Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the conformational dynamics of PD1 in complex with different ligands: What we can learn for designing novel PD1 signaling blockers?

Activation of T cells triggers the expression of regulatory molecules like the programmed cell death 1 (PD1) protein. The association of PD1 with the natural ligands PDL1 and PDL2 induces an inhibitory signal that prevents T cells from proliferating and exerting effector functions. However, little is known about how the binding of the ligands induce the PD1 inhibitory signal over T cells effector functions. Here, we explore the dynamics of PD1 free, and in complex with different PDL1 variants as well as the therapeutic antibodies nivolumab and pembrolizumab in order to assess the conformational changes in PD1 related to the signaling process. Our simulations suggest a pre‐conformational selection mechanism for the binding of the different PDL1 variants, while an induced‐fit model fits better for the molecular recognition process of the therapeutic antibodies. A deep analysis of the changes on PD1 movement upon the binding to different ligands revealed that as larger is the difference in the conformation adopted by loop C′D with respect to the complex with PDL1 is higher the ligand ability to reduce the PD1 inhibitory signaling. This behavior suggests that targeting specific conformations of this loop can be useful for designing therapies able to recover T cells effector functions.
A Cadaveric Anatomical and Histological Study of Recipient Intercostal Nerve Selection for Sensory Reinnervation in Autologous Breast Reconstruction

Abstract Background Autologous breast reconstruction (ABR) has grown in popularity due to improved aesthetic and long-term patient reported outcomes, but data regarding sensory reinnervation of autologous flaps remain limited. Traditionally, the lateral cutaneous branch of the fourth intercostal nerve has been used for flap neurotization, but the use of the anterior cutaneous branch of the intercostal nerves (ACB) offer a more optimal location to the microsurgical field when using internal mammary vessels for the microanastomosis. This study aimed to evaluate the optimum ACB recipient site level for sensory nerve coaptation in ABR. Methods Twelve hemi-chests were dissected from six fresh cadaveric females. Costal cartilages were removed and the anterior cutaneous intercostal nerve (ACB) and the lateral (subcutaneous) division of the anterior cutaneous branch (LACB) of the intercostal nerve were exposed. Anatomical measurements were recorded, and nerve samples were evaluated histologically with carbonic anhydrase staining to differentiate sensory fascicles. Assessment of fascicular diameter, axonal counts, and fascicular area were compared. Results A total of 75 nerve specimens were assessed. The ACB was identified at all levels (100%) and the subcutaneous LACB was noted consistently in the second to fourth rib space (96% cadavers), with a median length of 43, 37.5, and 37 mm, respectively. Across all rib spaces, the fascicular and axonal counts were comparable between the LACB and ACB. Nerves in the second intercostal space had a significantly larger mean fascicular area mean (112,816 ± 157,120 µm2) compared with that in the fourth (mean 26,474 ± 38,626 µm2), p = 0.03. Axonal count of sensory fascicles was the highest in the second intercostal nerves (p < 0.05). Conclusion This study provides anatomical and histological basis to determine the optimum recipient site choice for sensory coaptation in microsurgical breast reconstruction. This would aid in operative decision-making regarding the ideal recipient anterior cutaneous intercostal nerve branches for recipient site coaptation in ABR.
Nutritional problems and their non‐pharmacological treatment in adults undergoing haematopoietic stem cell transplantation—A systematic review

Abstract Objective This systematic review aimed to identify the most relevant problems related to malnutrition in adult patients undergoing haematopoietic stem cell transplantation (HSCT) and to identify non‐pharmacological interventions to treat these problems. Methods A systematic search for each research question was performed in MEDLINE, CINAHL, Embase, the Cochrane Library, Google Scholar and reference lists in the period 2009–2019. Results Six and nine studies were included respectively. Quantitative pooling of data was not possible due to the heterogeneity of the studies. Oral mucositis (OM), nausea/vomiting, diarrhoea and dysgeusia were the most frequently reported nutritional problems. Cryotherapy and laser therapy seem to be effective in the prevention and treatment of OM. Recommendations for or against the use of mouth rinses and light therapy in the treatment of OM cannot be made, as too few studies have been conducted in this area. The evidence for non‐pharmacological treatment options in the case of nausea/vomiting and diarrhoea is rather limited. No study was identified with regard to treatment of dysgeusia. Conclusion Nutrition in HSCT patients has not yet been studied to a satisfactory extent. There is an urgent need for high‐quality studies to be conducted in this area to optimise the care of patients undergoing haematopoietic stem cell transplantation.
Is congener abundance related to vocal adjustments that minimize acoustic interference?

Abstract. Interactions between heterospecific species with similar sexual signals can lead to errors in mate attraction and species recognition. As a consequence sexual signals might diverge to reduce communication errors. Since high-density populations create more noise than low-density populations we hypothesize that individuals should suffer less acoustic interference from sympatric congeners with low-density populations than higher density populations of congeners. Even though species might be sympatric at multiple sites, only populations at sites with a relatively high abundance of both species should require one species to make vocal adjustments that minimize acoustic interference. To test this hypothesis we studied Eleutherodactylus coqui populations in the presence of relatively high numbers of E. portoricensis and in the presence of relatively low abundance of E. portoricensis. We found subtle differences in advertisement calls of E. coqui at locations where E. portoricensis had relatively high abundance compared to locations where E. portoricensis was absent or had relatively lower abundance. Differences in E. coqui call structure were linked to the portion of the call used for mate attraction and did not affect the portion of the advertisement call that is used for territorial interactions. The results indicate that the relative abundance of a congener is an important factor that can promote differentiation amongst vocal signals to increase signal discrimination between the calls of multiple species.
Comprehensive study and multipurpose role of the CLV3/ESR‐related (CLE) genes family in plant growth and development

The CLAVATA3/endosperm surrounding region‐related (CLE) is one of the most important signaling peptides families in plants. These peptides signaling are common in the cell to cell communication and control various physiological and developmental processes, that is cell differentiation and proliferation, self‐incompatibility, and the defense response. The CLE signaling systems are conserved across the plant kingdom but have a diverse mode of action in various developmental processes in different species. In this review, we concise various methods of peptides identification, structure, and molecular identity of the CLE family, the developmental role of CLE genes/peptides in plants, environmental stimuli, and CLE family and some other novel progress in CLE genes/peptides in various crops, and so forth. According to previous literature, about 1,628 CLE genes were identified in land plants, which deeply explained the tale of plant development. Nevertheless, some important queries need to be addressed to get clear insights into the CLE gene family in other organisms and their role in various physiological and developmental processes. Furthermore, we summarized the power of the CLE family around the environment as well as bifunctional activity and the crystal structure recognition mechanism of CLE peptides by their receptors and CLE clusters functions. We strongly believed that the discovery of the CLE family in other organisms would provide a significant breakthrough for future revolutionary and functional studies.
Effects of mood episodes and comorbid anxiety on neuropsychological impairment in patients with bipolar spectrum disorder

Cases of patients with bipolar disorder (BD) having neuropsychological impairment have been reported, although inconsistently. The possibility of comorbidity with anxiety disorder (AD) has been suggested. The association between mood episodes and AD comorbidity on neuropsychological performance is unclear and thus was investigated in the current study.
Changes in Stage Distribution and Disease-Specific Survival in Differentiated Thyroid Cancer with Transition to American Joint Committee on Cancer 8th Edition: A Systematic Review and Meta-Analysis.

BACKGROUND Recent revision significantly changed the American Joint Committee on Cancer (AJCC) staging criteria for differentiated thyroid cancer (DTC). To quantitatively evaluate resulting changes in patient stage distribution and the associated disease-specific survival (DSS) incorporating diverse populations, we performed a meta-analysis of studies comparing the AJCC 7th edition (AJCC-7) with 8th edition (AJCC-8) staging for DTC. MATERIALS AND METHODS After PROSPERO registration (#CRD42019123657), publications in English reporting DSS of DTC with AJCC-7 and AJCC-8 from inception to June 2019 were identified by search of MEDLINE and PubMed. Random-effects meta-analyses were conducted to compare differences in survival between AJCC-7 and AJCC-8. Pooled hazard ratios, 10-year DSS, and corresponding interval estimates were calculated for AJCC subgroups. Differences in survival between editions were assessed using subgroup analysis with nonoverlapping confidence intervals indicating statistical significance. RESULTS Final analysis included six studies with 10,850 subjects and median follow-up from 55 to 148 months. Use of AJCC-8 shifted classification to earlier stages: stage I, from 60% to 81%; stage II, from 5% to 13%; stage III, from 21% to 2%; stage IV, from 10% to 3%. Ten-year DSS was significantly lower in AJCC-8 versus AJCC-7 in patients with stage II (88.6%, 95% confidence interval [CI] 82.7-94.6% vs. 98.1%, 95% CI 96.6-99.6%, respectively) and stage III disease (70.5%, 95% CI 59.1-83.9% vs. 96.8%, 95% CI 94.1-99.64%, respectively). CONCLUSION Meta-analysis of revised AJCC staging for DTC, incorporating diverse populations, demonstrates redistribution of patients toward earlier clinical stages and better stratification of disease-specific mortality risk, specifically among patients now classified with stage II and III disease. IMPLICATIONS FOR PRACTICE This study provides updated estimates of disease-specific survival for patients with differentiated thyroid cancer determined by the American Joint Committee on Cancer staging system that are generalizable to broader populations and support improved stratification using the recently revised criteria.
Type 1 Diabetes Mellitus Virtual Patient Network as a Peer Support Community: Protocol for Social Network Analysis and Content Analysis

Background Type 1 Diabetes Mellitus Virtual Patient Network (T1DM-VPN) is a private Facebook group for youths with type 1 diabetes mellitus (T1DM) in Canada intended to facilitate peer-to-peer support. It was built on the finding that stigma is prevalent among youth with T1DM and impedes self-management. Objective We aim to determine if T1DM-VPN provides support as intended and to ascertain what type of members provide support. Specifically, we will (1) identify text consistent with any one of 5 social support categories, (2) describe the network by visualizing its structure and reporting basic engagement statistics, and (3) determine whether being a designated peer leader is related to a member’s centrality (ie, importance in the network) and how frequently they offer social support. Methods We will manually extract interaction data from the Facebook group (posts, comments, likes/reactions, seen) generated from June 21, 2017 (addition of first member), to March 1, 2020. Two researchers will independently code posts and comments according to an existing framework of 5 social support categories—informational, emotional, esteem, network, and tangible—with an additional framework for nonsocial support categories. We will calculate how frequently each code is used. We will also report basic engagement statistics (eg, number of posts made per person-month) and generate a visualization of the network. We will identify stable time intervals in the history of T1DM-VPN by modeling monthly membership growth as a Poisson process. Within each interval, each member’s centrality will be calculated and standardized to that of the most central member. We will use a centrality formula that considers both breadth and depth of connections (centrality = 0.8 × total No. of connections + 0.2 × total No. of interactions). Finally, we will construct multivariate linear regression models to assess whether peer leader status predicts member centrality and the frequency of offering social support. Other variables considered for inclusion in the models are gender and age at diagnosis. Results T1DM-VPN was launched in June 2017. As of March 1, 2020, it has 196 patient-members. This research protocol received ethics approval from the McGill University Health Centre Research Ethics Board on May 20, 2020. Baseline information about each group member was collected upon addition into the group, and collection of interaction data is ongoing as of May 2020. Conclusions This content analysis and social network analysis study of a virtual patient network applies epidemiological methods to account for dynamic growth and activity. The results will allow for an understanding of the topics of importance to youth with T1DM and how a virtual patient network evolves over time. This work is intended to serve as a foundation for future action to help youth improve their experience of living with diabetes. International Registered Report Identifier (IRRID) PRR1-10.2196/18714
Pain modulation effect on motor cortex after optogenetic stimulation in shPKCγ knockdown dorsal root ganglion-compressed Sprague-Dawley rat model

Neuropathic pain can be generated by chronic compression of dorsal root ganglion (CCD). Stimulation of primary motor cortex can disrupt the nociceptive sensory signal at dorsal root ganglion level and reduce pain behaviors. But the mechanism behind it is still implicit. Protein kinase C gamma is known as an essential enzyme for the development of neuropathic pain, and specific inhibitor of protein kinase C gamma can disrupt the sensory signal and reduce pain behaviors. Optogenetic stimulation has been emerged as a new and promising conducive method for refractory neuropathic pain. The aim of this study was to provide evidence whether optical stimulation of primary motor cortex can modulate chronic neuropathic pain in CCD rat model. Animals were randomly divided into CCD group, sham group, and control group. Dorsal root ganglion-compressed neuropathic pain model was established in animals, and knocking down of protein kinase C gamma was also accomplished. Pain behavioral scores were significantly improved in the short hairpin Protein Kinase C gamma knockdown CCD animals during optic stimulation. Ventral posterolateral thalamic firing inhibition was also observed during light stimulation on motor cortex in CCD animal. We assessed alteration of pain behaviors in pre-light off, stimulation-light on, and post-light off state. In vivo extracellular recording of the ventral posterolateral thalamus, viral expression in the primary motor cortex, and protein kinase C gamma expression in dorsal root ganglion were investigated. So, optical cortico-thalamic inhibition by motor cortex stimulation can improve neuropathic pain behaviors in CCD animal, and knocking down of protein kinase C gamma plays a conducive role in the process. This study provides feasibility for in vivo optogenetic stimulation on primary motor cortex of dorsal root ganglion-initiated neuropathic pain.
Morphology and DNA Barcoding Reveal a New Species of Eagle Ray from the Southwestern Atlantic: Myliobatis ridens sp. nov. (Chondrichthyes: Myliobatiformes: Myliobatidae)

from the Southwestern Atlantic: Myliobatis ridens sp. nov. (Chondrichthyes: Myliobatiformes: Myliobatidae) Natalia L. Ruocco1,*, Luis O. Lucifora2,3,4, Juan M. Diaz de Astarloa2,5, Ezequiel Mabragana2,5, and Sergio M. Delpiani2,5 1Instituto Nacional de Investigacion y Desarrollo Pesquero, Paseo Victoria Ocampo s/n, B7602HSA, Mar del Plata, Buenos Aires, Argentina 2Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina 3Instituto de Biologia Subtropical – Iguazu, CONICET, Universidad Nacional de Misiones, Casilla de Correo 9, N3370AVQ, Puerto Iguazu, Misiones, Argentina 4Centro de Investigaciones del Bosque Atlantico, Casilla de Correo 9, N3370AVQ, Puerto Iguazu, Misiones, Argentina 5Laboratorio de Biotaxonomia Morfologica y Molecular de Peces, Instituto de Investigaciones Marinas y Costeras (IIMyC)-CONICET, FCEyN, Universidad Nacional de Mar del Plata, Funes 3350, B7602AYL, Mar del Plata, Buenos Aires, Argentina
StARTalking: An Arts and Health Program to Support Undergraduate Mental Health Nursing Education

Abstract Community arts and health programs are recognized as powerful contributors to mental health and wellbeing, reducing social isolation and strengthening community connection. They attract individuals with diverse lived experience and are invaluable learning environments for consumers and undergraduate mental health nursing students. This paper reports on the evaluation of StARTalking, a community arts and health program in Melbourne, Australia. The study aimed to better understand the consumer and student experience participating in the program. The themes, Finding connection/Taking time out, clearly indicate that embedding arts and health in mental health nursing education supports consumer and student learning, health and wellbeing.
Macrophages expedite cell proliferation of prostate intraepithelial neoplasia through their downstream target ERK

The risk factors for prostate cancer include a high‐fat diet and obesity, both of which are associated with an altered cell environment including increased inflammation. It has been shown that chronic inflammation due to a high‐fat diet or bacterial infection has the potential to accelerate prostate cancer as well as its precursor, prostatic intraepithelial neoplasia (PIN), development. However, the underlying mechanism of how chronic inflammation promotes prostate cancer development, especially PIN, remains unclear. In this study, we showed that more macrophages were present in PIN areas as compared to the normal areas of human prostate. When co‐culturing PIN cells with macrophages in 3D, more PIN cells had nuclear localized cyclin D1, indicating that macrophages enhanced PIN cell proliferation. We identified ICAM‐1 and CCL2 as chemoattractants expressed by PIN cells to recruit macrophages. Furthermore, we discovered that macrophage‐secreted cytokines including C5a, CXCL1, and CCL2 were responsible for increased PIN cell proliferation. These three cytokines activated ERK and JNK signaling in PIN cells through a ligand‐receptor interaction. However, only blockade of ERK abolished macrophage cytokines‐induced cell proliferation of PIN. Overall, our results provide a mechanistic view on how macrophages activated through chronic inflammation can expedite PIN progression during prostate cancer development. The information from our work can facilitate a comprehensive understanding of prostate cancer development, which is required for improvement of current strategies for prostate cancer therapy.
An Association Between Serotonin 1A Receptor, Gray Matter Volume, and Sociability in Healthy Subjects and in Autism Spectrum Disorder

Central serotonin is an important molecular pathway, involved in the regulation of social behavior and gray matter volume (GMV). In men with autism spectrum disorders (ASD), the serotonergic system and the GMV have been found disrupted. Here, we investigated the relation between serotonin, GMV, and social personality in men with typical development (TD) and in men with ASD. We combined anatomical magnetic resonance imaging, Positron emission tomography scan with 2′‐methoxyphenyl‐(N‐2′‐pyridinyl)‐p‐18F‐fluoro‐benzamidoethylpiperazine radioligand and revised NEO personality inventory personality questionnaire to examine the association between serotonin 1A receptor (5‐HT1AR) binding potential, GMV and social personality in 24 adult male TD subjects and 18 male men with ASD. In both groups, we found a positive correlation between 5‐HT1AR binding potential and GMV in a region dependent manner. In the TD group, we observed a negative correlation between 5‐HT1AR and GMV in the left and right posterior putamen. 5HT1AR binding and GMV in the putamen further correlated with social personality scores in the TD group. None of these associations were found in men with ASD, although no differences were observed for 5‐HT1AR concentration among the two groups. Our findings point to a deregulation of 5‐HT1AR density in the striatum of men with ASD, a failure that might contribute to their social disturbances. Serotonin is suspected to be involved in the pathophysiology of autism. We provide evidence for a role of serotonin 1A receptor in social behavior through a specific regulation of GMV in the putamen region in neurotypical subjects but not in men with autism. This suggests a potential impairment of the serotonergic system in men with autism which may contribute to patients' social disturbances. Our findings suggest further investigation on the role of serotonin 1A receptor and its activity in the striatum to regulate social behavior. Autism Res 2020, 13: 1843‐1855. © 2020 International Society for Autism Research and Wiley Periodicals LLC
Skull vibration-induced nystagmus in vestibular neuritis

Abstract Background As described by Dumas, an 80–100 Hz vibration applied to the mastoid produces a horizontal nystagmus, with quick phases beating away from the affected side in patients with unilateral vestibular loss (UVL). Aim/objectives To elucidate the characteristics of skull vibration-induced nystagmus (SVIN) in patients suffering from vestibular neuritis and how these characteristics are related to information provided by the video head impulse test (vHIT). Material and methods Sixty-three patients were enrolled to perform a vHIT to measure the gain in both ears. SVIN was induced with stimulation at 30 Hz, 60 Hz, and 100 Hz. The slow phase velocity (SPV) of the SVIN was measured. Results The SVIN test was positive in 25/63 patients at 30 Hz, 36/63 at 60 Hz and 46/63 at 100 Hz. Mean gain difference between both ears to obtain a positive SVIN at 30 Hz was observed to be 0.38 ± 0.25, decreasing to 0.35 ± 0.23 at 60 Hz, and 0.31 ± 0.24 at 100 Hz (p = .025). We found a significant positive linear correlation between the gain asymmetry measured using horizontal vHIT and SPV in SVIN at 100 Hz. Conclusions and significance There is a close relationship between the difference in the gains of both ears as measured using VHIT and the SPV of the nystagmus induced by SVIN at 100 Hz.