bluuebunny/crossref_metadata_2025 huggingface dataset:
Geological, geophysical, and geochemical constraints on the time-space evolution of Akan composite caldera, Hokkaido, Japan
Authors: Hasegawa Takeshi , Nakagawa Mitsuhiro , Kamiyama Hiroyuki , Yamamoto Akihiko
Published: September 2022

Some calderas are geometrically complex that may be related not to a single eruption, magma body, or structure. In order to reveal their forming processes, multidisciplinary methods should be applied. Akan volcano has E-W elongated and irregular-shaped caldera (24 × 13 km), implying a complex mechanism of formation. Akan caldera results from successive explosive eruptions from 1.4 to 0.1 Ma. On the basis of duration of dormancy and petrological features (mainly whole-rock major element compositions) of juvenile materials, these eruptions have been grouped into 17 eruptive groups (Ak1–Ak17), each of which consists of a single or a sequential phase. In order to investigate the processes of caldera formation, we focus on the younger eruptive groups (Ak1–Ak7: 0.8 to 0.2 Ma) that have relatively large magnitudes (>10 km3) and likely control the present caldera shape. We performed component analysis of lithic fragments from pyroclastic fallout deposits, whole-rock trace element analysis of juveniles, and gravitational survey of the caldera. We grouped Ak1–Ak7 into three types, namely, type A (Ak1, Ak2), type B (Ak3–Ak5), and type C (Ak6, Ak7), based on the lithic componentry, most of which are accessary and accidental fragments from vent and conduit areas. The characteristic lithic component in each type is as follows: altered rock in type A, aphyric dacite in type B, and pyroxene andesite in type C. These data suggest that explosive eruptions of each type are derived from distinct sources. The whole-rock composition of juvenile materials of each type also shows distinct trends on Harker diagrams. These three chemical trends are nearly parallel, suggesting that three different magma systems were active. This is consistent with the lithic componentry showing three spatially distinct vent sources. The geological and petrological evidence is supported by a Bouguer anomaly map. Akan caldera is characterized by three circular closed minima, indicative of three depressed segments that correspond to the source regions, each of which possibly discharged the three types of magma. Caldera-forming eruptions of Akan caldera occurred from at least three distinct sources with distinct magma systems. In conclusion, Akan caldera is a composite caldera, and its shape reflects the distribution of multiple source regions. The case study of Akan caldera shows a possible time-space evolutionary pathway for a caldera complex where several smaller calderas are nested.
Laboratory investigation of the influence of fractures on CO2 flooding
Authors: Qing-Fu Zhang
Published: September 2022

CO2 injection is a promising method for low-permeability reservoirs. CO2 is much easier to inject underground compared with water. The solubility of CO2 in oil decreases the oil density and viscosity, leading to an enhancement of the oil recovery. CO2 flooding could achieve the dual purpose of developing oil effectively and reducing greenhouse gas. Therefore, this technique has both economic and social benefits and is an essential technology for achieving green development. Natural fractures are widely developed in low-permeability reservoirs, and artificial fractures are often used to improve oil development. These fractures have a significant influence on flow patterns during CO2 flooding. In addition, fractures are also one of the key factors of CO2 channeling. Therefore, the influence of fractures on CO2 flooding pressure distribution, fluid composition, and displacement efficiency needs to be studied. In this work, a CO2 flooding experiment was implemented to test the pressure distribution and outlet composition changes during CO2 flooding under different fracture lengths and apertures. The experiment shows that a long and wide fracture could effectively reduce the injection-production pressure difference. However, fractures also had a negative effect on oil development. Fracture length and aperture had a significant effect on the gas phase composition at the outlet, but had little effect on the oil phase composition.
Experimental study on rockburst fragment characteristic of granite under different loading rates in true triaxial condition
Authors: Sun Feiyue , Guo Jiaqi , Fan Junqi , Liu Xiliang
Published: September 2022

In order to study the effect of loading rate on rockburst, an indoor test of single-face fast unloading-three directions and five-face stress-vertical continuous loading is conducted under different loading rates using a new true-triaxial rockburst test system. The entire process of rockburst inoculation-occurrence-development is completely and accurately reproduced. The fragmentation degree, fractal dimension, and Weibull distribution characteristics of rockburst fragments under different loading rates are compared and analyzed. The results indicate that the rockburst ejection failure process can be summarized as four stages: grain ejection, rock spalling into plates, rock shearing into fragments, and rock fragment ejection. Rockburst fragments are mostly coarse-grained, medium-grained, and fine-grained. The macroscopic block characteristics of rockburst fragments reflect the fragmentation degree of rock, and the fragmentation degree of rockburst fragments increases with the loading rate. The fractal dimension shows the same trend with different loading rates, that is, the fractal dimension grows as the loading rate increases. As the loading rate increases, the crack expansion rate accelerates, which aggravates the damage to the rock specimen by decreasing its compressive strength and causing greater fragmentation when the specimen is failed. The loading rate has a significant effect on the energy consumption of rockburst fragments.
Clinical, hormonal and pathomorphological markers of somatotroph pituitary neuroendocrine tumors predicting the treatment outcome in acromegaly
Authors: Tomasik Agnieszka , Stelmachowska-Banaś Maria , Maksymowicz Maria , Czajka-Oraniec Izabella , Raczkiewicz Dorota , Zieliński Grzegorz , Kunicki Jacek , Zgliczyński Wojciech
Published: September 2022

Background

Transsphenoidal adenomectomy (TSS) of somatotroph pituitary neuroendocrine tumor (PitNET) is the first-line treatment of acromegaly. Pharmacological treatment is recommended if surgery is contraindicated or did not lead to disease remission. The choice of treatment best fitting each patient should be based on thorough investigation of patients’ characteristics. The current analysis attempts to create a tool for personalized treatment planning.

Aim

This study aimed to assess whether clinical, biochemical, imaging and pathological characteristics can predict surgical remission and response to first-generation somatostatin receptor ligands (SRLs) and pasireotide-LAR in acromegaly.

Patients and methods

A retrospective study of 153 acromegaly patients, treated in the Department of Endocrinology in Bielanski Hospital in Warsaw, Poland was performed. Data on demographics, hormonal and imaging results, pathological evaluation, and treatment outcome was extracted from the Polish Acromegaly Registry collecting information from 11 endocrinology centers in Poland and analyzed.

Results

Patients with surgical remission had lower GH and IGF-1 concentrations at diagnosis (median GH 5.5 µg/L [IQR: 3.1-16.0]vs. 19.9 µg/L [IQR: 9.8-42.4], p=<0.001 and mean IGF-1 3.1xULN ± SD=1.2 vs. 3.7xULN ± SD=1.2, p=0.007, respectively) and smaller tumors (median 12.5mm [IQR: 9-19] vs. 23mm [IQR: 18-30], p<0.001). These tumors were more often densely granulated (DG) (73.2% vs. 40.0%, p=0.001) with positive staining for alpha-subunit (α-SU) (58.3% vs. 35.5%, p=0.021) and lower Ki-67 index (p=0.002). Patients responding well to SRLs were more often male (55.6% vs 44.4%, p=0.026), presented lower GH concentration (median GH 17.2 µg/L [IQR: 6.2-29.0] vs. 23.8 µg/L [IQR: 11.2-49.5], p=0.048) and had more often DG tumors (63.0% vs. 14.3%, p<0.001). No significant differences between good and poor-response to pasireotide-LAR groups were found. In multivariate logistic regression analysis fasting GH concentration <8.63 µg/L, maximal tumor diameter <15.5mm, normoprolactinemia and DG tumor turned out to be independent predictors of surgical remission (OR=0.92, p=0.026; OR=0.87, p=0.069, OR=3.86, p=0.096 and OR=3.05, p=0.181, respectively). Fasting GH concentration <36.6 µg/L and DG tumor turned out to be independent predictors of good response to first-generation SRLs (OR=0.96, p=0.06 and OR=10.68, p=0.002, respectively).

Conclusions

Younger age at diagnosis, male sex, lower GH, IGF-1 and PRL concentrations, smaller tumor size at diagnosis as well as positive α-SU staining, lower Ki-67 index and DG tumors predicted better treatment outcome in acromegaly patients.
Termites are the main dung removals in a degraded landscape in Brazil
Authors: Alves Frederico R. , Aguilera-Olivares Daniel , Rocha Mauricio Martins , Arab Alberto
Published: September 2022

Termites are one of the most relevant groups for recycling nutrients and keeping the flow of energy in ecosystems. Although their role as lignocellulose decomposers is the focus of studies, they also act as dung recyclers, but their importance in this process is poorly understood. Here we performed manipulation experiments to determine dung removal by termites in forest remnants and cattle pastures in a fragmented Atlantic Forest landscape. We used wire bags of different mesh sizes placed along transects in three forest fragments and pastures for 10 days to compare the contribution of termites and other coprophagous macrodetritivores to dung removal. Our results indicated that termites removed more dung in pastures than in the forest fragments. In addition, dung beetle exclusion significantly reduced the percentage of dung removal within forest fragments, but not on pastures, indicating termites are important dung recyclers in pastures.
MicroRNAs in the regulation of Th17/Treg homeostasis and their potential role in uveitis
Authors: Tang Fen , Zhou Zhou , Huang Kongqian , Deng Wen , Lin Jiali , Chen Ruoyun , Li Min , Xu Fan
Published: September 2022

Th17 and regulatory T cells (Tregs) play crucial roles in the pathogenesis of autoimmune diseases. Th17/Treg homeostasis is critically involved in maintaining the immune balance. Disturbed Th17/Treg homeostasis contributes to the progression of autoimmune diseases. MicroRNAs (miRNAs) have emerged as a new vital factor in the regulation of disturbed Th17/Treg homeostasis. To better understand the epigenetic mechanisms of miRNAs in regulating Treg/Th17 homeostasis, we included and evaluated 97 articles about autoimmune diseases and found that miRNAs were involved in the regulation of Treg/Th17 homeostasis from several aspects positively or negatively, including Treg differentiation and development, Treg induction, Treg stability, Th17 differentiation, and Treg function. Uveitis is one of the ocular autoimmune diseases, which is also characterized with Th17/Treg imbalance. However, our understanding of the miRNAs in the pathogenesis of uveitis is elusive and not well-studied. In this review, we further summarized miRNAs found to be involved in autoimmune uveitis and their potential role in the regulation of Th17/Treg homeostasis.
Reactogenicity and immunogenicity of the second COVID-19 vaccination in patients with inborn errors of immunity or mannan-binding lectin deficiency
Authors: Göschl Lisa , Mrak Daniel , Grabmeier-Pfistershammer Katharina , Stiasny Karin , Haslacher Helmuth , Schneider Lisa , Deimel Thomas , Kartnig Felix , Tobudic Selma , Aletaha Daniel , Burgmann Heinz , Bonelli Michael , Pickl Winfried F. , Förster-Waldl Elisabeth , Scheinecker Clemens , Vossen Matthias Gerhard
Published: September 2022

Background

Patients with inborn errors of immunity (IEI) are at increased risk for severe courses of SARS-CoV-2 infection. COVID-19 vaccination provides effective protection in healthy individuals. However, it remains unclear whether vaccination is efficient and safe in patients with constitutional dysfunctions of the immune system. Thus, we analyzed the humoral response, adverse reactions and assessed the disease activity of the underlying disease after COVID-19 vaccination in a cohort of patients suffering from IEIs or mannan-binding lectin deficiency (MBLdef).

Methods

Vaccination response was assessed after basic immunization using the Elecsys anti-SARS-CoV-2 S immunoassay and via Vero E6 cell based assay to detect neutralization capabilities. Phenotyping of lymphocytes was performed by flow cytometry. Patient charts were reviewed for disease activity, autoimmune phenomena as well as immunization status and reactogenicity of the vaccination. Activity of the underlying disease was assessed using a patient global numeric rating scale (NRS).

Results

Our cohort included 11 individuals with common variable immunodeficiency (CVID), one patient with warts hypogammaglobulinemia immunodeficiency myelokathexis (WHIM) syndrome, two patients with X-linked agammaglobulinemia (XLA), one patient with Muckle Wells syndrome, two patients with cryopyrin-associated periodic syndrome, one patient with Interferon-gamma (IFN-gamma) receptor defect, one patient with selective deficiency in pneumococcal antibody response combined with a low MBL level and seven patients with severe MBL deficiency. COVID-19 vaccination was generally well tolerated with little to no triggering of autoimmune phenomena. 20 out of 26 patients developed an adequate humoral vaccine response. 9 out of 11 patients developed a T cell response comparable to healthy control subjects. Tested immunoglobulin replacement therapy (IgRT) preparations contained Anti-SARS-CoV-2 S antibodies implicating additional protection through IgRT.

In summary the data support the efficacy and safety of a COVID-19 vaccination in patients with IEIs/MBLdef. We recommend evaluation of the humoral immune response and testing for virus neutralization after vaccination in this cohort.
SOOTHER TRIAL: Observational study of an over-the-counter ointment to heal anal itch
Authors: Felemovicius Isaac , Ganz Robert A. , Saremi Mohammad , Christopfel William
Published: September 2022

Introduction

Pruritus ani, or rectal or anal itch, is a common perianal disorder that affects ~5% of the population of the developed world. Treatments for this disorder are somewhat limited and include conservative non-medical perianal hygiene care, and topical medical treatments including topical steroids, antibacterial and antifungal agents, and topical anesthetic/analgesics such as lidocaine or capsaicin; astringents and vasoconstrictors such as ephedrine can also be used.

Methods

The study was IRB approved. We assessed the efficacy of a novel, composite, over-the-counter, topical lidocaine ointment that included an epidermal barrier and antimicrobial effect along with the typical lidocaine anesthetizing effect, in a single arm, observational, longitudinal, population of 20 ambulatory pruritus ani patients. Patients applied the ointment twice daily, and were studied for 2 weeks; primary outcomes included time to symptom resolution and clinical exam resolution as measured on a 5-point visual analog scale.

Results

Twenty-nine consecutive patients were screened and 20 patients (12 males; 8 females) were enrolled in the study. Ninety percent of patients achieved 100% symptom resolution by 2 weeks, and most were improved within 72 h of initiating treatment; 95% of patients had a normal visual exam by the 2 week endpoint. There were no significant adverse events attributable to the therapy.

Conclusion

Use of a novel composite topical lidocaine agent, demonstrated rapid and effective relief of pruritus ani in an ambulatory population. Additional studies are underway.

Clinical trial registered

Clinicaltrials.gov, identifier NCT05288907.
Pregnancy in women with Hereditary Angioedema due to C1-inhibitor deficiency: Results from the ITACA cohort study on outcome of mothers and children with in utero exposure to plasma-derived C1-inhibitor
Authors: Triggianese P. , Senter R. , Petraroli A. , Zoli A. , Lo Pizzo M. , Bignardi D. , Di Agosta E. , Agolini S. , Arcoleo F. , Rossi O. , Modica S. , Greco E. , Chimenti M. S. , Spadaro G. , De Carolis C. , Cancian M.
Published: September 2022

Background

In women with Hereditary Angioedema (HAE) due to C1-inhibitor (C1INH) deficiency (C1INH-HAE), pregnancy counseling and treatment can be challenging. Despite the evidence of the immediate favorable outcome and safety of plasma-derived (pd)C1INH concentrate, there are no data regarding any difference among women who underwent or not pdC1INH during pregnancy or on children with in utero exposure to pdC1INH. The present interview study aimed at analyzing outcome of C1INH-HAE mothers and children according to pdC1INH-exposure during pregnancies.

Methods

C1INH-HAE women who experienced at least 1 pregnancy were included from seven centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). The interview study retrospectively analyzed pregnancies who underwent (group 1) or not (group 2) pdC1INH. The overall goals of the study included immediate and long-term outcomes, in terms of outcomes in the time interval between pregnancy and survey.

Results

A total of 168 pregnancies from 87 included women were analyzed. At term delivery (>37 gestation-week, GW) has been registered in 73.8% of cases, while spontaneous abortion (SA) occurred in 14.2% of cases with a mean GW 7 ± 2. The group 1 including pdC1INH-treated pregnancies comprised a third of the cohort (51/168, time interval 1.5 ± 10.4 yrs), while the group 2 represented 69.6% (117/168, time interval 32.8 ± 14 yrs). The same prevalence of SA occurred when comparing group 1 (11.7%) with group 2 (15.4%) with a similar GW at SA. The group 1 was older at the pregnancy time and younger at the interview than the group 2 (P < 0.01 for both); moreover, the group 1 showed a higher prevalence of cesarean delivery (P < 0.0001). The overall prevalence of obstetrical syndromes was similar between two groups: however, gestational diabetes was described only in pdC1INH-untreated pregnancies. In utero pdC1INH-exposed children (n = 45) did not show differences compared with unexposed ones (n = 99) in neonatal short-term outcomes.

Conclusion

Through appropriate management and counseling, most of C1INH-HAE women undergo successful pregnancy and delivery. For pregnant C1INH-HAE women being treated with pdC1INH, our findings are reassuring and might lead to an improvement of both the knowledge about treatments and the experience of HAE itself.
A single-center retrospective study comparing safety and efficacy of endoscopic biliary stenting only vs. EBS plus nasobiliary drain for obstructive jaundice
Authors: Liu Huan , Shi Chuanke , Yan Zhideng , Luo Ming
Published: September 2022

Purpose

Biliary drainage is an important modality for extrahepatic obstructive jaundice both in patients with palliative and resectable. Currently, endoscopic biliary drainage is preferred in clinical practice, including endoscopic nasobiliary drainage (ENBD) and endoscopic biliary stenting (EBS), both of which have their own advantages and disadvantages. The purpose of our study was to compare the safety and efficacy of endoscopic biliary stenting (EBS) only vs. EBS plus nasobiliary drain for obstructive jaundice.

Methods

We consecutively reviewed patients with endoscopic biliary drainage in our institution from November 2014 to March 2021. Combined (ENBD plus stent) and single approach (EBS only) were defined as combined approach and single modality, respectively, and all eligible patients were divided into a combined approach group and a single modality group. We compared combined vs. single modality approaches to investigate whether there were statistical differences in liver chemistries, postoperative adverse events, and stent patency time.

Results

In 271 patients, a total of 356 times endoscopic biliary drainages were performed. All eligible patients were divided into the combined approach group (n = 74) and the single modality group (n = 271). The combined approach was associated with a lower incidence of postoperative cholangitis and bleeding and greater improvement in liver chemistries, although it was not statistically significant. However, it was superior to the single modality group in terms of hospital stay (12.7 ± 5.2 vs. 14.5 ± 7.9 days, p = 0.020 < 0.05) and stent patency time (8.1 ± 3.9 vs. 4.3±2.7 months, p = 0.001 < 0.05).

Conclusion

Endoscopic combined (ENBD plus stent) drainage is a more advantageous biliary drainage method that is characterized by more adequate biliary drainage, a lower incidence of postoperative adverse events, and longer effective biliary drainage time.
H2G-Net: A multi-resolution refinement approach for segmentation of breast cancer region in gigapixel histopathological images
Authors: Pedersen André , Smistad Erik , Rise Tor V. , Dale Vibeke G. , Pettersen Henrik S. , Nordmo Tor-Arne S. , Bouget David , Reinertsen Ingerid , Valla Marit
Published: September 2022

Over the past decades, histopathological cancer diagnostics has become more complex, and the increasing number of biopsies is a challenge for most pathology laboratories. Thus, development of automatic methods for evaluation of histopathological cancer sections would be of value. In this study, we used 624 whole slide images (WSIs) of breast cancer from a Norwegian cohort. We propose a cascaded convolutional neural network design, called H2G-Net, for segmentation of breast cancer region from gigapixel histopathological images. The design involves a detection stage using a patch-wise method, and a refinement stage using a convolutional autoencoder. To validate the design, we conducted an ablation study to assess the impact of selected components in the pipeline on tumor segmentation. Guiding segmentation, using hierarchical sampling and deep heatmap refinement, proved to be beneficial when segmenting the histopathological images. We found a significant improvement when using a refinement network for post-processing the generated tumor segmentation heatmaps. The overall best design achieved a Dice similarity coefficient of 0.933±0.069 on an independent test set of 90 WSIs. The design outperformed single-resolution approaches, such as cluster-guided, patch-wise high-resolution classification using MobileNetV2 (0.872±0.092) and a low-resolution U-Net (0.874±0.128). In addition, the design performed consistently on WSIs across all histological grades and segmentation on a representative × 400 WSI took ~ 58 s, using only the central processing unit. The findings demonstrate the potential of utilizing a refinement network to improve patch-wise predictions. The solution is efficient and does not require overlapping patch inference or ensembling. Furthermore, we showed that deep neural networks can be trained using a random sampling scheme that balances on multiple different labels simultaneously, without the need of storing patches on disk. Future work should involve more efficient patch generation and sampling, as well as improved clustering.
Amelioration of dextran sulfate sodium-induced colitis by autoinducer-2-deficient Lactiplantibacillus plantarum is mediated by anti-inflammatory effects and alleviation of dysbiosis of the gut microbiota
Authors: Qian Yilin , Ma Lei , Zeng Mingyong , Liu Zunying
Published: September 2022

Lactic acid bacteria (LAB) attenuate dextran sulfate sodium (DSS)-induced colitis in mice by restoring gut flora homeostasis and modulating the immune response. Because synchronous behavior can be controlled by autoinducer-2 (AI-2)/LuxS-mediated quorum sensing, the Caco-2 cell model and DSS-induced model in C57BL/6 mice were used to explore the unknown effects of these communications involving AI-2 among various intestinal symbiotic species. The results of the cell viability and lactate dehydrogenase leakage assays indicated that the tested strains (the wild-type strains and AI-2-deficient mutants) were characterized by equal cytoprotection from hydrogen peroxide-induced injury independently of AI-2. The results of the assays of multiple indicators and proinflammatory cytokines characteristic for the symptoms of colitis in mice showed that oral administration of AI-2-deficient mutants for 7 days was more effective in ameliorating inflammation than the treatment with the wild-type strains. The treatment with AI-2-deficient mutants enriched potential probiotics (e.g., Lactobacillaceae) and controlled the proliferation of potentially harmful bacteria (e.g., Helicobacteraceae) to achieve the transformation of intestinal flora. These mutants regulated short-chain fatty acids and the intestinal epithelial barrier, thereby promoting the maintenance of relatively favorable intestinal homeostasis. These results demonstrated that the AI-2-deficient mutants provided a more pronounced ameliorative effect on colitis in a mouse model, suggesting that the background of the LAB effect is associated with the alterations in colonic flora induced by AI-2.
Systemic tryptophan homeostasis
Authors: Klaessens Simon , Stroobant Vincent , De Plaen Etienne , Van den Eynde Benoit J.
Published: September 2022

Tryptophan is an essential amino acid, which is not only a building block for protein synthesis, but also a precursor for the biosynthesis of co-enzymes and neuromodulators, such as NAD/NADP(H), kynurenic acid, melatonin and serotonin. It also plays a role in immune homeostasis, as local tryptophan catabolism impairs T-lymphocyte mediated immunity. Therefore, tryptophan plasmatic concentration needs to be stable, in spite of large variations in dietary supply. Here, we review the main checkpoints accounting for tryptophan homeostasis, including absorption, transport, metabolism and elimination, and we discuss the physiopathology of disorders associated with their dysfunction. Tryptophan is catabolized along the kynurenine pathway through the action of two enzymes that mediate the first and rate-limiting step of the pathway: indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). While IDO1 expression is restricted to peripheral sites of immune modulation, TDO is massively expressed in the liver and accounts for 90% of tryptophan catabolism. Recent data indicated that the stability of the TDO protein is regulated by tryptophan and that this regulation allows a tight control of tryptophanemia. TDO is stabilized when tryptophan is abundant in the plasma, resulting in rapid degradation of dietary tryptophan. In contrast, when tryptophan is scarce, TDO is degraded by the proteasome to avoid excessive tryptophan catabolism. This is triggered by the unmasking of a degron in a non-catalytic tryptophan-binding site, resulting in TDO ubiquitination by E3 ligase SKP1-CUL1-F-box. Deficiency in TDO or in the hepatic aromatic transporter SLC16A10 leads to severe hypertryptophanemia, which can disturb immune and neurological homeostasis.
Selection of RNA aptamers targeting hypoxia in cancer
Authors: Nuzzo Silvia , Iaboni Margherita , Ibba Maria Luigia , Rienzo Anna , Musumeci Domenica , Franzese Monica , Roscigno Giuseppina , Affinito Alessandra , Petrillo Gianluca , Quintavalle Cristina , Ciccone Giuseppe , Esposito Carla Lucia , Catuogno Silvia
Published: September 2022

Hypoxia plays a crucial role in tumorigenesis and drug resistance, and it is recognised as a major factor affecting patient clinical outcome. Therefore, the detection of hypoxic areas within the tumour micro-environment represents a useful way to monitor tumour growth and patients’ responses to treatments, properly guiding the choice of the most suitable therapy. To date, non-invasive hypoxia imaging probes have been identified, but their applicability in vivo is strongly limited due to an inadequate resistance to the low oxygen concentration and the acidic pH of the tumour micro-environment. In this regard, nucleic acid aptamers represent very powerful tools thanks to their peculiar features, including high stability to harsh conditions and a small size, resulting in easy and efficient tumour penetration. Here, we describe a modified cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) approach that allows the isolation of specific RNA aptamers for the detection of the hypoxic phenotype in breast cancer (BC) cells. We demonstrated the effectiveness of the proposed method in isolating highly stable aptamers with an improved and specific binding to hypoxic cells. To our knowledge, this is the first example of a cell-SELEX approach properly designed and modified to select RNA aptamers against hypoxia-related epitopes expressed on tumour cell surfaces. The selected aptamers may provide new effective tools for targeting hypoxic areas within the tumour with great clinical potential.
Development and validation of virtual reality-based Rey Auditory Verbal Learning Test
Authors: Gottlieb Amihai , Doniger Glen M. , Kimel-Naor Shani , Ben-Gal Oran , Cohen Maya , Iny Hila , Beeri Michal Schnaider , Plotnik Meir
Published: September 2022

Objective

Translations and adaptations of traditional neuropsychological tests to virtual reality (VR) technology bear the potential to increase their ecological validity since the technology enables simulating everyday life conditions in a controlled manner. The current paper describes our translation of a commonly used neuropsychological test to VR, the Rey Auditory Verbal Learning Test (RAVLT). For this aim, we developed a VR adaptation of the RAVLT (VR-RAVLT) Which is based on a conversation with a secretary in a virtual office using a fully immersive VR system. To validate the VR-RAVLT, we tested its construct validity, its age-related discriminant validity and its test-retest validity in reference to the original gold standard RAVLT (GS-RAVLT).

Method

Seventy-eight participants from different age groups performed the GS-RAVLT and the VR-RAVLT tests in a counterbalanced order in addition to other neuropsychological tests. Construct validity was validated using Pearson’s correlations coefficients and serial position effects; discriminant validity was validated using receiver operating characteristic area under the curve values and test-retest reliability was validated using intraclass correlation coefficients.

Results

Comparing both RAVLTs’ format results indicates that the VR-RAVLT has comparable construct, discriminant and test–retest validities.

Conclusion

the novel VR-RAVLT and the GS-RAVLT share similar psychometric properties suggesting that the two tests measure the same cognitive construct. This is an indication of the feasibility of adapting the RAVLT to the VR environment. Future developments will employ this approach for clinical diagnosis and treatment.
Dreamers’ evaluation of the emotional valence of their day-to-day dreams is indicative of some mood regulation function
Authors: Barbeau Kheana , Turpin Chloé , Lafrenière Alexandre , Campbell Emma , De Koninck Joseph
Published: September 2022

Dreams may contribute to psychological adaptation by aiding in mood regulation. One way it could be achieved is through a desensitization process whereby negative events are replayed within the dream under lower conditions of negative emotionality. Evidence of this theory is supported by the tendency of dreamers to evaluate their emotions felt in their dreams more positively compared to an independent judge (i.e., positivity bias). Additionally, it has been observed that while dream emotions are typically more negative than pre-sleep emotions, morning emotions are more positive, suggesting that emotional regulation occurs overnight and may help improve mood in the morning. The present study aimed to examine the relationships between pre-sleep, dream, and morning mood and the potential desensitization function of remembered dreams as indicated by their effects on morning mood and stress.

Methodology: Participants (N = 188; Mean age = 19.2, SD = 3.0) recorded their dreams (N = 345 dreams) and self-reported their stress and mood at bedtime, during their dream retrospectively, and upon waking. A judge also evaluated the subjects’ dream moods. Subjects’ positivity bias was defined as the difference between the subjects and the judge’s evaluation of the positive emotions in the dream.

Results: A MANOVA revealed that subjects perceived a higher level of positive emotions in their dreams compared to a judge. Multi-group path analysis revealed that some relationships between pre-sleep, dream, and morning emotions and stress differed in positive and negative dream nights. In both groups, the strongest predictors of morning mood and stress were pre-sleep mood and stress, respectively. The second strongest predictor of positive morning mood was the subjects’ dream positivity bias.

Conclusion: Results provide some support for the association of dreaming in mood regulation attributable to REM sleep. They also highlight that pathways implicated in mood regulation may be distinct from stress regulation.
Regenerated hair cells in the neonatal cochlea are innervated and the majority co-express markers of both inner and outer hair cells
Authors: Heuermann Mitchell L. , Matos Sophia , Hamilton Deborah , Cox Brandon C.
Published: September 2022

After a damaging insult, hair cells can spontaneously regenerate from cochlear supporting cells within the first week of life. While the regenerated cells express several markers of immature hair cells and have stereocilia bundles, their capacity to differentiate into inner or outer hair cells, and ability to form new synaptic connections has not been well-described. In addition, while multiple supporting cell subtypes have been implicated as the source of the regenerated hair cells, it is unclear if certain subtypes have a greater propensity to form one hair cell type over another. To investigate this, we used two CreER mouse models to fate-map either the supporting cells located near the inner hair cells (inner phalangeal and border cells) or outer hair cells (Deiters’, inner pillar, and outer pillar cells) along with immunostaining for markers that specify the two hair cell types. We found that supporting cells fate-mapped by both CreER lines responded early to hair cell damage by expressing Atoh1, and are capable of producing regenerated hair cells that express terminal differentiation markers of both inner and outer hair cells. The majority of regenerated hair cells were innervated by neuronal fibers and contained synapses. Unexpectedly, we also found that the majority of the laterally positioned regenerated hair cells aberrantly expressed both the outer hair cell gene, oncomodulin, and the inner hair cell gene, vesicular glutamate transporter 3 (VGlut3). While this work demonstrates that regenerated cells can express markers of both inner and outer hair cells after damage, VGlut3 expression appears to lack the tight control present during embryogenesis, which leads to its inappropriate expression in regenerated cells.
Real-time numerical system convertor via two-dimensional WS2-based memristive device
Authors: Xin Xing , Sun Liyao , Chen Jiamei , Bao Youzhe , Tao Ye , Lin Ya , Bian Jingyao , Wang Zhongqiang , Zhao Xiaoning , Xu Haiyang , Liu Yichun
Published: September 2022

The intriguing properties of two-dimensional (2D) transition metal dichalcogenides (TMDCs) enable the exploration of new electronic device architectures, particularly the emerging memristive devices for in-memory computing applications. Implementation of arithmetic logic operations taking advantage of the non-linear characteristics of memristor can significantly improve the energy efficiency and simplify the complexity of peripheral circuits. Herein, we demonstrate an arithmetic logic unit function using a lateral volatile memristor based on layered 2D tungsten disulfide (WS2) materials and some combinational logic circuits. Removable oxygen ions were introduced into WS2 materials through oxygen plasma treatment process. The resistive switching of the memristive device caused by the thermophoresis-assisted oxygen ions migration has also been revealed. Based on the characteristics of excitatory postsynaptic current (EPSC), paired-pulse facilitation (PPF), and spike rate dependent plasticity (SRDP), a real-time numerical system convertor was successfully accomplished, which is a significant computing function of arithmetic logic unit. This work paves a new way for developing 2D memristive devices for future arithmetic logic applications.
General anesthesia but not conscious sedation improves functional outcome in patients receiving endovascular thrombectomy for acute ischemic stroke: A meta-analysis of randomized clinical trials and trial sequence analysis
Authors: Lee Chia-Wei , Chang Yang-Pei , Huang Yen-Ta , Hsing Chung-Hsi , Pang Yu-Li , Chuang Min-Hsiang , Wu Su-Zhen , Sun Cheuk-Kwan , Hung Kuo-Chuan
Published: September 2022

Background

This study aimed at comparing the difference in prognostic outcomes between patients receiving general anesthesia (GA) and conscious sedation (CS) for endovascular thrombectomy after acute ischemic stroke.

Methods

Databases from Medline, Embase, Google scholar, and Cochrane library were searched for randomized controlled studies (RCTs) comparing patients undergoing GA and CS for endovascular thrombectomy following anterior circulation ischemic stroke. The primary outcome was frequency of 90-day good functional outcome [defined as modified Rankin Scale score of ≤ 2], while secondary outcomes included successful recanalization rate (SRR) [i.e., modified thrombolysis in cerebral infarction = 2b or 3], mortality risk, symptomatic intracranial hemorrhage (ICH), procedure-related complications, hypotension, pneumonia, neurological outcome at post-procedure 24–48 h, and puncture-to-recanalization time.

Results

Six RCTs including 883 patients published between 2016 and 2022 were included. Merged results revealed a higher SRR [risk ratio (RR) = 1.11, 95% CI: 1.03–1.2, p = 0.007; I2 = 29%] and favorable neurological outcomes at 3-months (RR = 1.2, 95% CI: 1.01–1.41, p = 0.04; I2 = 8%) in the GA group compared to CS group, without difference in the risk of mortality (RR = 0.88), symptomatic ICH (RR = 0.91), procedure-related complications (RR = 1.05), and pneumonia (RR = 1.9) as well as post-procedure neurological outcome (MD = −0.21) and successful recanalization time (MD = 3.33 min). However, GA was associated with a higher risk of hypotension compared with that of CS.

Conclusion

Patients with acute anterior circulation ischemic stroke receiving GA were associated with a higher successful recanalization rate as well as a better 3-month neurological outcome compared to the use of CS. Further investigations are warranted to verify our findings.

Systematic review registration

www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022342483, identifier: CRD42022342483.
Incidence, kinetics, and risk factors for intra- and extracranial cerebral arteriopathies in a newborn sickle cell disease cohort early assessed by transcranial and cervical color Doppler ultrasound
Authors: Bernaudin Françoise , Arnaud Cécile , Kamdem Annie , Hau Isabelle , Madhi Fouad , Jung Camille , Epaud Ralph , Verlhac Suzanne
Published: September 2022

The risk of stroke in children with sickle cell disease (SCD) is detected by abnormal intracranial arterial time-averaged mean of maximum velocities (TAMVs ≥200 cm/s). Recently, extracranial internal carotid artery (eICA) arteriopathy has been reported, and a cross-sectional study showed that eICA-TAMVs ≥160 cm/s are significantly associated with eICA kinkings and stenosis. The cumulative incidence of and predictive risk factors for intracranial arteriopathy are well described in sickle cell anemia (SCA=SS/Sβ0) but are lacking for SC/Sβ+ children, as is the cumulative incidence of eICA arteriopathy. We report a prospective longitudinal cohort study including 493 children with SCD (398 SCA, 95 SC/Sβ+), all assessed by transcranial and cervical color Doppler ultrasound. Cerebral MRI/MRA data were available in 375 children with SCD and neck MRA in 365 children. eICA kinkings were defined as eICA tortuosities on neck MRA, with an internal acute angle between the two adjacent segments <90°. The median follow-up was 10.6 years. The cumulative incidence of kinkings was significantly lower in SC/Sβ+ children than in children with SCA, and no SC/Sβ+ child developed intra- or extracranial stenotic arteriopathy. The 10-year KM estimate of cumulative incidence (95% CI) for eICA-TAMVs ≥160 cm/s revealed its development in the 2nd year of life in children with SCA, reaching a plateau of 17.4% (13.2–21.6%) by about 10 years of age, while the plateau for eICA stenosis was 12.3% (8.3–16.3%). eICA assessment identified 13.5% (9.3–17.7%) patients at risk of stroke who were not detected by transcranial color Doppler ultrasound. We also show, for the first time, that in addition to a congenital origin, eICA kinkings sin patients with SCD can develop progressively with aging as a function of eICA-TAMVs, themselves related to anemia severity. Ongoing hydroxyurea treatment was significantly associated with a lower risk of abnormal intracranial arteriopathy and eICA kinkings. After adjustment with hydroxyurea, baseline low hemoglobin, high reticulocyte, and WBC counts remained independent risk factors for intracranial arteriopathy, while low hemoglobin and SEN β-haplotype number were independent risk factors for extracranial arteriopathy. The association between extracranial arteriopathy and SEN β-haplotype number suggested a genetic link between the ethnic origin and incidence of eICA kinkings. This prospective cohort study shows the importance of systematically assessing the eICA and of recording biological parameters during the 2nd year of life before any intensive therapy to predict the risk of cerebral arteriopathy and treat patients with severe baseline anemia.
New evidence on the association of occupation with amyotrophic lateral sclerosis: A register-based case-control study in Finland
Authors: Saastamoinen Peppiina , Laaksovirta Hannu , Leino-Arjas Päivi , Rahkonen Ossi
Published: September 2022

Objectives

Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disease that usually leads to death within a few years from diagnosis. The risk factors for ALS are still largely unknown. However, it is assumed that environmental factors play a role in disease onset. Occupation is suggested as a potential risk factor, but findings are inconsistent. The aim of this study was to assess the association of occupation with ALS in Finland. Register data were used to avoid recall bias and to obtain a large enough sample to detect the potential associations.

Methods

This case-control study included ALS cases that occurred between 1980 and 2015 in Finland (n = 4,781). ALS cases were identified from the causes of death register. For each ALS case, six controls were selected matched for sex and birth-year. The date of death of the ALS case was set as index date. Information on occupation was obtained from Statistics Finland for all subjects. The focus was on the longest-held occupation on 2-digit level (70 groups). The association of occupation with ALS was analyzed using conditional logistic regression.

Results

Compared to “clerical work and other office work,” the risk of ALS was increased in “packing and wrapping work” (OR 1.53, 95% CI 1.08–2.17), “laundering, dry cleaning and pressing work” (OR 1.83, 95% CI 1.08–3.08), and “travel service work” (OR 8.75, CI 2.76–27.74). A decreased risk was found in “planning, administrative and research work in the technical fields” (OR 0.69, 95% CI 0.48–0.98). Of the significant associations identified, only “travel service work” was significant after FDR multiple testing correction.

Conclusions

This study identified occupations in which the risk of ALS was increased. Further studies are needed to pinpoint the potential exposures in these occupations that may trigger the disease.
Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients
Authors: Cont Celine , Stute Nathalie , Galli Anastasia , Schulte Christina , Logmin Kazimierz , Trenado Carlos , Wojtecki Lars
Published: September 2022

Introduction

Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation therapy that uses short, repetitive shockwaves through a neuro-navigated device. Current research suggests that these pulses lead to a wide range of vascular, metabolic, and neurotrophic changes. This relatively new CE-marked treatment provided first promising results in a clinical pilot study for improving cognition in mild-to-moderate Alzheimer's. Data from other centers is lacking, so here we analyzed safety and pilot real-world short-term results of TPS from the first center in Germany. To gain information about effects in different stages, patients with not only mild but also moderate-to-severe Alzheimer's were analyzed.

Methods

A total of 11 patients were retrospectively examined for cognitive and emotional function before and after the first stimulation series. The effect was assessed using several neuropsychological tests [Alzheimer's Disease Assessment Scale (ADAS), including the ADAS cognitive score (ADAS Cog) and ADAS affective scores, Mini-Mental Status Examination (MMSE), and Montreal Cognitive Assessment (MoCA)] including in comparison between the groups of mild-to-severe patients. Moreover, subjective improvement of symptom severity, potential effects on depressive symptoms, and side effects were analyzed using Numeric Rating Scales (NRS).

Results

Side effects were rare (in 4% of sessions) with moderate subjective severity and only transient. Patients significantly improved in the ADAS and ADAS Cog, while there was no significant effect in MMSE and MoCA. Patients' self-reported symptom severity improved significantly. The depressive symptoms measured in an ADAS subscale also improved significantly. Statistical data analyses revealed no significant correlation of clinical improvement with baseline symptom severity.

Conclusion

TPS might be a safe and promising add-on therapy for Alzheimer's, even for moderate-to-severe patients. More research on long-term effects in patients as well as studies with sham control groups is needed. Moreover, translational research on the mechanisms of action and effects on cerebral network physiology will be needed to understand this new neuromodulation technique.