Vitamin B₁₂ deficiency has been shown to affect bone mass in rodents and negatively impact bone formation in humans. In this study using mouse models we define the effect of B₁₂ supplementation in the wild-type mother and B₁₂ deficiency in a mouse genetic model (Gif-/- mice) during gestation on the bone and muscle architecture, and mechanical properties in the offspring. Analysis of bones from 4 weeks-old offspring of the wild-type mother following vehicle or B₁₂ supplementation during gestation (From embryonic day 0.5-20.5) showed an increase in bone mass caused by an isolated increase in bone formation in the B₁₂ supplemented group compared to vehicle controls. Analysis of effect of B₁₂ deficiency in the mother in a mouse genetic model (Gif-/- mice) on long bone architecture of the offspring showed a compromised cortical and trabecular bone mass, which was completely prevented by a single injection of B₁₂ in the B₁₂-deficient Gif-/- mothers.Biomechanical analysis of long bones of the offspring born from B₁₂ supplemented wild-type mothers showed an increase in bone strength, and conversely offspring born from B₁₂-deficient Gif-/- mothers revealed a compromised bone strength, which could be rescued by a single injection of B₁₂ in the B₁₂-deficient Gif-/- mother. Muscle structure and function analysis however revealed no significant effect on muscle mass, structure and grip strength of B₁₂ deficiency or supplementation in Gif-/- mice compared to littermate controls. Together, these results demonstrate the beneficial effect of maternally-derived B₁₂ in the regulation of bone structure and function in the offspring.

Keywords: Bone; Gut; Muscle; Osteoblasts; Vitamin B12.

Background: Gastrointestinal fistulization (GIF) is a rare and potentially fatal complication of acute necrotizing pancreatitis (ANP). There is paucity of data on clinical course and outcome of GIF in walled of necrosis (WON).

Objective: To evaluate frequency, clinical as well as imaging findings and outcome of spontaneous symptomatic GIF in patients with WON.

Methods: Retrospective analysis of database of patients with asymptomatic WON on regular follow-up over last six years to identify patients with symptomatic GIF.

Results: Out of 138 patients with asymptomatic WON seen during the study period, 16 (11.5%) patients (all males; mean age 41.7 ± 9.9 years) developed symptomatic GIF. The mean size of WON in patients who developed GIF was 9.5 ± 2.4 cm, and fistulization occurred after 65.1 ± 17.8 days of the onset of ANP. The site of fistulization was stomach, duodenum, jejunum, colon, and esophagus in seven (43.7%), five (31.2%), one (6.2%), two (12.5%), and one (6.2%) patients, respectively. GIF resulted in spontaneous resolution in two patients (stomach 1 and esophagus 1). The remaining patients with gastric (six patients) and duodenal (five patients) fistulization were successfully treated endoscopically by placing multiple plastic stents in the necrotic cavity after balloon dilatation of the fistulous tract. Patients with colonic fistulization required surgery. None of the patients succumbed to the illness.

Conclusion: Symptomatic GIF of WON usually occurs within the first three months of onset of ANP. It commonly occurs in either stomach or duodenum and can be successfully managed endoscopically.

Keywords: Computed tomography; Fistula; Pancreatic necrosis; Pancreatitis; Stent.

Purpose: To verify the effectiveness of the speech language intervention in the communicative behavior in group of individuals diagnosed with schizophrenia.

Methods: This is a semi-experimental, quantitative analytical-exploratory study. Users of a Psychosocial Care Center III (CAPS III) with a diagnosis of schizophrenia were included, divided into 2 groups: Experimental Group (EG), comprising the Speech Therapy Intervention Group (STIG) and Control Group (CG). The communicative behavior was evaluated through the Brief MAC Battery. The STIG was performed in 2 weekly sessions, during 12 weeks, totalizing 24 sessions. After this period, individuals were reassessed. Data were analyzed through Mann Whitney non-parametric Test, and Pearson's Correlation Test.

Results: A total of 19 individuals of both sexes participated, who are between 19 and 59 years old with a minimum schooling of 5 years, 14 participating in EG and 5 in CG. In the EG, it was possible to observe that there was improvement in the communicative behavior after the speech language intervention in all the tasks evaluated, except in the writing task. In CG, no significant changes were observed comparing evaluation and reevaluation after 12 weeks.

Conclusion: The speech-language intervention in group was effective as a socialization tool and contributing to the improvement of the living conditions of these people with schizophrenia.

Objetivo: Verificar a efetividade da intervenção fonoaudiológica grupal no comportamento comunicativo de indivíduos com diagnóstico de esquizofrenia.

Método: Trata-se de um estudo quase experimental, quantitativo analítico-exploratório. Foram incluídos usuários de um Centro de Atenção Psicossocial III (CAPS III) com diagnóstico de esquizofrenia, divididos em 2 grupos: Grupo Experimental (GE), compondo o Grupo de Intervenção Fonoaudiológica (GIF) e Grupo Controle (GC). O comportamento comunicativo foi avaliado através da Bateria MAC Breve. O GIF foi realizado em 2 sessões semanais, totalizando 24 sessões. Após esse período, os indivíduos foram reavaliados. A análise ocorreu por meio dos Testes não paramétricos de Mann Whitney e o Teste de Correlação de Pearson.

Resultados: Participaram 19 indivíduos, de ambos os sexos, com idade entre 19 e 59 anos, escolaridade mínima de 5 anos, sendo que 14 participaram do GE e 5 do GC. No GE, foi possível observar que houve melhora no comportamento comunicativo após a intervenção fonoaudiológica em todas as tarefas avaliadas, exceto na tarefa de Escrita. Já no GC, não foram observadas alterações significativas comparando a avaliação e a reavaliação após 12 semanas.

Conclusão: A intervenção fonoaudiológica grupal foi efetiva, utilizando a comunicação como instrumento de socialização e contribuindo para a melhoria das condições de vida de indivíduos com diagnóstico de esquizofrenia.

Objective: Mobile technologies allow for accessible and cost-effective health monitoring and intervention delivery. Despite these advantages, mobile health (mHealth) engagement is often insufficient. While monetary incentives may increase engagement, they can backfire, dampening intrinsic motivations and undermining intervention scalability. Theories from psychology and behavioral economics suggest useful nonmonetary strategies for promoting engagement; however, examinations of the applicability of these strategies to mHealth engagement are lacking. This proof-of-concept study evaluates the translation of theoretically-grounded engagement strategies into mHealth, by testing their potential utility in promoting daily self-reporting.

Method: A microrandomized trial (MRT) was conducted with adolescents and emerging adults with past-month substance use. Participants were randomized multiple times daily to receive theoretically-grounded strategies, namely reciprocity (the delivery of inspirational quote prior to self-reporting window) and nonmonetary reinforcers (e.g., the delivery of meme/gif following self-reporting completion) to improve proximal engagement in daily mHealth self-reporting.

Results: Daily self-reporting rates (62.3%; n = 68) were slightly lower than prior literature, albeit with much lower financial incentives. The utility of specific strategies was found to depend on contextual factors pertaining to the individual's receptivity and risk for disengagement. For example, the effect of reciprocity significantly varied depending on whether this strategy was employed (vs. not employed) during the weekend. The nonmonetary reinforcement strategy resulted in different outcomes when operationalized in various ways.

Conclusions: While the results support the translation of the reciprocity strategy into this mHealth setting, the translation of nonmonetary reinforcement requires further consideration prior to inclusion in a full scale MRT. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Trial registration: ClinicalTrials.gov NCT03255317.

Background: The piriform cortex (PC) occupies both banks of the endorhinal sulcus and has an important role in the pathophysiology of temporal lobe epilepsy (TLE). A recent study showed that resection of more than 50% of PC increased the odds of becoming seizure free by a factor of 16.

Objective: We report the feasibility of manual segmentation of PC and application of the Geodesic Information Flows (GIF) algorithm to automated segmentation, to guide resection.

Methods: Manual segmentation of PC was performed by two blinded independent examiners in 60 patients with TLE (55% Left TLE, 52% female) with a median age of 35 years (IQR, 29-47 years) and 20 controls (60% Women) with a median age of 39.5 years (IQR, 31-49). The GIF algorithm was used to create an automated pipeline for parcellating PC which was used to guide excision as part of temporal lobe resection for TLE.

Results: Right PC was larger in patients and controls. Parcellation of PC was used to guide anterior temporal lobe resection, with subsequent seizure freedom and no visual field or language deficit.

Conclusion: Reliable segmentation of PC is feasible and can be applied prospectively to guide neurosurgical resection that increases the chances of a good outcome from temporal lobe resection for TLE.

Keywords: Epilepsy surgery; imaging; piriform cortex; segmentation; temporal lobe epilepsy.

Oxidative stress has been implicated in the aging process and the progression of many neurodegenerative disorders. We previously reported that a novel oxindole compound, GIF-0726-r, effectively prevents endogenous oxidative stress, such as oxytosis/ferroptosis, an iron-dependent form of non-apoptotic cell death, in mouse hippocampal cells. In this study, using two hundred compounds that were developed based on the structure-activity relationship of GIF-0726-r, we screened for the most potent compounds that prevent glutamate- and erastin-induced oxytosis and ferroptosis. Using submicromolar concentrations, we identified nine neuroprotective compounds that have N,N-dimethylaniline as a common structure but no longer contain an oxindole ring. The most potent derivatives, GIF-2114 and GIF-2197-r (the racemate of GIF-2115 and GIF-2196), did not affect glutathione levels, had no antioxidant activity in vitro, or ability to activate the Nrf2 pathway, but prevented oxytosis/ferroptosis via reducing reactive oxygen production and decreasing ferrous ions. Furthermore, we developed fluorescent probes of GIF-2114 and GIF-2197-r to image their distribution in live cells and found that they preferentially accumulated in late endosomes/lysosomes, which play a central role in iron metabolism. These results suggest that GIF-2114 and GIF-2197-r protect hippocampal cells from oxytosis/ferroptosis by targeting late endosomes and lysosomes, as well as decreasing ferrous ions.

Keywords: Ferroptosis; Lysosomes; N,N-dimethylaniline derivatives; Neurodegeneration; Neuroprotection; Oxytosis.

Objective: This study attempted to screen and combine effective biomarkers to analyse the association between these biomarkers and gastrointestinal failure (GIF) in critically ill patients.

Methods: A total of 110 critically ill patients with acute gastrointestinal injury (AGI) admitted to ICU were enrolled. The AGI grade was determined by the AGI classification proposed by ESICM. There were 67 patients in gastrointestinal dysfunction (GID) group (AGI grade II), 43 patients in GIF group (AGI grade III-IV), and 41 healthy adults in healthy control (HC) group. APACHE II and SOFA score were used to evaluate the disease severity. Peripheral blood samples of patients were collected within 24 hours of admission to the ICU (prior-treatment) and after the conventional medication therapy for 7 consecutive days (post-treatment). Citrulline serum level was detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and D-lactate and lipopolysaccharide (LPS) serum levels were measured by ELISA. Pearson correlation, logistic regression, and ROC curve analysis were used.

Results: Patients with GID or GIF had lower serum level of citrulline, while higher levels of D-lactate and LPS than HC. Compared with GID patients, serum level of citrulline was reduced, while D-lactate and LPS were elevated in GIF patients. Correlation analysis displayed that serum levels of citrulline, D-lactate, and LPS were associated with the APACHE II and SOFA score in patients with GID or GIF. Logistics regression analysis showed that citrulline and D-lactate were risk for both GID and GIF. ROC curve analysis exhibited that combination of citrulline and D-lactate had relatively high value to distinguish GID from HC, GIF from GID, and GIF from HC.

Conclusion: Serum citrulline and D-lactate were associated with severity of GIF, combination of citrulline and D-lactate improved the diagnostic efficacy to identify GIF in critically ill patients.

Keywords: D-lactate; citrulline; critically ill patients; gastrointestinal dysfunction; gastrointestinal failure.

Background and aims: We previously reported that 3 endoscopic findings of melanosis, whitish epithelium, and vasodilation in the soft palate are associated with a high risk of esophageal squamous cell carcinoma (ESCC). Conventional endoscopic systems require observation under magnification to evaluate vasodilation. This case series aims to present the evaluation of vasodilation without magnification using an endoscopic system with enhanced depth-of-field (EDOF) imaging.

Methods: We observed the soft palate of 3 patients with early ESCC using an endoscopic system with EDOF (GIF-EZ1500 and EVIS X1 CV-1500, Olympus Co, Tokyo, Japan).

Results: The patient in case 1 had marked melanosis, whitish epithelium, and vasodilation (focal type) in the soft palate. The patient in case 2 had melanosis and vasodilation (diffuse type) in the soft palate. The vasodilation in cases 1 and 2 could be evaluated sufficiently without magnification. The patient in case 3 had melanosis and whitish epithelium in the soft palate. The color tone of melanosis became sharpened using texture and color enhancement imaging.

Conclusions: The endoscopic system with EDOF enabled us to evaluate all 3 soft palate findings associated with a high risk of ESCC, without magnification.

Keywords: EDOF, enhanced depth-of-field; ER, endoscopic resection; ESCC, esophageal squamous cell carcinoma; NBI, narrow-band imaging; TXI, texture and color enhancement imaging.

Purpose: High-resolution synchrotron radiation X-ray phase contrast microtomography (PC-μCT) images often suffer from severe ring artifacts, which are mainly caused by undesirable responses of detector elements. In the medical imaging field, the existence of ring artifacts can lead to degraded visual quality and can directly affect diagnosis accuracy. Thus, removing or at least effectively reducing ring artifacts is indispensable.

Method: The existing ring artifacts removal algorithms mainly focus on two-dimensional (matrix-based) priors, and these algorithms fail to consider correlations hidden in sequential CT images. This paper proposed a novel three-dimensional (tensor-based) ring artifacts removal algorithm for synchrotron radiation X-ray PC-μCT images. In the sinogram domain, ring artifacts manifest as vertical stripe artifacts. From an image decomposition perspective, a degraded sinogram can be decomposed into a stripe artifacts component and an underlying clean sinogram component. The proposed algorithm is designed to detect and remove stripe artifacts from a degraded sinogram by fully identifying the characteristics of the two components. Specifically, for the stripe artifacts component, tensor Tucker decomposition is used to describe its low-rank character. For the underlying clean sinogram component, spatial-sequential total variation regularization is adopted to enhance the piecewise smoothness. Moreover, the Frobenius norm term is further used to model Gaussian noise. An efficient augmented Lagrange multiplier method is designed to solve the proposed optimization model.

Results: The proposed method is evaluated utilizing both simulations and real data containing different ring artifacts patterns. In the simulations, the human chest CT images are used for evaluating the proposed method. We compare the peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and mean absolute error (MAE) results of our algorithm with the Naghia's method, the RRRTV method, the Wavelet-FFT method, and the SDRSD-GIF method. The proposed method was also evaluated on real data from rat liver samples and rat tooth samples. Our proposed method outperforms the competing methods in terms of both qualitative and quantitative evaluation results. Additionally, the 3D visualization results were presented to make the ring artifacts removal effect more intuitive.

Conclusion: The experimental results on simulations and real data clearly demonstrated that the proposed algorithm can significantly improve the quality of PC-μCT images compared with the existing popular algorithms, and it has great potential to promote the application of high-resolution imaging for visualizing biological tissues. This article is protected by copyright. All rights reserved.

Keywords: 3D ring artifacts removaly; X-ray phase contrast microtomography; low-rank tensor decomposition.

Objective: Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM.

Design: Gastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers.

Results: We demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury.

Conclusion: Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.

Keywords: gastric epithelial cell function; gastric metaplasia; mucosal injury.

Hyper-reflective foci (HRF) refers to the spot-shaped, block-shaped areas with characteristics of high local contrast and high reflectivity, which is mostly observed in retinal optical coherence tomography (OCT) images of patients with fundus diseases. HRF mainly appears hard exudates (HE) and microglia (MG) clinically. Accurate segmentation of HE and MG is essential to alleviate the harm in retinal diseases. However, it is still a challenge to segment HE and MG simultaneously due to similar pathological features, various shapes and location distribution, blurred boundaries, and small morphology dimensions. To tackle these problems, in this paper, we propose a novel global information fusion and dual decoder collaboration-based network (GD-Net), which can segment HE and MG in OCT images jointly. Specifically, to suppress the interference of similar pathological features, a novel global information fusion (GIF) module is proposed, which can aggregate the global semantic information efficiently. To further improve the segmentation performance, we design a dual decoder collaborative workspace (DDCW) to comprehensively utilize the semantic correlation between HE and MG while enhancing the mutual influence on them by feedback alternately. To further optimize GD-Net, we explore a joint loss function which integrates pixel-level with image-level. The dataset of this study comes from patients diagnosed with diabetic macular edema at the department of ophthalmology, University Medical Center Groningen, the Netherlands. Experimental results show that our proposed method performs better than other state-of-the-art methods, which suggests the effectiveness of the proposed method and provides research ideas for medical applications.

Using fusion splicing and hydroxide catalysis bonding (HCB) technology, an all-silica inline fiber-optic sensor with high-pressure survivability, high-resolution salinity measurement capability, and corrosion resistance for deep sea explorations is proposed and experimentally demonstrated. Two extrinsic Fabry-Perot interferometers (EFPIs) and a fiber Bragg grating (FBG) are cascaded in one single-mode fiber (SMF), enabling structural integration of single lead-in fiber and versatility of the sensing probe for temperature, depth, and salinity monitoring. The HCB technology offers a polymer adhesive-free assembly of one open-cavity EFPI for refractive index (RI) (salinity) sensing under normal pressure and temperature (NPT) conditions, showing obvious advantages of strong bonding strength, reliable effectiveness, and no corrosive chemicals requirements. The other EFPI formed by a fused structure is designed for pressure (depth) measurement. The cascading of EFPIs, especially the open-cavity EFPI immersed in water, will result in large light transmission loss and bring challenges to signal interrogation. Graded-index fiber (GIF) micro-collimators and reflective films are added to prevent dramatic degradations of signal intensity and fringe visibility underwater. Thereby, a Fabry-Perot (FP) cavity of several hundreds of microns in length and an open cavity of a thousand microns can be cascaded for underwater applications, effectively enhancing sensitivities and underwater signal readout simultaneously. Results show that the proposed sensor can well operate in the deep-sea pressure range of 0∼2039.43 mH₂O, RI range of 1.33239∼1.36885 RIU, and temperature range of 23∼80 °C, with resolutions of 0.033 MPa, 4.16×10^-7 RIU, and 0.54 °C, respectively. With the multi-parameter measurement capability, all-silica construction, and inline compact structure, the proposed sensor could be a potential candidate for deep sea exploration.

The yeast-to-hypha transition is tightly associated with pathogenicity in many human pathogenic fungi, such as the model fungal pathogen Cryptococcus neoformans, which is responsible for approximately 180,000 deaths annually. In this pathogen, the yeast-to-hypha transition can be initiated by distinct stimuli: mating stimulation or glucosamine (GlcN), the monomer of cell wall chitosan. However, it remains poorly understood how the signal specificity for Cryptococcus morphological transition by disparate stimuli is ensured. Here, by integrating temporal expression signature analysis and phenome-based clustering evaluation, we demonstrate that GlcN specifically triggers a unique cellular response, which acts as a critical determinant underlying the activation of GlcN-induced filamentation (GIF). This cellular response is defined by an unusually hyperactive cell wall synthesis that is highly ATP-consuming. A novel cell surface protein Gis1 was identified as the indicator molecule for the GlcN-induced cell wall response. The Mpk1-directed cell wall pathway critically bridges global cell wall gene induction and intracellular ATP supply, ensuring the Gis1-dependent cell wall response and the stimulus specificity of GIF. We further reveal that the ability of Mpk1 to coordinate the cell wall response and GIF activation is conserved in different Cryptococcus pathogens. Phosphoproteomics-based profiling together with genetic and phenotypic analysis revealed that the Mpk1 kinase mediates the regulatory specificity of GIF through a coordinated downstream regulatory network centered on Skn7 and Crz1. Overall, our findings discover an unprecedented and conserved cell wall biosynthesis-dependent fungal differentiation commitment mechanism, which enables the signal specificity of pathogenicity-related dimorphism induced by GlcN in Cryptococcus pathogens.

Endoscopic optical coherence tomography of large airways poses unique challenges. A hybrid lens is described that consists of a section of coreless fiber and graded index fiber (GIF), followed by a ball lens section. This design produces low numerical aperture beams better suited for large airway imaging. The performance of this lens is compared against conventional GIF and ball lens designs. Forward- and side-viewing probes were modeled, fabricated, and tested. The impact of a sheath on the beam profile was also investigated. Probes with working distances larger than 10 mm and depth-of-focus exceeding 12 mm are demonstrated with the proposed design.

Introduction: Several techniques for PEG-J tube placement have been described, commonly requiring fluoroscopic guidance and/or fixation of the jejunostomy tube (J-tube) into the small intestine. We describe a modified technique for placing jejunostomy tubes under direct visualization through a PEG with the use of ultra-thin endoscopes and steel guidewire.

Methods: A retrospective study at a single tertiary academic center evaluating patients who underwent PEG-J placement between 2010 and 2020. All PEG tubes were placed with a pull-through technique. The Olympus GIF-N180 endoscope was advanced through the PEG to the jejunum and a Savary-Gilliard guidewire was used for placement of the J-tube extension.

Results: Fifty-eight patients underwent PEG-J placement (median age 61 years; women 52%). Surgically altered gastric anatomy was observed in 11 patients (19%). Median procedure time was 44 min for new PEG-J tube placement (range 26-103) and 20 min for placement of a J-tube extension through an existing PEG tube (range 9-86) or gastrostomy tract. Technical success rate was in 100%. Sixty-two repeat procedures were performed for J-tube exchange in 27 patients (46%, range 1-9 per patient), of which 51 procedures (82%) were done using the same technique. The most common indication for tube replacement was tube dysfunction (63%, n = 39). The median procedure time for tube exchange was 20 min (range 2-62). No major adverse events were encountered.

Conclusion: PEG-J tubes can be placed effectively, rapidly, and safely using an ultra-thin caliber endoscope and a stiff steel wire through the PEG tube or mature gastrostomy site, precluding the need for fluoroscopy or oral access. J-tubes can be easily replaced utilizing the same technique.

Keywords: Aspiration; Jejunostomy tubes; N180 endoscope; Savary-Gilliard guidewire.

The crustacean marine isopod species Haploniscus bicuspis (Sars, 1877) shows circum-Icelandic distribution in a wide range of environmental conditions and along well-known geographic barriers, such as the Greenland-Iceland-Faroe (GIF) Ridge. We wanted to explore population genetics, phylogeography and cryptic speciation as well as investigate whether previously described, but unaccepted subspecies have any merit. Using the same set of specimens, we combined mitochondrial COI sequences, thousands of nuclear loci (ddRAD), and proteomic profiles, plus selected morphological characters using confocal laser scanning microscopy (CLSM). Five divergent genetic lineages were identified by COI and ddRAD, two south and three north of the GIF Ridge. Assignment of populations to the three northern lineages varied and detailed analyses revealed hybridization and gene flow between them, suggesting a single northern species with a complex phylogeographic history. No apparent hybridization was observed among lineages south of the GIF Ridge, inferring the existence of two more species. Differences in proteomic profiles between the three putative species were minimal, implying an ongoing or recent speciation process. Population differentiation was high, even among closely associated populations, and higher in mitochondrial COI than nuclear ddRAD loci. Gene flow is apparently male-biased, leading to hybrid zones and instances of complete exchange of the local nuclear genome through immigrating males. This study did not confirm the existence of subspecies defined by male characters, which probably instead refer to different male developmental stages.

Keywords: Haploniscus bicuspis; DNA barcoding; Haploniscidae; MALDI-TOF; cryptic species; ddRAD.

For the segmentation of magnetic resonance brain images into anatomical regions, numerous fully automated methods have been proposed and compared to reference segmentations obtained manually. However, systematic differences might exist between the resulting segmentations, depending on the segmentation method and underlying brain atlas. This potentially results in sensitivity differences to disease and can further complicate the comparison of individual patients to normative data. In this study, we aim to answer two research questions: 1) to what extent are methods interchangeable, as long as the same method is being used for computing normative volume distributions and patient-specific volumes? and 2) can different methods be used for computing normative volume distributions and assessing patient-specific volumes? To answer these questions, we compared volumes of six brain regions calculated by five state-of-the-art segmentation methods: Erasmus MC (EMC), FreeSurfer (FS), geodesic information flows (<em>GIF</em>), multi-atlas label propagation with expectation-maximization (MALP-EM), and model-based brain segmentation (MBS). We applied the methods on 988 non-demented (ND) subjects and computed the correlation (PCC-v) and absolute agreement (ICC-v) on the volumes. For most regions, the PCC-v was good ( <math><mrow><mo>></mo> <mn>0.75</mn></mrow> </math> ), indicating that volume differences between methods in ND subjects are mainly due to systematic differences. The ICC-v was generally lower, especially for the smaller regions, indicating that it is essential that the same method is used to generate normative and patient data. To evaluate the impact on single-subject analysis, we also applied the methods to 42 patients with Alzheimer's disease (AD). In the case where the normative distributions and the patient-specific volumes were calculated by the same method, the patient's distance to the normative distribution was assessed with the z-score. We determined the diagnostic value of this z-score, which showed to be consistent across methods. The absolute agreement on the AD patients' z-scores was high for regions of thalamus and putamen. This is encouraging as it indicates that the studied methods are interchangeable for these regions. For regions such as the hippocampus, amygdala, caudate nucleus and accumbens, and globus pallidus, not all method combinations showed a high ICC-z. Whether two methods are indeed interchangeable should be confirmed for the specific application and dataset of interest.

Keywords: brain region segmentation; comparison study; magnetic resonance imaging; normative modeling; subcortical.

Forest tree breeding efforts have focused mainly on improving traits of economic importance, selecting trees suited to new environments or generating trees that are more resilient to biotic and abiotic stressors. This review describes various methods of forest tree selection assisted by genomics and the main technological challenges and achievements in research at the genomic level. Due to the long rotation time of a forest plantation and the resulting long generation times necessary to complete a breeding cycle, the use of advanced techniques with traditional breeding have been necessary, allowing the use of more precise methods for determining the genetic architecture of traits of interest, such as genome-wide association studies (GWASs) and genomic selection (GS). In this sense, main factors that determine the accuracy of genomic prediction models are also addressed. In turn, the introduction of genome editing opens the door to new possibilities in forest trees and especially clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). It is a highly efficient and effective genome editing technique that has been used to effectively implement targetable changes at specific places in the genome of a forest tree. In this sense, forest trees still lack a transformation method and an inefficient number of genotypes for CRISPR/Cas9. This challenge could be addressed with the use of the newly developing technique GRF-GIF with speed breeding.

Keywords: BLUP; Bayesian genomic prediction; CRISPR/Cas9; GRF-GIF; forest tree improvement.

Melanogenesis and melanosome secretion are regulated by several mechanisms. In this study, we found that the oxindole derivative GIF-2209 accelerated melanogenesis associated with the discrimination in the expression and intracellular distributions of two melanogenic enzymes, tyrosinase (TYR) and tyrosinase-related protein-1 (TYRP-1). GIF-2209 upregulated the expression of TYR via a microphthalmia transcription factor (MITF)-independent mechanism, leading to high expression of protein. In contrast, GIF-2209 did not alter the mRNA levels of TYRP-1 and suppressed its protein levels. GIF-2209 induced the dissociation of TYR from TYRP-1 but did not alter the association between TYR and CD63, a melanosome and lysosome marker. The protein levels of CD63 were also upregulated by GIF-2209. GIF-2209 induced lysosome expansion and redistribution in all areas of the cytosol, accompanied by autophagy acceleration (upregulation of LC3BII protein levels and downregulation of p62 protein levels). In addition, GIF-2209 stimulated the secretion of melanosomes containing high levels of TYR, TYRP-1, and CD63 proteins. The GIF-2209 mediated melanosome secretion was sensitive to the lysosome inhibitor chloroquine. These results suggest that GIF-2209 may activate lysosomal functions with TYR gene expression, while it accelerates melanosome secretion, which finally leads to the depletion of intracellular melanogenic enzyme, especially TYRP-1 protein.

Keywords: B16F10; SU5205; TYRP-1; lysosome; melanogenesis; melanosome; oxindole; tyrosinase.

Aims: We investigated whether faecal microbiota transplantation (FMT) decreases intra-abdominal pressure (IAP) and improves gastrointestinal (GI) dysfunction and infectious complications in acute pancreatitis (AP). Methods: In this first randomised, single-blind, parallel-group, controlled study, we recruited and enrolled consecutive patients with AP complicated with GI dysfunction. Eligible participants were randomly assigned to receive faecal transplant (n = 30) or normal saline (n = 30) via a nasoduodenal tube once and then again 2 days later. The primary endpoint was the rate of IAP decline; secondary endpoints were GI function, infectious complications, organ failure, hospital stay and mortality. Analyses were based on intention to treat. Results: We enrolled 60 participants and randomly assigned them to the FMT (n = 30) or control (n = 30) group. Baseline characteristics and disease severity were similar for both groups. IAP decreased significantly 1 week after intervention in both groups, with no difference in the IAP decline rate between FMT and Control group [0.1 (-0.6, 0.5) vs. 0.2 (-0.2, 0.6); P = 0.27]. Normal gastrointestinal failure (GIF) scores were achieved in 12 (40%) patients in the FMT group and 14 (47%) in the control group, with no significant difference (P = 0.60). However, D-lactate was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [-0.3 (-3.7, 0.8) vs. 0.4 (-1.1, 0.9); P = 0.01]. Infectious complications occurred in 15 (50%) and 16 (53.33%) patients in the FMT and control groups, respectively (P = 0.80). However, interleukin-6 (IL-6) was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [0.4 (-3.6, 0.9) vs. 0.8 (-1.7, 1.0); P = 0.03]. One participant experienced transient nausea immediately after FMT, but no serious adverse events were attributed to FMT. Conclusion: FMT had no obvious effect on IAP and infectious complications in AP patients, though GI barrier indictors might be adversely affected. Further multi-centre studies are needed to confirm our findings. The study was registered at https://clinicaltrials.gov (NCT02318134).

Keywords: acute pancreatitis; faecal microbiota transplantation; gastrointestinal dysfunction; gut microbiota dysbiosis; infected pancreatic necrosis.

Rice Growth-Regulating Factors (GRFs) were originally identified to be gibberellin (GA)-induced, but the nature of GA induction has remained unknown because most reports thereafter focused on revealing their roles in growth-promoting activities. GRFs have the WRC (Trp, Arg, Cys) domain to target DNA and contain the QLQ (Gln, Leu, Gln) domain to interact with GRF-Interacting Factor (GIF), which recruits ATP-dependent DNA translocase Switch/Sucrose Non-fermenting (SWI/SNF) for chromatin remodeling. Both GRFs and GIFs exhibit transcriptional activities but GIFs lack a DNA-binding domain. So, GRFs act like a navigator in the GRF-GIF-SWI/SNF complex, determining when and where the complex should work on. The levels of most rice GRFs can be sensitively regulated by miR396, which responds to many developmental and environmental factors. Recent clues from several studies highlight the original question of how GRFs participate in GA signaling. DELLA (contain DELLA motif) protein plays dual roles in controlling the level of GRFs by regulating the level of miR396 and interacting with GRFs. Here we address the question of why this complex plays an essential role in controlling plant growth focusing on the action of GA signaling pivot, DELLA.

Keywords: DELLA; GA signaling; GIF; GRF; SWI/SNF.