bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and HPLC-based approaches for detection of aflatoxin B1 and ochratoxin A released from toxigenic Aspergillus species in processed meat
Authors: Algammal Abdelazeem M. , Elsayed Mahmoud E. , Hashem Hany R. , Ramadan Hazem , Sheraba Norhan S. , El-Diasty Eman M. , Abbas Sarah M. , Hetta Helal F.
Published: March 2021

Background

Meat-products are considered an enriched media for mycotoxins. This study aimed to investigate the prevalence of toxigenicAspergillusspecies in processed meat samples, HPLC-quantitative measurement of aflatoxin B1and ochratoxin A residues, and molecular sequencing ofaflR1andpksgenes. One hundred and twenty processed beef meat specimens (basterma, sausage, and minced meat;n = 40 for each) were collected from Ismailia Province, Egypt. Samples were prepared for total mold count, isolation, and identification ofAspergillusspecies. All samples were analyzed for the production of both Aflatoxin B1and Ochratoxin A mycotoxins by HPLC. Molecular identification ofAspergillus flavusandAspergillus ochraceuswas performed using PCR amplification of the internal transcribed spacer (ITS) region; furthermore, theaflR1andpksgenes were sequenced.

Results

The total mold count obtained from sausage samples was the highest one, followed by minced meat samples. The prevalence ofA. flavuswas (15%), (7.5%), and (10%), while the prevalence ofA. ochraceuswas (2.5%), (10%), and (0%) in the examined basterma, sausage, and minced meat samples, respectively. Using PCR, the ITS region was successfully amplified in all the testedA. flavusandA. ochraceusstrains. Aflatoxin B1was detected in six basterma samples (15%). Moreover, the ochratoxin A was detected only in four sausage samples (10%). TheaflR1andpksgenes were amplified and sequenced successfully and deposited in the GenBank with accession numbers MF694264 and MF694264, respectively.

Conclusions

To the best of our knowledge, this is the first report concerning the HPLC-Molecular-based approaches for the detection of aflatoxin B1and ochratoxin A in processed beef meat in Egypt. The production of aflatoxin B1and ochratoxin A in processed meat constitutes a public health threat. Aflatoxin B1is commonly associated with basterma samples. Moreover, ochratoxin A was detected frequently in sausage samples. The routine inspection of mycotoxins in processed meat products is essential to protect human consumers.
Outcome after polyaxial locking plate osteosynthesis in proximal tibia fractures: a prospective clinical trial
Authors: Völk Dominik , Neumaier Markus , Einhellig Heike , Biberthaler Peter , Hanschen Marc
Published: March 2021

Background

The aim of this study was to evaluate the clinical and/or radiologic outcome using different polyaxial locking plates for the treatment of proximal tibia fractures, the Non-Contact-Briding plate (NCB-PT®) by Zimmer or the Variable Angle Locking Compression Plate (VA-LCP®) by Synthes.

Methods

This study enrolled 28 patients with proximal tibia fractures (AO/ OTA 41 B-C) and indication for locking plate osteosynthesis. All patients were treated with a polyaxial locking plate system. Depending on the fracture morphology, patients were either treated with a NCB-PT® or VA-LCP®. The implant was chosen according to the surgeon’s experience and preference, in case of a higher degree of comminution the tendency was observed to use the NCB-PT® plate. After a time interval of 12 months postoperative we conducted clinical (e.g.exempli gratia range of motion, the Rasmussen score) and radiological (e.g. primary/secondary loss of reduction) follow-ups.

Results

Patients provided with the NCB-PT® (9 patients) showed longer operation time, use of longer implants, longer interval from injury to surgery and lower clinical scores after the 12 months follow-up compared with the VA-LCP® group (19 patients). Interestingly, the results showed no significant differences regarding the clinical and radiologic outcome.

Conclusions

The small number of patients as well as the heterogeneity of fractures constitute a limitation of this study. Nevertheless, the differentiated use of implants is associated with comparable clinical and radiological outcomes. This trial emphasizes the need for further prospective randomised trials with higher patient numbers.

Trial registration

Retrospectively registered 21.12.2020. Registration numberNCT04680247.
Up-regulation of sex-determining region Y-box 9 (SOX9) in growth hormone-secreting pituitary adenomas
Authors: Shirian Farzad Izak , Ghorbani Mohammad , Khamseh Mohammad E. , Imani Mehrnaz , Panahi Mahshid , Alimohammadi Alimohammad , Nourbakhsh Mitra , Salimi Vahid , Tavakoli-Yaraki Masoumeh
Published: March 2021

Background

Pituitary adenomas are benign brain tumors that cause considerable morbidity and neurological symptoms. SOX9 as a regulatory transcriptional mediator affects normal and tumor cell growth with an undefined role in pituitary adenomas pathogenesis. Thus, in the present study, the expression pattern of SOX9 in GH-secreting pituitary tumors and normal pituitary tissues is investigated.

Methods

The SOX9 gene expression level was evaluated in 60 pituitary tissues including different types of GH-secreting adenomas and normal pituitary tissues through Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry. The correlations of SOX9 gene and protein expression level with the patient’s clinical and pathological features were considered.

Results

The SOX9 over-expression was detected in GH-secreting adenomas tumor tissues compared to normal pituitary tissues which were accompanied by overexpression of SOX9 protein in tumor tissues. The over-expression of SOX9 had a significant impact on GH-secreting adenomas tumor incidence with the odds ratio of 8.4 and the diagnostic value of SOX9 was considerable. The higher level of SOX9 expression was associated with invasive and macro tumors in GH-secreting pituitary adenoma patients. The positive correlation of SOX9 gene and protein level was observed and the tumor size and tumor invasive features were valuable in predicting SOX9 expression level in GH-producing pituitary tumors.

Conclusion

The study provided the first shreds of evidence regarding the expression pattern of SOX9 in the GH- secreting pituitary adenomas at both gene and protein levels which may emphasize the possible involvement of SOX9 as a mediator in pituitary adenoma tumor formation also open up new intrinsic molecular mechanism regarding pituitary adenoma pathogenesis.
Resource allocation across the dementia continuum: a mixed methods study examining decision making on optimal dementia care among health and social care professionals
Authors: Keogh Fiona , Pierse Tom , Challis David , O’Shea Eamon
Published: March 2021

Background

The understanding of appropriate or optimal care is particularly important for dementia, characterised by multiple, long-term, changing needs and the increasing expectations of people using services. However, the response of health and social care services is limited by resource constraints in most countries. This study sought to determine the optimal level, mix and cost of services for different dementia case types across the dementia continuum, and to better understand the resource allocation decision making process among health and social care professionals (HSCPs).

Methods

A balance of care framework was applied to the study questions and developed in three ways; firstly by considering optimality across the course of dementia and not just at the margin with residential care; secondly, through the introduction of a fixed budget to reveal constrained optimisation strategies; and thirdly through the use of a mixed methods design whereby qualitative data was collected at workshops using nominal group technique and analysed to obtain a more detailed understanding of the decision-making process. Twenty four HSCPs from a variety of disciplines participated in the resource allocation decision-making exercise.

Results

HSCPs differentiated between case type severity; providing 2.6 times more resources to case types with higher level needs than those with lower level needs. When a resource constraint was introduced there was no evidence of any disproportionate rationing of services on the basis of need, i.e. more severe case types were not favoured over less severe case types. However, the fiscal constraint led to a much greater focus on meeting physical and clinical dependency needs through conventional social care provision. There was less emphasis on day care and psychosocial provision when resources were scarcer following the introduction of a fixed budget constraint.

Conclusions

HSCPs completed complex resource allocation exercises for people with dementia, including expected differentiation across case type severity. When rationing was introduced, HSCPs did not discriminate in favour of case types with high levels of need. They did, however, support conventional home care provision over psychosocial care, although participants were still keen to provide some residual cover for the latter, especially for case types that might benefit.
The lobular neoplasia enigma: management and prognosis in a long follow-up case series
Authors: Metovic Jasna , Abate Simona Osella , Borella Fulvio , Vissio Elena , Bertero Luca , Mariscotti Giovanna , Durando Manuela , Senetta Rebecca , Ala Ada , Benedetto Chiara , Sapino Anna , Cassoni Paola , Castellano Isabella
Published: March 2021

Background

Many oncologists debate if lobular neoplasia (LN) is a risk factor or an obligatory precursor of more aggressive disease. This study has three aims: (i) describe the different treatment options (surgical resection vs observation), (ii) investigate the upgrade rate in surgically treated patients, and (iii) evaluate the long-term occurrences of aggressive disease in both operated and unoperated patients.

Methods

A series of 122 patients with LN bioptic diagnosis and follow-up information were selected. Clinical, radiological, and pathological data were collected from medical charts. At definitive histology, either invasive or ductal carcinoma in situ was considered upgraded lesions.

Results

Atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and high-grade LN (HG-LN) were diagnosed in 44, 63, and 15 patients, respectively. The median follow-up was 9.5 years. Ninety-nine patients were surgically treated, while 23 underwent clinical-radiological follow-up. An upgrade was observed in 28/99 (28.3%). Age ≥ 54 years (OR 4.01, CI 1.42–11.29, p = 0.009), Breast Imaging-Reporting and Data System (BI-RADS) categories 4–5 (OR 3.76, CI 1.37–10.1, p = 0.010), and preoperatory HG-LN diagnosis (OR 8.76, 1.82–42.27, p = 0.007) were related to upgraded/aggressive disease. During follow-up, 8 patients developed an ipsilateral malignant lesion, four of whom were not initially operated (4/23, 17%).

Conclusions

BI-RADS categories 4–5, HG-LN diagnosis, and age ≥ 54 years were features associated with an upgrade at definitive surgery. Moreover, 17% of unoperated cases developed an aggressive disease, emphasizing that LN patients need close surveillance due to the long-term risk of breast cancer.
Circ-KIAA0907 inhibits the progression of oral squamous cell carcinoma by regulating the miR-96-5p/UNC13C axis
Authors: Dong Wenjie , Zhao Lei , Zhang Shiyang , Zhang Shijie , Si Hongyun
Published: March 2021

Background

Circular RNA (circRNA) plays an important role in regulating cell biological function and has been shown to be involved in cancer progression, including oral squamous cell carcinoma (OSCC). Circ-KIAA0907 has been found to play an anti-cancer role in OSCC, so it is worth exploring more functions and new mechanisms of circ-KIAA0907 in OSCC progression.

Methods

Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ-KIAA0907, microRNA (miR)-96-5p, and unc-13 homolog C (UNC13C). Transwell assay, flow cytometry, and colony formation assay were employed to measure the migration, invasion, apoptosis, and radiosensitivity of cells. Besides, glucose uptake, lactate production, and extracellular acidification rate (ECAR) were determined to evaluate the glycolysis ability of cells. Dual-luciferase reporter assay and RIP assay were performed to confirm the interactions among circ-KIAA0907, miR-96-5p, and UNC13C. And RNA pull-down assay was used to verify the binding degree of miR-96-5p to its targets. Moreover, UNC13C protein level was examined using western blot (WB) analysis. OSCC xenograft models were constructed to perform in vivo experiments.

Results

Circ-KIAA0907 was a stability circRNA with lowly expression in OSCC. Overexpressed circ-KIAA0907 could inhibit migration, invasion, and glycolysis, while promoting apoptosis and radiosensitivity in OSCC cells. In the terms of mechanism, circ-KIAA0907 could sponge miR-96-5p to regulate UNC13C expression. MiR-96-5p overexpression could reverse the inhibitory effect of circ-KIAA0907 on OSCC progression, and UNC13C knockdown also could overturn the suppressive effect of miR-96-5p inhibitor on OSCC progression. Animal experiments revealed that circ-KIAA0907 could reduce the tumor growth of OSCC by regulating the miR-96-5p/UNC13C axis.

Conclusion

Our study suggests that circ-KIAA0907 restrains OSCC progression via the miR-96-5p/UNC13C axis, indicating that it may be a potential target for OSCC treatment.
Fatigue in young adults with juvenile idiopathic arthritis 18 years after disease onset: data from the prospective Nordic JIA cohort
Authors:   on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR), Arnstad Ellen Dalen , Glerup Mia , Rypdal Veronika , Peltoniemi Suvi , Fasth Anders , Nielsen Susan , Zak Marek , Aalto Kristiina , Berntson Lillemor , Nordal Ellen , Herlin Troels , Romundstad Pål Richard , Rygg Marite
Published: March 2021

Background

To study fatigue in young adults with juvenile idiopathic arthritis (JIA) 18 years after disease onset, and to compare with controls.

Methods

Consecutive children with onset of JIA between 1997 and 2000, from geographically defined areas of Norway, Sweden, Denmark and Finland were followed for 18 years in a close to population-based prospective cohort study. Clinical features, demographic and patient-reported data were collected. Inclusion criteria in the present study were a baseline visit 6 months after disease onset, followed by an 18-year follow-up with available self-reported fatigue score (Fatigue Severity Scale (FSS), 1–7). Severe fatigue was defined as FSS ≥4. For comparison, Norwegian age and sex matched controls were used.

Results

Among 377 young adults with JIA, 26% reported severe fatigue, compared to 12% among controls. We found higher burden of fatigue among participants with sleep problems, pain, poor health, reduced participation in school/work, physical disability, active disease, or use of disease-modifying anti-rheumatic drugs (DMARDs)/biologics/systemic steroids. In contrast, participants without these challenges, had fatigue scores similar to controls. Active disease assessed at all three time points (baseline, 8-year and 18-year follow-up) was associated with higher mean fatigue score and higher percentage of severe fatigue compared to disease courses characterized by periods of inactive disease. Predictors of fatigue at the 18-year follow-up were female sex and diagnostic delay of ≥6 months at baseline, and also pain, self-reported poor health, active disease, and previous/ongoing use of DMARDs/biologics at 8 years.

Conclusions

Fatigue is a prominent symptom in young adults with JIA, with higher fatigue burden among participants with poor sleep, pain, self-reported health problems, active disease, or use of DMARDs/biologics. Participants without these challenges have results similar to controls. Patient- and physician-reported variables at baseline and during disease course predicted fatigue at 18-year follow-up.
Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation
Authors: Fernández Andrés , Quintana Elena , Velasco Patricia , Moreno-Jimenez Belén , de Andrés Belén , Gaspar Maria Luisa , Liste Isabel , Vilar Marçal , Mira Helena , Cano Eva
Published: March 2021

Background

Aging and age-related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain’s immune response, plays an important role in aged associated degeneration of central nervous system (CNS). There is a need for well characterized animal models that will allow the scientific community to understand and modulate this process.

Methods

We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their senescence resistant control mice (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and determined the appearance of Iba1+ clustered cells with aging. To analyze specific constant brain areas, we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch), and analyzed their response to systemic lipopolysaccharide (LPS)-driven inflammation.

Results

Aged 10 months old SAMP8 mice present many of the hallmarks of aging-dependent neuroinflammation when compared with their SAMR1 control, i.e., increase of protein aggregates, presence of Iba1+ clusters, but not an increase in the number of Iba1+ cells. We have further observed an increase of main inflammatory mediator IL-1β, and an augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch) have been analyzed, showing that there is not a significant increase of CD45+ cells from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL-1β) transcription is enhanced in CD45+BP cells. Furthermore, LPS-driven systemic inflammation produces inflammatory cytokines mainly in border bMyC, sensed to a lesser extent by the BP bMyC, showing that IL-1β expression is further augmented in aged SAMP8 compared to control SAMR1.

Conclusion

Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of pro-inflammatory cytokines such as IL-1β, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.
Do changes in pulse pressure variation and inferior vena cava distensibility during passive leg raising and tidal volume challenge detect preload responsiveness in case of low tidal volume ventilation?
Authors: Taccheri Temistocle , Gavelli Francesco , Teboul Jean-Louis , Shi Rui , Monnet Xavier
Published: March 2021

Background

In patients ventilated with tidal volume (Vt) < 8 mL/kg, pulse pressure variation (PPV) and, likely, the variation of distensibility of the inferior vena cava diameter (IVCDV) are unable to detect preload responsiveness. In this condition, passive leg raising (PLR) could be used, but it requires a measurement of cardiac output. The tidal volume (Vt) challenge (PPV changes induced by a 1-min increase in Vt from 6 to 8 mL/kg) is another alternative, but it requires an arterial line. We tested whether, in case of Vt = 6 mL/kg, the effects of PLR could be assessed through changes in PPV (ΔPPVPLR) or in IVCDV (ΔIVCDVPLR) rather than changes in cardiac output, and whether the effects of the Vt challenge could be assessed by changes in IVCDV (ΔIVCDVVt) rather than changes in PPV (ΔPPVVt).

Methods

In 30 critically ill patients without spontaneous breathing and cardiac arrhythmias, ventilated with Vt = 6 mL/kg, we measured cardiac index (CI) (PiCCO2), IVCDV and PPV before/during a PLR test and before/during a Vt challenge. A PLR-induced increase in CI ≥ 10% defined preload responsiveness.

Results

At baseline, IVCDV was not different between preload responders (n = 15) and non-responders. Compared to non-responders, PPV and IVCDV decreased more during PLR (by − 38 ± 16% and − 26 ± 28%, respectively) and increased more during the Vt challenge (by 64 ± 42% and 91 ± 72%, respectively) in responders. ∆PPVPLR, expressed either as absolute or as percent relative changes, detected preload responsiveness (area under the receiver operating curve, AUROC: 0.98 ± 0.02 for both). ∆IVCDVPLR detected preload responsiveness only when expressed in absolute changes (AUROC: 0.76 ± 0.10), not in relative changes. ∆PPVVt, expressed as absolute or percent relative changes, detected preload responsiveness (AUROC: 0.98 ± 0.02 and 0.94 ± 0.04, respectively). This was also the case for ∆IVCDVVt, but the diagnostic threshold (1 point or 4%) was below the least significant change of IVCDV (9[3–18]%).

Conclusions

During mechanical ventilation with Vt = 6 mL/kg, the effects of PLR can be assessed by changes in PPV. If IVCDV is used, it should be expressed in percent and not absolute changes. The effects of the Vt challenge can be assessed on PPV, but not on IVCDV, since the diagnostic threshold is too small compared to the reproducibility of this variable.

Trial registration: Agence Nationale de Sécurité du Médicament et des Produits de santé: ID-RCB: 2016-A00893-48.
Aedes larval bionomics and implications for dengue control in the paradigmatic Jaffna peninsula, northern Sri Lanka
Authors: Surendran Sinnathamby N. , Jayadas Tibutius T. P. , Thiruchenthooran Vaikunthavasan , Raveendran Selvarajah , Tharsan Annathurai , Santhirasegaram Sharanga , Sivabalakrishnan Kokila , Karunakaran Suthakar , Ponnaiah Bharathy , Gomes Laksiri , Malavige Gathsaurie N. , Ramasamy Ranjan
Published: March 2021

Background

The larval bionomics ofAedesacross the Jaffna peninsula in northern Sri Lanka was investigated to obtain information needed for developing more effective larval source reduction measures to control endemic arboviral diseases.

Methods

The habitats of preimaginal stages ofAedesmosquitoes were surveyed, and ovitrap collections were carried out in densely populated areas of the Jaffna peninsula.Aedeslarval productivities were analysed against habitat characteristics, rainfall and dengue incidence. Adults emerging from collected larvae were tested for dengue virus (DENV).

Results

OnlyAedes aegypti,Ae. albopictusandAe. vittatuswere identified in the field habitat collections and ovitraps.Aedes aegyptiwas the predominant species in both the field habitat and ovitrap collections, followed byAe. albopictusand small numbers ofAe. vittatus. Tires and open drains were the preferred field habitats forAe. aegypti, although larval productivity was higher in discarded plastic containers. The threeAedesspecies differed in field habitat preferences. Concomitant presence of the threeAedesspecies was observed in the field habitats and ovitraps. Larval productivities were inversely correlated with the salinity of the field habitat. Rainfall in the preceding month significantly correlated with larval productivity in the field habitats. DENV serotype 2 was detected inAe. aegypticollected from ovitraps in the city of Jaffna. High Breteau, House and Container indices of 5.1, 5.1 and 7.9%, respectively, were observed in the field habitat surveys and ovitrap indices of up to 92% were found in Jaffna city.

Conclusions

Aedeslarval indices in populated areas of the peninsula showed a high potential for dengue epidemics. Unacceptable littering practices, failure to implement existing dengue control guidelines, vertical transmission of DENV in vector mosquitoes and preimaginal development in brackish water and open surface drains, as well as in domestic wells that provide potable water, are serious constraints to the currentAedeslarval source reduction methods used to control dengue in the Jaffna peninsula. Similar shortcomings in arboviral disease control are likely present in other resource-constrained tropical coastal zones worldwide.

Graphical Abstract
Enhancing magnetic resonance imaging-driven Alzheimer’s disease classification performance using generative adversarial learning
Authors: Zhou Xiao , Qiu Shangran , Joshi Prajakta S. , Xue Chonghua , Killiany Ronald J. , Mian Asim Z. , Chin Sang P. , Au Rhoda , Kolachalama Vijaya B.
Published: March 2021

Background

Generative adversarial networks (GAN) can produce images of improved quality but their ability to augment image-based classification is not fully explored. We evaluated if a modified GAN can learn from magnetic resonance imaging (MRI) scans of multiple magnetic field strengths to enhance Alzheimer’s disease (AD) classification performance.

Methods

T1-weighted brain MRI scans from 151 participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), who underwent both 1.5-Tesla (1.5-T) and 3-Tesla imaging at the same time were selected to construct a GAN model. This model was trained along with a three-dimensional fully convolutional network (FCN) using the generated images (3T*) as inputs to predict AD status. Quality of the generated images was evaluated using signal to noise ratio (SNR), Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE) and Natural Image Quality Evaluator (NIQE). Cases from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL,n = 107) and the National Alzheimer’s Coordinating Center (NACC,n = 565) were used for model validation.

Results

The 3T*-based FCN classifier performed better than the FCN model trained using the 1.5-T scans. Specifically, the mean area under curve increased from 0.907 to 0.932, from 0.934 to 0.940, and from 0.870 to 0.907 on the ADNI test, AIBL, and NACC datasets, respectively. Additionally, we found that the mean quality of the generated (3T*) images was consistently higher than the 1.5-T images, as measured using SNR, BRISQUE, and NIQE on the validation datasets.

Conclusion

This study demonstrates a proof of principle that GAN frameworks can be constructed to augment AD classification performance and improve image quality.
RECIST 1.1 and lesion selection: How to deal with ambiguity at baseline?
Authors: Iannessi Antoine , Beaumont Hubert , Liu Yan , Bertrand Anne-Sophie
Published: March 2021

Response Evaluation Criteria In Solid Tumors (RECIST) is still the predominant criteria base for assessing tumor burden in oncology clinical trials. Despite several improvements that followed its first publication, RECIST continues to allow readers a lot of freedom in their evaluations. Notably in the selection of tumors at baseline. This subjectivity is the source of many suboptimal evaluations. When starting a baseline analysis, radiologists cannot always identify tumor malignancy with any certainty. Also, with RECIST, some findings can be deemed equivocal by radiologists with no confirmatory ground truth to rely on. In the specific case of Blinded Independent Central Review clinical trials with double reads using RECIST, the selection of equivocal tumors can have two major consequences: inter-reader variability and modified sensitivity of the therapeutic response. Apart from the main causes leading to the selection of an equivocal lesion, due to the uncertainty of the radiological characteristics or due to the censoring of on-site evaluations, several other situations can be described more precisely. These latter involve cases where an equivocal is selected as target or non-target lesions, the management of equivocal lymph nodes and the case of few target lesions. In all cases, awareness of the impact of selecting a non-malignant lesion will lead radiologists to make selections in the most rational way. Also, in clinical trials where the primary endpoint differs between phase 2 (response-related) and phase 3 (progression-related) trials, our impact analysis will help them to devise strategies for the management of equivocal lesions.
Incidental findings in and around the prostate on prostate MRI: a pictorial review
Authors: Trivedi Janki , Sutherland Tom , Page Mark
Published: March 2021

Prostate MRI has seen rapid growth in use in recent years as an advanced diagnostic modality to detect focal areas of clinically significant prostate cancer, to identify an area for targeted biopsy and to guide management and surveillance. The increase in use has also led to increased diagnosis of incidental lesions arising from structures around the prostate. These incidental findings may be related to the genitourinary system or non- genitourinary system and may have a benign aetiology which needs no additional follow-up, or it may require surveillance and management. The field of view in a multiparametric prostate MRI includes other pelvic organs, neurovascular bundles, bowel, lymph nodes and bones. Being familiar with standard MRI characteristics and a sound knowledge of anatomy of the prostate and surrounding structures can help in distinguishing normal anatomy from pathology. Given that patients undertaking a prostate MRI are usually a cohort with increased anxiety from their known or suspicion of prostate cancer, it is important that radiologists are familiar with these common incidental findings to minimise anxiety to the patient, have a well-informed discussion with the referring clinician and reduce costs associated with unnecessary further testing and follow-up of benign incidental findings. Additionally, being able to diagnose more serious incidental pathologies early can be life-saving and potentially significantly alter patient management.
Repair abilities of mouse autologous adipose-derived stem cells and ShakeGel™3D complex local injection with intrauterine adhesion by BMP7-Smad5 signaling pathway activation
Authors: Zhao Yun-xia , Chen Shao-rong , Huang Qiao-yi , Chen Wei-can , Xia Tian , Shi Yan-chuan , Gao Hong-zhi , Shi Qi-yang , Lin Shu
Published: March 2021

Background

The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGel™3D transplantation to activate the BMP7-Smad5 signaling pathway to treat intrauterine adhesions (IUA).

Methods

Autologous ADSCs were isolated and then merged with ShakeGel™3D. The IUA model was established by mechanical injury. The third generation of autologous ADSCs was injected directly into the uterus in combination with ShakeGel™3D. After 7 days of treatment, endometrial morphology, number of endometrial glands, endometrial fibrosis area, and fibrosis biomarker analysis by RT-PCR and IHC were examined. BMP7 and phosphorylation of Smad5 were also detected, and the recovery of infertility function in treated mice was evaluated.

Results

Fluorescence-activated cell sorting (FACS) showed that autologous ADSCs expressed CD105 (99.1%), CD29 (99.6%), and CD73 (98.9%). Autologous ADSCs could still maintain a good growth state in ShakeGel™3D. Histological examination revealed that the number of endometrial glands increased significantly, and the area of fibrosis decreased. At the same time, the expression of BMP7 and Smad5 in the ADSCs + Gel group was significantly upregulated, and the final reproductive function of this group was partly recovered.

Conclusions

Autologous ADSCs can be used in combination with ShakeGel™3D to maintain functionality and create a viable three-dimensional growth environment. The combined transplantation of autologous ADSCs and ShakeGel™3D promotes the recovery of damaged endometrial tissue by increasing BMP7-Smad5 signal transduction, resulting in endometrium thickening, increased number of glands, and decreased fibrosis, leading to restoration of partial fertility.
GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line
Authors: Välimäki Mika J. , Leigh Robert S. , Kinnunen Sini M. , March Alexander R. , de Sande Ana Hernández , Kinnunen Matias , Varjosalo Markku , Heinäniemi Merja , Kaynak Bogac L. , Ruskoaho Heikki
Published: March 2021

Background

Pharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.

Methods

Transcription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.

Results

GATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.

Conclusions

Collectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.
MolFinder: an evolutionary algorithm for the global optimization of molecular properties and the extensive exploration of chemical space using SMILES
Authors: Kwon Yongbeom , Lee Juyong
Published: March 2021

Here, we introduce a new molecule optimization method, MolFinder, based on an efficient global optimization algorithm, the conformational space annealing algorithm, and the SMILES representation. MolFinder finds diverse molecules with desired properties efficiently without any training and a large molecular database. Compared with recently proposed reinforcement-learning-based molecule optimization algorithms, MolFinder consistently outperforms in terms of both the optimization of a given target property and the generation of a set of diverse and novel molecules. The efficiency of MolFinder demonstrates that combinatorial optimization using the SMILES representation is a promising approach for molecule optimization, which has not been well investigated despite its simplicity. We believe that our results shed light on new possibilities for advances in molecule optimization methods.
Genomic diversity of Mycobacterium avium subsp. paratuberculosis: pangenomic approach for highlighting unique genomic features with newly constructed complete genomes
Authors: Lim Jaewon , Park Hong-Tae , Ko Seyoung , Park Hyun-Eui , Lee Gyumin , Kim Suji , Shin Min-Kyoung , Yoo Han Sang , Kim Donghyuk
Published: March 2021

Mycobacterium avium subsp. paratuberculosis (MAP) is a causative agent of Johne’s disease, which is a chronic granulomatous enteropathy in ruminants. Determining the genetic diversity of MAP is necessary to understand the epidemiology and biology of MAP, as well as establishing disease control strategies. In the present study, whole genome-based alignment and comparative analysis were performed using 40 publicly available MAP genomes, including newly sequenced Korean isolates. First, whole genome-based alignment was employed to identify new genomic structures in MAP genomes. Second, the genomic diversity of the MAP population was described by pangenome analysis. A phylogenetic tree based on the core genome and pangenome showed that the MAP was differentiated into two major types (C- and S-type), which was in keeping with the findings of previous studies. However, B-type strains were discriminated from C-type strains. Finally, functional analysis of the pangenome was performed using three virulence factor databases (i.e., PATRIC, VFDB, and Victors) to predict the phenotypic diversity of MAP in terms of pathogenicity. Based on the results of the pangenome analysis, we developed a real-time PCR technique to distinguish among S-, B- and C-type strains. In conclusion, the results of our study suggest that the phenotypic differences between MAP strains can be explained by their genetic polymorphisms. These results may help to elucidate the diversity of MAP, extending from genomic features to phenotypic traits.
Liver organoids in domestic animals: an expected promise for metabolic studies
Authors: Baquerre Camille , Montillet Guillaume , Pain Bertrand
Published: March 2021

The liver is one of the most important organs, both in terms of the different metabolic processes (energy, lipid, ferric, uric, etc.) and of its central role in the processes of detoxification of substances of food origin or noxious substances (alcohol, drugs, antibiotics, etc.). The development of a relevant model that reproduces some of the functions of this tissue has become a challenge, in particular for human medicine. Thus, in recent years, most studies aimed at producing hepatocytes in vitro with the goal of developing hepatic 3D structures have been carried out in the human model. However, the tools and protocols developed using this unique model can also be considered to address physiological questions specific to this tissue in other species, such as the pig, chicken, and duck. Different strategies are presently being considered to carry out in vitro studies of the hepatic metabolism of these agronomic species.
Improved two-way double-relay selection technique for cooperative wireless communications
Authors: Alabed Samer , Maaz Issam , Al-Rabayah Mohammad
Published: March 2021

In this article, a novel two-way double-relay selection strategy with its bit error rate (BER) performance analysis is proposed. In this novel strategy, as a first step we choose two relays out of a set of relay-nodes in a way to maximize the system performance in terms of BER and complexity. In the second step, the selected relays apply orthogonal space-time coding scheme using the three-phase protocol to establish a two-way communication between the transceivers, which will lead to a significant improvement in the achievable diversity and coding gain with a very low decoding complexity by using a symbol-wise decoder. Furthermore, the performance of the overall system is further enhanced through the use of a network coding method at the selected relay-nodes. Moreover, this paper proposes the analytical approximation of the BER performance. As well, we show that the analytical results match perfectly the simulated ones. In addition, we prove that our strategy outperforms the current state-of-the-art ones by proposing a better cooperative communication system in terms of BER.
Low-complexity sparse-aware multiuser detection for large-scale MIMO systems
Authors: Ran Rong , Oh Hayoung
Published: March 2021

Sparse-aware (SA) detectors have attracted a lot attention due to its significant performance and low-complexity, in particular for large-scale multiple-input multiple-output (MIMO) systems. Similar to the conventional multiuser detectors, the nonlinear or compressive sensing based SA detectors provide the better performance but are not appropriate for the overdetermined multiuser MIMO systems in sense of power and time consumption. The linear SA detector provides a more elegant tradeoff between performance and complexity compared to the nonlinear ones. However, the major limitation of the linear SA detector is that, as the zero-forcing or minimum mean square error detector, it was derived by relaxing the finite-alphabet constraints, and therefore its performance is still sub-optimal. In this paper, we propose a novel SA detector, named single-dimensional search-based SA (SDSB-SA) detector, for overdetermined uplink MIMO systems. The proposed SDSB-SA detector adheres to the finite-alphabet constraints so that it outperforms the conventional linear SA detector, in particular, in high SNR regime. Meanwhile, the proposed detector follows a single-dimensional search manner, so it has a very low computational complexity which is feasible for light-ware Internet of Thing devices for ultra-reliable low-latency communication. Numerical results show that the the proposed SDSB-SA detector provides a relatively better tradeoff between the performance and complexity compared with several existing detectors.
Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota
Authors: Xiang Shasha , Ye Kun , Li Mian , Ying Jian , Wang Huanhuan , Han Jianzhong , Shi Lihua , Xiao Jie , Shen Yubiao , Feng Xiao , Bao Xuan , Zheng Yiqing , Ge Yin , Zhang Yalin , Liu Chang , Chen Jie , Chen Yuewen , Tian Shiyi , Zhu Xuan
Published: March 2021

Background

Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts.

Results

In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate.

Conclusions

Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs.
Can we change binge eating behaviour by interventions addressing food-related impulsivity? A systematic review
Authors: İnce Başak , Schlatter Johanna , Max Sebastian , Plewnia Christian , Zipfel Stephan , Giel Katrin Elisabeth , Schag Kathrin
Published: March 2021

Background

An extensive amount of research has underlined the potential role of impulsivity in the development and maintenance of binge eating behaviour. Food-related impulsivity has particularly received attention given its close relationship with overeating and binge eating episodes. Besides the available evidence, our understanding regarding the effectiveness of treatment modalities for binge eating targeting impulsivity and related constructs (e.g., food craving, inhibitory control, and reward sensitivity) is limited. Thus, this systematic review aimed to investigate whether binge eating behaviour is changeable by interventions that are impulsivity-focused and food-related and whether one of these interventions is superior to the others.

Method

A search on PubMed and PsycINFO was performed for relevant articles published up to September 2020. Studies delivering food-related impulsivity treatment to individuals suffering from binge eating episodes and including a control condition without this treatment were investigated. Following the search, 15 studies meeting the eligibility criteria were analysed.

Results

Analyses revealed that available impulsivity-focused approaches can be categorised as psychotherapy, pharmacotherapy, computer-assisted cognitive training, and direct neuromodulation interventions. Regarding their effectiveness, it appeared that all of these approaches might be promising to change food-related impulsivity in individuals with binge eating episodes, particularly to decrease binge eating symptoms. However, a superior intervention approach in this early state of evidence could not be determined, although food-related cue exposure, transcranial direct current stimulation, and the combination of several interventions seem fruitful.

Conclusion

Efforts to treat binge eating behaviour with interventions focusing on food-related impulsivity appear to be promising, particularly concerning binge eating frequency, and also for food craving and inhibitory control. Given limited research and varying methods, it was not possible to conclude whether one impulsivity-focused intervention can be considered superior to others.
A false-pouch closure technique with an intact superior peroneal retinaculum for recurrent dislocation of the peroneal tendon
Authors: Matsui Tomohiro , Kumai Tsukasa , Shinohara Yasushi , Kanzaki Noriyuki , Noguchi Koji , Tanaka Hirofumi , Sugimoto Takeshi , Yabiku Hiroki , Higashiyama Ichiro
Published: March 2021

Purpose

To evaluate the usefulness of the false-pouch closure technique with an intact superior peroneal retinaculum (SPR).

Methods

From 2016 to 2020, 30 patients with recurrent dislocation of the peroneal tendon were treated with the current procedure. Clinical outcomes, including the time to resume running, the rate and time to return to sports, and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hind Foot score, were evaluated preoperatively and at the last follow-up.

Results

The rate of return to the pre-injury level of sports activity was 93.3%, and the mean duration to return to running and sports was 8.0 ± 2.8 weeks (range: 3–12 weeks) and 14.4 ± 3.2 weeks (range: 10–24 weeks), respectively. The mean preoperative AOFAS score was 79.7 ± 9.6 points (range: 41–90), which improved significantly to 98.9 ± 3.2 (87–100) postoperatively (p < 0.01).

Conclusion

The false-pouch closure technique with suture tape and anchors had a reliable clinical outcome and can enable the early return of patients to their sports activities.

Level of evidence

IV, Case series