bluuebunny/crossref_metadata_2025 huggingface dataset:
Degrees of demand: a task-based analysis of the British graduate labour market
Authors: Henseke Golo , Felstead Alan , Gallie Duncan , Green Francis
Published: April 2024

This study investigates the evolving demand for graduate skills in the British workforce, leveraging a task-based approach with data from the Skills and Employment Survey Series. Focused on the changing importance of job tasks related to graduate skills, the research explores the mapping of these tasks to educational attainment, discerns the price employers pay for tasks requiring graduate skills, and addresses regional variation in graduate supply and demand. Despite a slowing growth of graduate skills requirements post-2006, we find a stable assignment of graduate education with job tasks and an overall flat task price related to graduate skills requirements. We present regional evidence showing education expansion rather than exogenous factors drove high-skills demand, balancing the development of supply and demand in the British graduate labour market over 1997–2017.
Thirty-year trends of triple burden of disease in the adult population of Pakistan
Authors: Raheem Ahmed , Soomar Salman Muhammad , Issani Ali , Rahim Komal Abdul , Dhalla Zeyanna , Soomar Sarmad Muhammad , Mian Asad Iqbal , Khan Nadeem Ullah
Published: April 2024

Background

The triple burden of disease, i.e. communicable diseases, non-communicable diseases and injuries, has significantly affected the healthcare system of Pakistan during the last three decades. Therefore, this study aims to determine and analyse the 30-year disease burden trends through prevalence, death rates and percentages.

Methods

The data for the last three decades, i.e. 1990 to 2019, was extracted from the Global Burden of Disease for Pakistan. Percentage change in prevalence and deaths over 30 years was calculated. Poisson regression analysis was performed to evaluate the triple disease burden trends and the incidence rate ratio.

Results

A relative decrease of 23.4% was noted in the prevalence rate of communicable diseases except for human immunodeficiency virus and dengue fever. A relative increase of 1.4% was noted in the prevalence rate of non-communicable diseases. A relative increase of 56.1% was recorded in the prevalence rate of injuries. The prevalence rate ratios of communicable diseases significantly decreased to 0.9796 [95% CI: 0.9887–0.9905], but the prevalence rate of injury increased to 1.0094 [95% CI: 1.0073–1.01145], respectively.

Conclusion

Pakistan must take the next steps and develop strategies to decrease this burden and mortality rates in the population to create better outcomes and therefore help the healthcare system overall.
The quality landscape of economics: The top five and beyond
Authors: Hylmö Anders , Steffy Kody , Thomas Duncan A , Langfeldt Liv
Published: April 2024

Whereas a growing number of studies evidence that research quality notions and evaluative practices are field- and context-specific, many focus on single evaluative practices or moments. This paper introduces the concept of quality landscape to capture dynamics of interrelated quality notions, evaluative moments and practices in a research field. This concept shifts focus to (1) the field-specific universe of practices, devices and notions of research quality; (2) ways that interrelated valuations provide structure and boundeness to a landscape; (3) ways that perspectives on a shared landscape may change with position within the landscape; and (4) ways in which a quality landscape is intertwined with the field’s socio-epistemic conditions. With extensive interview data from top ranked departments in three Scandinavian countries, we use economics as a case for exploring the value of a quality landscape lens. We find that the field’s journal hierarchy and its ‘Top 5’ journals dominate the landscape, while other important evaluative practices beyond the top five are interlinked with the journal hierarchy. However, quantitative evaluative metrics common in other fields are virtually absent. We further find that national and local policy reinforce the journal hierarchy emphasis, and that career stages affect quality perspectives. We argue that the quality landscape is structured as a quality hierarchy with a focus on the core ‘general interest’, and suggest the notion of ordinalization (the process of rank ordering) as an organizing principle linking the quality landscape to the field’s socio-epistemic conditions. Finally, we offer suggestions for further research.
P030 Multiple autoantibody formation post COVID-19 infection
Authors: Islam Samsul , Erb Nicola
Published: April 2024

Background/Aims

COVID-19 has been linked to the formation of a number of autoantibodies. This case is an important reminder to clinicians interpreting autoantibody results in conjunction with clinical manifestations.

A previously fit 51 year old gentleman, with no prior history of autoimmune disease required admission with respiratory symptoms in April 2020 consistent with COVID-19 infection. His acute respiratory illness was complicated by empyema and left-sided pneumothorax requiring left pleural decortication and adhesiolysis under (VATS). Persistent respiratory symptoms and fatigue lead to investigations for long COVID. Positive antibodies detected were dsDNA 166IU/ml, Proteinase 3 antibodies 20IU/ml, Myeloperoxidase antibodies 32IU/ml, IgG anticardiolipin antibodies 90IU/ml and Glomerular basement membrane antibodies 351 IU/ml. Negative autoantibodies included ANA, RF, aCCP, b2GPI, smooth muscle, AMA and myositis related antibodies.

Methods

There were no clinical signs or symptoms of inflammatory arthropathy, vasculitis, thrombosis or connective tissue disease. Other investigations included a CT thorax showing no new lung lesions, unremarkable urine dipstick, normal urine ACR, normal US abdomen, CT sinuses and MRI brain.

Results

Trial course of prednisolone was given therapeutically due to long COVID symptoms. There was no significant impact on symptoms/ autoantibody titres thus steroids were discontinued. The patient was followed closely by the rheumatology team for two years. During that time, the autoantibody levels gradually decreased, and he did not develop clinical signs of autoimmune disease. His long COVID symptoms persisted, and he remains under the long COVID clinical team.

Conclusion

COVID-19 infection is known to cause an immune response. There have been published cases of positive ANA, U1-snRNP anti-SS-B/La, ANCA, anti-phospholipid and anti-SRP antibody formation following COVID-19 infection. The link between the pathophysiology of COVID-19, autoantibody formation and the role of autoimmunity is still unclear. This man's case was unusual in the number and variety of autoantibodies formed post COVID, this has not been reported in the literature to date. Some of the autoantibodies detected are highly specific for certain conditions, for example anti-GBM antibodies have a high specificity for Goodpasture’s syndrome, thus this case also illustrates the need to interpret positive autoantibodies in the context of clinical findings and history.

Disclosure

S. Islam: None. N. Erb: None.
P032 Designing a workshop for a temporal artery biopsy simulation
Authors: Rehan Shahzaib , Watts Patrick , Williams Ian , Hennessy Paul , O’Flaherty Caomhnad , Haridas Anjana
Published: April 2024

Background/Aims

A temporal artery biopsy (TAB) is performed to confirm a diagnosis of giant cell arteritis (GCA) and it is recommended by clinical practice guidelines. Historically there have been limited opportunities to perform this procedure and teaching has been largely informal and non standardised. This impacts a trainee’s confidence and competence and potentially patient safety. Simulation is crucial in modern day surgical education and so we designed, organised and delivered a wetlab to teach the steps of TAB to address these issues.

Methods

The event took place at the Welsh Institute for Minimal Access Therapy (WIMAT) centre in Cardiff. The WIMAT team developed the TAB models to be used. The event covered all of the theoretical aspects of performing a TAB, a demonstration on how to map the temporal artery, how to perform an ultrasound doppler procedure to locate the temporal artery and finally hands on experience performing a TAB with two different complexity models. Participants were asked to complete a 30 item Google Forms Questionnaire to help us to evaluate pre and post session knowledge, understanding and learning experiences pertaining to TAB.

Results

Participants noted significant improvements in their knowledge and understanding pertaining to all domains covered. A lack of knowledge, a lack of procedures previously performed, concern about damaging the facial nerve and lack of senior support/supervision were all identified as reasons as to why trainees get apprehensive when it comes to performing a TAB.

Conclusion

This novel formal teaching event provides a blueprint for deaneries to use in their teaching of TAB’s which can benefit trainees and patients. Modern surgical education benefits from wetlabs with expert supervision. Our findings also emphasise the benefits of cross specialty collaborative work.

Disclosure

S. Rehan: None. P. Watts: None. I. Williams: None. P. Hennessy: None. C. O’Flaherty: None. A. Haridas: None.
E056 Particularities of the lipid profile in rheumatoid arthritis
Authors: Fenniche Insaf , Somai Mehdi , Rachdi Imene , Arbaoui Ibrahim , Daoud Fatma , Kochbati Samir , Daoud Besma , Aydi Zohra , Boussema Fatma
Published: April 2024

Background/Aims

Rheumatoid arthritis (RA), like all autoimmune diseases, is associated with a high cardiovascular risk. This risk is essentially linked to the chronic inflammation and dyslipidaemia engendered by this chronic inflammatory rheumatism. The objective of this work was to study the particularities of the lipid profile in RA.

Methods

We conducted a retrospective study including patients with RA according to ACR- EULAR 2010 criteria, followed in an internal medicine department between 2015 and 2022. Lipid profile data (total cholesterol (TC), high-density lipoproteins (HDLc), low-density lipoproteins (LDLc), and triglycerides (TG)) were collected.

Results

Eighty patients with RA were studied. The mean age was 60.79 years [range 30-91]. The sex ratio (F/H) was 4.33, with a clear female predominance. The mean age of disease onset was 46.34 years [extremes: 22-82]. A personal history of dyslipidaemia was noted in 19 patients: hypercholesterolemia, hypertriglyceridemia, and mixed dyslipidaemia were found in 8, 4 and 7 cases. Other comorbidities were arterial hypertension in 35% of cases (n = 28), diabetes in 30% of cases (n = 24), renal insufficiency in 6.25% of cases (n = 5) and a cardiovascular accident in 5% of cases (n = 4). Obesity was present in 15% of patients and smoking in 5%. 69 patients had a lipid panel. Dyslipidaemia was present in 66.7% of cases (n = 46). The mean TC level was 4.47 ± 1.0 mmol/L [range: 2.32 - 6.96 mmol/L], the mean TG level was 2.64 ± 0.81 [range: 0.90 - 4 mmol/L], the mean HDLc level was 1.106 ± 0.394 mmol/L [0.50 - 2] and the mean LDLc level was 1.38 ± 0.565 mmol/L [0.56 - 3.59 mmol/L]. Hypercholesterolemia (21.3%) and hypocholesterolaemia (21.3%) were the most common lipid abnormalities. Hypertriglyceridemia was observed in 10% of cases (n = 8). A low HDLc was observed in 20% of cases (n = 16). Only one patient had a high HDLc, with HDLc= 2 mmol/l. A low LDL was present in 10% of cases (n = 8).

Conclusion

In our study, hypolipidemia was the most common dyslipidaemia. This confirms the lipid paradox found in RA. Indeed, systemic inflammation is responsible for quantitative and qualitative alterations in lipoproteins. Stabilization of the disease leads to normalization of the lipid balance and improved control of cardiovascular risk.

Disclosure

I. Fenniche: None. M. Somai: None. I. Rachdi: None. I. Arbaoui: None. F. Daoud: None. S. Kochbati: None. B. Daoud: None. Z. Aydi: None. F. Boussema: None.
Quality competition on markets: a socio-economic account
Authors: Doehne Malte
Published: April 2024

When, and for whom, does it pay to make high-quality products? This article models how quality competition incentivizes producers to make products of particular qualities. Quality is defined as an abstract property of products that explains relative markups on prices that buyers will pay for otherwise comparable goods. Relative differences in quality sustain interlinked quality niches whose appeal to producers vary. The ordering of niches by quality and its implications for profitability establish the market’s quality order of production. The model yields testable predictions for the locus of quality-related innovations. An analysis of the bottle closures used on 52 880 German wines by 1028 winemakers in three winemaking regimes supports the general claim that, and a specific claim as to how, quality competition incentivizes producers to pursue different quality-related strategies. The presented model situates quality competition and the socially embedded quality order of production at the heart of a socio-economic account of markets.
Child Labor Bans, Employment, and School Attendance: Evidence from Changes in the Minimum Working Age
Authors: Kozhaya Mireille , Flores Fernanda Martínez
Published: April 2024

This paper investigates the effect of a unique child labor ban regulation on employment and school enrollment. The ban, implemented in Mexico in 2015, increased the minimum working age from 14 to 15, introduced restrictions to employing underage individuals, and imposed stricter penalties for violation of the law. Our identification strategy relies on a DiD approach that exploits the date of birth as a natural cutoff to assign individuals into treatment and control groups. The ban led to a decrease in the probability to work by 1.2 percentage points, resembling a 16 percent decrease in the probability to work relative to the pre-reform mean, and an increase in the probability of being enrolled in school by 2.2 percentage points for the treatment group. These results are driven by a reduction in employment in paid work, and in the manufacturing and services sectors. The effects are persistent several years after the ban.
Biocontrol Potential of Cladosporium sphaerospermum Against the Wheat Powdery Mildew Fungus Blumeria graminis f. sp. tritici
Authors: Zhu (朱墨) Mo , Zhang Wanwan , Duan Xiao , Yan Shaonan , Cai Yinxia , Gong Shuangjun , Fahad Shah , Qiu Zongbo
Published: April 2024

Cladosporium spp. are known to be mycoparasites and inhibit phytopathogenic fungi. However, so far, little information is available on the impact of Cladosporium spp. on powdery mildews. Based on the morphological characteristics and molecular analysis, C. sphaerospermum was identified as a mycoparasite on the wheat powdery mildew fungus Blumeria graminis f. sp. tritici (Bgt), recently named B. graminis s. str. C. sphaerospermum was capable of preventing colony formation and conidial distribution of Bgt. The biomasses of Bgt notably decreased by 1.3, 2.2, 3.6, and 3.8 times at 2, 4, 6, and 8 days postinoculation (dpi), respectively. In addition, biomasses of C. sphaerospermum at 2, 4, 6, and 8 dpi significantly increased to 5.6, 13.9, 18.2, and 67.3 times, respectively. In vitro, C. sphaerospermum exudates significantly impaired appressorial formation of Bgt. Thus, C. sphaerospermum acts as a potential biological control agent by suppressing the formation, distribution, and development of Bgt conidia and is a viable alternative for managing the wheat powdery mildew. These results suggest that C. sphaerospermum is an antagonistic parasite of the wheat powdery mildew fungus and, hence, provide new knowledge about the biological control of phytopathogenic fungi.
Comparison of Insecticide Sprays in Alternate Rows and in All Rows on Asian Citrus Psyllid Control and Huanglongbing Progress in Sweet Orange Orchards
Authors: Primiano Isabela Vescove , Barbosa Junior Jonas Tadeu , Bassanezi Renato Beozzo
Published: April 2024

One strategy to reduce huanglongbing (HLB) is controlling its insect vector, the Asian citrus psyllid (ACP) Diaphorina citri, by preventive insecticide sprays. The recommendation is to spray insecticide in all rows (conventional spray [CONV]), but some growers empirically spray in alternate rows (ALT) to increase the spray frequency without increasing the operating cost. Therefore, this work compared the effect of ALT with CONV on the ACP population and HLB incidence. The spray deposition (amount of metallic copper per leaf area), coverage (percentage of water-sensitive paper area covered by spray), and efficacy (ACP mortality) of each treatment were also evaluated on both sides of the trees. Two field trials were performed: Trial #1 compared ALT every 7 days (ALT7) with CONV every 14 days (CONV14), and trial #2 compared different spray frequencies of ALT with CONV every 7 days (CONV7). In trial #1, no differences were observed in the ACP population or HLB progress between ALT7 and CONV14 after 5 years. In trial #2, ALT7 presented the highest percentage of ACP and cumulative HLB incidence than CONV7 and ALT every 3 to 4 days, after 2 years. Hence, when the frequency of ALT was half the frequency of CONV, similar results were observed. Spray deposition, coverage, and efficacy were similar between tree sides in CONV, but they were uneven in ALT, resulting in higher values on the tree side that directly received the spray. Insecticide spray should be performed with the frequency enough to keep new shoots protected during their growth.
The binding of PKCε and MEG2 to STAT3 regulates IL‐6‐mediated microglial hyperalgesia during inflammatory pain
Authors: Li Xiongjuan , Wang Junliang , Liao Changjian , Yang Xinping , Zhao Zhao , Liu Yuqiang , Xue Qingsheng , Luo Yan , Liu Xuesheng , Liu Zhiheng
Published: April 2024

Studies have suggested that microglial IL‐6 modulates inflammatory pain; however, the exact mechanism of action remains unclear. We therefore hypothesized that PKCε and MEG2 competitively bind to STAT3 and contribute to IL‐6‐mediated microglial hyperalgesia during inflammatory pain. Freund's complete adjuvant (FCA) and lipopolysaccharide (LPS) were used to induce hyperalgesia model mice and microglial inflammation. Mechanical allodynia was evaluated using von Frey tests in vivo. The interaction among PKCε, MEG2, and STAT3 was determined using ELISA and immunoprecipitation assay in vitro. The PKCε, MEG2, t‐STAT3, pSTAT3Tyr705, pSTAT3Ser727, IL‐6, GLUT3, and TREM2 were assessed by Western blot. IL‐6 promoter activity and IL‐6 concentration were examined using dual luciferase assays and ELISA. Overexpression of PKCε and MEG2 promoted and attenuated inflammatory pain, accompanied by an increase and decrease in IL‐6 expression, respectively. PKCε displayed a stronger binding ability to STAT3 when competing with MEG2. STAT3Ser727 phosphorylation increased STAT3 interaction with both PKCε and MEG2. Moreover, LPS increased PKCε, MEG2, pSTAT3Tyr705, pSTAT3Ser727, IL‐6, and GLUT3 levels and decreased TREM2 during microglia inflammation. IL‐6 promoter activity was enhanced or inhibited by PKCε or MEG2 in the presence of STAT3 and LPS stimulation, respectively. In microglia, overexpression of PKCε and/or MEG2 resulted in the elevation of tSTAT3, pSTAT3Tyr705, pSTAT3Ser727, IL‐6, and TREM2, and the reduction of GLUT3. PKCε is more potent than MEG2 when competitively binding to STAT3, displaying dual modulatory effects of IL‐6 production, thus regulating the GLUT3 and TREM2 in microglia during inflammatory pain sensation.
A Comparison of Criteria for Defining Metabolic Acidemia in Live-Born Neonates and Its Effect on Predicting Serious Adverse Neonatal Outcomes
Authors: Kraus Alexandria C. , Saucedo Alexander M. , Byrne John J. , Chalak Lina F. , Pruszynski Jessica E. , Spong Catherine Y.
Published: April 2024

(Abstracted from Am J Obstet Gynecol 2023;229:439.e1–439.e11

It is common for fetal oxygenation and pH to decline during labor. However, severe oxygen deprivation can cause fetuses to develop metabolic acidemia, a risk factor for moderate to severe neonatal encephalopathy that can progress to cerebral palsy.
The Efficacy, Safety, and Tolerability of an Estrogen-Free Oral Contraceptive Drospirenone 4 mg (24/4-Day Regimen) in Obese Users
Authors: Creinin Mitchell D. , Angulo Alicyoy , Colli Enrico , Archer David F.
Published: April 2024

(Abstracted from Contraception 2023;128:1–7

There is a lack of data regarding the safety and efficacy of oral contraceptives in people with a body mass index (BMI) over 35. Drospirenone 4 mg is a new progestogen-only contraceptive pill that is taken in a 24 + 4 pattern, with 24 hormonal and 4 placebo pills.
First Babies Conceived With Automated Intracytoplasmic Sperm Injection
Authors: Costa-Borges Nuno , Munne Santiago , Albo Eduard , Mas Sergi , Castello Carolina , Giralt Guillem , Lu Zhuo , Chau Charles , Acacio Monica , Mestres Enric , Matia Queralt , Marques Laura , Rius Mariona , Marquez Carmen , Vanrell Ivette , Pujol Aïda , Mataro Daniel , Seth-Smith Michelle , Mollinedo Luis , Calderon Gloria , Zhang John
Published: April 2024

(Abstracted from Reprod Biomed Online 2023;47:103237

Intracytoplasmic sperm injection (ICSI) is a common procedure used in approximately 70% of in vitro fertilization (IVF) cycles. The procedure involves using glass micropipettes to penetrate the oolemma and injection of sperm into the oocyte.
Perspectives in the validation of DEFASE: a paradigm shift in food allergy management
Authors: Arasi Stefania , Mazzuca Carmen , Urbani Sara , Cafarotti Arianna , Fiocchi Alessandro
Published: April 2024

Purpose of review

To explore the groundbreaking international consensus on the DEFASE (DEfinition of Food Allergy Severity) project as a revolutionary grading system for IgE-mediated food allergy severity. Against the backdrop of the growing public health challenge posed by food allergy, this article delves into the importance of validating and implementing DEFASE in real-world clinical settings.

Recent findings

With new therapeutic options available for food allergy, including biologics alongside immunotherapy, it is urgent to properly support clinical decision-making in the management of the disease. The DEFASE score is the first international consensus-based grading system of severity associated with food allergy as a whole disease embracing multidisciplinary perspectives from different stakeholders involved. In its current version, this comprehensive scoring system has been developed to be used in research settings.

The review emphasizes the potential impact of DEFASE on patient outcomes, healthcare management, and resource allocation, underscoring its significance for the allergy scientific community. Future research should focus on internal and external validation of the scoring system, targeting these models to various food allergenic sources, populations, and settings.
Association of Relative Dysglycemia With Hospital Mortality in Critically Ill Patients: A Retrospective Study*
Authors: Okazaki Tomoya , Nabeshima Tadanori , Santanda Takushi , Hoshina Yuiko , Kondo Yuki , Yaegashi Yu , Nakazawa Taichi , Tokuda Yasuharu , Norisue Yasuhiro
Published: April 2024

OBJECTIVES:

Relative dysglycemia has been proposed as a clinical entity among critically ill patients in the ICU, but is not well studied. This study aimed to clarify associations of relative hyperglycemia and hypoglycemia during the first 24 hours after ICU admission with in-hospital mortality and the respective thresholds.

DESIGN:

A single-center retrospective study.

SETTING:

An urban tertiary hospital ICU.

PATIENTS:

Adult critically ill patients admitted urgently between January 2016 and March 2022.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Maximum and minimum glycemic ratio (GR) was defined as maximum and minimum blood glucose values during the first 24 hours after ICU admission divided by hemoglobin A1c-derived average glucose, respectively. Of 1700 patients included, in-hospital mortality was 16.9%. Nonsurvivors had a higher maximum GR, with no significant difference in minimum GR. Maximum GR during the first 24 hours after ICU admission showed a J-shaped association with in-hospital mortality, and a mortality trough at a maximum GR of approximately 1.12; threshold for increased adjusted odds ratio for mortality was 1.25. Minimum GR during the first 24 hours after ICU admission showed a U-shaped relationship with in-hospital mortality and a mortality trough at a minimum GR of approximately 0.81 with a lower threshold for increased adjusted odds ratio for mortality at 0.69.

CONCLUSIONS:

Mortality significantly increased when GR during the first 24 hours after ICU admission deviated from between 0.69 and 1.25. Further evaluation will necessarily validate the superiority of personalized glycemic management over conventional management.
Anti–VEGFR2-Interferon α Promotes the Infiltration of CD8+ T Cells in Colorectal Cancer by Upregulating the Expression of CCL5
Authors: Huang Linhua , Gao Rui , Nan Lidi , Qi Jingyao , Yang Siyu , Shao Shuai , Xie Jiajun , Pan Mingzhu , Qiu Tianquan , Zhang Juan
Published: April 2024

Immunocytokines are a promising immunotherapeutic approach in cancer therapy. Anti–VEGFR2-interferon α (IFNα) suppressed colorectal cancer (CRC) growth and enhanced CD8+ T-cell infiltration in the tumor microenvironment, exhibiting great clinical translational potential. However, the mechanism of how the anti–VEGFR2-IFNα recruits T cells has not been elucidated. Here, we demonstrated that anti–VEGFR2-IFNα suppressed CRC metastasis and enhanced CD8+ T-cell infiltration. RNA sequencing revealed a transcriptional activation of CCL5 in metastatic CRC cells, which was correlated with T-cell infiltration. IFNα but not anti-VEGFR2 could further upregulate CCL5 in tumors. In immunocompetent mice, both IFNα and anti–VEGFR2-IFNα increased the subset of tumor-infiltrating CD8+ T cells through upregulation of CCL5. Knocking down CCL5 in tumor cells attenuated the infiltration of CD8+ T cells and dampened the antitumor efficacy of anti–VEGFR2-IFNα treatment. We, therefore, propose upregulation of CCL5 is a key to enhance infiltration of CD8+ T cells in metastatic CRC with IFNα and IFNα-based immunocytokine treatments. These findings may help the development of IFNα related immune cytokines for the treatment of less infiltrated tumors.
20(S)-Protopanaxatriol Improves Atherosclerosis by Inhibiting Low-Density Lipoprotein Receptor Degradation in ApoE KO Mice
Authors: Huang Ye-wei , Luo Fang , Zhang Meng , Wang Litian , Meng WenLuer , Hu Dandan , Yang Jinbo , Sheng Jun , Wang Xuanjun
Published: April 2024

Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S)-protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE−/− mice (high-cholesterol diet-fed group). Additionally, 20(S)-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20(S)-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.
Thrombin in Pregnancy and Preeclampsia: Expression, Localization, and Vasoactivity in Brain and Microvessels From Rats
Authors: O'Brien Olivia M. , Tremble Sarah M. , Kropf Ari , Cipolla Marilyn J.
Published: April 2024

Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in the brain and may have a nonhemostatic role. We characterized thrombin expression and vasoactivity in brain cerebral parenchymal arterioles (PAs) in rat models of pregnancy and PE. PAs were isolated and pressurized from nonpregnant (NP) and late-pregnant (LP) rats and rats with experimental preeclampsia (ePE). Reactivity to thrombin (1–50 U/mL) was measured in the absence and presence of inhibition of cyclooxygenase and nitric oxide synthase. Plasma levels of prothrombin, thrombin–antithrombin (TAT), tissue plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) and cerebrospinal fluid levels of TAT were compared using enzyme-linked immunosorbent assay. Expression of protease-activated receptor types 1 and 2 in PAs were measured by Western blot and immunohistochemistry. Neuronal thrombin expression was quantified in brains from all groups by immunohistochemistry. Prothrombin and TAT were elevated in ePE plasma compared with NP and LP. TAT was detected in cerebrospinal fluid from all groups and significantly elevated in LP (NP: 0.137 ± 0.014 ng/mL, LP: 0.241 ± 0.015 ng/mL, ePE: 0.192 ± 0.028 ng/mL; P < 0.05). Thrombin caused modest vasoconstriction in PAs from all groups regardless of cyclooxygenase or nitric oxide synthase inhibition. PAR1 and PAR2 were found in PAs from all groups colocalized to smooth muscle. Thrombin expression in central neurons was decreased in both LP and ePE groups compared with NP. These findings suggest a role for thrombin and other hemostatic changes during pregnancy and PE beyond coagulation.
The natural history of unrecognized diaphragmatic hernias after blunt trauma: A narrative review and presentation of three clinical cases
Authors: Siquini Walter , Silvestrini Nicola , Carrieri Angeloantonio , Tranà Cristian , Cardinali Alessandro , Scibè Rodolfo , Gesuelli Guido-Cesare , Lapponi Carlo Alberto , Sartelli Massimo
Published: April 2024

A diaphragmatic hernia may be the consequence of a blunt traumatic diaphragm rupture, representing a frequently misunderstood post-traumatic complication. Although it is uncommon, it may be associated with high morbidity and mortality when diagnosed late. An extensive review was conducted using the PubMed/MEDLINE (National Library of Medicine, Bethesda, USA) database for articles published in the English language. Three very interesting clinical cases are presented to demonstrate the clinical aspects of the reviewed evidence. They can show how the misrecognition of a left diaphragmatic rupture after a closed trauma can cause serious complications. Tension viscerothorax associated with hemodynamic shock is an example, which represents both an extremely rare and life-threatening complication.
Neonatal Sepsis Due to Multidrug-resistant Bacteria at a Tertiary Teaching Hospital in Ethiopia
Authors: Gashaw Mulatu , Ali Solomon , Berhane Melkamu , Tesfaw Getnet , Eshetu Beza , Workneh Netsanet , Seeholzer Thomas , Froeschl Guenter , Kroidl Arne , Wieser Andreas , Gudina Esayas Kebede
Published: April 2024

Background:

The burden of multidrug-resistant bacterial infections in low-income countries is alarming. This study aimed to identify the bacterial etiologies and antibiotic resistance patterns among neonates in Jimma, Ethiopia.

Methods:

An observational longitudinal study was conducted among 238 presumptive neonatal sepsis cases tested with blood and/or cerebrospinal fluid culture. The bacterial etiologies were confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. The antibiotic resistance patterns were determined using the automated disc diffusion method (Bio-Rad) and the results were interpreted based on the European Committee on Antimicrobial Susceptibility Testing 2021 breakpoints. Extended-spectrum β-lactamases were detected using a double disc synergy test and confirmed by Mast discs (Mast Diagnostica GmbH).

Results:

A total of 152 pathogens were identified. Of these, Staphylococcus aureus (18.4%) was the predominant isolate followed by Klebsiella pneumoniae (15.1%) and Escherichia coli (10.5%). All the isolates exhibited a high rate of resistance to first- and second-line antibiotics ranging from 73.3% for gentamicin to 93.3% for ampicillin. Furthermore, 74.4% of the Gram-negative isolates were extended-spectrum β-lactamase producers and 57.1% of S. aureus strains were methicillin resistant. The case fatality rate was 10.1% and 66.7% of the deaths were attributable to infections by multidrug-resistant pathogens.

Conclusions:

The study revealed a high rate of infections with multidrug-resistant pathogens. This poses a significant challenge to the current global and national target to reduce neonatal mortality rates. To address these challenges, it is important to employ robust infection prevention practices and continuous antibiotic resistance testing to allow targeted therapy.
Construction and validation of a predictive model for major adverse cardiovascular events in the long term after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction
Authors: Yang Yangyang , Yin Xiaoyan , Zhang Yuanzhuo , Ren Lei
Published: April 2024

Purpose

Construction of a prediction model to predict the risk of major adverse cardiovascular events (MACE) in the long term after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).

Method

Retrospective analysis of STEMI patients treated with PCI from April 2018 to April 2021 in Fuyang People’s Hospital. Lasso regression was used to screen the risk factors for the first occurrence of MACE in patients, and multifactorial logistic regression analysis was used to construct a prediction model. The efficacy was evaluated by area under the ROC curve (AUC), Hosmer–Lemeshow deviance test, calibration curve, clinical decision curve (DCA) and clinical impact curve (CIC).

Results

Logistic regression results showed that hypertension, diabetes mellitus, left main plus three branches lesion, estimated glomerular filtration rate and medication adherence were influential factors in the occurrence of distant MACE after PCI in STEMI patients (P < 0.05). The AUC was 0.849 in the modeling group and 0.724 in the validation group; the calibration curve had a good fit to the standard curve, and the result of the Hosmer–Lemeshow test of deviance was x2 = 7.742 (P = 0. 459); the DCA and the CIC indicated that the predictive model could provide a better net clinical benefit for STEMI patients.

Conclusion

A prediction model constructed from a total of five predictor variables, namely hypertension, diabetes, left main + three branches lesions, eGFR and medication adherence, can be used to assess the long-term prognosis after PCI in STEMI patients and help in early risk stratification of patients.
Integrating the patient voice: patient-centred and equitable clinical risk prediction for kidney health and disease
Authors: Harrison Tyrone G. , Elliott Meghan J. , Tonelli Marcello
Published: April 2024

Purpose of review

Personalized approaches to care are increasingly common in clinical nephrology. Although risk prediction models are developed to estimate the risk of kidney-disease related outcomes, they infrequently consider the priorities of patients they are designed to help.

Recent findings

This review discusses certain steps in risk prediction tool development where patients and their priorities can be incorporated. Considering principles of equity throughout the process has been the focus of recent literature.

Applying a person-centred lens has implications for several aspects of risk prediction research. Incorporating the patient voice may involve partnering with patients as researchers to identify the target outcome for the tool and/or determine priorities for outcomes related to the kidney disease domain of interest. Assessing the list of candidate predictors for associations with inequity is important to ensure the tool will not widen disparity for marginalized groups. Estimating model performance using person-centred measures such as model calibration may be used to compare models and select a tool more useful to inform individual treatment decisions. Finally, there is potential to include patients and families in determining other elements of the prediction framework and implementing the tool once development is complete.
Food insecurity in children with heart disease
Authors: Burns Joseph , Norton Derek M. , Cooper Paul N. , Day Patrick E. , Rao Mounica Y. , Sanchez Parra Carlos Andres , Kiener Alexander J.
Published: April 2024

Purpose of Review

This review discusses the epidemiology of food insecurity (FI) and its consequences in children with congenital heart disease. We aimed to highlight current interventions to screen and address food insecurity in the context of pediatric cardiology and to offer strategies for providers to engage in this meaningful work.

Recent Findings

Food insecurity is consistently associated with poor health outcomes in children. In the United States, 17.3% of households with children experience FI. Nonwhite and single-parent families are disproportionately affected. Interestingly, because of a low-quality diet, FI is associated with childhood obesity, putting affected children at increased risk for cardiovascular morbidity and mortality over time. Children with congenital heart disease are susceptible to poor outcomes due to unique altered metabolic demands, increased risk for growth impairment, frequent need for specialized feeding regimens, and additional morbidity associated with heart surgery in underweight children.

Today, the burden of screening for FI is most commonly placed on general pediatricians. Considering the importance of nutrition to cardiovascular health and general wellbeing, and the ease with which screening can be performed, pediatric cardiologists and other subspecialists should take a more active role in FI screening.
Revisiting dexamethasone use in the pediatric emergency department
Authors: Weinstein Rebecca , Naber Catherine E. , Brumme Kristina
Published: April 2024

Purpose of review

Dexamethasone is an essential treatment for common pediatric inflammatory, airway, and respiratory conditions. We aim to provide up-to-date recommendations for treatment of anaphylaxis, croup, coronavirus disease, multisystem inflammatory syndrome in children, and asthma with dexamethasone for use in the pediatric emergency department.

Recent findings

Literature largely continues to support the use of dexamethasone in most of the above conditions, however, recommendations for dosing and duration are evolving.

The findings discussed in this review will enable pediatric emergency medicine providers to use dexamethasone effectively as treatment of common pediatric conditions and minimize the occurrence of side-effects caused by gratuitous corticosteroid use.
Genetic therapies and respiratory outcomes in patients with neuromuscular disease
Authors: Chen Diana , Ni Jeff , Buu MyMy
Published: April 2024

Purpose of review

Genetic therapies made a significant impact to the clinical course of patients with spinal muscular atrophy and Duchenne muscular dystrophy. Clinicians and therapists who care for these patients want to know the changes in respiratory sequelae and implications for clinical care for treated patients.

Recent findings

Different genetic therapy approaches have been developed to replace the deficient protein product in spinal muscular atrophy and Duchenne muscular dystrophy. The natural history of these conditions needed to be understood in order to design clinical trials. Respiratory parameters were not the primary outcome measures for the clinical trials. The impact of these therapies is described in subsequent clinical trial reports or real-world data.

Genetic therapies are able to stabilize or improve the respiratory sequelae in patients with spinal muscular atrophy and Duchenne muscular dystrophy. Standardized reporting of these outcomes is needed to help inform the future revisions of clinical standards of care and practice guidelines.
Emerging therapies for childhood-onset movement disorders
Authors: Vogt Lindsey , Quiroz Vicente , Ebrahimi-Fakhari Darius
Published: April 2024

Purpose of review

We highlight novel and emerging therapies in the treatment of childhood-onset movement disorders. We structured this review by therapeutic entity (small molecule drugs, RNA-targeted therapeutics, gene replacement therapy, and neuromodulation), recognizing that there are two main approaches to treatment: symptomatic (based on phenomenology) and molecular mechanism-based therapy or ‘precision medicine’ (which is disease-modifying).

Recent findings

We highlight reports of new small molecule drugs for Tourette syndrome, Friedreich's ataxia and Rett syndrome. We also discuss developments in gene therapy for aromatic l-amino acid decarboxylase deficiency and hereditary spastic paraplegia, as well as current work exploring optimization of deep brain stimulation and lesioning with focused ultrasound.

Childhood-onset movement disorders have traditionally been treated symptomatically based on phenomenology, but focus has recently shifted toward targeted molecular mechanism-based therapeutics. The development of precision therapies is driven by increasing capabilities for genetic testing and a better delineation of the underlying disease mechanisms. We highlight novel and exciting approaches to the treatment of genetic childhood-onset movement disorders while also discussing general challenges in therapy development for rare diseases. We provide a framework for molecular mechanism-based treatment approaches, a summary of specific treatments for various movement disorders, and a clinical trial readiness framework.
Practical guidelines for eating disorder risk mitigation in patients undergoing obesity treatment for the pediatric provider
Authors: Gordon Katelyn , Matthews Abigail , Zeller Meg H. , Lin Jessica
Published: April 2024

Purpose of review

Pediatric obesity is a growing concern globally. Patients with a history of overweight/obesity often experience stigmatization, especially in the healthcare setting, and are at increased risk of developing psychological comorbidities including eating disorders. This review appraises the most recent studies evaluating eating disorder risk in youth undergoing treatment for obesity, identifies gaps in the literature, and offers practical guidelines to pediatric providers regarding the management of this population.

Recent findings

Recent studies suggest that structured weight management programs may decrease the risk of and/or improve symptoms of certain eating disorders such as binge eating disorder and bulimia nervosa. There is a paucity of research on some components of obesity management such as obesity pharmacotherapeutics and eating disorder risk.

Children and adolescents with obesity are a psychologically vulnerable population with increased risk for the development of eating disorders. Further study is needed to evaluate general risk in the setting of specialized and primary care obesity interventions and develop appropriate screening and mitigation tools. Some evidence-based strategies can aid pediatric providers in both weight management and eating disorder prevention and risk assessment.
Relationships Between Socio-behavioral Factors and the Symptoms Among Asian American Breast Cancer Survivors
Authors: Kim Seo Yun , Kim Heejung , Chee Wonshik , Im Eun-Ok
Published: April 2024

Background

Despite increased research on breast cancer survivors, little is known about how socio-behavioral factors influence the symptoms among racial/ethnic minority breast cancer survivors, particularly Asian American breast cancer survivors (AABCS).

Objective

This study examined the relationship between multiple socio-behavioral factors in AABCS, including attitudes, perceived barriers, and social influences, and their symptom experiences, with an emphasis on the mediating effect of self-efficacy.

Methods

This secondary analysis used data collected from 195 AABCS women recruited through online and offline communities from January 2017 to June 2020. Study variables were measured using validated instruments such as the Questions on Attitudes, Self-Efficacy, Perceived Barriers, and Social Influences; the Cancer Behavior Inventory; and the Memorial Symptom Assessment Scale-Short Form. For structural equation modeling based on Bandura’s self-efficacy theory, mediation analysis was performed using SPSS version 26.0 and AMOS 28.

Results

The overall fitness of the hypothetical model to the data is acceptable (χ2= 51.36,P< .001; goodness-of-fit index = 0.95, adjusted goodness-of-fit index = 0.89, comparative fit index = 0.96, Tucker-Lewis index = 0.94, normed fit index = 0.94, and root-mean-square error of approximation index = 0.08). Both attitudes and social influences indirectly influenced symptom distress through self-efficacy (β = −0.054,P =.019, and β = −0.053,P =.017, respectively). Perceived barriers had indirect effects through self-efficacy (β = 0.121,P =.024) and significant direct effects (β = 0.605,P =.003) on symptom distress.

Conclusions

Our findings supported that the self-efficacy for coping mediated their symptom experience among AABCS. In addition, there were significant relationships among attitudes, perceived barriers, social influences, and symptom experience.

Implications for Practice

Future theory-driven interventions need to consider self-efficacy and socio-behavioral factors in symptom management among AABCS.
The Impact of Vaginal Probiotics on Pessary Use: A Randomized Controlled Trial
Authors: Sappenfield Elisabeth C. , Mellen Colleen , Wilcox Jennifer , O'Hanlon Deirdre Elizabeth , O'Sullivan David M. , Tunitsky-Bitton Elena
Published: April 2024

(Abstracted from Urogynecology 2024;30:50–58

Pelvic organ prolapse can be effectively treated with the nonsurgical use of pessaries. Some minor adverse effects occur with the use of this treatment, such as bleeding, vaginal discharge, and pessary extrusion.
Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses
Authors: Hesami Mina , Blake Michael , Anderson Mark A. , Asmundo Luigi , Kilcoyne Aoife , Najmi Zahra , Caravan Peter D. , Catana Ciprian , Czawlytko Cynthia , Abdar Esfahani Shadi , Kambadakone Avinash R. , Samir Anthony , McDermott Shaunagh , Domachevsky Liran , Ursprung Stephan , Catalano Onofrio A.
Published: April 2024

Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.