bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life and care burden among family caregivers of people with severe mental illness: mediating effects of self-esteem and psychological distress
Authors: Cheng Wan-Lin , Chang Chih-Cheng , Griffiths Mark D. , Yen Cheng-Fang , Liu Jiun-Horng , Su Jian-An , Lin Chung-Ying , Pakpour Amir H.
Published: October 2022

Background

Family caregivers are important allies for healthcare providers in facilitating the recovery process among people with mental illness (PWMI). The present study examined the factors associated with quality of life (QoL) among family caregivers of PWMI.

Methods

A multi-center cross-sectional survey was conducted. Family caregivers of people with schizophrenia, major depressive disorder, and bipolar disorder were recruited using convenience sampling. A survey assessing their QoL, depression, anxiety, and self-esteem was completed with self-rated psychometric scales including the Rosenberg Self-Esteem Scale, Caregiver Burden Inventory, Taiwanese Depression Questionnaire, Beck Anxiety Inventory, and World Health Organization Quality of Life Instrument Short Form. A mediation model was constructed with QoL as the dependent variable, care burden as the independent variable, and psychological distress (including depression and anxiety) with self-esteem as mediating variables.

Results

Family caregivers of people with schizophrenia had worse QoL compared with counterparts of people with major depression and bipolar disorder. The sociodemographic of both caregivers and PWMI had less impact on QoL when psychological factors were considered. Caregivers with lower self-esteem, higher levels of psychological distress, and heavier care burdens had poorer QoL. Care burden had a significant total effect on QoL. Both self-esteem and psychological distress were significant mediators.

Conclusion

The findings indicated that caregivers’ psychological health and care burden influenced their QoL. Interventions that target family caregivers’ self-esteem and psychological distress may attenuate the effect from care burden, and further improve their QoL.
Protective behavior and SARS-CoV-2 infection risk in the population – Results from the Gutenberg COVID-19 study
Authors: Baumkötter Rieke , Yilmaz Simge , Zahn Daniela , Fenzl Katharina , Prochaska Jürgen H. , Rossmann Heidi , Schmidtmann Irene , Schuster Alexander K. , Beutel Manfred E. , Lackner Karl J. , Münzel Thomas , Wild Philipp S.
Published: October 2022

Background

During the SARS-CoV-2 pandemic, preventive measures like physical distancing, wearing face masks, and hand hygiene have been widely applied to mitigate viral transmission. Beyond increasing vaccination coverage, preventive measures remain urgently needed. The aim of the present project was to assess the effect of protective behavior on SARS-CoV-2 infection risk in the population.

Methods

Data of the Gutenberg COVID-19 Study (GCS), a prospective cohort study with a representative population-based sample, were analyzed. SARS-CoV-2 infections were identified by sequential sampling of biomaterial, which was analyzed by RT-qPCR and two antibody immunoassays. Self-reported COVID-19 test results were additionally considered. Information on protective behavior including physical distancing, wearing face masks, and hand hygiene was collected via serial questionnaire-based assessments. To estimate adjusted prevalence ratios and hazard ratios, robust Poisson regression and Cox regression were applied.

Results

In total, 10,250 participants were enrolled (median age 56.9 [43.3/68.6] years, 50.8% females). Adherence to preventive measures was moderate for physical distancing (48.3%), while the use of face masks (91.5%) and the frequency of handwashing (75.0%) were high. Physical distancing appeared to be a protective factor with respect to SARS-CoV-2 infection risk independent of sociodemographic characteristics and individual pandemic-related behavior (prevalence ratio [PR] = 0.77, 95% confidence interval [CI] 0.62–0.96). A protective association between wearing face masks and SARS-CoV-2 transmission was identified (PR = 0.73, 95% CI 0.55–0.96). However, the protective effect declined after controlling for potential confounding factors (PR = 0.96, 95% CI 0.68–1.36). For handwashing, this investigation did not find a beneficial impact. The adherence to protective behavior was not affected by previous SARS-CoV-2 infection or immunization against COVID-19.

Conclusion

The present study suggests primarily a preventive impact of physical distancing of 1.5 m, but also of wearing face masks on SARS-CoV-2 infections, supporting their widespread implementation. The proper fit and use of face masks are crucial for effectively mitigating the spread of SARS-CoV-2 in the population.
Ambient air pollution associated with incidence and dynamic progression of type 2 diabetes: a trajectory analysis of a population-based cohort
Authors: Wu Yinglin , Zhang Shiyu , Qian Samantha E. , Cai Miao , Li Haitao , Wang Chongjian , Zou Hongtao , Chen Lan , Vaughn Michael G. , McMillin Stephen Edward , Lin Hualiang
Published: October 2022

Background

Though the association between air pollution and incident type 2 diabetes (T2D) has been well documented, evidence on the association with development of subsequent diabetes complications and post-diabetes mortality is scarce. We investigate whether air pollution is associated with different progressions and outcomes of T2D.

Methods

Based on the UK Biobank, 398,993 participants free of diabetes and diabetes-related events at recruitment were included in this analysis. Exposures to particulate matter with a diameter ≤ 10 μm (PM10), PM2.5, nitrogen oxides (NOx), and NO2 for each transition stage were estimated at each participant’s residential addresses using data from the UK’s Department for Environment, Food and Rural Affairs. The outcomes were incident T2D, diabetes complications (diabetic kidney disease, diabetic eye disease, diabetic neuropathy disease, peripheral vascular disease, cardiovascular events, and metabolic events), all-cause mortality, and cause-specific mortality. Multi-state model was used to analyze the impact of air pollution on different progressions of T2D. Cumulative transition probabilities of different stages of T2D under different air pollution levels were estimated.

Results

During the 12-year follow-up, 13,393 incident T2D patients were identified, of whom, 3791 developed diabetes complications and 1335 died. We observed that air pollution was associated with different progression stages of T2D with different magnitudes. In a multivariate model, the hazard ratios [95% confidence interval (CI)] per interquartile range elevation in PM2.5 were 1.63 (1.59, 1.67) and 1.08 (1.03, 1.13) for transitions from healthy to T2D and from T2D to complications, and 1.50 (1.47, 1.53), 1.49 (1.36, 1.64), and 1.54 (1.35, 1.76) for mortality risk from baseline, T2D, and diabetes complications, respectively. Generally, we observed stronger estimates of four air pollutants on transition from baseline to incident T2D than those on other transitions. Moreover, we found significant associations between four air pollutants and mortality risk due to cancer and cardiovascular diseases from T2D or diabetes complications. The cumulative transition probability was generally higher among those with higher levels of air pollution exposure.

Conclusions

This study indicates that ambient air pollution exposure may contribute to increased risk of incidence and progressions of T2D, but to diverse extents for different progressions.
Comprehensive approach to costing cervical cancer prevention and control: a case study in the United Republic of Tanzania using the Cervical Cancer Prevention and Control Costing (C4P) tool
Authors: Levin Ann , Yuma Safina , Swai Edwin , Morgan Winthrop , Gauvreau Cindy L. , Broutet Nathalie , Yeung Karene Hoi Ting , Hutubessy Raymond
Published: October 2022

Background

The World Health Organization (WHO) has developed a costing tool, the Cervical Cancer Prevention and Control Costing (C4P) tool, to estimate the comprehensive cost of cervical cancer primary, secondary and tertiary prevention in low- and middle-income countries. The tool was piloted in the United Republic of Tanzania, a country with a high incidence of cervical cancer with 62.5 cases per 100,000 women in 2020. This paper presents the costing tool methods as well as the results from the pilot in Tanzania.

Methods

The C4P tool estimates the incremental costs of cervical cancer prevention and control programmes. It estimates the financial (monetary costs to the government) and economic costs (opportunity costs). For the pilot, the study team collected data on costs and programme assumptions for human papillomavirus (HPV) vaccination of 14-year-old girls and scaling up of cervical cancer screening (visual inspection with acetic acid and HPV-DNA testing) and treatment for women for 2020–2024. Assumptions were made on how vaccination coverage would increase over the 5 years as well as developing additional screening and treatment capacity through health personnel training and infrastructure strengthening.

Results

The total financial and economic costs of the comprehensive programme during 2020–2024 are projected to be US$68 million and US$124 million, respectively. The financial and economic costs of a fully immunized girl with HPV vaccine are estimated to be US$6.68 and US$17.31, respectively, while the costs per woman screened for cervical cancer are, on average, US$4.02 and US$5.83, respectively; US$6.44 and US$9.37 for pre-cancer treatment, respectively; and US$101 and US$107 for diagnosis of invasive cancer, respectively. The cost of treating and managing invasive cancer range from US$7.05 and US$7.83 for outpatient palliative care to US$800.21 and US$893.80 for radiotherapy, respectively.

Conclusions

The C4P costing tool can assist national cervical cancer programmes to estimate monetary resources needed as well as opportunity costs of reducing national cervical cancer incidence through primary, secondary and tertiary prevention.
ColdZyme® protects airway epithelia from infection with BA.4/5
Authors: Zaderer Viktoria , Dichtl Stefanie , Bellmann Weiler Rosa , Lass Flörl Cornelia , Posch Wilfried , Wilflingseder Doris
Published: October 2022

Vaccines against SARS-CoV-2 protect from critical or severe pathogenesis also against new variants of concern (VOCs) such as BA.4 and BA.5, but immediate interventions to avoid viral transmission and subsequent inflammatory reactions are needed. Here we applied the ColdZyme® medical device mouth spray to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI). We found using VOCs BA.1 and BA.4/5 that this device effectively blocked respiratory tissue infection. While infection with these VOCs resulted in intracellular complement activation, thus enhanced inflammation, and drop of transepithelial resistance, these phenomena were prevented by a single administration of this medical device. Thus, ColdZyme® mouth spray significantly shields epithelial integrity, hinders virus infection and blocks in a secondary effect intrinsic complement activation within airway cultures also in terms of the highly contagious VOCs BA.4/5. Crucially, our in vitro data suggest that ColdZyme® mouth spray may have an impact to protect against SARS-CoV-2 transmission, also in case of the Omicron BA.1, BA.4 and BA.5 variants.
Impact of sleep-related hypoventilation in patients with pleuroparenchymal fibroelastosis
Authors: Yabuuchi Yuki , Saito Takefumi , Hirano Hitomi , Nonaka Mizu , Arai Naoki , Hyodo Kentaro , Kanazawa Jun , Miura Yukiko , Usui Shingo , Tamura Katsumi , Kasamatsu Tomotaka , Oh-ishi Shuji , Hayashihara Kenji , Matsuyama Masashi , Hizawa Nobuyuki
Published: October 2022

Background

Pleuroparenchymal fibroelastosis (PPFE) is a rare fibrosing lung disease with a predilection for the upper lobe and its progression causes hypoventilation, resulting in hypercapnia. Even though the association between sleep-related hypoventilation (SRH) and chronic obstructive pulmonary disease was well documented, its impact in patients with PPFE was not evaluated. The aim of this study is to clarify the impact of SRH on prognosis in PPFE.

Methods

A retrospective review of the medical records of 52 patients with PPFE who underwent transcutaneous carbon dioxide monitoring during sleep was done.

Patients were stratified into SRH (n = 28) and non-SRH (n = 24) groups based on American Academy of Sleep Medicine criteria. The impact of SRH on the prognosis of PPFE, as well as the clinical factors and comorbidities of PPFE associated with SRH, were evaluated.

Results

Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLco) in the SRH group were significantly lower than the non-SRH group (P < .01). Chronic pulmonary aspergillosis (CPA) was found at a higher rate in the SRH group (P = .02). The median survival time for SRH patients was 330 days, whereas roughly 80% of non-SRH patients were alive during the 3-year observation period (P < .01). Body mass index was a significant prognostic factor in PPFE patients with SRH (HR .78; 95% CI; .64–.94; P < .01). Home oxygen therapy (HOT) during the day and noninvasive positive pressure ventilation (NPPV) at night while sleeping tended to improve prognosis in the SRH group, as indicated by HR of .25 (P = .07).

Conclusions

SRH may be a poor prognostic factor for PPFE. Additionally, SRH may modify susceptibility to Aspergillosis in patients with PPFE. HOT plus NPPV may improve the disease outcomes in patients with SRH.
Spatial-temporal analysis of cerebral infarction mortality in Hokkaido, Japan: an ecological study using a conditional autoregressive model
Authors: Ohashi Kazuki , Osanai Toshiya , Fujiwara Kensuke , Tanikawa Takumi , Tani Yuji , Takamiya Soichiro , Sato Hirotaka , Morii Yasuhiro , Bando Kyohei , Ogasawara Katsuhiko
Published: October 2022

Background:

Accessibility to stroke treatments is a challenge that depends on the place of residence. However, recent advances in medical technology have improved health outcomes. Nevertheless, the geographic heterogeneity of medical resources may increase regional disparities. Therefore, evaluating spatial and temporal influences of the medical system on regional outcomes and advanced treatment of cerebral infarction are important from a health policy perspective. This spatial and temporal study aims to identify factors associated with mortality and to clarify regional disparities in cerebral infarction mortality at municipality level.

Methods:

This ecological study used public data between 2010 and 2020 from municipalities in Hokkaido, Japan. We applied spatial and temporal condition autoregression analysis in a Bayesian setting, with inference based on the Markov chain Monte Carlo simulation. The response variable was the number of deaths due to cerebral infarction (ICD-10 code: I63). The explanatory variables were healthcare accessibility and socioeconomic status.

Results:

The large number of emergency hospitals per 10,000 people (relative risk (RR) = 0.906, credible interval (Cr) = 0.861 to 0.954) was associated with low mortality. On the other hand, the large number of general hospitals per 10,000 people (RR = 1.123, Cr = 1.068 to 1.178) and longer distance to primary stroke centers (RR = 1.064, Cr = 1.014 to 1.110) were associated with high mortality. The standardized mortality ratio decreased from 2010 to 2020 in Hokkaido by approximately 44%. Regional disparity in mortality remained at the same level from 2010 to 2015, after which it narrowed by approximately 5% to 2020. After mapping, we identified municipalities with high mortality rates that emerged in Hokkaido’s central and northeastern parts.

Conclusion:

Cerebral infarction mortality rates and the disparity in Hokkaido improved during the study period (2010–2020). This study emphasized that healthcare accessibility through places such as emergency hospitals and primary stroke centers was important in determining cerebral infarction mortality at the municipality level. In addition, this study identified municipalities with high mortality rates that require healthcare policy changes. The impact of socioeconomic factors on stroke is a global challenge, and improving access to healthcare may reduce disparities in outcomes.
The emerging role of exosomes in radiotherapy
Authors: Yang Zhenyi , Zhong Wen , Yang Liang , Wen Ping , Luo Yixuan , Wu Chunli
Published: October 2022

Presently, more than half of cancer patients receive radiotherapy to cure localized cancer, palliate symptoms, or control the progression of cancer. However, radioresistance and radiation-induced bystander effects (RIBEs) are still challenging problems in cancer treatment. Exosomes, as a kind of extracellular vesicle, have a significant function in mediating and regulating intercellular signaling pathways. An increasing number of studies have shown that radiotherapy can increase exosome secretion and alter exosome cargo. Furthermore, radiation-induced exosomes are involved in the mechanism of radioresistance and RIBEs. Therefore, exosomes hold great promise for clinical application in radiotherapy. In this review, we not only focus on the influence of radiation on exosome biogenesis, secretion and cargoes but also on the mechanism of radiation-induced exosomes in radioresistance and RIBEs, which may expand our insight into the cooperative function of exosomes in radiotherapy.
Whole-cell tumor vaccines desialylated to uncover tumor antigenic Gal/GalNAc epitopes elicit anti-tumor immunity
Authors: Huang Jianmei , Li Meiying , Mei Bingjie , Li Junyang , Zhu Yi , Guo Qiaoshan , Huang Jianming , Zhang Guonan
Published: October 2022

Background

Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC).

Methods

Sialic acid (Sia) and Gal/GalNAc residues on OC A2780, OVCAR3, and ID8 cells treated with α2-3 neuraminidase (α2-3NA) and α2-6NA, and Sigec-9 or Siglec-E and MGL on DCs pulsed with desialylated OC cells were identified using flow cytometry (FCM); RT-qPCR determined IFNG expression of T cells, TRBV was sequenced using Sanger sequencing and cytotoxicity of αβ T cells was measured with LDH assay; Anti-tumor immunity in vivo was validated via vaccination with desialylated whole-cell ID8 vaccine (ID8 DWCTVs).

Results

Gal/GalNAc but not Sia residues were significantly increased in the desialylated OC cells. α2-3NA-modified DWCTV increased MGL but decreased Siglec-9 or Siglec E expression on DCs. MGLbright/Siglec-9dim DCs significantly up-regulated IFNG expression and CD4/CD8 ratio of T cells and diversified the TCR repertoire of αβ T-cells that showed enhanced cytotoxic activity. Vaccination with α2-3NA-modified ID8 DWCTVs increased MGLbright/Siglec-Edim DCs in draining lymph nodes, limited tumor growth, and extended survival in tumor-challenged mice.

Conclusion

Desialylated tumor cell vaccine could promote anti-tumor immunity and provide a strategy for OC immunotherapy in a clinical setting.
Adeno-associated virus infection and its impact in human health: an overview
Authors: Sant’Anna Thaís B , Araujo Natalia M
Published: October 2022

Discovered as a contaminant of adenovirus stocks in the 1960s, adeno-associated virus (AAV) is a mono-stranded DNA virus that depends on helper factors to replicate. Even though AAV is endemic in the human population (35–80%), it is remarkable that many issues concerning the natural infection by this virus remain unanswered. In this study, we reflect on the main basic aspects of AAV biology and provide an overview of the studies exploring the impact of AAV infection on human health, focusing on three major research areas including, (i) cervical and (ii) liver cancer, and (iii) reproductive system disorders. Conflicting results have been obtained into the association of AAV infection with the occurrence of adverse reproductive outcomes, such as placental complications, spontaneous abortion, and fertility disorders, or with a protective role in HPV-related cervical carcinogenesis. Noteworthy, recent reports have identified AAV insertional mutagenesis as a novel risk factor for the development of hepatocellular carcinoma. This latest finding raises concern regarding the widespread usage of AAV vectors in liver-targeted gene therapy.
The association between parenteral nutrition and pancreatic injury in adult patients: a retrospective observational study
Authors: Zhang Xiao-min , Zhou Yi-quan , Wan Yan-ping , Li Hao-jie , Chen Zhi-qi , Song An-qi , Tang Mo-lian , Xu Renying , Cai Wei
Published: October 2022

Background and objective

Patients on parenteral nutrition (PN) are at high risk of both liver and pancreatic injury. More efforts were focused on liver, however, limited data is available to evaluate the effects of PN on pancreas. Thus, we performed a retrospective observational study to evaluate the association between PN and pancreatic injury in Chinese adult patients.

Methods

Adult patients (18–80 years), who received PN for a week or longer, and with repeated measurements of pancreatic enzymes, were included in the analysis. Pancreatic injury was confirmed by serum level of pancreatic amylase (P-AMYwas 53 U/L or higher) or lipase (LP was 63 U/L or higher), which were evaluated at baseline and following every week during PN duration. Age, sex, body weight, height, diagnosis of diseases, history of diseases, surgery, white blood cell, c-reactive protein, liver and renal function, fasting blood glucose, lipid profile, and daily energy supplied by PN and enteral nutrition were abstracted from medical records.

Results

A total number of 190 adult patients (125 men, 65 women) were included in the study. The average age and BMI were 61.8 ± 13.0 years and 21.7±3.3 kg/m2, while medium serum level of P-AMY and LP were 29.0 U/L (quartile range: 18.0, 47.0) and 33.0 U/L (quartile range: 19.0, 58.0), respectively at baseline. The median duration of PN was 15 days (quartile range: 11.0, 21.0). The prevalence of pancreatic injury was 42.1% (80/190) while it was 28.4% (54/190), 43.3% (77/178), 47.8% (44/92) after one-, two-, and three-week or longer PN adminstration. The proportion of daily energy supplement by PN (OR = 3.77, 95%CI: 1.87, 7.61) and history of infection were positively (OR = 3.00, 95%CI: 1.23, 7.36), while disease history for diabetes mellitus (OR = 0.38, 95%CI: 0.15, 0.98) and cancer (OR = 0.46, 95%CI: 0.23, 0.95), were negetively associated with pancreatic injury. Total bile acids were associated with the increment of P-AMY (beta = 0.98, 95%CI: 0.39, 1.56) and LP (beta = 2.55, 95%CI: 0.98, 4.12) by multi-variate linear regression.

Conclusion

PN was associated with pancreatic injury, as demonstrated by the increase of both serum P-AMY and LP.
Anastomotic leak after minimally invasive anterior resection for rectal cancer with high versus low ligation of the inferior mesenteric artery: a study protocol for a multicentre randomized clinical trial
Authors: Lee Soo Young , Kim Sohyun , Son Gyung Mo , Kim Hye Jin , Park Soo Yeun , Park Jun Seok , Kim Chang Hyun , Ha Gi Won , Lee Kyung-Ha , Kim Jin Soo , Bae Ki Beom , Bae Sung Uk , Kang Sung Il ,   Korean ColoRectal surgeOn Study group of the Southern province (K-CROSS)
Published: October 2022

Background

Although many efforts have been made to decrease the incidence of anastomotic leak (AL), it remains one of the most serious complications of rectal cancer surgery. Many previous studies have reported an association between the ligation level of the inferior mesenteric artery (IMA) (high or low) and the incidence of AL after rectal cancer surgery. However, we cannot draw a solid conclusion because of the low quality and heterogeneity of those studies. Therefore, this study aims to investigate the impact of the IMA ligation level on the occurrence of AL after minimally invasive anterior resection of rectal cancer.

Methods/design

Patients with primary rectal cancer without distant metastases will be included after screening. They will be randomly assigned (1:1) to receive high or low ligation of the IMA. The primary endpoint is AL incidence; secondary endpoints are quality of life; urinary, sexual, and defecatory functions; and 3-year disease-free survival. We hypothesized that the incidence rate of AL would be 15% and 5% in the high- and low-ligation groups, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size is calculated to be 314 patients (157 per group), considering a 10% dropout rate.

Discussion

Although many studies have compared the short- and long-term outcomes of high and low ligation of the IMA in rectal cancer surgery, it is still debatable. This trial aims to help draw a more solid conclusion regarding the association between the IMA ligation level and AL incidence after rectal cancer surgery. We also hope to contribute to standardizing the method of rectal cancer surgery in this trial.

Trial registration

Clinical Research Information Service KCT0003523. Registered on February 18, 2019
Preliminary evaluation of the protective effects of recombinant AMA1 and IMP1 against Eimeria stiedae infection in rabbits
Authors: Xiao Jie , Zheng Ruoyu , Bai Xin , Pu Jiayan , Chen Hao , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou
Published: October 2022

Background

Eimeria stiedae parasitizes the bile duct, causing hepatic coccidiosis in rabbits. Coccidiosis control using anticoccidials led to drug resistance and residues; therefore, vaccines are required as an alternative control strategy. Apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1) are surface-located proteins that might contribute to host cell invasion, having potential as candidate vaccine antigens.

Methods

Herein, we cloned and expressed the E. stiedae EsAMA1 and EsIMP1 genes. The reactogenicity of recombinant AMA1 (rEsAMA1) and IMP1 (rEsIMP1) proteins were investigated using immunoblotting. For the vaccination-infection trial, rabbits were vaccinated with rEsAMA1 and rEsIMP1 (both 100 μg/rabbit) twice at 2-week intervals. After vaccination, various serum cytokines were measured. The protective effects of rEsAMA1 and rEsIMP1 against E. stiedae infection were assessed using several indicators. Sera were collected weekly to detect the specific antibody levels.

Results

Both rEsAMA1 and rEsIMP1 showed strong reactogenicity. Rabbits vaccinated with rEsAMA1 and rEsIMP1 displayed significantly increased serum IL-2 (F(4, 25) = 9.53, P = 0.000), IL-4 (F(4, 25) = 7.81, P = 0.000), IL-17 (F(4, 25) = 8.55, P = 0.000), and IFN-γ (F(4, 25) = 6.89, P = 0.001) levels; in the rEsIMP1 group, serum TGF-β1 level was also elevated (F(4, 25) = 3.01, P = 0.037). After vaccination, the specific antibody levels increased and were maintained at a high level. The vaccination-infection trial showed that compared with the positive control groups, rabbits vaccinated with the recombinant proteins showed significantly reduced oocyst output (F(5, 54) = 187.87, P = 0.000), liver index (F(5, 54) = 37.52, P = 0.000), and feed conversion ratio; body weight gain was significantly improved (F(5, 54) = 28.82, P = 0.000).

Conclusions

rEsAMA1 and rEsIMP1 could induce cellular and humoral immunity, protecting against E. stiedae infection. Thus, rEsAMA1 and rEsIMP1 are potential vaccine candidates against E. stiedae.

Graphic abstract
A point-of-care ultrasound education curriculum for pediatric critical care medicine
Authors: Bhargava Vidit , Haileselassie Bereketeab , Rosenblatt Samuel , Baker Mark , Kuo Kevin , Su Erik
Published: October 2022

Background

Diagnostic and procedural point-of-care ultrasound (POCUS) change patient management with the potential to improve outcomes. Pediatric critical care medicine trainees have limited access to education and training opportunities in diagnostic POCUS in the pediatric ICU. A dearth of published pediatric ICU curricular resources restricts these educational opportunities.

Methods

A 7-week longitudinal curriculum including lectures, practical skills sessions, and knowledge assessment covering core modules including (1) machine operation, (2) vascular access, (3) non-vascular procedures, (4) cardiac imaging, (5) hemodynamic assessment, (6) pulmonary imaging, and (7) abdominal imaging, was disseminated to pediatric critical care trainees and faculty at a single tertiary care pediatric hospital.

Results

The knowledge of trainees and participating faculty in procedural and diagnostic POCUS improved after implementing the curriculum. Pre-test scores mean and standard deviation (59.30% ± 14.15%) improved significantly (75.60% ± 9.43%) for all learners (p < 0.001). The overall self-reported comfort in diagnostic and procedural ultrasound improved for all learners. 100% of the learners reported utilizing diagnostic POCUS in their clinical practice four months after disseminating the curriculum.

Discussion

We describe a single center’s approach to POCUS education with improvement in knowledge, self-reported comfort, and attitudes towards procedural and diagnostic POCUS. The curricular resources for adaptation in a similar educational context are provided.
Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report
Authors: Küronya Zsófia , Danyi Tímea , Balatoni Tímea , Liszkay Gabriella , Tóth Erika , Biró Krisztina , Géczi Lajos
Published: October 2022

Background

The use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers.

Case presentation

A 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient’s inadequate compliance, and within 2 years, the patient’s cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient’s basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection.

Conclusions

Our patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.
Copy number variant analysis for syndromic congenital heart disease in the Chinese population
Authors: Li Ping , Chen Weicheng , Li Mengru , Zhao Zhengshan , Feng Zhiyu , Gao Han , Suo Meijiao , Xu Ziqing , Tian Guixiang , Wu Feizhen , Wei Sheng , Huang Guoying
Published: October 2022

Background

Syndromic congenital heart disease (CHD) is among the most severe conditions in the pediatric population. Copy number variant (CNV) is an important cause of syndromic CHD, but few studies focused on CNVs related to these patients in China. The present study aimed to identify pathogenic CNVs associated with syndromic CHD in the Chinese population.

Methods

A total of 109 sporadic patients with syndromic CHD were applied chromosomal microarray analysis (CMA). Phenotype spectrum of pathogenic or likely pathogenic CNVs was analyzed. CHD-related genes were prioritized from genes within pathogenic or likely pathogenic CNVs by VarElect, OVA, AMELIE, and ToppGene.

Results

Using CMA, we identified 43 candidate CNVs in 37/109 patients. After filtering CNVs present in the general population, 29 pathogenic/likely pathogenic CNVs in 24 patients were identified. The diagnostic yield of CMA for pathogenic/likely pathogenic CNVs was 23.1% (24/104), excluding 5 cases with aneuploidies or gross chromosomal aberrations. The overlapping analysis of CHD-related gene lists from different prioritization tools highlighted 16 CHD candidate genes.

Conclusion

As the first study focused on CNVs in syndromic CHD from the Chinese population, this study reveals the importance of CMA in exploring the genetic etiology of syndromic CHD and expands our understanding of these complex diseases. The bioinformatic analysis of candidate genes suggests several CHD-related genes for further functional research.
Can a parental sleep intervention in an individual setting improve the maternal and paternal sense of competence and parent–child interaction in parents of young sleep-disturbed children? findings from a single-arm pilot intervention study
Authors: Schnatschmidt Marisa , Lollies Friederike , Schlarb Angelika A.
Published: October 2022

Background

In early childhood sleep and regulatory problems, parental factors are often impaired but essential to overcoming them. This study aims to examine, in parents of young sleep-disturbed children, whether mothers’ and fathers’ sense of parenting competence were increased and dysfunctional parent–child interactions reduced with a parental sleep intervention, whether these changes were sustained over a 12-month follow-up period and if children’s symptomatic parameters could be related factors.

Methods

A total of 57 families with sleep-disturbed children aged 6 months to 4 years entered this single-arm pilot study. Each parent pair participated in six weekly individual face-to-face sessions of a multimodal cognitive-behavioral sleep intervention. The Parenting Sense of Competence Scale, Parental Stress Index Short Form, Child’s Sleep Diary and Child’s Questionnaire on Crying, Eating and Sleeping were obtained pre-, post-, 3, 6 and 12 months after the intervention.

Results

Maternal sense of competence and dysfunctional mother–child interaction improved significantly up to 6 months after the intervention. Factors related to lower maternal competence were the child’s more frequent nightly food intake and more crying due to defiance; factors related to dysfunctional mother–child interaction were more frequent crying episodes, more crying due to defiance and more eating difficulties; factors related to increased maternal competence were less duration of child’s night waking, less bed-sharing and lower frequency of crying episodes; factors related to increased paternal competence were less child’s nightly food intake and fewer episodes of unexplained and unsoothable crying; and factors related to improved father–child interaction were less frequent child’s night waking and fewer unexplained and unsoothable crying episodes.

Conclusion

For parents of sleep-disturbed young children, an intervention that addresses the child’s sleep could be promising to increase the parental sense of competence and reduce dysfunctional parent–child interactions, especially for mothers. Child symptomatic parameters may change, together with the parental sense of competence and parent–child interaction of both parents, after the intervention. Mothers with children with more severe symptomatology perceive their parenting competence as lower on average and their mother–child interaction as more dysfunctional. Future research with a larger sample and a randomized controlled design is needed.

Trial registration:

The study was retrospectively registered at the German Clinical Trials Register (ID: DRKS00028578; registration date: 21.03.2022).
Artificial intelligence-derived neurofibrillary tangle burden is associated with antemortem cognitive impairment
Authors: Marx Gabriel A. , Koenigsberg Daniel G. , McKenzie Andrew T. , Kauffman Justin , Hanson Russell W. , Whitney Kristen , Signaevsky Maxim , Prastawa Marcel , Iida Megan A. , White Charles L. , Walker Jamie M. , Richardson Timothy E. , Koll John , Fernandez Gerardo , Zeineh Jack , Cordon-Cardo Carlos , Crary John F. , Farrell Kurt ,   The PART working group
Published: October 2022

Tauopathies are a category of neurodegenerative diseases characterized by the presence of abnormal tau protein-containing neurofibrillary tangles (NFTs). NFTs are universally observed in aging, occurring with or without the concomitant accumulation of amyloid-beta peptide (Aβ) in plaques that typifies Alzheimer disease (AD), the most common tauopathy. Primary age-related tauopathy (PART) is an Aβ-independent process that affects the medial temporal lobe in both cognitively normal and impaired subjects. Determinants of symptomology in subjects with PART are poorly understood and require clinicopathologic correlation; however, classical approaches to staging tau pathology have limited quantitative reproducibility. As such, there is a critical need for unbiased methods to quantitatively analyze tau pathology on the histological level. Artificial intelligence (AI)-based convolutional neural networks (CNNs) generate highly accurate and precise computer vision assessments of digitized pathology slides, yielding novel histology metrics at scale. Here, we performed a retrospective autopsy study of a large cohort (n = 706) of human post-mortem brain tissues from normal and cognitively impaired elderly individuals with mild or no Aβ plaques (average age of death of 83.1 yr, range 55–110). We utilized a CNN trained to segment NFTs on hippocampus sections immunohistochemically stained with antisera recognizing abnormal hyperphosphorylated tau (p-tau), which yielded metrics of regional NFT counts, NFT positive pixel density, as well as a novel graph-theory based metric measuring the spatial distribution of NFTs. We found that several AI-derived NFT metrics significantly predicted the presence of cognitive impairment in both the hippocampus proper and entorhinal cortex (p < 0.0001). When controlling for age, AI-derived NFT counts still significantly predicted the presence of cognitive impairment (p = 0.04 in the entorhinal cortex;p = 0.04 overall). In contrast, Braak stage did not predict cognitive impairment in either age-adjusted or unadjusted models. These findings support the hypothesis that NFT burden correlates with cognitive impairment in PART. Furthermore, our analysis strongly suggests that AI-derived metrics of tau pathology provide a powerful tool that can deepen our understanding of the role of neurofibrillary degeneration in cognitive impairment.
Understanding the importance of quality control and quality assurance in preclinical PET/CT imaging
Authors: McDougald Wendy A. , Mannheim Julia G.
Published: October 2022

The fundamental principle of experimental design is to ensure efficiency and efficacy of the performed experiments. Therefore, it behoves the researcher to gain knowledge of the technological equipment to be used. This should include an understanding of the instrument quality control and assurance requirements to avoid inadequate or spurious results due to instrumentation bias whilst improving reproducibility. Here, the important role of preclinical positron emission tomography/computed tomography and the scanner's required quality control and assurance is presented along with the suggested guidelines for quality control and assurance. There are a multitude of factors impeding the continuity and reproducibility of preclinical research data within a single laboratory as well as across laboratories. A more robust experimental design incorporating validation or accreditation of the scanner performance can reduce inconsistencies. Moreover, the well-being and welfare of the laboratory animals being imaged is prime justification for refining experimental designs to include verification of instrumentation quality control and assurance. Suboptimal scanner performance is not consistent with the 3R principle (Replacement, Reduction, and Refinement) and potentially subjects animals to unnecessary harm. Thus, quality assurance and control should be of paramount interest to any scientist conducting animal studies. For this reason, through this work, we intend to raise the awareness of researchers using PET/CT regarding quality control/quality assurance (QC/QA) guidelines and instil the importance of confirming that these are routinely followed. We introduce a basic understanding of the PET/CT scanner, present the purpose of QC/QA as well as provide evidence of imaging data biases caused by lack of QC/QA. This is shown through a review of the literature, QC/QA accepted standard protocols and our research. We also want to encourage researchers to have discussions with the PET/CT facilities manager and/or technicians to develop the optimal designed PET/CT experiment for obtaining their scientific objective. Additionally, this work provides an easy gateway to multiple resources not only for PET/CT knowledge but for guidelines and assistance in preclinical experimental design to enhance scientific integrity of the data and ensure animal welfare.
Validation of a new scoring approach of a child dietary questionnaire for use in early childhood among low-income, Latino populations
Authors: Adams Laura E. , Sommer Evan C. , Truesdale Kimberly P. , Barkin Shari L. , Heerman William J.
Published: October 2022

Background

Measuring diet quality in early childhood requires time-intensive and costly measurements (e.g., 24-hour diet recall) that are especially burdensome for low-income, minority populations. This study aimed to validate a new method for calculating overall diet quality among low-income, Latino preschoolers.

Methods

This study was an observational study using data from a randomized controlled trial. Participants included parents of Latino preschoolers who reported child diet quality at baseline, 4-month, 7-month, 12-month, and 13-month follow-up. At each timepoint parents responded to a 28-item child dietary questionnaire (CDQ), based on the National Health and Nutrition Examination Survey (NHANES) dietary module, which generated the number of times/day that a child ate each of 28 foods in the past month. These 28 items were then used to create a total standardized child diet quality index (possible range 0-100), using a percent of maximum method. Parents were asked to complete three 24-hour diet recalls at the 13-month follow-up, from which the 2015 Healthy Eating Index (HEI) was derived. Construct validity was evaluated by Spearman’s rank correlations between the new child diet quality index and the 2015 HEI at the 13-month follow-up. Test-retest reliability was assessed by intraclass correlation coefficients (ICC) for sequential pairs of time points.

Results

Among 71 eligible parent-child pairs, mean child age was 4.2 (SD = 0.8) years, 50.7% of children were female, and mean child body mass index (BMI) was 17.8 (SD = 2.0) kg/m2. Mean Child Diet Quality Index was 45.2 (SD = 3.2) and mean HEI was 68.4 (SD = 10.5). Child Diet Quality Index and HEI total scores were significantly correlated (r = 0.37; p = 0.001). Test-retest ICCs were statistically significant between all sequential pairs of time points.

Conclusion

The new approach for calculating a measure of overall diet quality from the previously-validated 28-item dietary questionnaire demonstrated modest construct validity. When time and resources are limited, this new measure of overall diet quality may be an appropriate choice among low-income, Latino preschoolers.

Trial Registration

This reports presents observational data collected as a part of a clinical trial, which was registered on clinicaltrials.gov prior to participant enrollment (NCT03141151).
Absolute iodine concentration for dynamic perfusion imaging of the myocardium: improved detection of poststenotic ischaemic in a 3D-printed dynamic heart phantom
Authors: Hammel Johannes , Birnbacher Lorenz , Makowski Marcus R. , Pfeiffer Franz , Pfeiffer Daniela
Published: October 2022

Background

To investigate the detection capabilities of myocardial perfusion defects of dual-energy computed tomography (CT) technology using time-resolved iodine-based maps for functional assessment of coronary stenosis in a dynamic heart phantom.

Methods

An anatomical heart model was designed using a three-dimensional (3D) printing technique. The lumen of the right coronary artery was reduced to 25% of the original areal cross-section. Scans were acquired with a 64-slice dual-layer CT equipment using a perfusion protocol with 36 time points. For distinguishing haemodynamically affected from unaffected myocardial regions, conventional and spectral mean transit time (MTT) parameter maps were compared. A dose reduction technique was simulated by using a subset of time points of the time attenuation curves (TACs).

Results

The tracer kinetic modeling showed decreased errors on fit parameters from conventional to spectral TACs (42% reduction for A and 40% for λ). Three characteristic regions (highly, moderately, and not affected by the simulated stenosis) can be distinguished in all spectral perfusion maps. The best distinction was observed on MTT maps. An area under the curve (AUC) value of 1.00 for the voxel-wise differentiation of haemodynamically affected tissue was achieved versus a 0.89 AUC for conventional MTT maps. By temporal under-sampling, a dose reduction of approximately 78% from 19 to 4.3 mSv was achieved with a 0.96 AUC.

Conclusion

Dual-energy CT can provide time-resolved iodine density data, which enables the calculation of absolute quantitative perfusion maps with decreased fitting errors, improving the accuracy for poststenotic myocardial ischaemic detection in a 3D-printed heart phantom.