Lymphedema in a 7-year-old boy infected with Wuchereria bancrofti in Sierra Leone: A case report

We present a case of congenital lymphedema in a 7-year-old boy in Sierra Leone with active filarial infection and penile edema. The genital edema with onset at 6 months of age may have been due to a congenital abnormality in lymphatic drainage. Other possible causes of childhood lymphedema, including Milroy's disease, are discussed

Maternal bonding styles in smokers and non-smokers: a comparative study

BACKGROUND: Parental bonding has been implicated in smoking behavior, and the quality of maternal bonding (MB) has been associated with poor mental health and substance use. However, little is known about the association of MB and the smoking of the offspring. METHODS: In our study, 129 smokers and 610 non-smoker medical students completed the parental bonding instrument, which measures MB along two dimensions: care and overprotection. Four categories can be created by high and low scores on care and overprotection: optimal parenting (OP; high care/low overprotection); affectionless control (ALC; low care/high overprotection); affectionate constraint (AC; high care/high overprotection), and neglectful parenting (NP; low care/low overprotection). Nicotine dependence was assessed by the Fagerstrom Nicotine Dependence Test, exhaled CO level, and daily cigarette consumption (CPD). RESULTS: Higher CPD was significantly associated with lower overprotection (p = 0.016) and higher care (p = 0.023) scores. The odds for being a smoker were significantly higher in the neglectful maternal bonding style compared to the other rearing styles (p = 0.022). Besides, smokers showed significantly higher care and lower overprotection scores with the Mann-Whitney U-test than non-smokers, although these associations did not remain significant in multiple regression models. CONCLUSION: Our results indicate that focusing on early life relationship between patient and mother can be important in psychotherapeutic interventions for smoking. Registration trials retrospectively registered

SUSTAIN captures category learning, recognition, and hippocampal activation in a unidimensional vs information-integration task

There is a growing interest in alternative explanations to the dual-system account of how people learn category structures varying in their optimal decision bounds (unidimensional and information-integration structures). Recognition memory performance and hippocampal activation patterns in these tasks are two interesting findings, which have not been formally explained. Here, we carry out a formal simulation with SUSTAIN (Love, Medin, & Gureckis, 2004), an adaptive model of category learning, which had great success in accounting for recognition memory performance and fMRI activity patterns. We show, for the first time, that a formal single-system model of category learning can accommodate recognition performance after learning and is consistent with fMRI data obtained while participants learned these structures

Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics

Representing uncertainty in the Rescorla-Wagner model: Blocking, the redundancy effect, and outcome base rate

It is generally assumed that the Rescorla and Wagner (1972) model adequately accommodates the full results of simple cue competition experiments in humans (e.g. Dickinson et al., 1984), while the Bush and Mosteller (1951) model cannot. We present simulations that demonstrate this assumption is wrong in at least some circumstances. The Rescorla-Wagner model, as usually applied, fits the full results of a simple forward cue-competition experiment no better than the Bush-Mosteller model. Additionally, we present a novel finding, where letting the associative strength of all cues start at an intermediate value (rather than zero), allows this modified model to provide a better account of the experimental data than the (equivalently modified) Bush-Mosteller model. This modification also allows the Rescorla-Wagner model to account for a redundancy effect experiment (Uengoer et al., 2013); something that the unmodified model is not able to do. Furthermore, the modified Rescorla-Wagner model can accommodate the effect of varying the proportion of trials on which the outcome occurs (i.e. the base rate) on the redundancy effect (Jones et al., 2019). Interestingly, the initial associative strength of cues varies in line with the outcome base rate. We propose that this modification provides a simple way of mathematically representing uncertainty about the causal status of novel cues within the confines of the Rescorla-Wagner model. The theoretical implications of this modification are discussed. We also briefly introduce free and open resources to support formal modelling in associative learning. Keywords: associative learning, prediction error, uncertainty, modelling, blocking, redundancy effect, open science.</jats:p

Akt-Induced Phosphorylation of N-CoR at Serine 1450 Contributes to Its Misfolded Conformational Dependent Loss (MCDL) in Acute Myeloid Leukemia of the M5 Subtype

10.1371/journal.pone.0070891PLoS ONE88-POLN

Influence of mechanical treatment on starch obtained from pea seeds

The aim of this work is study the disordering of the crystalline structure of pea starch due to mechanical treatment.This research was carried out within the State Assignment to ISSCM SB RAS (project 0301-2019-0004)

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)

Is adrenalectomy necessary during unilateral nephrectomy for Wilms Tumor? A report from the Children\u27s Oncology Group.

PURPOSE: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome. METHODS: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy. RESULTS: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially in 194 patients (5.2%). Of the adrenal glands removed, 68 (4.4%) contained tumor. Adrenal involvement was more common in patients with stage 3 (9.8%) than stage 2 disease (1.9%; p \u3c 0.0001). After controlling for stage and histopathology, five-year EFS was similar whether or not the adrenal gland was removed (p = 0.48), or involved with tumor (p = 0.81); however, intraoperative spill rates were higher in patients undergoing adrenalectomy (26.1% vs 15.5%, p \u3c 0.0001), likely due to larger tumor size or technical factors. No patient had clinical evidence of adrenal insufficiency or tumor recurrence in the adrenal gland during follow-up (median 9.9 years). CONCLUSIONS: Sparing the adrenal gland during nephrectomy for unilateral Wilms tumor was not associated with a higher incidence of intraoperative spill and was associated with a similar oncologic outcome, on a per-stage basis, with cases where the adrenal was removed. Thus, adrenalectomy should not be considered mandatory during radical nephrectomy for Wilms tumor

Deep Learning–Based Retinoblastoma Protein Subtyping of Pulmonary Large-Cell Neuroendocrine Carcinoma on Small Hematoxylin and Eosin–Stained Specimens

Molecular subtyping of pulmonary large-cell neuroendocrine carcinoma (LCNEC) based on retinoblastoma protein (pRb) expression may influence systemic treatment decisions. Current histomorphologic assessments of hematoxylin and eosin–stained tissue samples cannot reliably differentiate LCNEC molecular subtypes. This study explores the potential of deep learning (DL) to identify histologic patterns that distinguish these subtypes, by developing a custom convolutional neural network to predict the binary expression of pRb in small LCNEC tissue samples. Our model was trained, cross-validated, and tested on tissue microarray cores from 143 resection specimens and biopsies from 21 additional patients, with corresponding immunohistochemical pRb status. The best-performing DL model achieved a patient-wise balanced accuracy value of 0.75 and an area under the receiver operating characteristic curve value of 0.77 when tested on biopsies, significantly outperforming the hematoxylin and eosin–based subtype classification by lung pathologists. Explainable artificial intelligence techniques further highlighted coarse chromatin patterns and distinct nucleoli as distinguishing features for pRb retained status. Meanwhile, pRb lost cases were characterized by limited cytoplasm and morphologic similarities with small cell lung cancer. These findings suggest that DL analysis of small histopathology samples could ultimately replace immunohistochemical pRb testing. Such a development may assist in guiding chemotherapy decisions, particularly in metastatic cases.</p