bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of interferon-gamma release assays for diagnosis of smear-negative pulmonary tuberculosis: a systematic review and meta-analysis
Authors: Petnak Tananchai , Eksombatchai Dararat , Chesdachai Supavit , Lertjitbanjong Ploypin , Taweesedt Pahnwat , Pornchai Angsupat , Thongprayoon Charat , Prokop Larry J. , Wang Zhen
Published: June 2022

Introduction

The diagnosis of smear-negative pulmonary tuberculosis (SNPTB) is challenging. Interferon gamma-release assays (IGRAs) may be helpful in early diagnosis among these patients resulting in prompt treatment and favorable outcomes.

Methods

We performed a comprehensive search from each databases’ inception to April 5, 2021. The studies that provided sufficient data regarding the sensitivity and specificity of IGRAs included QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB, or QuantiFERON-TB Gold Plus for diagnosis of SNPTB were included.

Results

Of 1,312 studies screened, 16 studies were included; 11 QFT-GIT, 2 T-SPOT.TB, and 3 QFT-GIT and T-SPOT.TB. For diagnosis of SNPTB, QFT-GIT had sensitivity of 0.77 (95% CI 0.71–0.82), specificity of 0.70 (95% CI 0.58–0.80), diagnostic odds ratio (DOR) of 8.03 (95% CI 4.51–14.31), positive likelihood ratio (LR) of 2.61 (95% CI 1.80–3.80), negative LR of 0.33 (95% CI 0.25–0.42), and area under receiver operating characteristic (AUROC) of 0.81 (95% CI 0.77–0.84). T-SPOT.TB had sensitivity of 0.74 (95% CI 0.71–0.78), specificity of 0.71 (95% CI 0.49–0.86), DOR of 6.96 (95% CI 2.31–20.98), positive LR of 2.53 (95% CI 1.26–5.07), negative LR of 0.36 (95% CI 0.24–0.55), and AUROC of 0.77 (95% CI 0.73–0.80). The specificity seemed lower in the subgroup analyses of studies from high tuberculosis burden counties compared to the studies from low tuberculosis burden.

Conclusion

IGRAs do have insufficient diagnostic performance for SNPTB. However, the tests are still helpful to exclude tuberculosis among patients with low pre-test probability.

Registry: PROSPERO: CRD42021274653.
Demographic and disease characteristics associated with pain intensity, kinesiophobia, balance, and fall self-efficacy among people with osteoarthritis: a cross-sectional study
Authors: Ekediegwu Ezinne Chika , Akpaenyi Chigbogu Earnest , Nwosu Ifeoma Blessing , Onyeso Ogochukwu Kelechi
Published: June 2022

Background

Osteoarthritis (OA) is a common degenerative joint disease leading to significant pain, mobility limitation, economic burden, reduced quality of life, and disability among adults globally. Psychological factors related to pain intensity (PI), kinesiophobia, fall self-efficacy (FSE), and balance may lead to a poor OA prognosis. This study was designed to explore the association between PI, kinesiophobia, FSE, balance, and age, gender, marital status, site of OA, duration, symmetry, comorbidity, and adaptive behaviours among patients with knee or hip OA.

Methods

This cross-sectional study involved 70 purposively selected participants aged 59.91 ± 11.12 years. Numeric pain rating scale, Tampa scale for kinesiophobia, fall-efficacy scale, and timed up and go test were used to measure PI, kinesiophobia, FSE, and balance, respectively. Statistical analyses were completed with the Pearson correlation test, independent samples t-test, and multiple linear regression.

Results

The participants were mainly women (n = 59, 84.3%). However, there was no gender difference in the reported PI, kinesiophobia, FSE, and balance. There was a significant correlation between FSE and balance (r = 0.422, p<0.001). Kinesiophobia was significantly associated with the presence of comorbidity (β = 0.240, p = 0.001) and knee OA (β = 0.208, p<0.042). There was an association between FSE and the use of a walking aid (β = ˗0.442, p<0.042), stop-for-rest during walking (β = ˗0.292, p = 0.002), presence of comorbidity (β = 0.209, p = 0.014), and bilateral lower limb OA (β = 0.167, p = 0.057). Balance was associated with the use of a walking aid (β = ˗0.421, p<0.001) and stop-for-rest during walking (β = − 0.294, p = 0.006).

Conclusion

Osteoarthritis-related psychological distress affects both men and women. This study support integration of psychological outcomes in the assessment, management, and follow-up of people with lower limb osteoarthritis. Moreover, comorbidity worsened psychological distress among people with osteoarthritis. Therefore, the traditional biomedical management of osteoarthritis can be optimised by timely diagnosis and treatment of comorbidities, and the inclusion of psychotherapy.
The radiographic soft tissue thickness is associated with wound complications after open reduction and internal fixation of patella fractures
Authors: Song Kai , Zhu Bowen , Jiang Qing , Xiong Jin , Shi Hongfei
Published: June 2022

Background

Displaced patella fracture is commonly treated with open reduction and internal fixation (ORIF). Wound complications after surgery often lead to prolonged hospitalization and dissatisfaction of patients. Periarticular adiposity and swelling may be associated with wound complications. The purpose of this study is to determine the relationship between periarticular soft tissue thickness and wound complications after ORIF of patella fractures.

Methods

We retrospectively studied 237 patients undergoing ORIF for patella fractures from June 2017 to February 2021 at our institution. We established periarticular soft tissue thickness ratio (PSTTR) to evaluate soft tissue status on lateral knee X-ray radiographs. Univariate analysis was performed to identify the association between PSTTR and postoperative wound complication. A receiver-operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of PSTTR.

Results

The incidence of postoperative wound complication was 10.5%. Minor wound complication occurred in 24 patients, and major wound complication occurred in one patient. The average femoral PSTTR (fPSTTR) was 0.94 ± 0.17 and the average tibial PSTTR (tPSTTR) was 0.66 ± 0.16. fPSTTR proved to be associated with postoperative wound complication. In the ROC analysis of fPSTTR predicting postoperative wound complication, the area under curve (AUC) was 0.676, which indicated a moderate predictive value.

Conclusions

PSTTR was a feasible method to assess periarticular soft tissue. The increased fPSTTR was associated with wound complications after ORIF of patella fractures.
Concurrent mutations of germline GPR101 and somatic USP8 in a pediatric giant pituitary ACTH adenoma: a case report
Authors: Bao Xu-dong , Lu Lin , Zhu Hui-juan , Yao Yong , Feng Ming , Wang Ren-zhi , Zhai Xiao , Fu Yong , Gong Feng-ying , Lu Zhao-lin
Published: June 2022

Background

Cushing’s disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD.

Case presentation

A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively.

Conclusions

We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.
The changes in the nursing practice environment brought by COVID-19 and improvement recommendations from the nurses’ perspective: a cross-sectional study
Authors: Jingxia Cheng , Longling Zhu , Qiantao Zuo , Weixue Peng , Xiaolian Jiang
Published: June 2022

Background

The COVID-19 pandemic has brought an opportunity to increase investment in the nursing practice environment, which has greatly impacted patients, nurses, and organizations. However, there were limited studies concerning the changes in the practice environment since the COVID-19 pandemic and the way to improve it from nurses’ perspectives.

Methods

A cross-sectional study was conducted among 460 nurses from seven hospitals in Sichuan, China. Both the quantitative and qualitative data were collected from an online questionnaire. The quantitative data were collected using the Chinese version of the Practice Environment Scale-Nursing Work Index and compared with available norms in 2010. The qualitative data were collected through an open question following the scale and analyzed by content analysis.

Results

The mean of the score of the practice environment scale was 3.44 (SD = 0.56) out of 4.00. The score of the total scale and the dimensions were significantly higher than the norms, apart from nurse-physician relations and nurse participation in hospital affairs. The qualitative findings revealed positive changes in nursing foundations for quality of care, nurse participation in hospital affairs and nurse-physician relations, and poor staffing and resource adequacy. The improvement in the working model and ward environment is the primary concern of nurses.

Conclusions

The COVID-19 pandemic brought some positive changes in the nursing practice environment, but more efforts are needed to solve those nagging and important problems, such as staff shortages and low participation. Nursing managers and hospital leaders were encouraged to listen to nurses’ concerns and value this suitable opportunity for changing and improving to achieve better health services and coping ability to deal with emergency events going forward. Improving the ward environment and taking a professional model instead of sticking to the tedious process might be worthwhile.
“Syndemic moral distress”: sexual health provider practices in the context of co-occurring, socially produced sexual and mental health epidemics
Authors: Salway Travis , Black Stéphanie , Kennedy Angel , Watt Sarah , Ferlatte Olivier , Gaspar Mark , Knight Rod , Gilbert Mark
Published: June 2022

Background

‘Syndemic’ refers to socially produced, intertwined, and co-occurring epidemics. Syndemic theory is increasingly used to understand the population-level relationships between sexual health (including HIV) and mental health (including problematic substance use) epidemics. Syndemic-informed clinical interventions are rare.

Methods

We therefore asked 22 sexual health practitioners from six sexual health clinics in British Columbia, Canada to define the word ‘syndemic’ and then asked how the theory related to their clinical practice.

Results

Responses to syndemic theory ranged widely, with some practitioners providing nuanced and clinically informed definitions, others expressing a vague familiarity with the term, and others still having no prior knowledge of it. Where practitioners acknowledged the relevance of syndemic theory to their practice, they articulated specific ways in which syndemics create moral distress, that is, feeling that the most ethical course of action is different from what they are mandated to do. While some practitioners routinely used open-ended questions to understand the social and economic contexts of patients’ sexual health needs, they described an uneasiness at potentially having surfaced concerns that could not be addressed in the sexual health clinic. Many observed persistent social, mental health, and substance use-related needs among their patients, but were unable to find feasible solutions to these issues.

Conclusions

We therefore propose that interventions are needed to support sexual health practitioners in addressing psychosocial health needs that extend beyond their scope of practice, thereby reducing ‘syndemic moral distress’.
A machine learning approach to small area estimation: predicting the health, housing and well-being of the population of Netherlands
Authors: Viljanen Markus , Meijerink Lotta , Zwakhals Laurens , van de Kassteele Jan
Published: June 2022

Background

Local policymakers require information about public health, housing and well-being at small geographical areas. A municipality can for example use this information to organize targeted activities with the aim of improving the well-being of their residents. Surveys are often used to gather data, but many neighborhoods can have only few or even zero respondents. In that case, estimating the status of the local population directly from survey responses is prone to be unreliable.

Methods

Small Area Estimation (SAE) is a technique to provide estimates at small geographical levels with only few or even zero respondents. In classical individual-level SAE, a complex statistical regression model is fitted to the survey responses by using auxiliary administrative data for the population as predictors, the missing responses are then predicted and aggregated to the desired geographical level. In this paper we compare gradient boosted trees (XGBoost), a well-known machine learning technique, to a structured additive regression model (STAR) designed for the specific problem of estimating public health and well-being in the whole population of the Netherlands.

Results

We compare the accuracy and performance of these models using out-of-sample predictions with five-fold Cross Validation (5CV). We do this for three data sets of different sample sizes and outcome types. Compared to the STAR model, gradient boosted trees are able to improve both the accuracy of the predictions and the total time taken to get these predictions. Even though the models appear quite similar in overall accuracy, the small area predictions at neighborhood level sometimes differ significantly. It may therefore make sense to pursue slightly more accurate models for better predictions into small areas. However, one of the biggest benefits is that XGBoost does not require prior knowledge or model specification. Data preparation and modelling is much easier, since the method automatically handles missing data, non-linear responses, interactions and accounts for spatial correlation structures.

Conclusions

In this paper we provide new nationwide estimates of health, housing and well-being indicators at neighborhood level in the Netherlands, see ’Online materials’. We demonstrate that machine learning provides a good alternative to complex statistical regression modelling for small area estimation in terms of accuracy, robustness, speed and data preparation. These results can be used to make appropriate policy decisions at a local level and make recommendations about which estimation methods are beneficial in terms of accuracy, time and budget constraints.
RAF1 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating LAGE1: an experimental research
Authors: Li Yanshi , Pan Min , Lu Tao , Yu Dan , Liu Chuan , Wang Zhihai , Hu Guohua
Published: June 2022

Background

Lymphatic metastasis was an independent prognostic risk factor for hypopharyngeal carcinoma and was the main cause of treatment failure. The purpose of this study was to screen the differential genes and investigate the mechanism of lymphatic metastasis in hypopharyngeal carcinoma.

Methods

Transcriptome sequencing was performed on primary tumors of patients, and differential genes were screened by bioinformatics analysis. The expression of differential genes was verified by qRT-PCR, western-blotting and immunohistochemical, and prognostic value was analyzed by Kaplan–Meier and log-rank test and Cox’s test. Next, FADU and SCC15 cell lines were used to demonstrate the function of differential genes both in vitro by EdU, Flow cytometry, Wound Healing and Transwell assays and in vivo by a foot-pad xenograft mice model. Proteomic sequencing was performed to screen relevant targets. In addition, in vitro and in vivo experiments were conducted to verify the mechanism of lymphatic metastasis.

Results

Results of transcriptome sequencing showed that RAF1 was a significantly differential gene in lymphatic metastasis and was an independent prognostic risk factor. In vitro experiments suggested that decreased expression of RAF1 could inhibit proliferation, migration and invasion of tumor cells and promote apoptosis. In vivo experiments indicated that RAF1 could promote tumor growth and lymphatic metastasis. Proteomic sequencing and subsequent experiments suggested that LAGE1 could promote development of tumor and lymphatic metastasis, and was regulated by RAF1.

Conclusions

It suggests that RAF1 can promote lymphatic metastasis of hypopharyngeal carcinoma by regulating LAGE1, and provide a basis for the exploring of novel therapeutic target and ultimately provide new guidance for the establishment of intelligent diagnosis and precise treatment of hypopharyngeal carcinoma.
Astrocytic Nrf2 expression protects spinal cord from oxidative stress following spinal cord injury in a male mouse model
Authors: Zhao Weiyi , Gasterich Natalie , Clarner Tim , Voelz Clara , Behrens Victoria , Beyer Cordian , Fragoulis Athanassios , Zendedel Adib
Published: June 2022

Background

Spinal cord injury (SCI) induces a multitude of deleterious processes, including neuroinflammation and oxidative stress (OS) which contributed to neuronal damage and demyelination. Recent studies have suggested that increased formation of reactive oxygen species (ROS) and the consequent OS are critical events associated with SCI. However, there is still little information regarding the impact of these events on SCI. Astrocytes are key regulators of oxidative homeostasis in the CNS and astrocytic antioxidant responses promote the clearance of oxidants produced by neurons. Therefore, dysregulation of astrocyte physiology might largely contribute to oxidative damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the main transcriptional regulator of cellular anti-oxidative stress responses.

Methods

In the current study, we hypothesized that astrocytic activation of Nrf2 protects the spinal cord post injury via suppression of neuroinflammation. Thus, using mice line with a GFAP-specific kelch-like ECH-associated protein 1 (Keap1)-deletion, we induced a hyperactivation of Nrf2 in astrocytes and further its effects on SCI outcomes. SCI-induction was performed in mice using the Infinite Horizon Spinal Cord Impactor with a force of 60 kdyn. To assess the quantitative pattern of Nrf2/ARE-activation, we included transgenic ARE-Luc mice. Data were analyzed with GraphPad Prism 8 (GraphPad Software Inc., San Diego, CA, USA). Brown–Forsythe test was performed to test for equal variances and normal distribution was tested with Shapiro–Wilk.

Results

In ARE-Luc mice, a significant induction of luciferase-activity was observed as early as 1 day post-injury, indicating a functional role of Nrf2-activity at the epicenter of SCI. Furthermore, SCI induced loss of neurons and oligodendrocytes, demyelination and inflammation in wild type mice. The loss of myelin and oligodendrocytes was clearly reduced in Keap1 KO mice. In addition, Keap-1 KO mice showed a significantly better locomotor function and lower neuroinflammation responses compared to wild type mice.

Conclusions

In summary, our in vivo bioluminescence data showed Nrf2-ARE activation during primary phase of SCI. Furthermore, we found that cell specific hyperactivation of Nrf2 was sufficient to protect the spinal cord against injury which indicate a promising therapeutic approach for SCI-treatment.
Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression
Authors: Wang Haixia , He Yi , Sun Zuoli , Ren Siyu , Liu Mingxia , Wang Gang , Yang Jian
Published: June 2022

Major depressive disorder is a highly debilitating psychiatric disorder involving the dysfunction of different cell types in the brain. Microglia are the predominant resident immune cells in the brain and exhibit a critical role in depression. Recent studies have suggested that depression can be regarded as a microglial disease. Microglia regulate inflammation, synaptic plasticity, and the formation of neural networks, all of which affect depression. In this review, we highlighted the role of microglia in the pathology of depression. First, we described microglial activation in animal models and clinically depressed patients. Second, we emphasized the possible mechanisms by which microglia recognize depression-associated stress and regulate conditions. Third, we described how antidepressants (clinical medicines and natural products) affect microglial activation. Thus, this review aimed to objectively analyze the role of microglia in depression and focus on potential antidepressants. These data suggested that regulation of microglial actions might be a novel therapeutic strategy to counteract the adverse effects of devastating mental disorders.
Clinical and genetic spectrum of 14 cases of NLRP3-associated autoinflammatory disease (NLRP3-AID) in China and a review of the literature
Authors: Zhou Yu , Wang Wei , Zhong Linqing , Wang Lin , Ma Mingsheng , Tang Xiaoyan , Li Zhuo , Wang Changyan , Gou Lijuan , Zhang Tiannan , Song Hongmei
Published: June 2022

Background

NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature.

Results

Fourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports.

Conclusion

In our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms.
Real-world clinicopathological features and outcome of thymic neuroendocrine tumors: a retrospective single-institution analysis
Authors: Chen Yeye , Zhang Jiaqi , Zhou Mengxin , Guo Chao , Li Shanqing
Published: June 2022

Background

Thymic neuroendocrine tumors comprise a heterogeneous group of rare diseases. This study aimed to investigate the real-world clinicopathological features and treatment outcomes of thymic neuroendocrine tumors.

Results

A total of 104 patients diagnosed with thymic neuroendocrine tumors in a single institution from 1983 to 2021 were eligible. Fourteen (13.46%) and 28 (26.92%) patients diagnosed with thymic neuroendocrine tumors suffered from multiple endocrine neoplasia and ectopic adrenocorticotropic hormone syndrome, respectively. Ninety-seven (93.27%) patients underwent surgical resection, including 79 (81.44%) with radical resection. Except for 5 patients lost during follow-up, the 1-, 3- and 5-year overall survival rates were 91.8%, 70.2% and 54.6%, respectively. The median overall survival was 61.57 months. Multivariate analysis revealed that years at diagnosis (HR 0.559, 95% CI 0.364–0.857, p = 0.008), radical resection (HR 2.860, 95% CI 1.392–5.878, p = 0.004), pathological grade (HR 1.963, 95% CI 1.058–3.644, p = 0.033) and Masaoka–Koga stage (HR 2.250, 95% CI 1.548–3.272, p = 0.000) exerted significant differences in overall survival among 99 patients. In the surgery group, multivariate Cox regression analysis exhibited significant overall survival differences in years at diagnosis (HR 0.563, 95% CI 0.367–0.866, p = 0.009), neoadjuvant therapy (HR 0.248, 95% CI 0.071–0.872, p = 0.030), radical resection (HR 3.674, 95% CI 1.685–8.008, p = 0.001), pathological grade (HR 2.082, 95% CI 1.098–3.947, p = 0.025) and Masaoka–Koga stage (HR 2.445, 95% CI 1.607–3.719, p = 0.000).

Conclusions

Radical resection and Masaoka–Koga stage were independent prognostic factors for the survival of patients with thymic neuroendocrine tumors. Systemic therapy and integrated management of patients with advanced-stage disease require high-level clinical evidence.
No evidence of uptake or propagation of reindeer CWD prions in environmentally exposed sheep
Authors: Harpaz Erez , Salvesen Øyvind , Rauset Geir Rune , Mahmood Aqsa , Tran Linh , Ytrehus Bjørnar , Benestad Sylvie Lafond , Tranulis Michael Andreas , Espenes Arild , Ersdal Cecilie
Published: June 2022

Background

Chronic wasting disease (CWD) is a prion disease of cervids first reported in North America in the 1960s. In Europe, CWD was first diagnosed in 2016 in a wild reindeer in Norway. Detection of two more cases in the same mountain area led to the complete culling of this partially confined reindeer population of about 2400 animals. A total of 19 CWD positive animals were identified. The affected area is extensively used for the grazing of sheep during summers. There are many mineral licks intended for sheep in the area, but these have also been used by reindeer. This overlap in area use raised concerns for cross-species prion transmission between reindeer and sheep. In this study, we have used global positioning system (GPS) data from sheep and reindeer, including tracking one of the CWD positive reindeer, to investigate spatial and time-relevant overlaps between these two species. Since prions can accumulate in lymphoid follicles following oral uptake, samples of gut-associated lymphoid tissue (GALT) from 425 lambs and 78 adult sheep, which had grazed in the region during the relevant timeframe, were analyzed for the presence of prions. The recto-anal mucosa associated lymphoid tissue (RAMALT) from all the animals were examined by histology, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), and the ileal Peyer's patch (IPP) from a subsample of 37 lambs were examined by histology and IHC, for the detection of prions.

Results

GPS data showed an overlap in area use between the infected reindeer herd and the sheep. In addition, the GPS positions of an infected reindeer and some of the sampled sheep showed temporospatial overlap. No prions were detected in the GALT of the investigated sheep even though the mean lymphoid follicle number in RAMALT and IPP samples were high.

Conclusion

The absence of prions in the GALT of sheep that have shared pasture with CWD-infected reindeer, may suggest that transmission of this novel CWD strain to sheep does not easily occur under the conditions found in these mountains. We document that the lymphoid follicle rich RAMALT could be a useful tool to screen for prions in sheep.
Linear DNA amplicons as a novel cancer vaccine strategy
Authors: Conforti Antonella , Salvatori Erika , Lione Lucia , Compagnone Mirco , Pinto Eleonora , Shorrock Clay , Hayward James A. , Sun Yuhua , Liang Ben Minghwa , Palombo Fabio , Viscount Brian , Aurisicchio Luigi
Published: June 2022

Background

DNA-based vaccines represent a simple, safe and promising strategy for harnessing the immune system to fight infectious diseases as well as various forms of cancer and thus are considered an important tool in the cancer immunotherapy toolbox. Nonetheless, the manufacture of plasmid DNA vaccines has several drawbacks, including long lead times and the need to remove impurities from bacterial cultures. Here we report the development of polymerase chain reaction (PCR)-produced amplicon expression vectors as DNA vaccines and their in vivo application to elicit antigen-specific immune responses in animal cancer models.

Methods

Plasmid DNA and amplicon expression was assessed both in vitro, by Hela cells transfection, and in vivo, by evaluating luciferase expression in wild-type mice through optical imaging. Immunogenicity induced by DNA amplicons was assessed by vaccinating wild-type mice against a tumor-associated antigen, whereas the antitumoral effect of DNA amplicons was evaluated in a murine cancer model in combination with immune-checkpoint inhibitors (ICIs).

Results

Amplicons encoding tumor-associated-antigens, such as telomerase reverse transcriptase or neoantigens expressed by murine tumor cell lines, were able to elicit antigen-specific immune responses and proved to significantly impact tumor growth when administered in combination with ICIs.

Conclusions

These results strongly support the further exploration of the use of PCR-based amplicons as an innovative immunotherapeutic approach to cancer treatment.
Neonatal presentation of Loeys-Dietz syndrome: two case reports and review of the literature
Authors: Baldo Francesco , Morra Laura , Feresin Agnese , Faletra Flavio , Al Naber Yasmin , Memo Luigi , Travan Laura
Published: June 2022

Background

Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical.

Case presentation

We report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hypermobility, arachnodactyly, and fingers joint contractures, as well as senile appearance and facial dysmorphisms. In the suspect of a connective tissue disorder, an echocardiography was performed and revealed an aortic root dilatation of 13 mm (Z score + 3). A trio based Whole Exome Sequencing found a novel de novo variant in the TGFBR2 gene. Despite the onset of a low-dose angiotensin receptor blocker therapy, the aneurysm progressed. The second case describes a female, born at 41 + 3 weeks of gestation. During the neonatal examination a cleft palate was noticed, as well as minor dysmorphisms. Since the family history was suspicious for connective tissue disorders, a genetic panel was performed and identified a pathogenetic variant in TGFB3 gene. In this case, the echocardiography revealed no abnormalities.

Conclusions

In addition to our cases, we identified 14 subjects with neonatal LDS in the medical literature. All of them had aortic involvement. Skeletal and face abnormalities, including eyes and palate malformations, were also highly frequent. Overall, 10 subjects required medical therapy to avoid aneurysm progression, and 8 patients underwent surgical procedures.

Benefits of an early diagnosis of LDS are various and imply a potential modification of the natural history of the disease with early interventions on its complications.
Living with Loss: study protocol for a randomized controlled trial evaluating an internet-based perinatal bereavement program for parents following stillbirth and neonatal death
Authors: Loughnan Siobhan A. , Boyle Frances M. , Ellwood David , Crocker Sara , Lancaster Ann , Astell Chrissie , Dean Julie , Horey Dell , Callander Emily , Jackson Claire , Shand Antonia , Flenady Vicki
Published: June 2022

Background

Stillbirth and neonatal death are devastating pregnancy outcomes with long-lasting psychosocial consequences for parents and families, and wide-ranging economic impacts on health systems and society. It is essential that parents and families have access to appropriate support, yet services are often limited. Internet-based programs may provide another option of psychosocial support for parents following the death of a baby. We aim to evaluate the efficacy and acceptability of a self-guided internet-based perinatal bereavement support program “Living with Loss” (LWL) in reducing psychological distress and improving the wellbeing of parents following stillbirth or neonatal death.

Methods

This trial is a two-arm parallel group randomized controlled trial comparing the intervention arm (LWL) with a care as usual control arm (CAU). We anticipate recruiting 150 women and men across Australia who have experienced a stillbirth or neonatal death in the past 2 years. Participants randomized to the LWL group will receive the six-module internet-based program over 8 weeks including automated email notifications and reminders. Baseline, post-intervention, and 3-month follow-up assessments will be conducted to assess primary and secondary outcomes for both arms. The primary outcome will be the change in Kessler Psychological Distress Scale (K10) scores from baseline to 3-month follow-up. Secondary outcomes include perinatal grief, anxiety, depression, quality of life, program satisfaction and acceptability, and cost-effectiveness. Analysis will use intention-to-treat linear mixed models to examine psychological distress symptom scores at 3-month follow-up. Subgroup analyses by severity of symptoms at baseline will be undertaken.

Discussion

The LWL program aims to provide an evidence-based accessible and flexible support option for bereaved parents following stillbirth or neonatal death. This may be particularly useful for parents and healthcare professionals residing in rural regions where services and supports are limited. This RCT seeks to provide evidence of the efficacy, acceptability, and cost-effectiveness of the LWL program and contribute to our understanding of the role digital services may play in addressing the gap in the availability of specific bereavement support resources for parents following the death of a baby, particularly for men.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12621000631808. Registered prospectively on 27 May 2021.
A self-efficacy-enhancing physical activity intervention in women with high-risk factors for gestational diabetes mellitus: study protocol for a randomized clinical trial
Authors: Yang Xiao , Zhang Ji , Wang Xiangzhi , Xu Yi , Sun Li , Song Yingli , Bai Ruijuan , Huang Hui , Zhang Jing , Zhang Ruixing , Guo Erfeng , Gao Lingling
Published: June 2022

Background

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Evidence has demonstrated that moderate-intensity physical activity may reduce the risk of gestational diabetes. However, women at risk of GDM spend most of their time performing sedentary behaviors. Although researchers identified self-efficacy as a mediator to overcome physical activity barriers, exercise intervention during pregnancy based on self-efficacy theory has not been discussed so far. Furthermore, there is conflicting evidence regarding the effects of a physical exercise intervention on the incidence of GDM and other maternal or neonatal outcomes in women at higher risk for GDM.

Methods/design

A single-center, parallel, randomized controlled trial will be conducted in a maternal–child health care center. A total of 244 pregnant women at high risk for GDM will be randomized into a study group receiving a self-efficacy-enhancing physical activity intervention or a control group receiving the usual care. The intervention will consist of four group sessions and everyday reminders by WeChat (Tencent, Shenzhen, China). The program will begin at approximately 13–14+6 gestational weeks and end at 36+6 gestational weeks. The primary outcomes will include the incidence of GDM, blood sugar values, and physical activity. The secondary outcomes will include physical activity self-efficacy, gestational weight gain, maternal outcomes, and neonatal outcomes.

Discussion

The findings of this research will contribute toward understanding the effects of a self-efficacy theory-oriented physical activity program on the incidence of GDM, blood sugar values, physical activity level, gestational weight gain, physical activity self-efficacy, maternal outcomes, and neonatal outcomes.

Trial registration

Chinese Clinical Trial Registry (CHiCTR) ChiCTR2200056355. Registered on February 4, 2022.
Influence of kinesiophobia on pain intensity, disability, muscle endurance, and position sense in patients with chronic low back pain—a case-control study
Authors: Kandakurti Praveen Kumar , Arulsingh Watson , S Patil Sharad
Published: June 2022

Background

Patients with chronic low back pain (CLBP) frequently present with kinesiophobia. Though large body of evidence reported the impact of kinesiophobia in patients with CLBP, there are paucity of studies in associating kinesiophobia to muscle endurance and position sense in patients with CLBP. The primary aim of the study is to compare the impact of kinesiophobia on lumbar extensor endurance, position sense in patient with CLBP, and asymptomatic individuals. Secondarily, we aim to examine the association between kinesiophobia and lumbar extensor endurance, position sense, pain intensity, and functional ability in patients with CLBP. Thirdly, we aim to assess the degree of association of various factors on CLBP, lumbar endurance, and position sense.

Material and methods

This case-control study will have 200 patients with CLBP and 400 controls. Kinesiophobia, lumbar endurance, and lumbar position sense will be assessed with Tampa Scale, Soren’s lumbar extensor test, and lumbar repositioning test respectively. Secondarily, the pain intensity will be assessed with visual analog scale and functional ability with Patient-specific Functional Scale in patients with CLBP. Lumbar endurance and joint position sense will be compared between subjects with and without kinesiophobia. Kinesiophobia scores will be compared with lumbar extensor endurance and proprioception joint position errors, pain intensity, and functional ability. Simple and multiple binary logistic regression will be used to determine crude and adjusted odd’s ratio for kinesiophobia, lumbar position sense and kinesiophobia, and lumbar endurance.

Discussion

The finding from this study can be generalized as this study has adequate sample size and subgroup analysis by adjusting the variables to draw a valid conclusion. The finding of this study will help the working physician to include assessment of kinesiophobia as part of musculoskeletal evaluation for patient with CLBP in a prospective diagnostic intervention.

Trial registration

ClinicalTrials.gov NCT05079893. Registered on 14 October 2021.
Database of non-target invertebrates recorded in field experiments of genetically engineered Bt maize and corresponding non-Bt maize
Authors: Meissle Michael , Naranjo Steven E. , Romeis Jörg
Published: June 2022

Objectives

To assess potential non-target effects of genetically engineered/modified (GM) maize that produces insecticidal proteins from Bacillus thuringiensis (Bt), numerous field experiments have been conducted worldwide. Field data are often variable and influenced by uncontrolled factors and meta-analyses can recognize general effects with increased statistical power compared to individual studies. This database represents a comprehensive collection of experimental field data on non-target invertebrates in Bt and non-Bt maize. It was created for a systematic review with the question if growing Bt maize changes abundance or ecological function of non-target animals compared to growing of non-GM maize. Systematic literature searches identified relevant data. Authors were contacted for additional information or raw data if needed and a critical appraisal scheme was developed and applied to each data record.

Data description

The database contains 7279 records of non-target invertebrate abundance, activity density, or predation or parasitism extracted from 120 articles. Records for individual species and life stages, but also aggregated data are available. Each record represents a comparison of invertebrates in Bt and non-Bt maize and includes means, standard deviations and sample sizes. Additional variables characterize publication details, experimental setup, cultivars, Bt proteins, geographic location, field management, insecticide treatments, sampling details, and taxonomy.
Comparisons of cell proliferation and cell death from tornaria larva to juvenile worm in the hemichordate Schizocardium californicum
Authors: Bump Paul , Khariton Margarita , Stubbert Clover , Moyen Nicole E. , Yan Jia , Wang Bo , Lowe Christopher J.
Published: June 2022

Background

There are a wide range of developmental strategies in animal phyla, but most insights into adult body plan formation come from direct-developing species. For indirect-developing species, there are distinct larval and adult body plans that are linked together by metamorphosis. Some outstanding questions in the development of indirect-developing organisms include the extent to which larval tissue undergoes cell death during the process of metamorphosis and when and where the tissue that will give rise to the adult originates. How do the processes of cell division and cell death redesign the body plans of indirect developers? In this study, we present patterns of cell proliferation and cell death during larval body plan development, metamorphosis, and adult body plan formation, in the hemichordate Schizocardium californium (Cameron and Perez in Zootaxa 3569:79–88, 2012) to answer these questions.

Results

We identified distinct patterns of cell proliferation between larval and adult body plan formation of S. californicum. We found that some adult tissues proliferate during the late larval phase prior to the start of overt metamorphosis. In addition, using an irradiation and transcriptomic approach, we describe a genetic signature of proliferative cells that is shared across the life history states, as well as markers that are unique to larval or juvenile states. Finally, we observed that cell death is minimal in larval stages but begins with the onset of metamorphosis.

Conclusions

Cell proliferation during the development of S. californicum has distinct patterns in the formation of larval and adult body plans. However, cell death is very limited in larvae and begins during the onset of metamorphosis and into early juvenile development in specific domains. The populations of cells that proliferated and gave rise to the larvae and juveniles have a genetic signature that suggested a heterogeneous pool of proliferative progenitors, rather than a set-aside population of pluripotent cells. Taken together, we propose that the gradual morphological transformation of S. californicum is mirrored at the cellular level and may be more representative of the development strategies that characterize metamorphosis in many metazoan animals.
RanDepict: Random chemical structure depiction generator
Authors: Brinkhaus Henning Otto , Rajan Kohulan , Zielesny Achim , Steinbeck Christoph
Published: June 2022

The development of deep learning-based optical chemical structure recognition (OCSR) systems has led to a need for datasets of chemical structure depictions. The diversity of the features in the training data is an important factor for the generation of deep learning systems that generalise well and are not overfit to a specific type of input. In the case of chemical structure depictions, these features are defined by the depiction parameters such as bond length, line thickness, label font style and many others. Here we present RanDepict, a toolkit for the creation of diverse sets of chemical structure depictions. The diversity of the image features is generated by making use of all available depiction parameters in the depiction functionalities of the CDK, RDKit, and Indigo. Furthermore, there is the option to enhance and augment the image with features such as curved arrows, chemical labels around the structure, or other kinds of distortions. Using depiction feature fingerprints, RanDepict ensures diversely picked image features. Here, the depiction and augmentation features are summarised in binary vectors and the MaxMin algorithm is used to pick diverse samples out of all valid options. By making all resources described herein publicly available, we hope to contribute to the development of deep learning-based OCSR systems.

Graphical Abstract
Ultrasound elastography in children — nice to have for scientific studies or arrived in clinical routine?
Authors: Mentzel Hans-Joachim , Glutig Katja , Gräger Stephanie , Krüger Paul-Christian , Waginger Matthias
Published: June 2022

Ultrasound elastography (USE) is a modality that in addition to fundamental B-mode, Doppler, and contrast-enhanced sonography is suitable to make qualitative and quantitative statements about the stiffness of tissues. Introduced more than 20 years ago in adults, USE becomes now a diagnostic tool also in children. The aim of this paper is to describe current available techniques for USE in children. The significance for routine use in children is shown, and further interesting applications are reported.
A green approach to clean iron stains from marble surfaces
Authors: Campanella Luigi , Cardellicchio Francesco , Dell’Aglio Emanuele , Reale Rita , Salvi Anna Maria
Published: June 2022

In the field of cultural heritage restoration, the removal of iron corrosion stains is a difficult problem to deal with, especially in stone materials. Many studies in recent years have been aimed at finding simple and reliable methods using non-toxic chelating compounds. The search for natural non-toxic compounds is therefore of great relevance, especially in the conservation of cultural heritage, where the use of toxic chemical compounds often involves risks for the environment and human health. Following this trend, the purpose of this preliminary work was to verify the use of two proteins, Lactotransferrin (Ltf) and Ovotransferrin (Ovt), for the removal of iron-based stains on marble surfaces. The two proteins, whose high affinity for iron “in vivo” has been widely documented, were extracted from their natural matrices. The protein extracts were then immobilized using a common cellulose pulp. The poultices obtained were spread on the surfaces of artificially stained marble specimens and, after a set time, were easily removed. The effectiveness of the removal, visually evident, was detected by spectrocolorimetry and image analysis. The surface analyses, before and after the treatment, carried out by X-ray photoelectron spectroscopy (XPS), confirmed that both proteins have a selective and effective complexing capacity for the ferric ions of rust stains.