bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the T cell receptor repertoire and melanoma tumor microenvironment upon combined treatment with ipilimumab and hTERT vaccination
Authors: Ellingsen Espen Basmo , Bounova Gergana , Kerzeli Iliana , Anzar Irantzu , Simnica Donjete , Aamdal Elin , Guren Tormod , Clancy Trevor , Mezheyeuski Artur , Inderberg Else Marit , Mangsbo Sara M. , Binder Mascha , Hovig Eivind , Gaudernack Gustav
Published: September 2022

Background

This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue samples with the goal of elucidating the effects of treatment on the T cell receptor repertoire and tumor microenvironment.

Methods

The trial was an open-label, single-center phase I/IIa study. Eligible patients had unresectable metastatic melanoma. Patients received up to 9 UV1 vaccinations and four ipilimumab infusions. Clinical responses were assessed according to RECIST 1.1. Patients were followed up for progression-free survival (PFS) and overall survival (OS). Whole-exome and RNA sequencing, and multiplex immunofluorescence were performed on the biopsies. T cell receptor (TCR) sequencing was performed on the peripheral blood and tumor tissues.

Results

Twelve patients were enrolled in the study. Vaccine-specific immune responses were detected in 91% of evaluable patients. Clinical responses were observed in four patients. The mPFS was 6.7 months, and the mOS was 66.3 months. There was no association between baseline tumor mutational burden, neoantigen load, IFN-γ gene signature, tumor-infiltrating lymphocytes, and response to therapy. Tumor telomerase expression was confirmed in all available biopsies. Vaccine-enriched TCR clones were detected in blood and biopsy, and an increase in the tumor IFN-γ gene signature was detected in clinically responding patients.

Conclusion

Clinical responses were observed irrespective of established predictive biomarkers for checkpoint inhibitor efficacy, indicating an added benefit of the vaccine-induced T cells. The clinical and immunological read-out warrants further investigation of UV1 in combination with checkpoint inhibitors.

Trial registration Clinicaltrials.gov identifier: NCT02275416. Registered October 27, 2014. https://clinicaltrials.gov/ct2/show/NCT02275416?term=uv1&draw=2&rank=6
Advancing qualitative rare disease research methodology: a comparison of virtual and in-person focus group formats
Authors: Dwyer Andrew A. , Uveges Melissa , Dockray Samantha , Smith Neil
Published: September 2022

Background

Rare disease research is hampered in part by the fact that patients are geographically dispersed. Rare disease patient communities are recognized for their use of the internet to learn about their condition and find peer-to-peer support. As such, web-based technologies offer promise for overcoming geographic barriers in rare disease research for many. Qualitative focus groups (FGs) are a widely used methodology used to understand patients and parents/families ‘lived experience’ and unmet needs is important to improve care for rare diseases. It is unclear if web-enabled (virtual) FGs are comparable to traditional in-person approaches. We conducted in-person (n = 3) and virtual (n = 3) FGs with rare disease patients to determine if virtual FGs produce similar results in-person FGs.

Results

Three in-person (n = 33 participants) and three virtual (n = 25 participants) FGs were conducted examining attitudes and beliefs regarding genetic testing and family communication of risk. Participants included 30 males, 18 females, and 10 parents/guardians. Two independent investigators identified excerpts (meaningful sections of text) and coded themes/sub-themes using a codebook. Inter-coder agreement across identified excerpts (n = 530) in both FG formats was 844/875 (96.5%). Two additional investigators reviewed coded excerpts and did not identify additional themes/sub-themes—supporting data saturation across FG formats. Virtual FGs accounted for 303/530 (57.2%) of total excerpts and 957/1721 (55.7%) of all identified themes/sub-themes. Formats were similar in terms of overall number of excerpts (101 ± 7.8 vs. 75.7 ± 18.8, p = 0.26) and themes/sub-themes (319 ± 6.1 vs. 254.7 ± 103.6, p = 0.34) between virtual and in-person FGs. However, virtual FGs had significantly more coded excerpts specifically relating to sensitive/intimate topics including ‘attitudes and beliefs’ (n = 320 vs. n = 235, p < 0.001), ‘information and support’ (n = 184 vs. n = 99, p < 0.001), and ‘family communication’ (n = 208 vs. n = 114, p < 0.001).

Conclusions

Virtual FGs yielded similar numbers of coded excerpts compared to traditional in-person FGs. Virtual FGs appear to support the relative anonymity of participants, resulting in richer discussion of highly sensitive, intimate topics. Findings support the validity and methodologic rigor of using web-enabled technologies for conducting FGs in rare diseases.
Efficacy and safety of 5% lidocaine patches for postoperative pain management in patients undergoing unilateral inguinal hernia repair: study protocol for a prospective, double-blind, randomized, controlled clinical trial
Authors: Ahn Hong-min , Oh Heung-Kwon , Kim Duck-Woo , Kang Sung-Bum , Koo Bon-Wook , Lee Pyung-Bok
Published: September 2022

Background

Acute postoperative pain is a common complication of inguinal hernia repair. Pain management using local application of anesthetic agents over the skin surrounding the surgical incision may reduce the requirement for other pain medications. Targeted topical analgesics such as 5% lidocaine patches have been known to improve acute and chronic pain. However, the clinical effect of lidocaine patches on postoperative pain after inguinal hernia repair has not been studied, especially in patients undergoing surgery at day surgery units.

Methods/design

This is a single-center, prospective, double-blind, randomized, controlled clinical trial. Participants with unilateral inguinal hernia will be randomized to the lidocaine patch group or the placebo patch group. Based on the randomized allocation sequence, either lidocaine patches or placebo patches will be attached near each participant’s surgical wound after open hernia repair under general anesthesia. Participants will be asked to follow up at our outpatient clinic on the first postoperative day and at 1 week after surgery. The primary outcome is pain intensity, which will be measured using the visual analog scale (VAS) at the time of discharge from the day surgery unit. The secondary outcomes are VAS score at 24 h and 1 week after surgery. We will collect and analyze the participants’ clinical data (amount of intraoperative opioid use, time to recovery, and pain intensity at 30 min after surgery) and demographic characteristics (age, sex, body weight, and height).

Discussion

This trial may not only provide evidence on the efficacy of a 5% lidocaine patch for acute postoperative pain management after unilateral inguinal hernia repair, but also demonstrate the efficacy and safety of the patch for post-discharge pain management.

Trial registration

ClinicalTrials.gov NCT04754451. Registered on February 10, 2021.
Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS)
Authors: Cai Guoqi , Jones Graeme , Cicuttini Flavia M. , Wluka Anita E. , Wang Yuanyuan , Hill Catherine , Keen Helen , Antony Benny , Wang Xia , de Graaff Barbara , Thompson Michael , Winzenberg Tania , Buttigieg Kathy , Aitken Dawn
Published: September 2022

Background

There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis.

Methods

We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0–3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses.

Discussion

This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype.

Trial registration

Australian and New Zealand Clinical Trial Registry ACTRN12618001656224. Registered on 08 October 2018.
Comprehensive comparison between azacytidine and decitabine treatment in an acute myeloid leukemia cell line
Authors: Aumer Tina , Gremmelmaier Constanze B. , Runtsch Leander S. , Pforr Johannes C. , Yeşiltaç G. Nur , Kaiser Stefanie , Traube Franziska R.
Published: September 2022

Azacytidine (AzaC) and decitabine (AzadC) are cytosine analogs that covalently trap DNA methyltransferases, which place the important epigenetic mark 5-methyl-2’-deoxycytidine by methylating 2’-deoxycytidine (dC) at the C5 position. AzaC and AzadC are used in the clinic as antimetabolites to treat myelodysplastic syndrome and acute myeloid leukemia and are explored against other types of cancer. Although their principal mechanism of action is known, the downstream effects of AzaC and AzadC treatment are not well understood and the cellular prerequisites that determine sensitivity toward AzaC and AzadC remain elusive. Here, we investigated the effects and phenotype of AzaC and AzadC exposure on the acute myeloid leukemia cell line MOLM-13. We found that while AzaC and AzadC share many effects on the cellular level, including decreased global DNA methylation, increased formation of DNA double-strand breaks, transcriptional downregulation of important oncogenes and similar changes on the proteome level, AzaC failed in contrast to AzadC to induce apoptosis efficiently in MOLM-13. The only cellular marker that correlated with this clear phenotypical outcome was the level of hydroxy-methyl-dC, an additional epigenetic mark that is placed by TET enzymes and repressed in cancer cells. Whereas AzadC increased hmdC substantially in MOLM-13, AzaC treatment did not result in any increase at all. This suggests that hmdC levels in cancer cells should be monitored as a response toward AzaC and AzadC and considered as a biomarker to judge whether AzaC or AzadC treatment leads to cell death in leukemic cells.
Roles of microglia/macrophage and antibody in cell sheet transplantation in the central nervous system
Authors: Honda Naoto , Watanabe Yasuhiro , Tokuoka Yuta , Hanajima Ritsuko
Published: September 2022

Background

We previously established a human mesenchymal stem cell (MSC) line that was modified to express trophic factors. Transplanting a cell sheet produced from this line in an amyotrophic lateral sclerosis mouse model showed a beneficial trend for mouse life spans. However, the sheet survived for less than 14 days, and numerous microglia and macrophages were observed within and adjacent to the sheet. Here, we examined the roles of microglia and macrophages as well as acquired antibodies in cell sheet transplantation.

Methods

We observed the effects of several MSC lines on macrophages in vitro, that is, phenotype polarization (M1 or M2) and migration. We then investigated how phenotypic polarization affected MSC survival using antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). We also confirmed the role of complement on cytotoxicity. Lastly, we selectively eliminated microglia and macrophages in vivo to determine whether these cells were cytoprotective to the donor sheet.

Results

In vitro co-culture with MSCs induced M2 polarization in macrophages and facilitated their migration toward MSCs in vitro. There was no difference between M1 and M2 phenotypes on ADCC and ADCP. Cytotoxicity was observed even in the absence of complement. Eliminating microglia/macrophage populations in vivo resulted in increased survival of donor cells after transplantation.

Conclusions

Acquired antibodies played a role in ADCC and ADCP. MSCs induced M2 polarization in macrophages and facilitated their migration toward MSCs in vitro. Despite these favorable characteristics of microglia and macrophages, deletion of these cells was advantageous for the survival of donor cells in vivo.
External validation: a simulation study to compare cross-validation versus holdout or external testing to assess the performance of clinical prediction models using PET data from DLBCL patients
Authors: Eertink Jakoba J. , Heymans Martijn W. , Zwezerijnen Gerben J. C. , Zijlstra Josée M. , de Vet Henrica C. W. , Boellaard Ronald
Published: September 2022

Aim

Clinical prediction models need to be validated. In this study, we used simulation data to compare various internal and external validation approaches to validate models.

Methods

Data of 500 patients were simulated using distributions of metabolic tumor volume, standardized uptake value, the maximal distance between the largest lesion and another lesion, WHO performance status and age of 296 diffuse large B cell lymphoma patients. These data were used to predict progression after 2 years based on an existing logistic regression model. Using the simulated data, we applied cross-validation, bootstrapping and holdout (n = 100). We simulated new external datasets (n = 100, n = 200, n = 500) and simulated stage-specific external datasets (1), varied the cut-off for high-risk patients (2) and the false positive and false negative rates (3) and simulated a dataset with EARL2 characteristics (4). All internal and external simulations were repeated 100 times. Model performance was expressed as the cross-validated area under the curve (CV-AUC ± SD) and calibration slope.

Results

The cross-validation (0.71 ± 0.06) and holdout (0.70 ± 0.07) resulted in comparable model performances, but the model had a higher uncertainty using a holdout set. Bootstrapping resulted in a CV-AUC of 0.67 ± 0.02. The calibration slope was comparable for these internal validation approaches. Increasing the size of the test set resulted in more precise CV-AUC estimates and smaller SD for the calibration slope. For test datasets with different stages, the CV-AUC increased as Ann Arbor stages increased. As expected, changing the cut-off for high risk and false positive- and negative rates influenced the model performance, which is clearly shown by the low calibration slope. The EARL2 dataset resulted in similar model performance and precision, but calibration slope indicated overfitting.

Conclusion

In case of small datasets, it is not advisable to use a holdout or a very small external dataset with similar characteristics. A single small testing dataset suffers from a large uncertainty. Therefore, repeated CV using the full training dataset is preferred instead. Our simulations also demonstrated that it is important to consider the impact of differences in patient population between training and test data, which may ask for adjustment or stratification of relevant variables.
Selecting pseudo supervision for unsupervised domain adaptive SAR target classification
Authors: Zhao Lingjun , He Qishan , Ding Ding , Zhang Siqian , Kuang Gangyao , Liu Li
Published: September 2022

In recent years, deep learning has brought significant progress for the problem of synthetic aperture radar (SAR) target classification. However, SAR image characteristics are highly sensitive to the change of imaging conditions. The inconsistency of imaging parameters (especially the depression angle) leads to the distribution shift between the training and test data and severely deteriorates the classification performance. To address this problem, in this paper we propose an unsupervised domain adaptation method based on selective pseudo-labelling for SAR target classification. Our method directly trains a deep model using the data from the target domain by generating pseudo-labels in the target domain. The key idea is to iteratively select valuable samples from the target domain and optimize the classifier. In each iteration, the breaking ties (BT) criterion is adopted to select the best samples with the highest scores of relative confidence. Besides, to avoid error accumulation in the iterative process, class confusion regularization is used to improve the accuracy of pseudo-labelling. Our method is compared with state-of-the-art methods, including supervised classification and unsupervised domain adaptation methods, over the moving and stationary target acquisition and recognition (MSTAR) dataset. The experimental results demonstrate that the proposed method can achieve better classification performance, especially when the difference of depression angles of the source and target domain images is large. Besides, our method also shows its superiority under limited-sample conditions.
Distributed ranking-based resource allocation for sporadic M2M communication
Authors: Chang Yunyan , Jung Peter , Zhou Chan , Stańczak S.ławomir
Published: September 2022

This work proposes a novel scheme for distributed ranking-based and contention-free resource allocation in large-scale machine-to-machine (M2M) communication networks. We partition a network of N devices into disjoint clusters based on service type, and assign to each cluster a cluster-specific signature for active cluster members to indicate their active status. The devices in each cluster are totally ordered in some a priori-known manner, which gives rise to an active ranking of active cluster members. In order to tackle complexity issues in large-scale M2M networks with a massive number of devices, we propose a distributed resource allocation scheme using the framework of compressed sensing (CS), which mainly consists of three phases: (i) In a full-duplex acquisition phase, the devices transmit their cluster-specific signatures simultaneously and the network activation pattern is collected in a distributed manner. (ii) The base station detects the active clusters and the number of active devices per cluster using block sketching, and allocates resources to each active cluster accordingly. (iii) Each active device determines its active ranking in the cluster and accesses a specific resource according to the ranking position. By exploiting the sparsity in the activation pattern of the M2M devices, the proposed scheme is formulated as a CS support recovery problem for a particular binary block-sparse signal $$x\in {\mathbb{B}}^N$$

x
∈

B

N

– with block sparsity $$K_{B}$$

K
B

and in-block sparsity $$K_{I}$$

K
I

over block size d. Our analysis shows that the proposed scheme efficiently reduces the signature length to $$\mathcal {O}(\max \{K_{B}\log N, K_{B}K_{I}\log d\})$$

O
(
max

{

K
B

log
N
,

K
B

K
I

log
d
}

)

and achieves less computational complexity of $$\mathcal {O}(dK_{I}^{2}+\frac{N}{d}\log N)$$

O
(
d

K

I

2

+

N
d

log
N
)

compared with standard CS algorithms. Moreover, numerical results suggest strong robustness of the proposed scheme under noisy conditions.
Screw fixation in the treatment of displaced intra-articular calcaneus fractures: a systematic review protocol
Authors: Wilmsen Leah , Neubert Anne , Windolf Joachim , Icks Andrea , Richter Bernd , Thelen Simon
Published: September 2022

Background

The Calcaneus is the largest bone of the foot and the most frequent tarsal bone to be fractured. Overall, it causes round about 10 cases per 100,000 residents per year mainly in men. Especially displaced intra-articular calcaneus fractures often have early and late complications and its associated disability. There are various strategies for the treatment of displaced intra-articular calcaneus fractures, but the gold standard is still subject of a long-standing controversy. Minimally invasive procedures became more common in an attempt to reduce the high rate of complications associated with open reduction and internal fixation. With the increase in minimally invasive techniques, screw fixation also gained in significance. The current literature does not sufficiently elucidate whether the screw fixation is superior to other treatment options especially in relation to adverse events, health-related quality of life and postoperative pain. This study aims to investigate benefits and harms of treating displaced intra-articular calcaneus fractures (types II, III and IV according to Sanders) with screw fixation in adults.

Methods

A systematic review will be conducted based on the principles described in the Cochrane Handbook. We will include adults with displaced intra-articular calcaneus fractures of Sanders type II, III and IV. The surgical method of screw fixation shall be compared to other surgical interventions to stabilise calcaneus fractures. Primary outcomes are serious adverse events, health-related quality of life and postoperative pain level. MEDLINE, CENTRAL, CINAHL, Web of Science and bibnet.org, ClinicalTrial.gov and the World Health Organization International Clinical Trials Registry Platform (ICTR) will be searched. Screening and data extraction will be performed by two authors independently. A third author will arbitrate disputes. Risk of Bias will be assessed with the Cochrane tool. Meta-analysis will be performed if participants, interventions, comparisons and outcomes are sufficiently similar to ensure a result that is clinically meaningful.

Discussion

Due to the increasing use of minimally invasive techniques and the increasing use of screw fixation instead of open reduction and plate fixation, it is important to analyse the benefits and harms of screw fixation for calcaneus fractures. Screw fixation could, in the future, help to operate in a less invasive and tissue preserving manner while still achieving an adequate functional result for the patient

Systematic review registration

CRD42021244695
The impact of the loss of first permanent molars on the duration of treatment in patients treated with orthodontic space closure and without skeletal anchorage
Authors: Cardoso Paula Coutinho , Mecenas Paulo , Normando David
Published: September 2022

Background

This study aims to evaluate the impact of the loss of permanent molars on the duration of orthodontic treatment for space closure and without skeletal anchorage.

Methods

Records at the beginning (T0) and the end (T1) of orthodontic treatment were selected retrospectively. Patients were divided into two groups: loss of molar (n = 19) and control, without loss (n = 24). The impact of loss on treatment time was assessed using multiple linear regression adjusted for the number of absences, bonding failures, age, sex, PAR index at T0 and T1 at p<0.05. Treatment time was also evaluated by the number of losses and which arches were involved (upper, lower). The systematic and random errors for the PAR index were verified using the intraclass correlation coefficient (ICC) and the Dahlberg formula, respectively.

Results

A small random error (1.51) and excellent replicability (ICC = 99.6) were observed. Overall average treatment time was 22.5 months (± 7.95) for the group without loss and 44.7 months (± 17.3) with a loss. Treatment time was longer in cases where there was a higher number of missing molars and when both arches were involved. In addition to the loss (β = 4.25, p < 0.001), the number of missed appointments (β = 2.88, p < 0.001) had a significant effect and increased treatment time. Bonding failures, gender, age, and PAR index at T0 and T1 were not significantly associated with treatment time in the multivariate model (p > 0.05).

Conclusion

Loss of the first permanent molar has a negative impact on orthodontic treatment time in cases of space closure. The treatment time is longer when there are more tooth losses and arches involved. Treatment time also increases with greater numbers of missed clinical appointments.
Scoping review on diagnostic criteria and investigative approach in sepsis of unknown origin in critically ill patients
Authors: Ling Lowell , Mui Oliver Oi Yat , Laupland Kevin B. , Lefrant Jean-Yves , Roberts Jason A. , Gopalan Pragasan Dean , Lipman Jeffrey , Joynt Gavin M. ,   for the CaBoOM investigators, Stelfox Tom , Niven Daniel , Paramalingam Rameiya , Vonderhaar Derek , Freebairn Ross , Joynt Gavin M. , Ling Lowell , Leung Patricia , Gopalan Dean , Lefrant Jean Yves , Lloret Sophie , Elotmani Loubna , Roberts Jason A. , Lipman Jeffrey , Laupland Kevin B. , Fourie Cheryl , Saba Renee , Carlisle Dougal , Edwards Felicity
Published: September 2022

Background

Up to 11% of critically ill patients with sepsis have an unknown source, where the pathogen and site of infection are unclear. The aim of this scoping review is to document currently reported diagnostic criteria of sepsis of unknown origin (SUO) and identify the types and breadth of existing evidence supporting diagnostic processes to identify the infection source in critically ill patients with suspected SUO.

Methods

A literature search of Embase, MEDLINE and PubMed for published studies from 1910 to August 19, 2021 addressing the topic of SUO was performed. Study type, country of origin according to World Bank classification, diagnostic criteria of sepsis of unknown origin, and investigative approaches were extracted from the studies.

Results

From an initial 722 studies, 89 unique publications fulfilled the inclusion and exclusion criteria and were included for full text review. The most common publication type was case report/series 45/89 (51%). Only 10/89 (11%) of studies provided a diagnostic criteria of SUO, but a universally accepted diagnostic criterion was not identified. The included studies discussed 30/89 (34%) history, 23/89 (26%) examination, 57/89 (64%) imaging, microbiology 39/89 (44%), and special tests 32/89 (36%) as part of the diagnostic processes in patients with SUO.

Conclusions

Universally accepted diagnostic criteria for SUO was not found. Prospective studies on investigative processes in critically ill patients managed as SUO across different healthcare settings are needed to understand the epidemiology and inform the diagnostic criteria required to diagnose SUO.
Whole-liver enhanced CT radiomics analysis to predict metachronous liver metastases after rectal cancer surgery
Authors: Liang Meng , Ma Xiaohong , Wang Leyao , Li Dengfeng , Wang Sicong , Zhang Hongmei , Zhao Xinming
Published: September 2022

Background

To develop a radiomics model based on pretreatment whole-liver portal venous phase (PVP) contrast-enhanced CT (CE-CT) images for predicting metachronous liver metastases (MLM) within 24 months after rectal cancer (RC) surgery.

Methods

This study retrospectively analyzed 112 RC patients without preoperative liver metastases who underwent rectal surgery between January 2015 and December 2017 at our institution. Volume of interest (VOI) segmentation of the whole-liver was performed on the PVP CE-CT images. All 1316 radiomics features were extracted automatically. The maximum-relevance and minimum-redundancy and least absolute shrinkage and selection operator methods were used for features selection and radiomics signature constructing. Three models based on radiomics features (radiomics model), clinical features (clinical model), and radiomics combined with clinical features (combined model) were built by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of models, and calibration curve and the decision curve analysis were performed to evaluate the clinical application value.

Results

In total, 52 patients in the MLM group and 60 patients in the non-MLM group were enrolled in this study. The radscore was built using 16 selected features and the corresponding coefficients. Both the radiomics model and the combined model showed higher diagnostic performance than clinical model (AUCs of training set: radiomics model 0.84 (95% CI, 0.76–0.93), clinical model 0.65 (95% CI, 0.55–0.75), combined model 0.85 (95% CI, 0.77–0.94); AUCs of validation set: radiomics model 0.84 (95% CI, 0.70–0.98), clinical model 0.58 (95% CI, 0.40–0.76), combined model 0.85 (95% CI, 0.71–0.99)). The calibration curves showed great consistency between the predicted value and actual event probability. The DCA showed that both the radiomics and combined models could add a net benefit on a large scale.

Conclusions

The radiomics model based on preoperative whole-liver PVP CE-CT could predict MLM within 24 months after RC surgery. Clinical features could not significantly improve the prediction efficiency of the radiomics model.
Management of multiple and unruptured cerebral aneurysms
Authors: Deniwar Mohamed Adel
Published: September 2022

The incidence of multiple aneurysms was 10.7–34% of CA. Multiple associated factors were found; hypertension was the most significant one and others like advancing age and female sex were also documented. The estimated prevalence of UA is 5–10%. They include those aneurysms that did not rupture and discovered incidentally and those presented with symptoms rather than SAH, e.g., cranial nerve palsy or mass effect. Unruptured intracranial aneurysms are diagnosed with higher frequency nowadays as a result of imaging techniques improvement. The reported annual rate of rupture of UA is approximately 0.7–1%. The natural history of unruptured cerebral aneurysms cannot be extrapolated from the evaluation of individuals with ruptured aneurysms. Multiple cerebral aneurysms pose an even greater risk than a single aneurysm; the risk of rebleeding from the original aneurysm is larger and occurs sooner. The natural course of the disease has led to a consensus that all multiple unruptured aneurysms should be treated when technically viable. However, the prophylactic treatment of multiple unruptured is still controversial. Weighing the risk of intervention to the risk of observation is a mandatory pathway. Factors like age of patients, size and location of the aneurysms influence the decision-making and the type of therapy to be elected.
The relationship between communication skills, sensory difficulties, and anxiety in children with autism spectrum disorder
Authors: Khaledi Hekmat , Aghaz Alireza , Mohammadi Alireza , Dadgar Hooshang , Meftahi Gholam Hossein
Published: September 2022

Background

Despite the high prevalence of communicational differences, anxiety, and sensory processing difficulties in children with autism spectrum disorder (ASD), little is known about the nature of their experiences. Thus, the present study aimed to explore the correlation between communication skills, sensory difficulties, and anxiety in children with ASD. Fifty-three children with ASD (Mage = 8.51, SD = 2.51; males = 42) were recruited. The Persian version of the Short Sensory Profile (SSP), the Children’s Communication Checklist (CCC), and the Spence Children’s Anxiety Scale (SCAS) was used to assess the variables.

Results

The overall sensory score of children with ASD was significantly and positively correlated with most of the communication skills (P < 0.05). The overall sensory score of children with ASD was significantly and negatively correlated with all anxiety subsets of these children (P < 0.05). The social relationships score of children with ASD had a significant and negative correlation with all subsets of anxiety and a significant and positive correlation with all sensory subsets (P < 0.05). The total score of communication was significantly and negatively related to all subsets of anxiety except separation anxiety (P < 0.05).

Conclusions

Sensory processing difficulties in ASD children appear to be significantly associated with communication skills and anxiety acts as a mediator between the two.
Continuous optical zoom microscope with extended depth of field and 3D reconstruction
Authors: Liu Chao , Jiang Zhao , Wang Xin , Zheng Yi , Zheng Yi-Wei , Wang Qiong-Hua
Published: September 2022

Microscope such as fluorescence microscope, confocal microscope and two-photon microscope plays an important role in life science, laser processing and other fields. However, most microscopes only have discrete zoom rates. In this paper, a continuous optical zoom microscope with extended depth of field and 3D reconstruction is demonstrated for the first time. It consists of a zoom objective lens, a microscope holder, an adjustable three-dimensional object stage, an Abbe condenser and an LED light source. The zoom objective lens is composed of several liquid lenses and solid lenses. By adjusting the applied voltage to the liquid lens, the proposed microscope can achieve a large continuous magnification from 10? to 60?. Moreover, an improved shape from focus (SFF) algorithm and image fusion algorithm are designed for 3D reproduction. Based on the liquid lenses, the axial focusing position can be adjusted to obtain images with different depths, and then the extended depth of field and 3D reconstruction can be realized. Our experimental results demonstrate the feasibility of the proposed microscope. The proposed microscope is expected to be applied in the fields of pathological diagnosis, biological detection, etc.
Delayed presentation of isolated female epispadias with urinary incontinence: a case report
Authors: Oyinloye Adewale Olaotan , Wabada Samuel , Abubakar Auwal Mohammed , Rikin Christopher Uruku
Published: September 2022

Background

Female epispadias is a rare congenital anomaly, with a quoted incidence of 1 in 480,000.These patients present with urinary incontinence and varying degrees of external genitalia abnormality. This report presents the delayed presentation and management of a 14-year-old female with urinary incontinence due to isolated epispadias.

Case presentation

This is the case report of a 14-year-old female with urinary incontinence noticed since infancy. Examination of the genitalia revealed a bifid clitoris, depressed mons pubis, underdeveloped labia, patulous urethral opening, and normal vagina. She had surgical repair of the anomaly and has subsequently achieved continence. She has been continent in the last 4 ½ years of follow-up and is now married with a 1-year-old child.

Conclusion

Female epispadias is a rare but often missed cause of incontinence. A high index of suspicion and careful genital examination will help in identifying this anomaly. Surgical correction achieves satisfactory outcome as regards continence and cleanliness. Long-term follow-up is essential.
Understanding microplastic pollution in the Nordic marine environment – knowledge gaps and suggested approaches
Authors: Jensen Sophie , Grøsvik Bjørn Einar , Halsband Claudia , Halldórsson Halldór Pálmar , Leslie Heather A. , Gunnlaugsdóttir Helga , Guls Hermann Dreki , Vorkamp Katrin , Granberg Maria E. , Sigurðsson Valtýr , Jörundsdóttir Hrönn Ólína
Published: September 2022

This paper examines a number of specific, practical recommendations to advance knowledge and move towards evidence-based solutions to microplastic (MP) pollution in the Nordic marine environment. The paper approaches the subject of MPs holistically, emphasises the knowledge gaps and challenges in answering pressing questions, discusses the limitations that so far have prevented these questions from being solved, and suggests approaches for answering them. The Nordic context is chosen due to the global importance of its ecosystem that is threatened by MP pollution, exacerbated by climate change. The research questions discussed pick up knowledge gaps identified in attempts to answer the most pressing questions of our time regarding marine MP pollution and are applicable to some or all seas of the Nordic region, from the Baltic and North Seas in the south to the Arctic in the north.

The research questions relate to sources, sinks and transport of MPs, and how food webs are potentially impacted in Nordic marine environments. In addition, we point out the relevance for stakeholders expected to use the emerging knowledge. Through this exercise, using concrete examples, we aim to invite discussions on how a concerted effort by the Nordic countries can bring MP research to a higher level of understanding needed to address the MP pollution problem in Nordic marine habitats.
Do sunscreens have more positive or negative effects? Study review
Authors: Ozga-Stachurska Alicja Maria , Wójcik-Grudzień Justyna , Pawłowska Paulina , Rozenbajgier Martyna
Published: September 2022

Introduction: UV radiation is related to skin cancers, skin photoaging and sunburn. It can be harmful for human skin, so it is crucial to have a protection against sun rays. Substances protecting people from sun are sunscreens, that block and absorb UV radiation. The first sunscreen was discovered in 1928 and, since then, there have been many concerns about its safety, efectiveness and impant on the environment. Types of accessible sunscreens are physical sunscreens, chemical sunscreens and a combination. This study review is performed to assess possible risks of using sunscreens and evaluate if there are more positive or negative effects of their action.
The aim of the study:  To evaluate positive and negative effects of sunscreens action.
Materials and methods: We searched Pubmed and ResearchGate in order to find relevant studies about sunscreens and their impact on human skin, human health and environment.
Results: There seem to be some adverse effects of sunblockers for the environment, such as destroying coral reefs, bioaccumulating in fish tissue and water sources. In some studies there was mentioned a negative impact of sunscreens on hormonal systems and pregnancy, as well as on human skin. On the other hand, many studies display that sunblockers inhibit the carcinogenic effect of sun rays, preventing people from developing skin cancers.
Conclusions: Althought sunscreens can have some negative effects, studies showed that there are more positive effects of their action. They can be harmful for the environment, but at the same time they can be a protection. Sunscreens protect skin from developing skin cancer and also delay skin aging. However, the protection against sun is complex.
Urinary tract infections in children - a review
Authors: Wojtachnio Dominika , Osiejewska Aleksandra , Bartoszewicz Jakub , Grądzik Anna , Nowakowska Izabela , Kudan Małgorzata , Gorajek Anna , Mikut Karolina
Published: September 2022

Introduction and purpose:

Urinary tract infection (UTI) is very common, mostly bacterial infection in childhood. UTI may affect the lower urinary tract or the upper urinary tract. Infection typically require antibiotics for treatment. 

Brief description of the state of knowledge:  

The prevalence of urinary tract infection is between 2 and 8% and it is more common in  female, infants and uncircumcised male infants. Most paediatric UTIs are caused by Gram negative bacteria Escherichia coli (E.coli). Symptoms of this infection are nonspecific and may be confused with signs of other clinical conditions. The most common symptoms are suprapubic pain, back pain, dysuria, urinary frequency and systemic symptoms such as fever, vomiting, lethargy.  Antibiotics are the standard treatment for urinary tract infections. 

Conclusion: 

This article reviews basic informations, epidemiology, clinical presentation, diagnosis and treatment of urinary tract infection.
Kancelaria sądu ziemskiego bytomskiego państwa stanowego w świetle inwentarza z lat czterdziestych XVII w.
Authors: Gojniczek Wacław
Published: September 2022

CHANCELLERY OF THE LAND COURT OF THE BYTOM STATE COUNTRY IN LIGHT OF THE INVENTORY FROM THE 1740S The land courts operating in the Silesian principalities and state countries were one of the pillars of the estates separation of the nobility from the rest of the society. The knowledge regarding the Upper Silesian land courts is relatively poor. The present study is devoted to the analysis and edition of the inventory of the Bytom state court from the early 1740s. The oldest information confirming the existence of the land court comes from the beginning of the 1410s, although its older origin is not excluded. From the end of the 15th century to the mid-17th century, the land court was composed of the staroste of Bytom (later referred to as a land staroste), a land judge and a land writer, and several assessors. The inventory of the archives of the Bytom land court was drawn up after January 1641. The sources do not provide information about the exact date and circumstances of its creation. The edited document of the land court in Bytom is kept in the resources of the State Archives in Katowice in the collection Group of Documents of the Municipal Archive in Bytom, with the reference number 2911. The annex to the article contains the inventory of the archives of the land court in Bytom from around 1641.
Reducing readmissions and bed occupancy using digital cardiac rehabilitation programmes
Authors: Hubbard Julia
Published: September 2022

Julia Hubbard, professor of clinical health education, explains how digital cardiac rehabilitation programmes could help to improve uptake and reduce pressure on emergency services.
The versatility of flowable composites. Part 2: clinical uses
Authors: AL-Rawas Matheel , Johari Yanti , Yusoff Nazrul M , Mohamad Dasmawati , Husein Adam
Published: September 2022

Flowable composite (FC) is a type of tooth-coloured restorative material with a lower viscosity compared to other types of resin composites. FC is considered as a versatile dental material, with a wide range of application. FCs have progressively gained importance in clinical dentistry. The increase in consumer demand has resulted in a gradual upsurge of dental professionals relying on composites in injectable form. Scientific and technological improvements in their properties and handling characteristics have not only seen FCs grow in popularity, but resulted in the development of different generations and types of dental FCs suitable for use in all cavity types, lining, core build-ups, and most recently, bulk-fill flowable composites.

CPD/Clinical Relevance: To provide clinicians with an overview of the indications and clinical applications of the conventional FCs.
CAPACIDADE ABSORTIVA PARA INOVAÇÃO: análise dos fatores internos e externos em startups catarinenses
Authors: Werlang Nathalia , Silva Maikeli , Cândido Ana Clara
Published: September 2022

Este trabalho teve como objetivo identificar as fontes internas e externas que potencializam a capacidade absortiva para inovação das startups catarinenses. Para isso foi realizada uma pesquisa quantitativa, descritiva, operacionalizada por meio de uma survey. Obteve-se como retorno da pesquisa, 15 respondentes, líderes estratégicos das empresas. Os resultados apontam que fatores externos como clientes, consumidores, concorrentes, interação com outras organizações e alianças estratégicas são determinantes para a capacidade absortiva. Já os fatores internos mais relevantes para a Capacidade Absortiva foram a cultura empresarial e empowerment dos funcionários, o conhecimento prévio e experiências, seguido da presença de indivíduo chave, liderança e capacidade absortiva individual.
On the Germanic and Old High German distance assimilation changes
Authors: Cercignani Fausto
Published: September 2022

This article revisits a vexed question, namely the phonological interpretation of the Germanic and Old High German distance assimilation changes. It will be argued that 1) the prehistoric Germanic subsystem of short vowels should be reconstructed with five phonemes (/i/, /e/, /u/, /o/, /a/), not with four (/i/, /e/, /u ~ o/, /a/) or with three (/i ~ e/, /u ~ o/, /a/); 2) the Old High German umlaut phenomena produced phonemic changes before the factors that triggered them off changed or disappeared, because the umlaut allophones gradually shifted to such a degree that they became distinctive in the phonological system of the language and contrastive at a lexical level.
Motivation zum Deutschlernen in Kroatien
Authors: Jeleč Marijana , Miletić Nikolina
Published: September 2022

The benefits of language learning of children and young people in Croatia have been brought to attention due to increasing global cooperation and international networking. Above all, the tourism sector, which is now the most important branch of the economy in the country, is partly responsible for the continuing motivation to learn foreign languages. Language acquisition is a complex topic that combines many aspects and perspectives. It is influenced by different factors (Riemer 2001) and can often be viewed in relation to specific regions – the latter has aroused our interest after many years of experience in higher education. Croatian students from Zagreb, Osijek, Rijeka and Zadar were asked about their motivation for learning German. Considering the differently developed regions in Croatia, it was investigated whether there are region-specific differences in attitudes towards the German language and motivation to learn German between students from the two geographical regions of Croatia (continental vs. Adriatic Croatia). The procedure was quantitatively oriented. The results come from a questionnaire survey that was carried out specifically for this purpose and they clearly indicate that students from Croatia make a very specific decision to study German and thus to learn German language. It was found that region-specific characteristics or the economic situation of the region and the job opportunities it offers also have an impact on the choice of study in Croatia.
The acquisition of the clitic ci among typically developing Italian preschoolers: preliminary data
Authors: Souzzi Alice , Gagliardi Gloria
Published: September 2022

This paper explores the acquisitional patterns of the Italian ci morpheme and its potential role as a clinical marker for Developmental Language Disorder (DLD) in Italian-speaking children, taking into account its distributional, sociolinguistic, and typological properties. To this purpose, we (i) administered a test for the elicited production of clitic pronouns in Italian – which we will refer to as “T-PEC” in the following – to 126 school-aged Italian speakers and (ii) developed a novel test focused on the ci morpheme in order to investigate its production by five-year-old typically developing children. The results and their theoretical interpretations are of particular interest since they could shed light on the acquisition of the morpheme, thus helping understand both typical and atypical grammar development. Given the continuity of the two, it could also be applied to the diagnosis and rehabilitation of DLD, which remains a major challenge for child neuropsychiatrists, psychologists, and speech-language therapists.