) of a class of nonautonomous bidirectional associative memory recurrent neural networks (BAMRNNs) with mixed time delays. By employing the Lyapunov method and useful inequality techniques, some sufficient conditions on the general decay synchronization for BAMRNNs are derived. In addition, an example with numerical simulations is presented to illustrate the obtained theoretical results.
Comparing weighted densities
Authors: Bukor József , Filip Ferdinánd , Šustek Jan , Tóth János T.
Published: November 2022

In this paper we study inequalities between weighted densities of sets of natural numbers corresponding to different weight functions. Depending on the asymptotic relation between the weight functions, we give sharp bounds for possible values of one density when the values of another density are given. In particular, we give a condition for two weight functions to generate equivalent weighted densities.
A novel Elzaki transform homotopy perturbation method for solving time-fractional non-linear partial differential equations
Authors: Iqbal Sajad , Martínez Francisco , Kaabar Mohammed K. A. , Samei Mohammad Esmael
Published: November 2022

This paper presents the solution of important types of non-linear time-fractional partial differential equations via the conformable Elzaki transform Homotopy perturbation method. We apply the proposed technique to solve four types of non-linear time-fractional partial differential equations. In addition, we establish the results on the uniqueness and convergence of the solution. Finally, the numerical results for a variety of α values are briefly examined. The proposed method performs well in terms of simplicity and efficiency.
Single-dose intravenous ketamine or intramuscular naltrexone for high-utilization inpatients with alcohol use disorder: pilot trial feasibility and readmission rates
Authors: Terasaki Dale , Loh Ryan , Cornell Anastasia , Taub Julie , Thurstone Christian
Published: November 2022

Background

Alcohol use disorder (AUD) accounts for millions of acute care encounters annually in the United States. Hospitalization represents a vital opportunity to intervene pharmacologically, but low medication adherence is a significant barrier. Two single-dose, adherence-independent interventions are well suited for pre-discharge administration: intravenous (IV) ketamine and intramuscular (IM) naltrexone. Their feasibility and readmission-reducing efficacy in hospital settings are not well-established.

Methods

A 3-arm, open-label randomized trial was conducted at our safety-net medical hospital among high-utilization inpatients with severe AUD. Consented adults (age 18–65) were randomized to (1) IV ketamine (KET) 0.5 mg/kg over 40 min, (2) IM naltrexone (NTX) 380 mg once, or (3) linkage alone (LA). The primary clinical outcome was 30-day all-cause hospital readmission rate. All were provided enhanced linkage to outpatient addiction clinic.

Results

We consented and randomized 44 participants (n = 13, 14, 17 for KET, NTX, LA, respectively), with a mean of 3.2 past-year hospitalizations. Compared to the LA arm, both the KET arm (RR 0.37, p = 0.17) and NTX arm (RR 0.52, p = 0.27) had a lower 30-day readmission rate, though the differences were nonsignificant. Immediate acceptability ratings of KET and NTX were 9.50 and 9.17 out of 10, respectively. No serious adverse events or illicit ketamine use was reported.

Conclusions

Both interventions are feasible and showed promise in reducing readmissions for high-utilization AUD inpatients. Despite randomization, baseline characteristics may have differed in ways that biased against the control arm. Additional pragmatic studies—with larger sample size, blinding, and robust follow-up data collection—are needed to verify findings and better understand mediating factors.

ClinicalTrials.gov Identifier NCT04562779. Registered 24 September 2020. https://clinicaltrials.gov/ct2/show/NCT04562779
Bifidobacterium animalis subsp. lactis Probio-M8 undergoes host adaptive evolution by glcU mutation and translocates to the infant’s gut via oral-/entero-mammary routes through lactation
Authors: Zhong Zhi , Tang Hai , Shen Tingting , Ma Xinwei , Zhao Feiyan , Kwok Lai-Yu , Sun Zhihong , Bilige Menghe , Zhang Heping
Published: November 2022

Background

Most previous studies attempting to prove the phenomenon of mother-to-infant microbiota transmission were observational, performed only at genus/species-level resolution, and relied entirely on non-culture-based methodologies, impeding interpretation.

Results

This work aimed to use a biomarker strain, Bifidobacterium animalis subsp. lactis Probio-M8 (M8), to directly evaluate the vertical transmission of maternally ingested bacteria by integrated culture-dependent/-independent methods. Our culture and metagenomics results showed that small amounts of maternally ingested bacteria could translocate to the infant gut via oral-/entero-mammary routes through lactation. Interestingly, many mother-infant-pair-recovered M8 homologous isolates exhibited high-frequency nonsynonymous mutations in a sugar transporter gene (glcU) and altered carbohydrate utilization preference/capacity compared with non-mutant isolates, suggesting that M8 underwent adaptive evolution for better survival in simple sugar-deprived lower gut environments.

Conclusions

This study presented direct and strain-level evidence of mother-to-infant bacterial transmission through lactation and provided insights into the impact of milk microbiota on infant gut colonization.
Across the deserts and sea: inter-individual variation in migration routes of south-central European barn swallows (Hirundo rustica)
Authors: Pancerasa Mattia , Ambrosini Roberto , Romano Andrea , Rubolini Diego , Winkler David W. , Casagrandi Renato
Published: November 2022

Background

The spatiotemporal organization of migratory routes of long-distance migrants results from trade-offs between minimizing the journey length anden routerisk of migration-related mortality, which may be reduced by avoiding crossing inhospitable ecological barriers. Despite flourishing avian migration research in recent decades, little is still known about inter-individual variability in migratory routes, as well as the carry-over effects of spatial and temporal features of migration on subsequent migration stages.

Methods

We reconstructed post- and pre-breeding migration routes, barrier crossing behaviour and non-breeding movements of the largest sample (N = 85) analysed to date of individual barn swallows breeding in south-central Europe, which were tracked using light-level geolocators.

Results

Most birds spent their non-breeding period in the Congo basin in a single stationary area, but a small fraction of itinerant individuals reaching South Africa was also observed. Birds generally followed a ‘clockwise loop migration pattern’, moving through the central Mediterranean and the Sahara Desert during post-breeding (north to south) migration yet switching to a more western route, along the Atlantic coast of Africa, Iberia and western Mediterranean during the pre-breeding (south to north) migration. Southward migration was straighter and less variable, while northward migration was significantly faster despite the broader detour along the Atlantic coast and Iberia. These patterns showed limited sex-related variability. The timing of different circannual events was tightly linked with previous migration stages, considerably affecting migration route and speed of subsequent movements. Indeed, individuals departing late from Africa performed straighter and faster pre-breeding migrations, partly compensating for the initial departure delays, but likely at the cost of performing riskier movements across ecological barriers.

Conclusions

Different spatiotemporal migration strategies during post- and pre-breeding migration suggest that conditionsen routemay differ seasonally and allow for more efficient travelling along different migration corridors in either season. While highlighting patterns of inter-individual variability, our results support increasing evidence for widespread loop migration patterns among Afro-Palearctic avian migrants. Also, they suggest that carry-over effects acting across different phases of the annual cycle of migratory species can have major impacts on evolutionary processes.