bluuebunny/crossref_metadata_2025 huggingface dataset:
EQ-5D-Y-3L and EQ-5D-Y-5L proxy report: psychometric performance and agreement with self-report
Authors: Fitriana Titi Sahidah , Purba Fredrick Dermawan , Stolk Elly , Busschbach Jan J. V.
Published: June 2022

Background

Self-report is the standard for measuring people’s health-related quality of life (HRQoL), including children. However, in certain circumstances children cannot report their own health. For this reason, children’s HRQoL measures often provide both a self-report and a proxy-report form. It is not clear whether the measurement properties will be the same for these two forms. We investigated whether it would be beneficial to extend the classification system of the EQ-5D-Y proxy questionnaire from 3 to 5 response levels. The agreement between self-report and proxy-report was assessed for both EQ-5D-Y measures.

Methods

The study included 286 pediatric patients and their caregivers as proxies. At three consecutive measurements—baseline, test–retest and follow-up—the proxies assessed the child’s HRQoL using the EQ-5D-Y-3L, EQ-5D-Y-5L, the PedsQL Generic, and matched disease-specific instruments. The proxy versions of EQ-5D-Y-3L and EQ-5D-Y-5L were compared in terms of feasibility, distribution properties, convergent validity, test–retest and responsiveness. Agreement between both EQ-5D-Y proxy versions to their respective self-report versions was assessed at baseline and follow-up.

Results

The proportion of missing responses was 1% for the EQ-5D-Y-3L and 1.4% for the EQ-5D-Y-5L. The frequency of health state with no problems in all dimensions (11111) was slightly lower for the EQ-5D-Y-5L (21.3% vs 16.7%). Regarding the convergent validity with the PedsQL and disease-specific measures, the proxy versions of EQ-5D-Y-3L and EQ-5D-Y-5L had similar magnitudes of associations between similar dimensions. The means of test–retest coefficients between the two versions of the EQ-5D-Y proxy were comparable (0.83 vs. 0.84). Regarding reported improved conditions, responsiveness of the EQ-5D-Y-5L proxy (26.6–54.1%) was higher than that of the EQ-5D-Y-3L proxy (20.7–46.4%). Except for acutely ill patients, agreement between the EQ-5D-Y-5L proxy and self-reports was at least moderate.

Conclusions

Extending the number of levels of the proxy version of EQ-5D-Y can improve the classification accuracy and the ability to detect health changes over time. The level structure of EQ-5D-Y-5L was associated with a closer agreement between proxy and self-report. The study findings support extending the EQ-5D-Y descriptive system from 3 to 5 levels when administered by a proxy, which is often the case in the pediatric population.
A pyroptosis-related gene signature predicts prognosis and immune microenvironment in hepatocellular carcinoma
Authors: Jin Yifeng , Pu Xiaofan , Ping Dongnan , Huang Chaojie , Ding Guoping , Cao Liping
Published: June 2022

Background

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a very poor prognosis. Pyroptosis is an inflammatory form of cell death and plays an important role in cancer development. The prognostic value of pyroptosis-related genes (PRGs) in HCC has not been studied extensively.

Methods

Unsupervised consensus clustering analysis was performed to identify two subtypes based on the expression profiles of prognostic PRGs in the The Cancer Genome Atlas (TCGA) database, and the differences between the two subtypes were compared. A prognostic model based on four PRGs was established by further least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox regression analysis.

Results

Two subtypes (clusters 1 and 2) were identified by consensus clustering based on prognostic PRGs in HCC. Survival outcomes, biological function, genomic alterations, immune cell infiltration, and immune checkpoint genes were compared between the subtypes. Cluster 2 had a worse survival outcome than cluster 1. Cluster 2 was enriched for hallmarks of cancer progression, TP53 mutation, tumor-promoting immune cells, and immune checkpoint genes, which may contribute to the poor prognosis. A prognostic risk signature that predicted the overall survival (OS) of patients was constructed and validated. Consequently, a risk score was calculated for each patient. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor for survival of HCC patients. Further analysis revealed that the risk score was closely associated with the levels of immune cell infiltration and the expression profiles of immune checkpoint genes.

Conclusions

Collectively, our study established a prognostic risk signature for HCC and revealed a significant correlation between pyroptosis and the HCC immune microenvironment.
Metastatic gastric adenocarcinoma to the uterine cervix—a case report and review of the literature
Authors: Bahall Vishal , De Barry Lance , Barrow Mickhaiel , Ramnarace Rene
Published: June 2022

Background

Poorly differentiated diffuse-type gastric adenocarcinoma often presents at an advanced stage. While gastric cancer typically metastasizes to the liver, lung and bone, metastasis to the uterine cervix is extremely rare. To our knowledge, less than forty cases have been described in the medical literature.

Case presentation

We report a case of a 47-year-old woman who presented to us with symptomatic uterine leiomyomas and subsequently underwent a successful total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. The diagnosis of metastatic cancer involving the cervix was established incidentally on histopathology, which demonstrated atypical signet ring cells in the lymphovascular spaces of the cervix. Further investigations for a primary malignancy revealed a poorly differentiated diffuse-type gastric adenocarcinoma.

Conclusion

Gastric cancer involving the uterine cervix is rare and associated with a poor prognosis. When presented with isolated cervical metastases, the gastrointestinal tract should be considered as a possible primary source. Due to the limited publications on this clinical entity, we expect to raise awareness and study this unique manifestation of gastric cancer by presenting our case.
Exploring static and dynamic relationships between burden of disease and research funding in the United States
Authors: Nimgaonkar Alok , Mughal Anisa Y. , Heimer Hakon , Nimgaonkar Vishwajit , Greenstein Dede , Wright Alexandra
Published: June 2022

Background

The relationship between burden of disease and research funding has been examined cross-sectionally, but temporal patterns have not been investigated. It is logical to assume that temporal improvements in disability-adjusted life-years (DALYs) reflect benefits from research funding; such assumptions are tempered by an unknown lag time for emergence of benefits from research.

Methods

We studied National Institutes of Health (NIH) research fund allocations and United States DALY estimates for overlapping disease categories (matched disease categories, MDC, N = 38). Using a general linear model, we separately analysed DALYs for MDCs in 2017 in relation to NIH research allocations in 2017 and 2007. We also examined how changes in DALYs were related to cumulative NIH research funding (2006–2017). After regressing DALY change on summed funding, we obtained model residuals as estimates of the discrepancy for each MDC between observed and expected change in burden, given funding.

Results

In 2017, there was a positive association between NIH research fund allocations and DALYs for the same year (F1,36 = 16.087, p = 0.0002921; slope = 0.35020; model R2 = 0.3088), suggesting proportionate allocation. There was a positive association between 2017 DALYs and 2007 NIH research allocation, implying a beneficial impact of research (F1,36 = 15.754, p = 0.0003; slope = 0.8845; model R2 = 0.3044). In contrast, there was a nonsignificant association between summed NIH funding and percent change in DALYs over 2006–2017 (F1,36 = 0.199; p = 0.65; beta coefficient = −1.144). When MDCs were ordered based on residuals, HIV/AIDS ranked first. Mental, neurologic or substance abuse (MNS) disorders comprised most residuals in the lower half.

Conclusions

NIH fund allocation is proportional to DALYs for MDCs. Temporal changes in DALYs vary by MDCs, but they are not significantly related to cumulative research outlays. Further analysis of temporal changes in DALYs could help to inform research outlays for MDCs and to study the impact of research.
Leading the way together: a cluster randomised controlled trial of the 5R Shared Leadership Program in older adult walking groups
Authors: Fransen Katrien , Cruwys Tegan , Haslam Catherine , Iserbyt Peter , Seghers Jan , Vanderlinden Julie , van Uffelen Jannique , Verbaanderd Elvire , Boen Filip
Published: June 2022

Background

With a rapidly ageing society, healthy ageing has become a key challenge. Engagement in physical activity, and particularly walking, is a key strategy that contributes to healthy ageing amongst older adults. The purpose of the present study was to evaluate the efficacy of a group walking program for older adults that incorporates the 5R Shared Leadership Program (5RS). By implementing a structure of shared leadership and strengthening peer leaders’ identity leadership, 5RS aims to cultivate a shared social identity amongst participants, which has in other contexts been associated with greater performance and well-being.

Methods

A cluster randomised controlled trial was conducted to test the efficacy of the 5RS group walking program on group identification, group cohesion, walking activity, and well-being, compared to a regular group walking program for older adults. Nineteen older adult walking groups (i.e., the clusters; N = 503; Mage = 69.23 years, SD = 6.68) all participated in a 12-week structured group walking program. Nine walking groups (n = 304) were randomly assigned to the intervention in which participants received the 5RS program in addition to regular group walking.

Results

5RS was successful in strengthening the identity leadership qualities of the appointed peer leaders. Multilevel regressions showed that 5RS succeeded in increasing group cohesion and walking activity to a greater extent than a regular group walking program, while participants’ group identification and well-being increased to a similar extent in both conditions. Furthermore, structural equation modelling revealed that group identification mediated the impact of peer leaders’ identity leadership on group cohesion and well-being (but not walking activity).

Conclusion

By harnessing the capacity of the group and its peer leaders, the 5RS program offers a promising intervention to engage older adults in physical activity.

Trial registration

The study was retrospectively registered as clinical trial on 9 September 2021 (NCT05038423).
Nicotinamide drives T cell activation in the mammary tumor microenvironment
Authors: Hu Yang , Bloy Norma , Elemento Olivier , Buqué Aitziber
Published: June 2022

Nicotinamide (NAM, a variant of vitamin B3) has recently been shown to accelerate the activation of human CD4+ and CD8+ T cells exposed to repeated CD3/CD28 agonism in vitro. Here, we demonstrate that T cells infiltrating mouse mammary carcinomas that are therapeutically controlled by NAM also express multiple markers of late-stage activation. Taken together, these findings lend additional support to the notion that the antineoplastic effects of NAM involve at least some degree of restored cancer immunosurveillance.
C-reactive protein and white blood cell are associated with frailty progression: a longitudinal study
Authors: Cheng Zongxue , He Di , Li Jun , Wu Qiong , Liu Zuyun , Zhu Yimin
Published: June 2022

Background

Systemic inflammation has been linked to diseases and frailty. However, little is known about the effect of systemic inflammation on frailty progression with a longitudinal study design.

Objectives

This study aimed to investigate the associations of two inflammation indicators, C-reactive protein (CRP) and white blood cell (WBC), with frailty progression.

Methods

This study utilized data from the China Health and Retirement Longitudinal Study 2011–2018 (wave 1-wave 4). Frailty index (FI) was calculated using 40 items from wave 1 to wave 4 (range: 0 to 1). Two systemic inflammation biomarkers, CRP and WBC, were measured at baseline (wave 1) and logs transformed as continuous variables or grouped using quartiles. Linear mixed-effect models were used to analyze the associations of these two biomarkers with the progression of frailty with adjustment for potential confounding factors.

Results

The study enrolled 9111 middle-aged and older participants (52.7% females, mean age 58.8 ± 9.3 years). The median follow-up time was 7.0 years. In a fully adjusted model with further adjustment for baseline FI, higher CRP (β for the interaction with time = 0.239, 95% CI: 0.139 to 0.338) and WBC (β for the interaction with time = 0.425, 95% CI: 0.024 to 0.825) significantly accelerated the rate of increase in the FI during the follow-up period. The associations were more pronounced in younger people (< 60 years) than older people (≥60 years).

Conclusions

Higher CRP and WBC accelerated the progression of frailty, particularly in younger groups (< 60 years). The findings suggest the importance of systemic inflammation for the early identification of people at high risk of rapid progression of frailty.
Effects of control strategies on gait in robot-assisted post-stroke lower limb rehabilitation: a systematic review
Authors: Campagnini Silvia , Liuzzi Piergiuseppe , Mannini Andrea , Riener Robert , Carrozza Maria Chiara
Published: June 2022

Background

Stroke related motor function deficits affect patients' likelihood of returning to professional activities, limit their participation in society and functionality in daily living. Hence, robot-aided gait rehabilitation needs to be fruitful and effective from a motor learning perspective. For this reason, optimal human–robot interaction strategies are necessary to foster neuroplastic shaping during therapy. Therefore, we performed a systematic search on the effects of different control algorithms on quantitative objective gait parameters of post-acute stroke patients.

Methods

We conducted a systematic search on four electronic databases using the Population Intervention Comparison and Outcome format. The heterogeneity of performance assessment, study designs and patients’ numerosity prevented the possibility to conduct a rigorous meta-analysis, thus, the results were presented through narrative synthesis.

Results

A total of 31 studies (out of 1036) met the inclusion criteria, without applying any temporal constraints. No controller preference with respect to gait parameters improvements was found. However, preferred solutions were encountered in the implementation of force control strategies mostly on rigid devices in therapeutic scenarios. Conversely, soft devices, which were all position-controlled, were found to be more commonly used in assistive scenarios. The effect of different controllers on gait could not be evaluated since conspicuous heterogeneity was found for both performance metrics and study designs.

Conclusions

Overall, due to the impossibility of performing a meta-analysis, this systematic review calls for an outcome standardisation in the evaluation of robot-aided gait rehabilitation. This could allow for the comparison of adaptive and human-dependent controllers with conventional ones, identifying the most suitable control strategies for specific pathologic gait patterns. This latter aspect could bolster individualized and personalized choices of control strategies during the therapeutic or assistive path.
Detection of recombinant breakpoint in the genome of human enterovirus E11 strain associated with a fatal nosocomial outbreak
Authors: Rueca Martina , Lanini Simone , Giombini Emanuela , Messina Francesco , Castilletti Concetta , Ippolito Giuseppe , Capobianchi Maria Rosaria , Valli Maria Beatrice
Published: June 2022

Background

The aim of this study was to characterize the genome of a recombinant Enterovirus associated with severe and fatal nosocomial infection; it was typed as Echovirus 11 (E-11) according to the VP1 gene. Enterovirus infection is generally asymptomatic and self-limited, but occasionally it may progress to a more severe clinical manifestation, as in the case described here. Recombination plays a crucial role in the evolution of Enteroviruses (EVs) and has been recognized as the main driving force behind the emergence of epidemic strains associated with severe infection. Therefore, it is of utmost importance to monitor the circulation of recombinant strains for surveillance purposes.

Methods

Enterovirus-RNA was detected in the serum and liver biopsy of patients involved in the nosocomial cluster by commercial One-Step qRT-PCR method and the Enterovirus strains were isolated in vitro. The EVs typing was determined by analyzing the partial-length of the 5′UTR and VP1 sequences with the web-based open-access Enterovirus Genotyping Tool Version 0.1. The amplicons targeting 5′UTR, VP1 and overlapping fragments of the entire genome were sequenced with the Sanger method. Phylogenetic analysis was performed comparing the VP1 and the full-genome sequences of our strains against an appropriate reference set of Enterovirus prototypes of the Picornaviridae genera and species retrieved from the Enterovirus Genotyping Tool. Recombination analysis was performed using RDP4 software.

Results

The Neighbor-Joining tree of the VP1 gene revealed that the 4 patients were infected with an identical molecular variant of Echovirus 11 (E-11). While the phylogenetic and the RDP4 analysis of the full-genome sequences provided evidence that it was a chimeric strain between an E-11 and a Coxsackievirus B (CV-B).

Conclusions

The chimeric structure of the E-11 genome might have contributed to the severe infection and epidemic feature of the strain, but further biological characterizations are needed. The evidence reported in this study, highlights the limit of typing techniques based on the VP1 gene, as they fail to identify the emergence of recombinant strains with potentially more pathogenic or epidemic properties, thus providing only partial information on the epidemiology and pathogenesis of Enteroviruses.
Ptpn20 deletion in H-Tx rats enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus: an evidence of genetic risk for hydrocephalus in an experimental study
Authors: Xu Hanbing , Miyajima Masakazu , Nakajima Madoka , Ogino Ikuko , Kawamura Kaito , Akiba Chihiro , Kamohara Chihiro , Sakamoto Koichiro , Karagiozov Kostadin , Nakamura Eri , Tada Nobuhiro , Arai Hajime , Kondo Akihide
Published: June 2022

Background

Congenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus.

Methods

Comparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus.

Results

CGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats at 18 days gestation, encompassing the protein tyrosine phosphatase non-receptor type 20 (Ptpn20), a non-receptor tyrosine phosphatase, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20−/−) mice were generated and found to develop ventriculomegaly at 8 weeks. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20 from 8 weeks until 72 weeks.

Conclusions

This study determined the chromosomal location of the hydrocephalus-associated Ptpn20 gene in hydrocephalic H-Tx rats. The high level of pNKCC1 mediated by Ptpn20 deletion in CP epithelium may cause overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20−/− mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.
Health status assessment of a population of asylum seekers in Northern Italy
Authors: Manfredi Luca , Sciannameo Veronica , Destefanis Cinzia , Prisecaru Marta , Cossu Giorgia , Gnavi Roberto , Macciotta Alessandra , Catalano Alberto , Pepe Roberto Raffaele , Sacerdote Carlotta , Ricceri Fulvio
Published: June 2022

Background

Since 2011 Italy has faced an extraordinary increase in migrants arrivals, mainly from the Mediterranean route, one of the world’s most dangerous journeys. The purpose of the present article is to provide a comprehensive picture of the migrants' health status in the "T. Fenoglio" centre, Settimo Torinese (Turin, Italy).

Methods

A retrospective cross-sectional study was conducted using data collected from June 2016 to May 2018 on adult migrants (over 18 years old) from Africa, Middle East and South East Asia (Bangladesh, Cambodia, India, Nepal). Data was collected through the migrants' medical records. Descriptive statistics were performed on socio-demographic variables. The diagnosed diseases were anonymously registered and classified according to the International Classification of Primary Care (ICPC-2).

Conditional Inference Trees were used to perform a descriptive analysis of the sample and to detect the covariates with the strongest association with the variables Disease on arrival, Disease after arrival, ICPC on arrival and ICPC after arrival.

Results

Analyzed observations were 9 857. 81.8% were men, median age was 23 (Interquartile range: 20.0–27.4). 70.3% of the sample came from Sub-Saharan Africa. 2 365 individuals (24%) arrived at the centre with at least one disease. On arrival, skin (27.71%), respiratory (14.46%), digestive (14.73%) and generic diseases (20.88%) were the most frequent. During the stay respiratory diseases were the most common (25.70%). The highest probability of arriving with a disease occurred in 2018 and during the period September–November 2016, in particular for people from the Horn of Africa. During this period and also in the first half of 2017, skin diseases were the most reported. In seasons with lower prevalence of diseases on arrival the most common disease code was generic for both men and women (usually fever or trauma).

Conclusions

This study provides information on the diverse diseases that affect the asylum seekers population. In our sample, the Horn of Africa was the most troubled area of arrival, with severe conditions frequently reported regarding skin diseases, in particular scabies. 2018 was the most critical year, especially for migrants from the Horn of Africa and Sub-Saharan Africa. During the stay at the camp, the prevalence of respiratory diseases increased. However, skin diseases remained the main issue for people from the Horn of Africa. Overall, the most reported diseases in the sample were dermatological, respiratory, digestive and generic diseases, both on arrival and during the stay.

A better understanding of the health status of asylum seekers is an important factor to determine a more efficient reception and integration process and a better allocation of economic resources in the context of migrants' health care.
CT psoas calculations on the prognosis prediction of emergency laparotomy: a single-center, retrospective cohort study in eastern Asian population
Authors: Wu Xiao-Lin , Shen Jie , Danzeng Ci-Dian , Xu Xiang-Shang , Cao Zhi-Xin , Jiang Wei
Published: June 2022

Background

Emergency laparotomy (EL) has a high mortality rate. Clinically, frail patients have a poor tolerance for EL. In recent years, sarcopenia has been used as an important indicator of frailty and has received much attention. There have been five different calculation methods of psoas for computed tomography (CT) to measure sarcopenia, but lack of assessment of these calculation methods in Eastern Asian EL patients.

Methods

We conducted a 2-year retrospective cohort study of patients over 18 years of age who underwent EL in our institution. Five CT measurement values (PMI: psoas muscle index, PML3: psoas muscle to L3 vertebral body ratio, PMD: psoas muscle density, TPG: total psoas gauge, PBSA: psoas muscle to body face area ratio) were calculated to define sarcopenia. Patients with sarcopenia defined by the sex-specific lowest quartile of each measurement were compared with the rest of the cohort. The primary outcome was "ideal outcome", defined as: (1) No postoperative complications of Clavien-Dindo Grade ≥ 4; (2) No mortality within 30 days; (3) When discharged, no need for fluid resuscitation and assisted ventilation, semi-liquid diet tolerated, and able to mobilize independently. The second outcome was mortality at 30-days. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were used.

Results

Two hundred and twenty-eight patients underwent EL met the inclusion criteria, 192 (84.2%) patients had an ideal outcome after surgery; 32 (14%) patients died within 30 days. Multivariate analysis showed that, except PMD, each calculation method of psoas was independently related to clinical outcome (ideal outcome: PML3,P < 0.001; PMI,P = 0.001; PMD,P = 0.157; TPG,P = 0.006; PBSA,P < 0.001; mortality at 30-days: PML3,P < 0.001; PMI,P = 0.002; PMD,P = 0.088; TPG,P = 0.002; PBSA,P = 0.001). In ROC analysis, the prediction model containing PML3 had the largest area under the curve (AUC) value (AUC value = 0.922 and 0.920, respectively).

Conclusion

The sarcopenia determined by CT psoas measurements is significantly related to the clinical outcome of EL. The calculation of CT psoas measurement is suitable for application in outcome prediction of EL. In the future, it is necessary to develop a scoring tool that includes sarcopenia to evaluate the risk of EL better.
Influence of fixed titanium plate position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy
Authors: Liu Fa-jing , Ding Xiao-kun , Chai Yi , Qi Su-hong , Li Peng-fei
Published: June 2022

Background

During open-door laminoplasty, the position of the bone gutter is not fixed, and when the gutter migrates inward, the outer end of the titanium plate must be fixed on the lamina edge. It is unclear whether this will affect the clinical efficacy. This study aimed to observe the influence of the titanium plate fixation position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy (CSM).

Methods

A total of 98 patients with CSM who underwent open-door laminoplasty from August 2016 to October 2019 were included in this retrospective study. Fifty-five patients had the titanium plate fixed on the lateral mass (lateral mass group), and 43 patients had the titanium plate fixed on the lamina edge (lamina group). The opening angle, opening width, occurrence of hinge fracture, spinal cord drift distance, cervical curvature index (CCI), neurological function recovery (JOA score), neck function (NDI), C5 palsy and severity of axial symptoms were observed and compared between the two groups.

Results

The opening angle in the lamina group was significantly larger than that in the lateral mass group, while the opening width and the spinal cord drift distance were significantly smaller than those in the lateral mass group (P < 0.05). The occurrence of hinge fracture in the lamina group was significantly higher than that in the lateral group (25.6% and 9.1%, respectively) (P < 0.05). The CCI was maintained well in both groups (P > 0.05), and there was no significant difference between the groups (P > 0.05). After surgery, the JOA score significantly increased in both groups (P < 0.05), and the neurological recovery rates were similar between the two groups (62.6% vs. 64.5%). The NDI score significantly decreased in both groups (P < 0.05), but the lateral mass group recovered to a greater degree than the lamina group (P < 0.05). The occurrence of C5 palsy was 2.3% in the lamina group and 14.5% in the lateral mass group, and there was a significant difference between the groups (P < 0.05). Postoperative axial symptom severity was significantly worse in the lamina group than in the lateral mass group (P < 0.05).

Conclusions

In open-door laminoplasty, it is feasible to fix the titanium plate on the lateral mass or to the lamina due to the same neurological function recovery. However, fixing it to the lamina will increase the opening angle and decrease the opening width, making the hinge prone to fracture and increasing the severity of postoperative axial symptoms.
Comparative effectiveness research on proximal femoral nail versus dynamic hip screw in patients with trochanteric fractures: a systematic review and meta-analysis of randomized trials
Authors: Xu Hong , Liu Yang , Sezgin Erdem Aras , Tarasevičius Šarūnas , Christensen Robin , Raina Deepak Bushan , Tägil Magnus , Lidgren Lars
Published: June 2022

Background

The treatments for trochanteric fractures try to regain early mobility and limit morbidity and risk of reoperations. The most currently used dynamic hip screw (DHS) and the proximal femoral nail (PFN) are both with pros and cons. We aimed to assess the comparative effectiveness of these interventions for trochanteric fractures by evaluating the surgical performance and postoperative outcomes.

Methods

PubMed, Web of Science and Cochrane Central Register were searched for RCTs comparing DHS and PFN for trochanteric fractures. All selected studies and the risk of bias were assessed. Clinical data including operative time, intraoperative blood loss, intraoperative fluoroscopy time, successful closed reduction and complications like nonunion, implant failure and reoperation were recorded. Random-effects models were used in Review Manager software, and GRADE was applied for the interpretation of the evidence.

Results

From 286 identified trials, twelve RCTs including 1889 patients were eligible for inclusion; six RCTs directly comparing DHS with PFN, while other six compared DHS with proximal femoral nail antirotation (PFNA). Compared to DHS, PFN had shorter operative time and led to less intraoperative blood loss. However, DHS need less intraoperative fluoroscopy time than PFN. No difference was seen for the achievement of closed reduction. For risk of postoperative complications, no difference was seen between PFN and DHS for non-union, risk of implant failure and revision surgery.

Conclusions

PFN(A) resulted in a shorter operative time and less intraoperative blood loss compared to DHS. However, no difference was seen for postoperative complications.

Trial registration PROSPERO: CRD42021239974.
Comparison of the levels of depression and anxiety in elderly aortic stenosis patients treated with surgical or transcatheter aortic valve replacement
Authors: Sun Jiao , Meng Qing-Tao , Wang Yu-Wei , Zhao Wei-Long , Sun Feng-Zhi , Liu Ji-Hong , Liu Ji-Yi
Published: June 2022

Objective

Currently, only a few studies have been conducted on the mental status recovery in elderly aortic stenosis (AS) patients after treatment. How transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differentially impinge on the mental status of elderly AS patients is completely unknown. The present prospective study aims to investigate this question by comparing the post-treatment levels of depression and anxiety, quality of life and frailty.

Methods

A total of 120 elderly patients (age above 70) with symptomatic AS were included, where 78 of them were treated with TAVR and 42 of them were treated with SAVR. Levels of depression and anxiety, quality of life and frailty were assessed by the Chinese version of Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD) and clinical frailty scale, respectively. Scores were recorded and compared at admission, 1 month, 4 months and 8 months after treatment.

Results

Before treatment, both patient groups had similar baseline characteristics and all mental parameters. During the follow-up period, patients in the TAVR group demonstrated significant improvement in all assessed mental parameters to certain extent compared to the SAVR group. Specifically, frailty was significantly improved in the TAVR-treated patients at all three follow-up time points. Levels of depression and anxiety were significantly improved 8 months after treatment, although the remaining patient number is limited. Quality of life was only significantly improved 1 month after treatment.

Conclusion

TAVR may provide a better mental recovery outcome in elderly AS patients.
Diagnostic value of congenital pulmonary airway malformation volume ratio for fetal hydrops due to congenital lung malformations: a systematic review and meta-analysis
Authors: Zhu Pei , Cheng Kaisheng , He Mingsheng , Wang Yutong , Shen Pengyue , He Kanglin , Xu Chang , Zhang Ben , Liu Zhenmi
Published: June 2022

Objective

Meta-analysis was used to evaluate the diagnostic value of a CVR cut-off value of 1.6 for fetal hydrops due to congenital lung malformation (CLM).

Methods

A systematic search of PubMed, Embase, Web of Science, CNKI, VIP, and Wanfang published before 7/30/2021 for the value of a congenital pulmonary airway malformation volume ratio (CVR) cut-off value of 1.6 for the diagnosis of fetal hydrops. According to the inclusion and exclusion criteria, the literature that met the requirements were obtained. A total of 75 articles were retrieved, and 12 articles were included for further analysis. The quality of these studies was evaluated according to the Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2) criteria. The Q test and heterogeneity I2 were used to evaluate the heterogeneity due to non-threshold effects, and Stata 15.0 was used for statistical analysis to evaluate the diagnostic value of the CVR cutoff value of 1.6 for fetal hydrops due to CLM.

Results

A total of 12 studies were included. The QUADAS-2 indicated that the risk of bias was relatively low, and the clinical applicability was relatively high. Statistical analysis was performed on included studies using a random effect model. Meta-analysis showed that the pooled sensitivity, specificity, diagnostic ratio and summary receiver operating characteristic (SROC) for the diagnosis of fetal hydrops by CVR were 0.86 (95% CI, 0.72–0.93; I2 = 59.84), 0.90 (95% CI, 0.88–0.93; I2 = 31.94), 58 (95% CI, 22–149; I2 = 100%), 0.93 (95% CI, 0.91–0.95).

Conclusions

The sensitivity and specificity of CVR cut-off value 1.6 for the diagnosis of CLM-induced fetal hydrops were high, no publication bias was observed, and the CVR cut-off value 1.6 is meaningful for the early diagnosis prediction of CLM-induced fetal hydrops.
Inducible localized delivery of an anti-PD-1 scFv enhances anti-tumor activity of ROR1 CAR-T cells in TNBC
Authors: Harrasser Micaela , Gohil Satyen Harish , Lau Hiu , Della Peruta Marco , Muczynski Vincent , Patel Dominic , Miranda Elena , Grigoriadis Kristiana , Grigoriadis Anita , Granger David , Evans Rachel , Nathwani Amit Chunilal
Published: June 2022

Background

Chimeric antigen receptor (CAR)-T cells can induce powerful immune responses in patients with hematological malignancies but have had limited success against solid tumors. This is in part due to the immunosuppressive tumor microenvironment (TME) which limits the activity of tumor-infiltrating lymphocytes (TILs) including CAR-T cells. We have developed a next-generation armored CAR (F i-CAR) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is expressed at high levels in a range of aggressive tumors including poorly prognostic triple-negative breast cancer (TNBC). The F i-CAR-T is designed to release an anti-PD-1 checkpoint inhibitor upon CAR-T cell activation within the TME, facilitating activation of CAR-T cells and TILs while limiting toxicity.

Methods

To bolster potency, we developed a F i-CAR construct capable of IL-2-mediated, NFAT-induced secretion of anti-PD-1 single-chain variable fragments (scFv) within the tumor microenvironment, following ROR1-mediated activation. Cytotoxic responses against TNBC cell lines as well as levels and binding functionality of released payload were analyzed in vitro by ELISA and flow cytometry. In vivo assessment of potency of F i-CAR-T cells was performed in a TNBC NSG mouse model.

Results

F i-CAR-T cells released measurable levels of anti-PD-1 payload with 5 h of binding to ROR1 on tumor and enhanced the cytotoxic effects at challenging 1:10 E:T ratios. Treatment of established PDL1 + TNBC xenograft model with F i-CAR-T cells resulted in significant abrogation in tumor growth and improved survival of mice (71 days), compared to non-armored CAR cells targeting ROR1 (F CAR-T) alone (49 days) or in combination with systemically administered anti-PD-1 antibody (57 days). Crucially, a threefold increase in tumor-infiltrating T cells was observed with F i-CAR-T cells and was associated with increased expression of genes related to cytotoxicity, migration and proliferation.

Conclusions

Our next-generation of ROR1-targeting inducible armored CAR platform enables the release of an immune stimulating payload only in the presence of target tumor cells, enhancing the therapeutic activity of the CAR-T cells. This technology provided a significant survival advantage in TNBC xenograft models. This coupled with its potential safety attributes merits further clinical evaluation of this approach in TNBC patients.
Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types
Authors: Pahl Matthew C. , Le Coz Carole , Su Chun , Sharma Prabhat , Thomas Rajan M. , Pippin James A. , Cruz Cabrera Emylette , Johnson Matthew E. , Leonard Michelle E. , Lu Sumei , Chesi Alessandra , Sullivan Kathleen E. , Romberg Neil , Grant Struan F. A. , Wells Andrew D.
Published: June 2022

Background

SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. COVID-19 disease severity has been associated with some pre-existing conditions and the magnitude of the adaptive immune response to SARS-CoV-2, and a recent genome-wide association study (GWAS) of the risk of critical illness revealed a significant genetic component. To gain insight into how human genetic variation attenuates or exacerbates disease following SARS-CoV-2 infection, we implicated putatively functional COVID risk variants in the cis-regulatory landscapes of human immune cell types with established roles in disease severity and used high-resolution chromatin conformation capture to map these disease-associated elements to their effector genes.

Results

This functional genomic approach implicates 16 genes involved in viral replication, the interferon response, and inflammation. Several of these genes (PAXBP1, IFNAR2, OAS1, OAS3, TNFAIP8L1, GART) were differentially expressed in immune cells from patients with severe versus moderate COVID-19 disease, and we demonstrate a previously unappreciated role for GART in T cell-dependent antibody-producing B cell differentiation in a human tonsillar organoid model.

Conclusions

This study offers immunogenetic insight into the basis of COVID-19 disease severity and implicates new targets for therapeutics that limit SARS-CoV-2 infection and its resultant life-threatening inflammation.
De novo reconstruction of cell interaction landscapes from single-cell spatial transcriptome data with DeepLinc
Authors: Li Runze , Yang Xuerui
Published: June 2022

Abstract

Based on a deep generative model of variational graph autoencoder (VGAE), we develop a new method, DeepLinc (deep learning framework for Landscapes of Interacting Cells), for the de novo reconstruction of cell interaction networks from single-cell spatial transcriptomic data. DeepLinc demonstrates high efficiency in learning from imperfect and incomplete spatial transcriptome data, filtering false interactions, and imputing missing distal and proximal interactions. The latent representations learned by DeepLinc are also used for inferring the signature genes contributing to the cell interaction landscapes, and for reclustering the cells based on the spatially coded cell heterogeneity in complex tissues at single-cell resolution.
Distal-less and spalt are distal organisers of pierid wing patterns
Authors: Wee Jocelyn Liang Qi , Das Banerjee Tirtha , Prakash Anupama , Seah Kwi Shan , Monteiro Antonia
Published: June 2022

Two genes, Distal-less (Dll) and spalt (sal), are known to be involved in establishing nymphalid butterfly wing patterns. They function in several ways: in the differentiation of the eyespot’s central signalling cells, or foci; in the differentiation of the surrounding black disc; in overall scale melanisation (Dll); and in elaborating marginal patterns, such as parafocal elements. However, little is known about the functions of these genes in the development of wing patterns in other butterfly families. Here, we study the expression and function of Dll and sal in the development of spots and other melanic wing patterns of the Indian cabbage white, Pieris canidia, a pierid butterfly. In P. canidia, both Dll and Sal proteins are expressed in the scale-building cells at the wing tips, in chevron patterns along the pupal wing margins, and in areas of future scale melanisation. Additionally, Sal alone is expressed in the future black spots. CRISPR knockouts of Dll and sal showed that each gene is required for the development of melanic wing pattern elements, and repressing pteridine granule formation, in the areas where they are expressed. We conclude that both genes likely play ancestral roles in organising distal butterfly wing patterns, across pierid and nymphalid butterflies, but are unlikely to be differentiating signalling centres in pierids black spots. The genetic and developmental mechanisms that set up the location of spots and eyespots are likely distinct in each lineage.
Artificial intelligence for radiological paediatric fracture assessment: a systematic review
Authors: Shelmerdine Susan C. , White Richard D. , Liu Hantao , Arthurs Owen J. , Sebire Neil J.
Published: June 2022

Background

Majority of research and commercial efforts have focussed on use of artificial intelligence (AI) for fracture detection in adults, despite the greater long-term clinical and medicolegal implications of missed fractures in children. The objective of this study was to assess the available literature regarding diagnostic performance of AI tools for paediatric fracture assessment on imaging, and where available, how this compares with the performance of human readers.

Materials and methods

MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1 January 2011 and 2021 using terms related to ‘fracture’, ‘artificial intelligence’, ‘imaging’ and ‘children’. Risk of bias was assessed using a modified QUADAS-2 tool. Descriptive statistics for diagnostic accuracies were collated.

Results

Nine eligible articles from 362 publications were included, with most (8/9) evaluating fracture detection on radiographs, with the elbow being the most common body part. Nearly all articles used data derived from a single institution, and used deep learning methodology with only a few (2/9) performing external validation. Accuracy rates generated by AI ranged from 88.8 to 97.9%. In two of the three articles where AI performance was compared to human readers, sensitivity rates for AI were marginally higher, but this was not statistically significant.

Conclusions

Wide heterogeneity in the literature with limited information on algorithm performance on external datasets makes it difficult to understand how such tools may generalise to a wider paediatric population. Further research using a multicentric dataset with real-world evaluation would help to better understand the impact of these tools.
Development and evaluation of a novel xeno-free culture medium for human-induced pluripotent stem cells
Authors: Hua Ying , Yoshimochi Kenji , Li Junjun , Takekita Kazuhiro , Shimotsuma Motoshi , Li Lingjun , Qu Xiang , Zhang Jingbo , Sawa Yoshiki , Liu Li , Miyagawa Shigeru
Published: June 2022

Background

Human-induced pluripotent stem cells (hiPSCs) are considered an ideal resource for regenerative medicine because of their ease of access and infinite expansion ability. To satisfy the sizable requirement for clinical applications of hiPSCs, large-scale, expansion-oriented, xeno-free, and cost-effective media are critical. Although several xeno-free media for hiPSCs have been generated over the past decades, few of them are suitable for scalable expansion of cultured hiPSCs because of their modest potential for proliferation and high cost.

Methods

In this study, we developed a xeno-free ON2/AscleStem PSC medium (ON2) and cultured 253G1 hiPSCs on different matrices, including iMatrix-511 and gelatin nanofiber (GNF) in ON2. Over 20 passages, we evaluated cell proliferation by doubling times; pluripotency by flow cytometry, immunofluorescence staining and qRT-PCR; and differentiation ability by three germ layer differentiation in vitro and teratoma formation in severe combined immunodeficiency mice, followed by histological analysis. In addition, we compared the maintenance effect of ON2 on hiPSCs with StemFit® AK02 (AK02N) and Essential 8™ (E8). Besides 253G1 hiPSCs, we cultivated different hiPSC lines, including Ff-l01 hiPSCs, ATCC® ACS-1020™ hiPSCs, and Down’s syndrome patient-specific ATCC® ACS-1003™ hiPSCs in ON2.

Results

We found that 253G1 hiPSCs in ON2 demonstrated normal morphology and karyotype and high self-renewal and differentiation abilities on the tested matrices for over 20 passages. Moreover, 253G1 hiPSCs kept on GNF showed higher growth and stemness, as verified by the shorter doubling time and higher expression levels of pluripotent markers. Compared to AK02N and E8 media, 253G1 hiPSCs grown in ON2 showed higher pluripotency, as demonstrated by the increased expression level of pluripotent factors. In addition, all hiPSC lines cultivated in ON2 were able to grow for at least 10 passages with compact clonal morphology and were positive for all detected pluripotent markers.

Conclusions

Our xeno-free ON2 was compatible with various matrices and ideal for long-term expansion and maintenance of not only healthy-derived hiPSCs but also patient-specific hiPSCs. This highly efficient medium enabled the rapid expansion of hiPSCs in a reliable and cost-effective manner and could act as a promising tool for disease modeling and large-scale production for regenerative medicine in the future.