bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of individualized PEEP on postoperative delirium among older patients in prone position: study protocol for a prospective randomized controlled trial
Authors: Zhang Wenchao , Han Shuang , Li Jianli
Published: December 2022

Background

Postoperative delirium (POD) is an acute mental disorder that often occurs in the elderly after surgery. It can delay functional recovery, extend hospital stay, and increase 1-year mortality and financial costs. Studies have shown that inflammation and cerebral desaturation are the potential pathogenesis of postoperative delirium. Prone-position surgery increases peak airway pressure and decreases lung compliance, exacerbating ventilator-induced inflammation response, as well as the decrease of the patient's cerebral oxygen saturation. Recent studies demonstrated that lung-protective ventilation strategy could reduce inflammatory response and improve cerebral oxygen saturation (rSO2) to prevent POD. In this trial, we aim to investigate the effect of the individualized PEEP on postoperative delirium in elderly patients during prone position.

Methods

A prospective, randomized clinical trial will be performed in Hebei General Hospital. 106 patients undergoing elective surgery in prone position will be randomly divided into controlled group (group C) and individualized PEEP group (group I). Lung-protective ventilation with tidal volume of 6ml/kg predictive body weight (PBW) and positive end-expiratory pressure (PEEP) of 5 cm H2O will be applied to patients in group C. Patients in group I will receive the same tidal volume as described in group C plus individualized PEEP corresponding to the maximum dynamic compliance (Cdyn) in the titration method. Our primary endpoint is the prevalence of postoperative delirium based on the Confusion Assessment Method (CAM) until postoperative day 3. Secondary endpoints include the intraoperative rSO2, respiratory variables, arterial blood gases, lung ultrasound score (LUS), postoperative VAS score, and plasma concentrations of IL-6, IL-1β and neuron-specific enolase (NSE).

Discussion

The results of the current protocol might provide evidence for individualized PEEP to prevent POD among older surgical patients in prone position.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2200056001). Registered 2022 January 30,http://www.chictr.org.cn/index.aspx.
Epileptic spasms related to neuronal differentiation factor 2 (NEUROD2) mutation respond to combined vigabatrin and high dose prednisolone therapy
Authors: Sakpichaisakul Kullasate , Boonkrongsak Rachata , Lertbutsayanukul Punjama , Iemwimangsa Nareenart , Klumsathian Sommon , Panthan Bhakbhoom , Trachoo Objoon
Published: December 2022

Background

Epileptic spasms are a devastating form of early infantile epileptic encephalopathy (EIEE) with various etiologies. Early diagnosis and a shorter lead time to treatment are crucial to stop the seizures and optimize the neurodevelopmental outcome. Genetic testing has become an integral part of epilepsy care that directly guides management and family planning and discovers new targeted treatments. Neuronal differentiation Factor 2 (NEUROD2) variants have recently been a cause of neurodevelopmental disorders (NDDs) and EIEEs with distinctive features. However, there is limited information about the clinical and electroencephalographic response of epileptic spasm treatment in NEUROD2-related NDD syndrome.

Case presentation

We report a female patient of Southeast Asian ethnicity with global developmental delay and epileptic spasms commencing in the first few months of life. A novel de novo heterozygous pathogenic NEUROD2 variant, p. E130Q, was subsequently identified by whole-exome sequencing. Electroencephalogram before treatment showed multifocal independent spikes predominantly in both posterior head regions and demonstrated marked improvement following combined vigabatrin and high-dose prednisolone treatment. However, multiple courses of relapse occurred after weaning off the antiseizure medication.

Conclusions

We propose that epileptic spasms related to de novo NEUROD2 pathogenic variant respond well to combined vigabatrin and high-dose prednisolone therapy. These findings may imply the benefit of using combination therapy to treat epileptic spasms in NEUROD2-related NDD syndrome.
Identification of CEACAM5 as a stemness-related inhibitory immune checkpoint in pancreatic cancer
Authors: Shi Haojun , Tsang Yiusing , Yang Yisi
Published: December 2022

Background

Immunotherapy has emerged as a new cancer treatment modality. However, tumour heterogeneity can diminish checkpoint blockade response and shorten patient survival. As a source of tumour heterogeneity, cancer stem cells act as an indispensable reservoir for local recurrence and distant metastasis. Thus, precision immunotherapy targeting tumour heterogeneity requires a comprehensive understanding of cancer stem cell immunology. Our study aimed to identify stemness-related inhibitory immune checkpoints and relevant regulatory pathways in pancreatic cancer.

Methods

Pancreatic cancer-specific datasets in The Cancer Genome Atlas and the Cancer Therapeutics Response Portal were collected for in-depth bioinformatic analysis. Differentially expressed genes between pancreatic cancers with high and low stemness index (mRNAsi) scores were compared to screen out inhibitory immune checkpoints. Survival analysis was used to predict the prognostic value of immune checkpoint plus immune infiltrate in patients with pancreatic cancer. The expression of stemness-related immune checkpoint across immune subtypes of pancreatic cancer was detected and gene set enrichment analysis was performed to figure out the relevant regulatory signallings.

Results

The abundance of cancer stemness predicted a low immunotherapy response to pancreatic cancer. The inhibitory immune checkpoint CEACAM5 that was enriched in pancreatic cancers with high mRNAsi scores also exhibited a strong correlation with invasive cell-enriched signature and Msi+ tumour-initiating cell-enriched signature. Levels of CEACAM5 expression were higher in the interferon-γ dominant immune subtype of pancreatic cancers that are characterized by high M1 macrophage infiltration. The patient group with high levels of CEACAM5 expression had a high risk of poor overall survival, even if accompanied by high infiltration of M1 macrophages. Furthermore, prostanoid and long-chain unsaturated fatty acid metabolic processes showed a significant association with cancer stemness and CEACAM5 expression.

Conclusions

Our findings suggest that CEACAM5 is a candidate stemness-related innate immune checkpoint in pancreatic cancer, and is potentially regulated by prostanoid and long-chain unsaturated fatty acid metabolic processes. Immune checkpoint blockade of CEACAM5, which synergizes with inhibition of those regulatory pathways, may improve the efficacy of precision immunotherapy targeting tumour heterogeneity caused by cancer stem cells.
Superficial capillary plexus vessel density/deep capillary plexus vessel density ratio in healthy eyes
Authors: Nam Ki-Yup , Lee Min-Woo , Lee Kook-Hyung , Kim Jung-Yeul
Published: December 2022

Background

To identify factors differently affecting the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in healthy eyes using their vessel density (VD) ratio.

Methods

Healthy eyes were enrolled. The ratio between the VD of SCP and DCP (SVD/DVD ratio) was calculated. Pearson correlation analyses were performed to identify the relationships between this ratio and other factors.

Results

The mean SVD and DVD were 36.2 ± 5.7 and 37.7 ± 4.9%, respectively, and the mean SVD/DVD ratio was 0.96 ± 0.15. The SVD was significantly correlated with the best-corrected visual acuity (BCVA) (r = − 0.368, P <  0.001), age (r = − 0.408, P <  0.001), and OCTA quality (r = 0.520, P <  0.001). The DVD was significantly correlated with the BCVA (r = − 0.150, P = 0.008), age (r = − 0.229, P <  0.001), and OCTA quality (r = 0.555, P <  0.001). Among various factors, age (r = − 0.296, P <  0.001), the BCVA (r = − 0.237, P <  0.001), axial length (r = 0.234, P <  0.001), and OCTA quality (r = 0.270, P < 0.001) were significantly correlated with the SVD/DVD ratio.

Conclusions

Age, BCVA, axial length, and OCTA image quality were significantly correlated with the SVD/DVD ratio. Age, the BCVA, and OCTA quality were more strongly correlated with the SCP, and the axial length was more strongly correlated with the DCP.
The impact of the COVID-19 pandemic on suicide rates in Hungary: an interrupted time-series analysis
Authors: Lantos Tamás , Nyári Tibor András
Published: December 2022

Background

From 2010 to 2019, suicide mortality fell steadily and substantially in Hungary: the declining trend remained stable, and the suicide rate decreased by more than one-third which was remarkable even from an international perspective. However, despite the declining trend, regional inequalities have always characterised the distribution of suicide mortality in Hungary. Following these favourable trends, COVID-19 appeared in Hungary on the 4th of March 2020 which might lead to an increase in suicides. We aimed to investigate this hypothesis in Hungary by gender, age, educational attainment, and region, as well.

Methods

To test whether the pandemic changed the declining trend of Hungarian suicide rates, the observed number of suicides during March–December 2020 (pre-vaccination period) was compared with the expected numbers (without the appearance of COVID-19). An interrupted time-series analysis was conducted by negative binomial regression using monthly data from January 2010 to February 2020 (pre-pandemic period).

Results

Suicide mortality increased significantly compared to the trend during the pre-pandemic period: overall (by 16.7%), among males (18.5%), in the age group 35–49 years (32.8%), and among vocational school graduates (26.1%). Additionally, significant growths in suicide rates were detected in the two regions (Central Hungary and Central Transdanubia) with the lowest COVID mortality rates (by 27.3% and 22.2%, respectively).

Conclusions

Our study revealed reversed trend in suicide mortality during the pre-vaccination period compared to the pre-pandemic period in Hungary. There were significant differences in the pattern of suicide rates by gender, age group, educational attainment, and region during the pre-vaccination period in Hungary, which might be attributed to the socio-economic effects of the COVID-19 pandemic. These findings could prove useful in preventive strategies as the identification of groups at higher risk may be important for suicide prevention; however, further investigations are needed to explore the reasons.
A case report involving the experience of pervasive pregnancy denial: detailed observation of the first 12 postpartum weeks
Authors: Chechko Natalia , Losse Elena , Stickel Susanne
Published: December 2022

Background

Pervasive pregnancy denial is a rare condition associated with distress and unassisted delivery.

Case presentation

The case involves a 38-year-old woman (NN), with two older children (ages 8 and 11), who was unaware, until delivery, that she had been pregnant. The case is discussed in the context of a 12-week observation of postpartum mood, stress, and mother-child attachment. NN and other 558 non-depressed women (mean age 32.41 years) were selected from the pool of participants in the RIPOD (risk of postpartum depression) study. All participants were recruited within 1–6 days of delivery. In addition to surveying depressed mood at childbirth, remote assessments of mood, mother-child attachment, and perceived stress were conducted at 3, 6, 9, and 12 weeks postpartum. Every other day, the participants also reported their current perceived stress levels based on a scale from 1 (low) to 10 (high). During the entire period of postpartum observation, NN reported no symptoms on the Edinburgh Postpartum Depression Scale, similar to only 1.6% of the sample, no stress as 0.7% of the sample, and above-average mother-infant bonding akin to only 4.6% of the sample. Her daily stress levels showed no disturbance, which was the case for only 3.32% of the total sample. On the day of delivery, NN reported a stress level of 1 (the minimum possible level), which was reported by only 4.2% of the total sample. However, NN reported the experience of delivery to be traumatic given that the child had fallen to the floor.

Conclusion

The experience of a denied pregnancy did not appear to disturb NN at any time point, not even on the day of delivery. Compared to NN, the other non-depressed participants reported wide fluctuations in stress levels during the observation period. NN did not report any risk factors for denied pregnancy. Thus, she belonged neither to any group of typical pregnancy deniers, as reported in the literature, nor to a typical postpartum group. We postulate, therefore, that the extent to which pregnancy denial can be deemed a normal variation, unrelated to a psychological or physiological condition, depends largely on personal traits.
Indoor bacterial and fungal aerosols as predictors of lower respiratory tract infections among under-five children in Ibadan, Nigeria
Authors: Fakunle Adekunle Gregory , Jafta Nkosana , Smit Lidwien A. M. , Naidoo Rajen N.
Published: December 2022

Background

This study aimed to investigate the association between exposure to diverse indoor microbial aerosols and lower respiratory tract infections (LRTI) among children aged 1 to 59 months in Ibadan, Nigeria.

Methods

One hundred and seventy-eight (178) hospital-based LRTI cases among under-five children were matched for age (± 3 months), sex and geographical location with 180 community-based controls (under-five children without LRTI). Following consent from caregivers of eligible participants, a child’s health questionnaire, clinical proforma and standardized home-walkthrough checklist were used to collect data. Participant homes were visited and sampled for indoor microbial exposures using active sampling approach by Anderson sampler. Indoor microbial count (IMC), total bacterial count (TBC), and total fungal count (TFC) were estimated and dichotomized into high (> median) and low (≤ median) exposures. Alpha diversity measures including richness (R), Shannon (H) and Simpson (D) indices were also estimated. Conditional logistic regression models were used to test association between exposure to indoor microbial aerosols and LRTI risk among under-five children.

Results

Significantly higher bacterial and fungal diversities were found in homes of cases (R = 3.00; H = 1.04; D = 2.67 and R = 2.56; H = 0.82; D = 2.33) than homes of controls (R = 2.00; H = 0.64; D = 1.80 and R = 1.89; H = 0.55; D = 1.88) p < 0.001, respectively. In the multivariate models, higher categories of exposure to IMC (aOR = 2.67, 95% CI 1.44–4.97), TBC (aOR = 2.51, 95% CI 1.36–4.65), TFC (aOR = 2.75, 95% CI 1.54–4.89), bacterial diversity (aOR = 1.87, 95% CI 1.08–3.24) and fungal diversity (aOR = 3.00, 95% CI 1.55–5.79) were independently associated with LRTI risk among under-five children.

Conclusions

This study suggests an increased risk of LRTI when children under the age of five years are exposed to high levels of indoor microbial aerosols.
The effects of different root canal irrigation protocols and artificial aging procedures on the bond strength between dentin and hybrid ceramic posts
Authors: Topbaş Celalettin , Çınar Şevki , Altan Bike , Şirin Dursun Ali , Fildişi Mehmet Ali
Published: December 2022

The purpose of this study is to investigate the effects of different root canal irrigation protocols applied to the dentin and artificial aging procedures on the micro pushout bond strength (mPBS) between dentin and hybrid ceramic posts. Seventy-five single-rooted mandibular premolar teeth were divided into 5 groups (Gr1-5). 50 of the teeth were used for the mPBS tests (n = 10), whereas 25 were used for the smear layer examinations (n = 5). Post space were prepared and irrigated with different irrigation-protocols in each group. (Gr1:[SS], Gr2:[NaOCl] + SS, Gr3:[EDTA] + NaOCl + SS, Gr4:[MA] + NaOCl + SS, Gr5:[Ch] + NaOCl + SS). Post and core pattern were fabricated with pattern resin and a fiber post, after scanning, the posts were milled with Vita Enamic resin ceramic block, and cemented. After 7 days the roots were sliced at thicknesses of 1 mm; half of them were subjected to mPBS test, while the other half were tested after undergoing mechanical cycling for artificial aging. For data analysis, the Shapiro-Wilk test was utilized to test normal distributions, 3-way analysis of variance was used to compare mPBS, and Tukey’s HSD test was conducted for multiple comparisons. SEM analysis was performed for examination of failure modes and smear layer removal. Different root canal irrigation protocols affected mPBS significantly. While Gr4 had the highest mPBS, Gr1 had the lowest. Regarding to different zones, the highest mPBS was in coronal zone, and the lowest one was in the apical zone. The aging procedure also led to a statistically-significant decrease in mPBS. Most frequent failure modes were cohesive failure in dentin and mixed failure. Irrigation with 7%MA (Gr4) showed better performance than 17% EDTA (Gr3) in smear layer removal, especially at the apical zone of the tooth. This is critical for the success of root canal treatment and increased the mPBS to a higher extent in all zones of the tooth.
Study protocol: understanding pain after dental procedures, an observational study within the National Dental PBRN
Authors: Kalenderian Elisabeth , White Joel , Yansane Alfa-Ibrahim , Urata Janelle , Holmes David , Funkhouser Kimberly , Mungia Rahma , Xiao Jin , Rauschenberger Cindy , Ibarra-Noriega Ana , Tran Duong , Rindal D. Brad , Spallek Heiko , Walji Muhammad
Published: December 2022

Background

Patient-reported outcome measures provide an essential perspective on the quality of health care provided. However, how data are collected, how providers value and make sense of the data, and, ultimately, use the data to create meaningful impact all influence the success of using patient-reported outcomes.

Objectives

The primary objective is to assess post-operative pain experiences by dental procedure type through 21 days post-procedure as reported by patients following dental procedures and assess patients’ satisfaction with pain management following dental surgical procedures. Secondary objectives are to: 1) assess post-operative pain management strategies 1 week following dental surgical procedures, as recommended by practitioners and reported by patients, and 2) evaluate practitioner and patient acceptance of the FollowApp.Care post visit patient monitoring technology (FollowApp.Care). We will evaluate FollowApp.Care usage, perceived usefulness, ease of use, and impact on clinical workload.

Design and methods

We describe the protocol for an observational study involving the use of the FollowApp.Care platform, an innovative mobile application that collects dental patients’ assessments of their post-operative symptoms (e.g., pain). The study will be conducted in collaboration with the National Dental Practice-based Research Network, a collective Network of dental practices that include private and group practices, public health clinics, community health centers and Federal Qualified Health Centers, academic institutional settings, and special patient populations. We will recruit a minimum of 150 and up to 215 dental providers and up to 3147 patients who will receive push notifications through text messages FollowApp.Care on their mobile phones at designated time intervals following dental procedures. This innovative approach of implementing an existing and tested mobile health system technology into the real-world dental office setting will actively track pain and other complications following dental procedures. Through patients’ use of their mobile phones, we expect to promptly and precisely identify specific pain levels and other issues after surgical dental procedures.

The study’s primary outcome will be the patients’ reported pain experiences. Secondary outcomes include pain management strategies and medications implemented by the patient and provider and perceptions of usefulness and ease of use by patients and providers.
Application of two level count regression modeling on the determinants of fertility among married women in Ethiopia
Authors: Hussen Nuru Mohammed
Published: December 2022

Background

Fertility is the element of population dynamics that has a vital contribution toward changing population size and structure over time. The global population showed a major increment from time to time due to fertility. This increment was higher in south Asia and sub-Saharan Africa including Ethiopia. So this study targeted the factors affecting fertility among married women in Ethiopia through the framework of multilevel count regression analysis using the 2016 Ethiopian Demographic and Health Survey data.

Methods

Secondary data set on the birth records were obtained from the 2016 Ethiopia Demographic and Health Survey. The survey was a population-based cross-sectional study with a two-stage stratified cluster sampling design, where stratification was achieved by separating every region into urban and rural areas except the Addis Ababa region because it is entirely urban. A two-level negative binomial regression model was fitted to spot out the determinants of fertility among married women in Ethiopia.

Results

Among the random sample of 6141 women in the country, 27,150 births were recorded based on the 2016 Ethiopian Demographic and Health Survey report. The histograms showed that the data has a positively skewed distribution not extremely picked at the beginning. Findings from the study revealed that the contraception method used, residence, educational level of women, women’s age at first birth, and proceeding birth interval were the major predictors of fertility among married women in Ethiopia. Moreover, the estimates from the random effect result revealed that there is more fertility variation between the enumeration areas than within the enumeration areas.

Conclusion

Unobserved enumeration area fertility differences that cannot be addressed by a single-level approach were determined using a two-level negative binomial regression modeling approach. So, the application of standard models by ignoring this variation ought to embrace spurious results, then for such hierarchical data, multilevel modeling is recommended.
Cancer prevention in females with and without obesity: Does perceived and internalised weight bias determine cancer prevention behaviour?
Authors: Bernard Marie , Löbner Magrit , Lordick Florian , Mehnert-Theuerkauf Anja , Riedel-Heller Steffi G. , Luck-Sikorski Claudia
Published: December 2022

Background

Women with obesity are not only at higher risk of developing cancer such as gynaecological malignancies but are also less likely to attend cancer prevention screenings (CPS). In this study, we aimed to obtain a better database for Germany and to investigate whether women with obesity are less likely to undergo CPS compared to women without obesity. Moreover, we aimed to identify factors that determine CPS behaviour.

Methods

A quantitative cross-sectional telephone survey was conducted that assessed data of 1003 females in the general public with obesity (BMI ≥ 30 kg/m2; n = 500) and without obesity (BMI < 30 kg/m2; n = 503). We assessed participants’ utilisation of cervical, breast, and colorectal CPS. Group differences were investigated by using Chi-Square tests, whereas influencing factors that might determine CPS behaviour were examined by multivariate logistic regression analyses. Therefore, logistic regression models for (a) the full sample and (b) the obese sample were conducted. Explanatory factors (i.e., cancer awareness, the internalisation of weight bias (WBIS) and perceived weight-based discrimination) were included. Confounding factors such as sociodemographic variables were included in the multivariate analysis.

Results

Women with obesity were less likely to undergo Pap smear (χ2(1) = 13.90, p < 0.001) and clinical breast examination (χ2(4) = 14.41, p < 0.01) compared to women without obesity. In contrast, the utilisation of all other CPS methods did not differ between women with and without obesity. Logistic regression analyses revealed neither an association between CPS behaviour and WBI nor perceived weight bias. Instead, previous cancer diagnoses and knowledge about CPS forms were found to reinforce CPS behaviour.

Conclusion

Although data did not suggest that internalised or perceived weight bias deter women with obesity from undergoing CPS, the role of weight bias has not yet been conclusively clarified. Future studies should address potential methodological limitations and evaluate the effectiveness of most recently established cancer prevention programs and in particular how they affect CPS behaviour in women with obesity.
Project DECIDE, part 1: increasing the amount of valid advance directives in people with Alzheimer’s disease by offering advance care planning—a prospective double-arm intervention study
Authors: Baisch Stefanie , Abele Christina , Theile-Schürholz Anna , Schmidtmann Irene , Oswald Frank , Karakaya Tarik , Müller Tanja , Florack Janina , Garmann Daniel , Karneboge Jonas , Lindl Gregor , Pfeiffer Nathalie , Poth Aoife , Caba Bogdan Alin , Grond Martin , Hornke Ingmar , Prvulovic David , Reif Andreas , Ullrich Heiko , Haberstroh Julia
Published: December 2022

Background

Everybody has the right to decide whether to receive specific medical treatment or not and to provide their free, prior and informed consent to do so. As dementia progresses, people with Alzheimer’s dementia (PwAD) can lose their capacity to provide informed consent to complex medical treatment. When the capacity to consent is lost, the autonomy of the affected person can only be guaranteed when an interpretable and valid advance directive exists. Advance directives are not yet common in Germany, and their validity is often questionable. Once the dementia diagnosis has been made, it is assumed to be too late to write an advance directive. One approach used to support the completion of advance directives is ‘Respecting Choices’®—an internationally recognised, evidence-based model of Advance Care Planning (ACP), which, until now, has not been evaluated for the target group of PwAD. This study’s aims include (a) to investigate the proportion of valid advance directives in a memory clinic population of persons with suspected AD, (b) to determine the predictors of valid advance directives, and (c) to examine whether the offer of ACP can increase the proportion of valid advance directives in PwAD.

Method

We intend to recruit at leastN = 250 participants from two memory clinics in 50 consecutive weeks. Of these, the first 25 weeks constitute the baseline phase (no offer of ACP), the following 25 weeks constitute the intervention phase (offer of ACP). The existence and validity of an advance directive will be assessed twice (before and after the memory clinic appointment). Moreover, potential predictors of valid advance directives are assessed.

Discussion

The results of this study will enhance the development of consent procedures for advance directives of PwAD based on the ACP/Respecting Choices (R) approach. Therefore, this project contributes towards increasing the autonomy and inclusion of PwAD and the widespread acceptance of valid advance directives in PwAD.

Trial RegistrationDRKS, DRKS00026691, registered 15th of October 2021,https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00026691
Study protocol for the implementation and evaluation of a digital-robotic-based intervention for nurses and patients in a hospital: a quantitative and qualitative triangulation based on the Medical Research Council (MRC) framework for developing and evaluating complex interventions
Authors: Ohneberg Christoph , Warmbein Angelika , Stöbich Nicole , Rathgeber Ivanka , Kruppa Astrid , Nast-Kolb Julian , Träger Mattias Felix , Bahou Aissam , Stahl Oliver , Eberl Inge , Fischer Uli
Published: December 2022

Background

Nurses spend part of their working time on non-nursing tasks. Unnecessary walking distances and the assumption of service activities and other non-care-related tasks take up a lot of space, which reduces the time for direct patient care and demonstrably increases the dissatisfaction of the persons involved. The REsPonSe project aims to relieve nursing staff by using a smartphone app for communication in combination with an autonomous service robot to reduce walking distances and service activities. The technical systems are tested on a nuclear medicine ward and are intended to reduce the radiation exposure of the staff. The aim of this study is to test and evaluate the use and intervention of the technical systems, the acceptance of the users and the change in the utilisation of the nursing service. In addition to findings on usability and manageability, effects on nursing practice, as well as facilitating and inhibiting contextual factors for implementation, will be identified.

Methods

The Medical Research Council (MRC) Framework for Developing and Evaluating for Complex Interventions was chosen as the theoretical basis. The data collection in the Feasibility and Evaluation phase is a triangulation of quantitative and qualitative methods. Standardised observations are planned to collect data on non-care activities and walking distances, and a survey of utilisation by use of a questionnaire based on the NASA TLX. Qualitative individual interviews with patients and group discussions with nursing staff will be conducted. Statements on the subjective experiences, as well as the evaluation of the use of the digital-robotic system in the clinical setting, will be collected. The descriptive evaluation of the usage and retrieval data will provide information on duration, time, requests, and reduced contact times, as well as error and fault messages.

Discussion

The evaluation study will make it possible to represent a variety of perspectives from different interest groups. The results should contribute to the definition of implementation and evaluation criteria and facilitate the integration of digital-robotic assistance systems in nursing acute inpatient settings.

Trial registration

The trial was registered with the German Clinical Trials Register (DRKS) on 16.02.2022: DRKS00028127.
Registered nurses’ views on consideration of patient perspectives during multidisciplinary team meetings in cancer care
Authors: Rosell Linn , Melander Wenche , Lindahl Berit , Nilbert Mef , Malmström Marlene
Published: December 2022

Background

Multidisciplinary team meetings (MDTMs) represent an integral component of modern cancer care and have increasingly been implemented to ensure accurate and evidence-based treatment recommendations. During MDTMs, multiple and complex medical and patient-related information should be considered by a multi-professional team whose members contribute various perspectives. Registered nurses (RNs) are expected to share information on the patient perspective at MDTMs. However, research suggests that RNs’ contributions to case discussions are limited and that patient perspective is generally underrepresented. Our aim was to explore RNs’ views of the prerequisites for and barriers to the inclusion of the patient perspective in MDTMs in Swedish cancer care.

Methods

Data were collected from four focus group interviews with 22 RNs who worked as contact nurses in Swedish cancer care. Interviews were transcribed and analysed using inductive content analysis.

Results

The analysis identified two categories and five subcategories. The participants presented different views and expressed ambivalence about the patient perspective in MDTMs. Subcategories were related to medical versus holistic perspectives, the added value of patient perspective, and possibilities for patient contributions. The participants also discussed prerequisites for the patient perspective to be considered in MDTM decision-making process, with subcategories related to structures promoting attention to the patient perspective and determinants of RNs’ contributions to case discussions in MDTMs.

Conclusions

This study demonstrates various views related to the patient perspective in MDTMs and identifies a great need to clarify the RN’s role. Our results indicate that if enhanced presentation of the patient perspective in MDTMs is desired, key information points and structures must be established to collect and present relevant patient-related information.
Effect of different injection rates and doses of contrast medium on the image quality of computed tomographic angiography in African grey parrots (Psittacus erithacus)
Authors: Wang Wen-Lin , Chang Fang-Lun , Yu Pin-Huan
Published: December 2022

Background

Atherosclerosis is a common cardiovascular disease in parrots but theantemortemdiagnosis is challenging. In human medicine, computed tomography angiography (CTA) has been used widely for the diagnosis of atherosclerosis. By adjusting the injection rate and total dose of contrast medium, the image quality can be improved. To test the effects of different injection conditions on the image quality of major arteries, 10 African grey parrots (Psittacus erithacus) were used. Three injection rates (0.3, 0.4, 0.5 mL/s) and three doses (740, 370, 222 mg of iodine/bird) were tested while the other variables of the studies were fixed.

Result

A higher injection dose led to a significantly higher attenuation, image noise and diameter, with a lower signal-to-noise ratio and contrast-to-noise ratio of the six major arteries. The 370 mg of iodine/bird group showed significantly better subjective image quality. Furthermore, with increasing injection rates, the prevalence of heterogeneity decreased. However, we found an increased risk of injection failure for the 0.5 mL/s groups.

Conclusion

We recommend a combination of 370 mg of iodine/bird with 0.4 mL/s for clinical use to achieve better image quality for CTA.
Altered DNA methylation of CYP2E1 gene in schizophrenia patients with tardive dyskinesia
Authors: Zhang Ping , Li Yanli , Wang Kesheng , Huang Junchao , Su Brenda Bin , Xu Chun , Wang Zhiren , Tan Shuping , Yang Fude , Tan Yunlong
Published: December 2022

Background

About 20–30% of patients with schizophrenia develop tardive dyskinesia (TD). Oxidative stress is one potential causes of TD. CYP2E1 is considered as an oxidative stress-related gene, however, no study has been reported on the DNA methylation levels of the CYP2E1 in schizophrenia or TD.

Methods

A total of 35 schizophrenia patients with TD, 35 schizophrenia patients without TD (NTD), and 35 health controls (HCs) were collected in Beijing, China. DNA was extracted from peripheral blood samples. The promoter methylation levels of CYP2E1 were detected using pyrosequencing. The generalized linear model (GLM) was used to examine the methylation levels of three CpG sites among three diagnostic groups (TD vs. NTD vs. HC).

Results

The average methylation levels were 8.8 ± 10.0, 14.5 ± 11.9 and 15.1 ± 11.3 in TD, NTD and HC groups, respectively. The F-test in GLM revealed overall differences in the average of methylation levels of three CpG sites among three diagnostic groups (p = 0.0227) and in the third CpG site (p = 0.0026). Furthermore, the TD group had lower average methylation levels than HC and NTD groups (p = 0.0115 and 0.0268, respectively). Specifically, TD group showed lower methylation levels in the third CpG site than HC and NTD groups (p = 0.0012 and 0.0072, respectively). Additionally, associations of the methylation levels with clinical features in the TD group were observed using Spearman correlation analysis.

Conclusion

This study provides the first evidence of DNA methylation levels in the promoter of CYP2E1 gene associated with schizophrenia and TD. The abnormal DNA methylation might serve as a potential mechanism for TD.
Screening eaves of houses reduces indoor mosquito density in rural, western Kenya
Authors: Abong’o Bernard , Gimnig John E. , Omoke Diana , Ochomo Eric , Walker Edward D.
Published: December 2022

Background

Despite the scale-up of insecticide-treated nets and indoor residual spraying, the bulk of malaria transmission in western Kenya still occurs indoors, late at night. House improvement is a potential long-term solution to further reduce malaria transmission in the region.

Methods

The impact of eave screening on mosquito densities was evaluated in two rural villages in western Kenya. One-hundred-and-twenty pairs of structurally similar, neighbouring houses were used in the study. In each pair, one house was randomly selected to receive eave screening at the beginning of the study while the other remained unscreened until the end of the sampling period. Mosquito sampling was performed monthly by motorized aspiration method for 4 months. The collected mosquitoes were analysed for species identification.

Results

Compared to unscreened houses, significantly fewer femaleAnopheles funestus(RR = 0.40, 95% CI 0.29–0.55),Anopheles gambiaeComplex (RR = 0.46, 95% CI 0.34–0.62) andCulexspecies (RR = 0.53, 95% CI 0.45–0.61) were collected in screened houses. No significant differences in the densities of the mosquitoes were detected in outdoor collections. Significantly fewerAnopheles funestuswere collected indoors from houses with painted walls (RR = 0.05, 95% CI 0.01–0.38) while cooking in the house was associated with significantly lower numbers ofAnopheles gambiaeComplex indoors (RR = 0.60, 95% CI 0.45–0.79). Nearly all house owners (99.6%) wanted their houses permanently screened, including 97.7% that indicated a willingness to use their own resources. However, 99.2% required training on house screening. The cost of screening a single house was estimated at KES6,162.38 (US$61.62).

Conclusion

Simple house modification by eave screening has the potential to reduce the indoor occurrence of bothAnophelesandCulexmosquito species. Community acceptance was very high although education and mobilization may be needed for community uptake of house modification for vector control. Intersectoral collaboration and favourable government policies on housing are important links towards the adoption of house improvements for malaria control.
Single-cell profiles reveal tumor cell heterogeneity and immunosuppressive microenvironment in Waldenström macroglobulinemia
Authors: Sun Hao , Fang Teng , Wang Tingyu , Yu Zhen , Gong Lixin , Wei Xiaojing , Wang Huijun , He Yi , Liu Lanting , Yan Yuting , Sui Weiwei , Xu Yan , Yi Shuhua , Qiu Lugui , Hao Mu
Published: December 2022

Background

Waldenström macroglobulinemia (WM) is a rare and incurable indolent B-cell malignancy. The molecular pathogenesis and the role of immunosuppressive microenvironment in WM development are still incompletely understood.

Methods

The multicellular ecosystem in bone marrow (BM) of WM were delineated by single-cell RNA-sequencing (scRNA-seq) and investigated the underlying molecular characteristics.

Results

Our data uncovered the heterogeneity of malignant cells in WM, and investigated the kinetic co-evolution of WM and immune cells, which played pivotal roles in disease development and progression. Two novel subpopulations of malignant cells, CD19+CD3+ and CD138+CD3+, co-expressing T-cell marker genes were identified at single-cell resolution. Pseudotime-ordered analysis elucidated that CD19+CD3+ malignant cells presented at an early stage of WM-B cell differentiation. Colony formation assay further identified that CD19+CD3+ malignant cells acted as potential WM precursors. Based on the findings of T cell marker aberrant expressed on WM tumor cells, we speculate the long-time activation of tumor antigen-induced immunosuppressive microenvironment that is involved in the pathogenesis of WM. Therefore, our study further investigated the possible molecular mechanism of immune cell dysfunction. A precursor exhausted CD8-T cells and functional deletion of NK cells were identified in WM, and CD47 would be a potential therapeutic target to reverse the dysfunction of immune cells.

Conclusions

Our study facilitates further understanding of the biological heterogeneity of tumor cells and immunosuppressive microenvironment in WM. These data may have implications for the development of novel immunotherapies, such as targeting pre-exhausted CD8-T cells in WM.
Parabiosis reveals the correlation between the recruitment of circulating antigen presenting cells to the retina and the induction of spontaneous autoimmune uveoretinitis
Authors: McPherson Scott W. , Heuss Neal D. , Abedin Md. , Roehrich Heidi , Pierson Mark J. , Gregerson Dale S.
Published: December 2022

Background

Characterizing immune cells and conditions that govern their recruitment and function in autoimmune diseases of the nervous system or in neurodegenerative processes is an area of active investigation. We sought to analyze the origin of antigen presenting cells associated with the induction of retinal autoimmunity using a system that relies on spontaneous autoimmunity, thus avoiding uncertainties associated with immunization with adjuvants at remotes sites or adoptive transfer of in vitro activated T cells.

Methods

R161H mice (B10.RIII background), which spontaneously and rapidly develop severe spontaneous autoimmune uveoretinitis (SAU), were crossed to CD11cDTR/GFPmice (B6/J) allowing us to track the recruitment to and/or expansion within the retina of activated, antigen presenting cells (GFPhicells) in R161H+/− × CD11cDTR/GFPF1mice relative to the course of SAU. Parabiosis between R161H+/− × CD11cDTR/GFPF1mice and B10.RIII × B6/J F1(wild-type recipient) mice was done to explore the origin and phenotype of antigen presenting cells crucial for the induction of autoimmunity. Analysis was done by retinal imaging, flow cytometry, and histology.

Results

Onset of SAU in R161H+/− × CD11cDTR/GFPF1mice was delayed relative to B10.RIII-R161H+/−mice revealing a disease prophase prior to frank autoimmunity that was characterized by expansion of GFPhicells within the retina prior to any clinical or histological evidence of autoimmunity. Parabiosis between mice carrying the R161H and CD11cDTR/GFPtransgenes and transgene negative recipients showed that recruitment of circulating GFPhicells into retinas was highly correlative with the occurrence of SAU.

Conclusions

Our results here contrast with our previous findings showing that retinal antigen presenting cells expanding in response to either sterile mechanical injury or neurodegeneration were derived from myeloid cells within the retina or optic nerve, thus highlighting a unique facet of retinal autoimmunity.
Technology-assisted assessment of spasticity: a systematic review
Authors: Guo Xinliang , Wallace Rebecca , Tan Ying , Oetomo Denny , Klaic Marlena , Crocher Vincent
Published: December 2022

Background

Spasticity is defined as “a motor disorder characterised by a velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks”. It is a highly prevalent condition following stroke and other neurological conditions. Clinical assessment of spasticity relies predominantly on manual, non-instrumented, clinical scales. Technology based solutions have been developed in the last decades to offer more specific, sensitive and accurate alternatives but no consensus exists on these different approaches.

Method

A systematic review of literature of technology-based methods aiming at the assessment of spasticity was performed. The approaches taken in the studies were classified based on the method used as well as their outcome measures. The psychometric properties and usability of the methods and outcome measures reported were evaluated.

Results

124 studies were included in the analysis. 78 different outcome measures were identified, among which seven were used in more than 10 different studies each. The different methods rely on a wide range of different equipment (from robotic systems to simple goniometers) affecting their cost and usability. Studies equivalently applied to the lower and upper limbs (48% and 52%, respectively). A majority of studies applied to a stroke population (N = 79). More than half the papers did not report thoroughly the psychometric properties of the measures. Analysis identified that only 54 studies used measures specific to spasticity. Repeatability and discriminant validity were found to be of good quality in respectively 25 and 42 studies but were most often not evaluated (N = 95 and N = 78). Clinical validity was commonly assessed only against clinical scales (N = 33). Sensitivity of the measure was assessed in only three studies.

Conclusion

The development of a large diversity of assessment approaches appears to be done at the expense of their careful evaluation. Still, among the well validated approaches, the ones based on manual stretching and measuring a muscle activity reaction and the ones leveraging controlled stretches while isolating the stretch-reflex torque component appear as the two promising practical alternatives to clinical scales. These methods should be further evaluated, including on their sensitivity, to fully inform on their potential.
Single-dose rAAV5-based vaccine provides long-term protective immunity against SARS-CoV-2 and its variants
Authors: Liao Guochao , Lau Hungyan , Liu Zhongqiu , Li Chinyu , Xu Zeping , Qi Xiaoxiao , Zhang Yu , Feng Qian , Li Runze , Deng Xinyu , Li Yebo , Zhu Qing , Zhu Sisi , Zhou Hua , Pan Hudan , Fan Xingxing , Li Yongchao , Li Dan , Chen Liqing , Ke Bixia , Cong Zhe , Lv Qi , Liu Jiangning , Liang Dan , Li An’an , Hong Wenshan , Bao Linlin , Zhou Feng , Gao Hongbin , Liang Shi , Huang Bihong , Wu Miaoli , Qin Chuan , Ke Changwen , Liu Liang
Published: December 2022

Abstracts

The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.