bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of remimazolam versus propofol for the induction of general anesthesia on cerebral blood flow and oxygen saturation in elderly patients undergoing carotid endarterectomy
Authors: Gao Jianling , Yang Chengdi , Ji Qiuyuan , Li Jian
Published: May 2023

Background

This study was conducted to investigate the effects and safety of remimazolam versus propofol on cerebral oxygen saturation and cerebral hemodynamics during the induction of general anesthesia in patients receiving carotid endarterectomy (CEA), so as to provide theoretical basis for better clinical application of remimazolam.

Methods

Forty-three patients (60–75 years old) with carotid artery stenosis (carotid artery stenosis greater than 70%) were randomly divided into the remimazolam group (R group) and the propofol group (P group). Anesthesia was induced with remimazolam (0.3 mg/kg) or propofol (1.5-2 mg/kg) individually. At time of admission (T0), post-anesthesia induction (T1), consciousness disappears (T2), 1 min after loss of consciousness (T3), 2 min after loss of consciousness (T4) and pre-endotracheal intubation (T5), measurement in patients with regional cerebral oxygen saturation (SrO2), average blood flow velocity (Vm), resistance index (RI), mean arterial pressure (MAP), heart rate (HR) and cardiac index (CI) were recorded.

Results

SrO2 increased significantly in both groups after induction of anesthesia compared with baseline (P < 0.05) and decreased after loss of consciousness (P < 0.05). There was no difference in the mean value of the relative changes in SrO2 between the groups. Meanwhile, the Vm, RI, HR and CI of each time point between two groups showed no statistically significant difference (P > 0.05) while MAP in group P at T5 was lower than that in group R individually(P < 0.05). In each group, Vm, HR, CI and MAP at T2-T5 were all significantly reduced compared with T1, with statistically differences(P < 0.05). Specifically, there was no difference of RI at each time between or within groups(P > 0.05).

Conclusions

Our study revealed that remimazolam can be administered safely and effectively during the induction of general anesthesia for carotid endarterectomy in elder population and it demonstrated superiority in hemodynamic changes compared with propofol.

Clinical trial registration

This trial was retrospectively registered with the Chinese Clinical Trial Registry. Registration number: ChiCTR2300070370. Date of registration: April 11, 2023.
“A disembodied voice over the telephone”: a qualitative study of healthcare practitioners’ experiences in geriatric medicine
Authors: Brown Frankie , Sanders Isabella , Watkins Ross , Grey Elisabeth , Smith Paula , Springett Daniella , Welsh Tomas , Gillison Fiona
Published: May 2023

Objectives

This study explored the experience of delivering care remotely among practitioners in a UK geriatric medicine clinic.

Methods

Nine semi-structured interviews were conducted with consultants (n = 5), nurses (n = 2), a speech and language and an occupational therapist, and thematically analysed.

Results

Four themes developed; Challenges of remote consultations; Perceived advantages of remote consultations; Disruption of involvement of family members; Impact on care staff. Participants felt that rapport and trust had been more feasible to develop remotely than they had anticipated, although this was more challenging for new patients and those with cognitive or sensory impairments. While practitioners identified advantages of remote consultations, including involving relatives, saving time, and reducing anxiety, they also experienced disadvantages such as consultations feeling like a ‘production line’, missing visual cues and reduced privacy. Some participants felt their professional identity was threatened by the lack of face-to-face contact, linked to feeling that remote consultations are not suitable for frail older adults or those with cognitive deficits.

Discussion

Staff perceived barriers to remote consultations that went beyond practical concerns, and suggest support for building rapport, involving families, and protecting clinician identity and job satisfaction may be warranted.
Sense of coherence mediates perceived social support and depressive and anxiety symptoms in cervical cancer patients: a cross-sectional study
Authors: Li Qi , Liu Li , Gu Zhihui , Li Mengyao , Liu Chunli , Wu Hui
Published: May 2023

Background

Depression and anxiety symptoms are two common psychological disturbances in cervical cancer patients. We tested whether sense of coherence (SOC) mediates the association of perceived social support (PSS) with depression and anxiety symptoms among cervical cancer patients in China.

Methods

We conducted a survey involving 294 cervical cancer patients aged ≥ 18 years from July to December 2020 at three hospitals in Liaoning Province, China; 269 patients completed the survey. We included a demographic questionnaire, the Multidimensional Scale of Perceived Social Support (MSPSS), Antonovsky’s Sense of Coherence Scale, the Hamilton Depression Rating Scale, and the Zung Self-Rating Anxiety Scale (SAS) in this study. We used hierarchical regression analysis to examine the relationship among PSS, SOC, and symptoms of depression and anxiety. We used asymptotic and resampling strategies to explore the mediating effect of SOC.

Results

PSS was negatively associated with depressive symptoms (r = − 0.439, P < 0.01) and anxiety symptoms (r = − 0.325, P < 0.01). SOC was negatively related to depressive symptoms (r = − 0.627, P < 0.01) and anxiety symptoms (r = − 0.411, P < 0.01). SOC partially mediated the association between PSS and depressive symptoms (a*b = − 0.23, BCa95% CI: [− 0.31, − 0.14]) and anxiety symptoms (a*b = − 0.15, BCa95% CI: [− 0.23, − 0.08]). The proportions of the mediating effect accounting for SOC were 49.78% and 41.73% for depressive symptoms and anxiety symptoms, respectively.

Conclusion

The study showed that SOC could mediate the association between PSS and symptoms of depression and anxiety. This suggests that SOC might serve as a potential target for intervention in symptoms of depression and anxiety that accompany cervical cancer.
Absconding among admitted patients with bipolar affective disorder diagnosis in Uganda
Authors: Abaatyo Joan , Favina Alain , Kaggwa Mark Mohan
Published: May 2023

Background

Hospitalization is often necessary for individuals with Bipolar affective Disorder (BAD) during severe manic or depressive episodes, as well as for stabilizing treatment regimens. However, a significant proportion of patients admitted for treatment of BAD abscond or leave the hospital without permission during their stay. In addition, patients managed for BAD may have unique characteristics that might force them into absconding. For example, the high prevalence of co-morbid substance use disorder – craving to use substances, suicidal behaviors – attempts to die by suicide, and cluster B personality disorders – characterized by impulsive acts. It is, therefore, essential to understand the factors contributing to absconding among patients with BAD, to facilitate designing strategies for preventing and managing this behavior.

Method

This study was based on a retrospective chart review of the inpatients diagnosed with BAD at a tertiary psychiatry facility in Uganda from January 2018 to December 2021.

Results

Approximately 7.8% of those with BAD absconded from the hospital. The likelihood of absconding among those with BAD increased with the use of cannabis [adjusted odds ratio (aOR) = 4.00, 95% confidence interval (CI) = 1.22–13.09, p-value = 0.022] and having mood lability [aOR = 2.15, 95% CI = 1.10–4.21,p-value = 0.025]. However, receiving psychotherapy during the admission (aOR = 0.44, 95 CI = 0.26–0.74,p-value = 0.002) and treatment with haloperidol (aOR = 0.39, 95% CI = 0.18–0.83,p-value = 0.014) reduced the likelihood of absconding.

Conclusion

Absconding among patients with BAD is common in Uganda. Those with symptoms of affective lability and those with comorbid cannabis use tend to abscond more, while those who receive haloperidol and psychotherapy are less likely to abscond.
Measurement of craving among gamers with internet gaming disorder using repeated presentations of game videos: a resting-state electroencephalography study
Authors: Park Sangin , Ha Jihyeon , Ahn Wonbin , Kim Laehyun
Published: May 2023

Background

Internet gaming disorder (IGD) is receiving increasing attention owing to its effects on daily living and psychological function.

Methods

In this study, electroencephalography was used to compare neural activity triggered by repeated presentation of a stimulus in healthy controls (HCs) and those with IGD. A total of 42 adult men were categorized into two groups (IGD,n = 21) based on Y-IAT-K scores. Participants were required to watch repeated presentations of video games while wearing a head-mounted display, and the delta (D), theta (T), alpha (A), beta (B), and gamma (G) activities in the prefrontal (PF), central (C), and parieto-occipital (PO) regions were analyzed.

Results

The IGD group exhibited higher absolute powers of DC, DPO, TC, TPO, BC, and BPOthan HCs. Among the IGD classification models, a neural network achieves the highest average accuracy of 93% (5-fold cross validation) and 84% (test).

Conclusions

These findings may significantly contribute to a more comprehensive understanding of the neurological features associated with IGD and provide potential neurological markers that can be used to distinguish between individuals with IGD and HCs.
Musculoskeletal disorders among doctors and nursing officers : an occupational hazard of overstrained healthcare delivery system in western Rajasthan, India
Authors: Mahajan Diksha , Gupta Manoj Kumar , Mantri Neha , Joshi Nitin Kumar , Gnanasekar Sridevi , Goel Akhil Dhanesh , Srinivasan Srikanth , Gonade Nitesh Manohar , Sharma Suresh Kumar , Garg Mahendra Kumar , Bhardwaj Pankaj
Published: May 2023

Background

The present study was conducted to estimate the prevalence and distribution of MSDs in different anatomical regions among Doctors and NO and to determine their ergonomic risk factors and predictors.

Methods

This cross-sectional study was conducted in an apex institution in Western India. The socio-demographic information, medical and occupational history, and other personal and work-related attributes were captured using a semi-structured questionnaire, which was developed and finalized by piloting on 32 participants (who were not part of the study). Nordic Musculoskeletal and International Physical Activity Questionnaires were used to assess MSDs and Physical activity. Data were analyzed using SPSS v.23. Prevalence of Musculoskeletal Symptoms (M.S.), Multisite Musculoskeletal Symptoms (MMS), and Widespread Musculoskeletal Symptoms (WMS) were calculated. A comparison was made to estimate the burden and distribution of MSD among Doctors and Nursing officers. Logistic regression was applied to identify the predictors of MSDs and pinpoint the risk factors associated with MSDs.

Results

A total of 310 participants, of which 38.7% were doctors, and 61.3% were Nursing Officers (NOs) were included in the study. The mean age of the respondents was 31.63 ± 4.9 years. Almost 73% (95%CI: 67.9–78.1) of participants had MSD in the last 12 months, with approximately 41.6% (95%CI: 36.1–47.3) suffering from MSDs in the previous seven days of the survey. The lower back (49.7%) and the neck (36.5%) were the most affected sites. Working in the same position for a long time (43.5%) and not taking adequate breaks (31.3%) were the highest self-reported risk factors. Females had significantly higher odds of having pain in the upper back [aOR:2.49(1.27–4.85)], neck [aOR:2.15(1.22–3.77)], shoulder [aOR:2.8 (1.54–5.11)], hips [aOR:9.46 (3.95–22.68)] and knee [aOR:3.8(1.99–7.26)].

Conclusions

Females, who are NOs, work for > 48 h per week, and fall in the obese category were significantly at more risk of developing MSDs. Working in an awkward position, treating an excessive number of patients in a day, working in the same position for a long period, performing repeated tasks, and not having enough rest breaks were significant risk factors for MSDs.
Herbal medicine use during pregnancy and childbirth: perceptions of women living in Lilongwe rural, Malawi – a qualitative study
Authors: Makombe Dziwenji , Thombozi Enalla , Chilemba Winnie , Mboma Alexander , Banda Kondwani Joseph , Mwakilama Elias
Published: May 2023

Background

Globally, use of herbal medicine during pregnancy and labour is often associated with adverse obstetric outcomes such as uterine rupture and fetal distress. However, in rural Malawi, information on the perceptions of women about the use of herbal medicine during pregnancy and labour is underreported despite the practice. Understanding women’s views and perceptions on use of herbal medicine during pregnancy and labour is therefore critical for understanding the basis of their practice and for setting up maternal and neonatal health care interventions to alleviate any possible pregnancy and labour complications.

Aims

To explore the perceptions of women on the use of herbal medicine during pregnancy and labour in rural Malawi.

Methods

We employed a qualitative descriptive (QD) study on the purposively identified participants (women with parity $$\ge 2$$

≥
2

), residing in four villages (Kagona, Champsinja, Mthupi and Manja) of Traditional Authority Malili, in Lilongwe rural district, Malawi. Qualitative data was collected through four Focus Groups of 6–8 women in each group that were conducted in each village. Data analysis was performed inductively, using reflexive thematic analysis approach.

Results

A total of 28 women of reproductive age 20 and above; 20–24 (32.14%), married (75%), average of 3 deliveries (57.14%), primary school education (75.0%), and Christians (92.86%) were recruited and interviewed. Two main themes emerged from the narratives: (1) perceived benefits of using herbal medicine: (i) hastens labour, (ii) prevents pregnancy complications and (iii) prevents and treats illnesses, and (2) perceived risks of using herbal medicine: (i) perceived maternal risks, (ii) perceived fetal risks.

Conclusion

In rural Malawi, the practice of using herbal medicine during pregnancy and labour is perceived as both risky and beneficial to women. These perceptions are shaped by the exposure to either personal or other people’s experiences, hence the continued practice. Therefore, inclusion of health education topics on maternal complications due to use of herbal medicine among women can help reduce maternal and neonatal mortality rates in rural Malawi. Further research is also warranted to explore accessibility and community pathway systems for herbal medicine use during pregnancy and labour among the pregnant women.
The ethanolic extract of Salvia lachnostachys Benth is not maternotoxic, does not alter reproductive performance, but has teratogenic potential
Authors: Ortiz Hudman Cunha , das Neves Silvia Cordeiro , Kassuya Cândida Aparecida Leite , Coelho Henrique Rodrigues Scherer , Martins Allana C. F. , Vilela Marcelo Luiz Brandão , do Nascimento Valter Aragão , Karuppusamy Arunachalam , Stefanello Maria Élida Alves , Oliveira Rodrigo Juliano , da Silva Gomes Roberto
Published: May 2023

Salvia lachnostachys Benth is native to Brazil and has anti-inflammatory, anti-arthritic, cytotoxic, antitumor, and antihyperalgesic activities. The population, including pregnant women, consume this plant to treat pain, inflammation, flu, spasms, insomnia, and depression, mainly. There are no safety reports on the use of this plant during pregnancy. The present study aimed to evaluate the effects of S. lachnostachys ethanolic extract (EESl) on reproductive performance, embryofetal development, and DNA integrity of pregnant female mice. Pregnant females were randomly divided into three experimental groups (n = 10): The Control group was treated with a vehicle, and treatment groups were administered with EESl at 100 and 1000 mg/kg, respectively. Treatment occurred by gavage throughout the gestational period until day 18. Afterward, reproductive performance, embryofetal development, and DNA integrity parameters were evaluated. The results indicated that EESl did not alter any reproductive performance parameters. However, it changed embryofetal outcome through reduced placental weight (EESl 100 mg/kg), decreased fetal weight (EESl 100 and 1000 mg/kg), and increased frequency of small for gestational age fetuses (EESl 1000 mg/kg). In addition, EES1 increased the frequency of external, visceral, and skeletal malformations. Because of the above, it is considered that EESl is not maternotoxic, does not alter reproductive performance, but does alter embryofetal development. Its use in the gestational period is not indicated due to its teratogenic potential.
Factors associated with perceived resilience among undergraduate nursing students: findings of the first cross-sectional study in Palestine
Authors: Alkaissi Aidah , Said Nizar B. , Qadous Shorooq , Alkony Mahdia , Almahmoud Omar
Published: May 2023

Background

Resilience has emerged as a concept that could explain and predict good academic and well-being of students in stressful and traumatic situations. This study was conducted to assess resilience and identify predictors of high or low resilience scores among future nurses in Palestine.

Methods

This cross-sectional study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology statement. Undergraduate nursing students in all academic years were recruited and asked to complete a questionnaire that contained the Trait Resilience Scale and the State-Resilience Scale. Multiple linear regression models were used to identify predictors of higher resilience scores and to control for potentially confounding factors.

Results

In this study, 290 students completed the questionnaire (response rate = 92.4%). The means of trait, state, and combined resilience scores were 71.4 (SD: 7.5), 62.7 (SD: 6.7), and 134.1 (SD: 12.8), respectively. There was a significant moderate positive correlation between state resilience scores and trait resilience scores (r = 0.63, p < 0.001). Having a study routine on daily basis predicted higher trait (β = -0.20, p < 0.001), state (β = -0.12, p = 0.032), and combined (β = -0.18, p = 0.001) resilience scores. Trait and combined resilience scores were predicted by the absence of chronic diseases (β = 0.12, p < 0.05), experiencing addiction issues (β = -0.11, p < 0.05), living in Israeli seized areas (β = 0.16, p < 0.05), and living in a house with enough number of rooms per siblings (β = 0.13, p < 0.05). On the other hand, state and combined resilience scores were predicted by being in the first academic year (β = -0.18, p < 0.01), and state resilience scores were predicted by living in urban areas (β = -0.12, p < 0.05).

Conclusions

Undergraduate nursing students in Palestine reported relatively high trait and state resilience scores. Higher trait, state, and combined resilience scores were predicted by having a study routine on daily basis. More studies are still needed to investigate the relationship between resilience scores, perceived well-being, willingness to care, and the future success of nursing students in Palestine.
A truncating variant altering the extreme C-terminal region of desmoplakin (DSP) suggests the crucial functional role of the region: a case report study
Authors: Pantou Malena P. , Gourzi Polyxeni , Vlagkouli Vasiliki , Papatheodorou Efstathios , Tsoutsinos Alexandros , Nyktari Eva , Degiannis Dimitrios , Anastasakis Aris
Published: May 2023

Background

Homozygous truncating mutations located in the C-terminal region of the desmoplakin gene (DSP) are known to mainly cause Carvajal syndrome, an autosomal recessive syndromic form of arrhythmogenic cardiomyopathy with an extra-cardiac cutaneous phenotype.

Case presentation

Here we describe a female proband with a documented arrhythmogenic left ventricular cardiomyopathy and a syncopal episode at the age of 13, who was found homozygous for the novel DSP variant: NM_004415.4:c.8586delC, p.(Ser2863Hisfs*20) at the extreme C-terminal region of the protein, just 8 amino acids upstream the stop codon. She did not have any of the typical dermatological symptoms that characterize Carvajal syndrome. Her brother had died suddenly at the age of 18 during exercise and was found homozygous for the same variant at the post-mortem, while their parents were heterozygous. The region of origin of both parents was the same geographic area of Greece, but they were not aware of any common ancestor. Detailed clinical examination revealed that the mother displayed a mild arrhythmic phenotype, while the father was asymptomatic.

Conclusion

These observations pinpoint to a significant functional role of the extreme C-terminal tail of the protein.
Liraglutide reduces plasma dihydroceramide levels in patients with type 2 diabetes
Authors: Denimal Damien , Bergas Victoria , Pais-de-Barros Jean-Paul , Simoneau Isabelle , Demizieux Laurent , Passilly-Degrace Patricia , Bouillet Benjamin , Petit Jean-Michel , Rouland Alexia , Bataille Amandine , Duvillard Laurence , Vergès Bruno
Published: May 2023

Background

Emerging evidence supports that dihydroceramides (DhCer) and ceramides (Cer) contribute to the pathophysiology of insulin resistance and liver steatosis, and that their circulating concentrations are independently associated with cardiovascular outcomes. Circulating DhCer levels are increased in patients with type 2 diabetes (T2D). On the other hand, the GLP-1 receptor agonist liraglutide reduces major adverse cardiac events, insulin resistance and liver steatosis in T2D patients. The main purpose of the present study was therefore to investigate whether liraglutide decreases circulating levels of DhCer and Cer in T2D patients, which could be a mechanism involved in its cardiometabolic benefits. The secondary purpose was to assess the relationship between liraglutide-induced changes in DhCer/Cer levels and insulin resistance and liver steatosis.

Methods

Plasma concentrations of 11 DhCer and 15 Cer species were measured by a highly-sensitive mass spectrometry system in 35 controls and 86 T2D patients before and after 6 months of liraglutide (1.2 mg/day). Insulin resistance was estimated by the triglyceride-glucose (TyG) index. Liver fat content (LFC) was assessed in 53 patients by proton magnetic resonance spectroscopy.

Results

Plasma levels of total DhCer, 7 DhCer and 7 Cer species were increased in T2D patients compared to controls. Liraglutide decreased total DhCer by 15.1% (p = 0.005), affecting 16:0 (p = 0.037), 18:0 (p < 0.0001), 18:1 (p = 0.0005), 20:0 (p = 0.0003), 23:0 (p = 0.005) and 24:1 (p = 0.04) species. Total plasma Cer did not significantly change after liraglutide (p = 0.18), but 5 Cer species decreased significantly, i.e. 18:0 and 18:1 (both p < 0.0001), 19:0 and 24:1 (both p < 0.01) and 26:1 (p = 0.04). In multivariate analysis, the reduction in DhCer after liraglutide was independently associated with the reduction in LFC (p = 0.0005) and in TyG index (p = 0.05).

Conclusions

Liraglutide reduces plasma levels of numerous DhCer and Cer species in T2D patients, which may contribute to the cardiovascular benefit observed in the LEADER trial. The independent association between the decrease in plasma DhCer level with the reduction in LFC and TyG index adds new insights regarding the relationship between DhCer, liver steatosis and insulin resistance.

Trial registration ClinicalTrials.gov identifier: NCT02721888.
High-level production of Aspergillus niger prolyl endopeptidase from agricultural residue and its application in beer brewing
Authors: Liu Minglu , Hu Meng , Zhou Hui , Dong Zhiyang , Chen Xiuzhen
Published: May 2023

Background

Prolyl endopeptidase from Aspergillus niger (AN-PEP) is a prominent serine proteinase with various potential applications in the food and pharmaceutical industries. However, the availability of efficient and low-cost AN-PEP remains a challenge owing to its low yield and high fermentation cost.

Results

Here, AN-PEP was recombinantly expressed in Trichoderma reesei (rAN-PEP) under the control of the cbh1 promoter and its secretion signal. After 4 days of shaking flask cultivation with the model cellulose Avicel PH101 as the sole carbon source, the extracellular prolyl endopeptidase activity reached up to 16.148 U/mL, which is the highest titer reported to date and the secretion of the enzyme is faster in T. reesei than in other eukaryotic expression systems including A. niger and Komagataella phaffii. Most importantly, when cultivated on the low-cost agricultural residue corn cob, the recombinant strain was found to secret a remarkable amount of rAN-PEP (37.125 U/mL) that is twice the activity under the pure cellulose condition. Furthermore, treatment with rAN-PEP during beer brewing lowered the content of gluten below the ELISA kit detection limit (< 10 mg/kg) and thereby, reduced turbidity, which would be beneficial for improving the non-biological stability of beer.

Conclusion

Our research provides a promising approach for industrial production of AN-PEP and other enzymes (proteins) from renewable lignocellulosic biomass, which provides a new idea with relevant researchers for the utilization of agricultural residues.
Association of socio-economic deprivation with COVID-19 incidence and fatality during the first wave of the pandemic in Italy: lessons learned from a local register-based study
Authors: Fortunato Francesca , Lillini Roberto , Martinelli Domenico , Iannelli Giuseppina , Ascatigno Leonardo , Casanova Georgia , Lopalco Pier Luigi , Prato Rosa
Published: May 2023

Background

COVID-19 has been characterised by its global and rapid spread, with high infection, hospitalisation, and mortality rates worldwide. However, the course of the pandemic showed differences in chronology and intensity in different geographical areas and countries, probably due to a multitude of factors. Among these, socio-economic deprivation has been supposed to play a substantial role, although available evidence is not fully in agreement. Our study aimed to assess incidence and fatality rates of COVID-19 across the levels of socio-economic deprivation during the first epidemic wave (March–May 2020) in the Italian Province of Foggia, Apulia Region.

Methods

Based on the data of the regional active surveillance platform, we performed a retrospective epidemiological study among all COVID-19 confirmed cases that occurred in the Apulian District of Foggia, Italy, from March 1st to May 5th, 2020. Geocoded addresses were linked to the individual Census Tract (CT) of residence. Effects of socio-economic condition were calculated by means of the Socio-Economic and Health-related Deprivation Index (SEHDI) on COVID-19 incidence and fatality.

Results

Of the 1054 confirmed COVID-19 cases, 537 (50.9%) were men, 682 (64.7%) were 0–64 years old, and 338 (32.1%) had pre-existing comorbidities. COVID-19 incidence was higher in the less deprived areas (p < 0.05), independently on age. The level of socio-economic deprivation did not show a significant impact on the vital status, while a higher fatality was observed in male cases (p < 0.001), cases > 65 years (p < 0.001), cases having a connection with a nursing home (p < 0.05) or having at least 1 comorbidity (p < 0.001). On the other hand, a significant protection for healthcare workers was apparent (p < 0.001).

Conclusions

Our findings show that deprivation alone does not affect COVID-19 incidence and fatality burden, suggesting that the burden of disease is driven by a complexity of factors not yet fully understood. Better knowledge is needed to identify subgroups at higher risk and implement effective preventive strategies.
A case-report of the unprovoked thrombotic event in a patient with thymoma and severe FVII deficiency
Authors: Li Lei , Wu Xi , Wu Wenman , Ding Qiulan , Wang Xuefeng
Published: May 2023

Background

Factor VII deficiency is a rare bleeding disorder caused by a deficiency of clotting factor VII. However, there have been some case reports of venous thrombosis in patients with factor VII deficiency, especially underlying the prothrombotic risk factors exposure. Patients with factor VII deficiency require special considerations before undergoing surgery to minimize the risk of bleeding or thrombogenesis.

Case presentation

Here, we described a patient with early-stage thymoma and severe factor VII deficiency who experienced an unprovoked thrombotic episode before thymectomy and a fatal thrombotic event after surgery. By adopting gene screening, a reported homozygousF7mutation (p.His408Gln) and a novel heterozygousPROS1mutation (p.Pro147Ala) were identified. The former resulted in severe factor VII deficiency but did not protect against thrombosis, and the latter was correlated with normal expression and cofactor activities of protein S through the thrombin generation test. The perioperative infusion of recombinant factor VII concentrate and the absence of antithrombotic prophylaxis may collectively contribute to her fatal thrombotic event after surgery.

Conclusions

For the patients with severe factor VII deficiency undergoing surgery, uniform replacement therapy may not be recommended, and antithrombotic prophylaxis should be used in the case with thrombotic history to minimize the risk of bleeding and thrombogenesis.
BACE1 regulates expression of Clusterin in astrocytes for enhancing clearance of β-amyloid peptides
Authors: Zhou John , Singh Neeraj , Galske James , Hudobenko Jacob , Hu Xiangyou , Yan Riqiang
Published: May 2023

Background

Abnormal accumulation of amyloid beta peptide (Aβ) in the brain induces a cascade of pathological changes in Alzheimer’s disease (AD), and inhibiting BACE1, which is required for Aβ generation, is therefore being explored for the treatment of AD by reducing Aβ accumulation. As Bace1 knockout mice exhibit increased number of reactive astrocytes and AD brains have reactive astrocytes that surround amyloid plaques, we investigated the role of BACE1 in astrocytes and determined whether BACE1 regulates astrocytic functions.

Methods

We conducted unbiased single cell RNA-seq (scRNA-seq) using purified astrocytes from Bace1 KO mice and wild type control littermates. Similar scRNA-seq was also conducted using AD mice with conditional deletion of Bace1 in the adult stage (5xFAD;Bace1fl/fl;UBC-creER compared to 5xFAD;Bace1fl/fl controls). We compared the transcriptomes of astrocyte and reactive astrocyte clusters and identified several differentially expressed genes, which were further validated using Bace1 KO astrocyte cultures. Mice with astrocyte-specific Bace1 knockout in 5xFAD background were used to compare amyloid deposition. Mechanistic studies using cultured astrocytes were used to identify BACE1 substrates for changes in gene expression and signaling activity.

Results

Among altered genes, Clusterin (Clu) and Cxcl14 were significantly upregulated and validated by measuring protein levels. Moreover, BACE1 deficiency enhanced both astrocytic Aβ uptake and degradation, and this effect was significantly attenuated by siRNA knockdown of Clu. Mechanistic study suggests that BACE1 deficiency abolishes cleavage of astrocytic insulin receptors (IR), and this may enhance expression of Clu and Cxcl14. Acutely isolated astrocytes from astrocyte-specific knockout of Bace1 mice (Bace1 fl/fl;Gfap-cre) show similar increases in CLU and IR. Furthermore, astrocyte-specific knockout of Bace1 in a 5xFAD background resulted in a significant attenuation in cortical Aβ plaque load through enhanced clearance.

Conclusion

Together, our study suggests that BACE1 in astrocytes regulates expression of Clu and Cxcl14, likely via the control of insulin receptor pathway, and inhibition of astrocytic BACE1 is a potential alternative strategy for enhancing Aβ clearance.
A CRISPR interference strategy for gene expression silencing in multiple myeloma cell lines
Authors: Escrivá-Fernández Josep , Cueto-Ureña Cristina , Solana-Orts Amalia , Lledó Elisa , Ballester-Lurbe Begoña , Poch Enric
Published: May 2023

Background

Multiple myeloma (MM) is the second most common hematologic neoplasm which is characterized by proliferation and infiltration of plasmatic cells in the bone marrow. Currently, MM is considered incurable due to resistance to treatment. The CRISPR/Cas9 system has emerged as a powerful tool for understanding the role of different genetic alterations in the pathogenesis of hematologic malignancies in both cell lines and mouse models. Despite current advances of gene editing tools, the use of CRISPR/Cas9 technology for gene editing of MM have not so far been extended. In this work, we want to repress Rnd3 expression, an atypical Rho GTPase involved in several cellular processes, in MM cell lines using a CRISPR interference strategy.

Results

We have designed different guide RNAs and cloning them into a lentiviral plasmid, which contains all the machinery necessary for developing the CRISPR interference strategy. We co-transfected the HEK 293T cells with this lentiviral plasmid and 3rd generation lentiviral envelope and packaging plasmids to produce lentiviral particles. The lentiviral particles were used to transduce two different multiple myeloma cell lines, RPMI 8226 and JJN3, and downregulate Rnd3 expression. Additionally, the impact of Rnd3 expression absence was analyzed by a transcriptomic analysis consisting of 3’ UTR RNA sequencing. The Rnd3 knock-down cells showed a different transcriptomic profile in comparison to control cells.

Conclusions

We have developed a CRISPR interference strategy to generate stable Rnd3 knockdown MM cell lines by lentiviral transduction. We have evaluated this strategy in two MM cell lines, and we have demonstrated that Rnd3 silencing works both at transcriptional and protein level. Therefore, we propose CRISPR interference strategy as an alternative tool to silence gene expression in MM cell lines. Furthermore, Rnd3 silencing produces changes in the cellular transcriptomic profile.
Functional characterization of age-dependent p16 epimutation reveals biological drivers and therapeutic targets for colorectal cancer
Authors: Yang Li , Chen Xiaomin , Lee Christy , Shi Jiejun , Lawrence Emily B. , Zhang Lanjing , Li Yumei , Gao Nan , Jung Sung Yun , Creighton Chad J. , Li Jingyi Jessica , Cui Ya , Arimura Sumimasa , Lei Yunping , Li Wei , Shen Lanlan
Published: May 2023

Background

Methylation of thep16promoter resulting in epigenetic gene silencing—known asp16epimutation—is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-relatedp16epimutation in intestinal tumorigenesis.

Methods

We established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs:Apcmutation andp16epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA sequencing (RNA-seq), quantitative PCR, and flow cytometry. We performed single-cell RNA sequencing (scRNA-seq) to characterize tumor-infiltrating immune cells throughout tumor progression. We tested whether anti-PD-L1 immunotherapy affects overall survival of tumor-bearing mice and whether inhibition of both epigenetic regulation and immune checkpoint is more efficacious.

Results

Mice carrying combinedApcmutation andp16epimutation had significantly shortened survival and increased tumor growth compared to those withApcmutation only. Intriguingly, colon tumors withp16epimutation exhibited an activated interferon pathway, increased expression of programmed death-ligand 1 (Pdl1), and enhanced infiltration of immune cells. scRNA-seq further revealed the presence ofFoxp3+Tregs and γδT17 cells, which contribute to an immunosuppressive tumor microenvironment (TME). Furthermore, we showed that a combined therapy using an inhibitor of DNA methylation and a PD-L1 immune checkpoint inhibitor is more effective for improving survival in tumor-bearing mice than blockade of either pathway alone.

Conclusions

Our study demonstrated that age-dependentp16epimutation creates a permissive microenvironment for malignant transformation of polyps to colon cancer. Our findings provide a mechanistic rationale for future targeted therapy in patients withp16epimutation.
Quality of life in children undergoing tonsillectomy: a cross-sectional survey
Authors: Zhou Ying , Peng Mingqi , Zhou Jing
Published: May 2023

Background

The quality of life in children undergoing tonsillectomy remains unclear. We aimed to analyze the current status and influencing factors of quality of life in children undergoing tonsillectomy, to provide useful insights to clinical postoperative care for children.

Methods

Children who underwent tonsillectomy in our hospital from June 1, 2021 to October 31, 2022 were selected. The characteristics of children were collected and Paediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0) was used for evaluating the quality of life in children. Pearson correlation, univariate and logistic regression analyses were condcuted to evaluate the influencing factors of quality of life in children undergoing tonsillectomy.

Results

A total of 118 children undergoing tonsillectomy were included. The total score of PedsQL™ 4.0 in children undergoing tonsillectomy was (70.28 ± 13.15). Pearson correlation analyses indicated that age(r = 0.586), courses of tonsillitis(r = 0.595), parental education level(r = 0.612) and monthly family income(r = 0.608) were associated with the PedsQL™ 4.0 total score in children undergoing tonsillectomy (all P < 0.05). Logistic regression analyses indicated that age ≤ 5y (OR = 2.009,95%CI: 1.826 ~ 2.401), courses of tonsillitis ≥ 3years (OR = 2.167,95%CI: 1.688 ~ 2.547), high school of parental education level (OR = 1.807,95%CI: 1.224 ~ 2.181) and monthly family income ≤ 5000 RMB(OR = 2.624,95%CI:2.092 ~ 3.077) were the independent influencing factors of quality of life in children with undergoing tonsillectomy (all P < 0.05).

Conclusions

The quality of life of children after tonsillectomy is not high, and the quality of life of children is affected by many factors. Medical staff should take early targeted nursing countermeasures tageted on those influencing factors to improve the quality of life of children.
Utility of eConsults for COVID-19 vaccine-related concerns in Ontario: a cross-sectional analysis
Authors: Walter Graham , Jeimy Samira , Liddy Clare , Guglani Sheena , Ellis Anne K. , Blair Amy , Kobayaa Hazar , Chad Zave , Keely Erin
Published: May 2023

Background

The Champlain BASE™ and Ontario eConsult services are virtual platforms that serve to facilitate contact between primary care providers and specialists across Ontario, relaying patient-specific questions to relevant specialists via a secure web-based platform. Despite ample evidence regarding the general effectiveness of these platforms, their utility as it pertains to clinical concerns regarding COVID-19 vaccines has not yet been explored.

Methods

We performed a cross-sectional descriptive analysis of COVID-19 vaccine related eConsults on Ontario patients completed by five allergy specialists between February and October of 2021. 4318 COVID-19 vaccine-related eConsults were completed in total during this time; with 1857 completed by the five allergists participating in this analysis. Question types/content were categorized using a taxonomy developed through consensus on a weighted monthly sample of 499 total cases. Data regarding whether external resources were required to answer each eConsult, impact on primary care provider referral decisions, and allergy consultant response times were collected. A 2-question survey was completed by primary care providers following eConsultation and results were collected.

Results

41.08% of eConsults received involved safety concerns regarding COVID-19 vaccine administration in the setting of prior allergic disease and another 36.1% involved a potential reaction the first dose of a COVID-19 vaccine. 72.1% of eConsults were answered by specialist without needing external resources, and only 9.8% of all eConsults received resulted in a recommendation for formal in-person referral to Clinical Immunology & Allergy specialist or another subspecialty. Average time to complete eConsult was 16.4 min, and 79.7% of PCP eConsult queries which would have traditionally resulted in formal consultation were resolved based on advice provided in the eConsult without need for in-person assessment.

Conclusions

Our study demonstrates the utility of the eConsult service as it pertains to COVID-19 vaccine-related concerns. The eConsult platform proved an effective tool in diverting the need for in-person assessment by an Allergist or other medical specialty. This is significant given the large volume of eConsults completed by Allergists, and demonstrates the impact of an effective electronic delivery of care model during a time of strained resources and public health efforts directed at mass vaccination.
COVID-19 risk perception and vaccine acceptance in individuals with self-reported chronic respiratory or autoimmune conditions
Authors: Smith Brianna A. , Ricotta Emily E. , Kwan Jennifer L. , Evans Nicholas G.
Published: May 2023

Background

COVID-19 disproportionately affects those with preexisting conditions, but little research has determined whether those with chronic diseases view the pandemic itself differently - and whether there are differences between chronic diseases. We theorized that while individuals with respiratory disease or autoimmune disorders would perceive greater threat from COVID-19 and be more supportive of non-pharmaceutical interventions (NPIs), those with autoimmune disorders would be less likely to support vaccination-based interventions.

Methods

We conducted a two-wave online survey conducted in February and November 2021 asking respondents their beliefs about COVID-19 risk perception, adoption and support of interventions, willingness to be vaccinated against COVID-19, and reasons for vaccination. Regression analysis was conducted to assess the relationship of respondents reporting a chronic disease and COVID-19 behaviors and attitudes, compared to healthy respondents adjusting for demographic and political factors.

Results

In the initial survey, individuals reporting a chronic disease had both stronger feelings of risk from COVID-19 as well as preferences for NPIs than healthy controls. The only NPI that was still practiced significantly more compared to healthy controls in the resample was limiting trips outside of the home. Support for community-level NPIs was higher among individuals reporting a chronic disease than healthy controls and remained high among those with respiratory diseases in sample 2. Vaccine acceptance produced more divergent results: those reporting chronic respiratory diseases were 6% more willing to be vaccinated than healthy controls, while we found no significant difference between individuals with autoimmune diseases and healthy controls. Respondents with chronic respiratory disease and those with autoimmune diseases were more likely to want to be vaccinated to protect themselves from COVID-19, and those with an autoimmune disease were more likely to report fear of a bad vaccine reaction as the reason for vaccine hesitancy. In the resample, neither those with respiratory diseases nor autoimmune diseases reported being more willing to receive a booster vaccine than healthy controls.

Conclusions

It is not enough to recognize the importance of health in determining attitudes: nuanced differences between conditions must also be recognized.
CheckList for EvaluAtion of Radiomics research (CLEAR): a step-by-step reporting guideline for authors and reviewers endorsed by ESR and EuSoMII
Authors: Kocak Burak , Baessler Bettina , Bakas Spyridon , Cuocolo Renato , Fedorov Andrey , Maier-Hein Lena , Mercaldo Nathaniel , Müller Henning , Orlhac Fanny , Pinto dos Santos Daniel , Stanzione Arnaldo , Ugga Lorenzo , Zwanenburg Alex
Published: May 2023

Even though radiomics can hold great potential for supporting clinical decision-making, its current use is mostly limited to academic research, without applications in routine clinical practice. The workflow of radiomics is complex due to several methodological steps and nuances, which often leads to inadequate reporting and evaluation, and poor reproducibility. Available reporting guidelines and checklists for artificial intelligence and predictive modeling include relevant good practices, but they are not tailored to radiomic research. There is a clear need for a complete radiomics checklist for study planning, manuscript writing, and evaluation during the review process to facilitate the repeatability and reproducibility of studies. We here present a documentation standard for radiomic research that can guide authors and reviewers. Our motivation is to improve the quality and reliability and, in turn, the reproducibility of radiomic research. We name the checklist CLEAR (CheckList for EvaluAtion of Radiomics research), to convey the idea of being more transparent. With its 58 items, the CLEAR checklist should be considered a standardization tool providing the minimum requirements for presenting clinical radiomics research. In addition to a dynamic online version of the checklist, a public repository has also been set up to allow the radiomics community to comment on the checklist items and adapt the checklist for future versions. Prepared and revised by an international group of experts using a modified Delphi method, we hope the CLEAR checklist will serve well as a single and complete scientific documentation tool for authors and reviewers to improve the radiomics literature.
Automatic differentiation of ruptured and unruptured intracranial aneurysms on computed tomography angiography based on deep learning and radiomics
Authors: Feng Junbang , Zeng Rong , Geng Yayuan , Chen Qiang , Zheng Qingqing , Yu Fei , Deng Tie , Lv Lei , Li Chang , Xue Bo , Li Chuanming
Published: May 2023

Objectives

Rupture of intracranial aneurysm is very dangerous, often leading to death and disability. In this study, deep learning and radiomics techniques were used to automatically detect and differentiate ruptured and unruptured intracranial aneurysms.

Materials and methods

363 ruptured aneurysms and 535 unruptured aneurysms from Hospital 1 were included in the training set. 63 ruptured aneurysms and 190 unruptured aneurysms from Hospital 2 were used for independent external testing. Aneurysm detection, segmentation and morphological features extraction were automatically performed with a 3-dimensional convolutional neural network (CNN). Radiomic features were additionally computed via pyradiomics package. After dimensionality reduction, three classification models including support vector machines (SVM), random forests (RF), and multi-layer perceptron (MLP) were established and evaluated via area under the curve (AUC) of receiver operating characteristics. Delong tests were used for the comparison of different models.

Results

The 3-dimensional CNN automatically detected, segmented aneurysms and calculated 21 morphological features for each aneurysm. The pyradiomics provided 14 radiomics features. After dimensionality reduction, 13 features were found associated with aneurysm rupture. The AUCs of SVM, RF and MLP on the training dataset and external testing dataset were 0.86, 0.85, 0.90 and 0.85, 0.88, 0.86, respectively, for the discrimination of ruptured and unruptured intracranial aneurysms. Delong tests showed that there was no significant difference among the three models.

Conclusions

In this study, three classification models were established to distinguish ruptured and unruptured aneurysms accurately. The aneurysms segmentation and morphological measurements were performed automatically, which greatly improved the clinical efficiency.

Clinical relevance statement

Our fully automatic models could rapidly process the CTA data and evaluate the status of aneurysms in one minute.

Graphical Abstract