Neurons in the monkey frontopolar cortex encode learning stage and goal during a fast learning task.

The frontopolar cortex (FPC) is, to date, one of the least understood regions of the prefrontal cortex. The current understanding of its function suggests that it plays a role in the control of exploratory behaviors by coordinating the activities of other prefrontal cortex areas involved in decision-making and exploiting actions based on their outcomes. Based on this hypothesis, FPC would drive fast-learning processes through a valuation of the different alternatives. In our study, we used a modified version of a well-known paradigm, the object-in-place (OIP) task, to test this hypothesis in electrophysiology. This paradigm is designed to maximize learning, enabling monkeys to learn in one trial, which is an ability specifically impaired after a lesion of the FPC. We showed that FPC neurons presented an extremely specific pattern of activity by representing the learning stage, exploration versus exploitation, and the goal of the action. However, our results do not support the hypothesis that neurons in the frontal pole compute an evaluation of different alternatives. Indeed, the position of the chosen target was strongly encoded at its acquisition, but the position of the unchosen target was not. Once learned, this representation was also found at the problem presentation, suggesting a monitoring activity of the synthetic goal preceding its acquisition. Our results highlight important features of FPC neurons in fast-learning processes without confirming their role in the disengagement of cognitive control from the current goals.

Timing measurements with silicon single photon avalanche diodes: principles and perspectives [Invited].

Picosecond timing of single photons has laid the foundation of a great variety of applications, from life sciences to quantum communication, thanks to the combination of ultimate sensitivity with a bandwidth that cannot be reached by analog recording techniques. Nowadays, more and more applications could still be enabled or advanced by progress in the available instrumentation, resulting in a steadily increasing research interest in this field. In this scenario, single-photon avalanche diodes (SPADs) have gained a key position, thanks to the remarkable precision they are able to provide, along with other key advantages like ruggedness, compactness, large signal amplitude, and room temperature operation, which neatly distinguish them from other solutions like superconducting nanowire single-photon detectors and silicon photomultipliers. With this work, we aim at filling a gap in the literature by providing a thorough discussion of the main design rules and tradeoffs for silicon SPADs and the electronics employed along them to achieve high timing precision. In the end, we conclude with our outlook on the future by summarizing new routes that could benefit from present and prospective timing features of silicon SPADs.

Neural representation of others during action observation in posterior medial prefrontal cortex.

Making decisions based on the actions of others is critical to daily interpersonal interactions. We investigated the representations of other's actions at single neural level in posterior medial prefrontal cortex (pmPFC) in two monkeys during the observation of actions of another agent, in a social interaction task. Each monkey separately interacted with a human partner. The monkey and the human alternated turns as actor and observer. The actor was required to reach one of two visual targets, avoiding the previously chosen target, while the observer monitored that action. pmPFC neurons decoupled in most cases self from others during both the execution and the observation of explicit actions. pmPFC neurons showed selective directional tuning specific for the agent who was executing the task. Moreover, we assessed the relationship of the response coding between the periods immediately before and after the action, by using a cross-modal decoding analysis. We found neural network stability from the action anticipation period to the observation of other's actions, suggesting a strong relationship between the anticipation and the execution of an action. When the monkey was the actor, the population coding appeared dynamic, possibly reflecting a goal-action transformation unique to the monkey's own action execution.

Dedicated Representation of Others in the Macaque Frontal Cortex: From Action Monitoring and Prediction to Outcome Evaluation.

Social neurophysiology has increasingly addressed how several aspects of self and other are distinctly represented in the brain. In social interactions, the self-other distinction is fundamental for discriminating one's own actions, intentions, and outcomes from those that originate in the external world. In this paper, we review neurophysiological experiments using nonhuman primates that shed light on the importance of the self-other distinction, focusing mainly on the frontal cortex. We start by examining how the findings are impacted by the experimental paradigms that are used, such as the type of social partner or whether a passive or active interaction is required. Next, we describe the 2 sociocognitive systems: mirror and mentalizing. Finally, we discuss how the self-other distinction can occur in different domains to process different aspects of social information: the observation and prediction of others' actions and the monitoring of others' rewards.

Adaptive one-class Gaussian processes allow accurate prioritization of oncology drug targets.

MOTIVATION: The cost of drug development has dramatically increased in the last decades, with the number new drugs approved per billion US dollars spent on R&D halving every year or less. The selection and prioritization of targets is one the most influential decisions in drug discovery. Here we present a Gaussian Process model for the prioritization of drug targets cast as a problem of learning with only positive and unlabeled examples. RESULTS: Since the absence of negative samples does not allow standard methods for automatic selection of hyperparameters, we propose a novel approach for hyperparameter selection of the kernel in One Class Gaussian Processes. We compare our methods with state-of-the-art approaches on benchmark datasets and then show its application to druggability prediction of oncology drugs. Our score reaches an AUC 0.90 on a set of clinical trial targets starting from a small training set of 102 validated oncology targets. Our score recovers the majority of known drug targets and can be used to identify novel set of proteins as drug target candidates. AVAILABILITY AND IMPLEMENTATION: The matrix of features for each protein is available at: https://bit.ly/3iLgZTa. Source code implemented in Python is freely available for download at https://github.com/AntonioDeFalco/Adaptive-OCGP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Integrated optical device for Structured Illumination Microscopy.

Structured Illumination Microscopy (SIM) is a key technology for high resolution and super-resolution imaging of biological cells and molecules. The spread of portable and easy-to-align SIM systems requires the development of novel methods to generate a light pattern and to shift it across the field of view of the microscope. Here we show a miniaturized chip that incorporates optical waveguides, splitters, and phase shifters, to generate a 2D structured illumination pattern suitable for SIM microscopy. The chip creates three point-sources, coherent and controlled in phase, without the need for further alignment. Placed in the pupil of a microscope's objective, the three sources generate a hexagonal illumination pattern on the sample, which is spatially translated thanks to thermal phase shifters. We validate and use the chip, upgrading a commercial inverted fluorescence microscope to a SIM setup and we image biological sample slides, extending the resolution of the microscope.

Involvement of the medial and lateral epicondyles in distal humeral coronal shear fractures: Case series and literature review.

PURPOSE: Epicondyle involvement in capitellar and trochlear fractures is often considered a simple associated lesion that does not substantially change treatment or prognosis. Although theoretically predicted in reviews, case series almost never report elbow prosthesis use in comminuted coronal shear injuries associated with epicondylar fracture in the elderly. The purpose of this study is to focus on this underestimated injury pattern that can be a negative risk factor for treatment and prognosis. METHODS: We retrospectively reviewed all cases with coronal shear fracture of the distal humerus treated from 2016 to 2019. Fractures were classified according to Dubberley. Open reduction and internal fixation (ORIF) were performed when possible. Partial or total elbow replacement was used in severely comminuted fractures with epicondylar involvement in four elderly patients. RESULTS: Nineteen consecutive patients were selected (mean age: 62.4 years), of which 10 had type 3A/3B fractures, and seven had both medial and lateral epicondylar involvement. The mean follow-up duration was 31.78 months. The average Mayo Elbow Performance Index (MEPI) score was 81.05 points, with 7 excellent, 8 good, 1 fair, and 3 poor results. The average MEPI score of Dubberley's type 1 and type 2 was better than that of type 3 (mean: 92 vs. 72, p = 0.02). Further, the results of average range of motion were better in patients who had sustained Dubberley types 1 and 2 lesions than those with Dubberley type 3 lesion (mean: 133° vs. 85°, p = 0.002). Two patients out of three who required intra-operative conversion to total elbow arthroplasty had poor outcomes. CONCLUSIONS: The simultaneous presence of fracture of one or both epicondyles are usually associated with severe joint comminutions and makes ORIF more challenging, especially among elderly women. In these cases, primary total elbow prosthesis implantation could be a valid treatment option.

Bringing data from curated pathway resources to Cytoscape with OmniPath.

SUMMARY: Multiple databases provide valuable information about curated pathways and other resources that can be used to build and analyze networks. OmniPath combines 61 (and continuously growing) network resources into a comprehensive collection, with over 120 000 interactions. We present here the OmniPath App, a Cytoscape plugin to flexibly import data from OmniPath via a simple and intuitive interface. Thus, it makes possible to directly access the large body of high-quality knowledge provided by OmniPath within Cytoscape for inspection and further use with other tools. AVAILABILITY AND IMPLEMENTATION: The OmniPath App has been developed for Cytoscape 3 in the Java programing language. The latest source code and the plugin can be found at: https://github.com/saezlab/Omnipath_Cytoscape and http://apps.cytoscape.org/apps/omnipath, respectively. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Custom silicon technology for SPAD-arrays with red-enhanced sensitivity and low timing jitter.

Single-photon detection is an invaluable tool for many applications ranging from basic research to consumer electronics. In this respect, the Single Photon Avalanche Diode (SPAD) plays a key role in enabling a broad diffusion of these techniques thanks to its remarkable performance, room-temperature operation, and scalability. In this paper we present a silicon technology that allows the fabrication of SPAD-arrays with an unprecedented combination of low timing jitter (95 ps FWHM) and high detection efficiency at red and near infrared wavelengths (peak of 70% at 650 nm, 45% at 800 nm). We discuss the device structure, the fabrication process, and we present a thorough experimental characterization of the fabricated detectors. We think that these results can pave the way to new exciting developments in many fields, ranging from quantum optics to single molecule spectroscopy.

Deep learning predicts short non-coding RNA functions from only raw sequence data.

Small non-coding RNAs (ncRNAs) are short non-coding sequences involved in gene regulation in many biological processes and diseases. The lack of a complete comprehension of their biological functionality, especially in a genome-wide scenario, has demanded new computational approaches to annotate their roles. It is widely known that secondary structure is determinant to know RNA function and machine learning based approaches have been successfully proven to predict RNA function from secondary structure information. Here we show that RNA function can be predicted with good accuracy from a lightweight representation of sequence information without the necessity of computing secondary structure features which is computationally expensive. This finding appears to go against the dogma of secondary structure being a key determinant of function in RNA. Compared to recent secondary structure based methods, the proposed solution is more robust to sequence boundary noise and reduces drastically the computational cost allowing for large data volume annotations. Scripts and datasets to reproduce the results of experiments proposed in this study are available at: https://github.com/bioinformatics-sannio/ncrna-deep.

Ankle joint re-balancing in the management of ankle fracture malunion using fibular lengthening: prospective clinical-radiological results at mid-term follow-up.

PURPOSE: An unsatisfactory reduction and internal fixation of an ankle fracture can result in an alteration of the anatomical axes and distribution of the load on the ankle, with consequent development of chronic pain and articular degeneration. The aim of this study is to evaluate the results of the articular re-balancing with realignment and lengthening of the fibula in case of malunited distal fibular fractures. METHODS: A review of prospectively collected data was performed for all patients with a diagnosis of malunion of the fibula and underwent ankle joint re-balancing with fibular lengthening. Twenty-three patients, with a mean age of 39.4 ± 13.1 years, have been evaluated using radiographic parameters, American Orthopaedic Foot and Ankle Surgeons ankle-hindfoot, Ankle Activity scale, and SF-36 score at six, 12, 24, and 36 months post-operatively. RESULTS: All cases treated showed at follow-up the osteotomy healed in good correction of the deformities. Clinical scores showed a clear improvement: final 36-month mean AOFAS was 74.0 ± 8.9 point, final 36-month mean HALASI score was 4.9 ± 0.9 points, 36-month follow-up SF-36 score showed an average score of 73.2 ± 10.7 points. Pre- and post-operative radiographic parameters have been registered and described. CONCLUSIONS: The ankle joint is a complex structure, and even minor changes of the structure of this joint can significantly compromise its functionality. Ankle joint re-balancing is an effective surgical procedure in case of fibular malunion. This procedure, in patients carefully selected, could procrastinate more disabling surgical procedure, as arthrodesis or prosthesis.

Outcome of short versus conventional stem for total hip arthroplasty in the femur with a high cortical index: a five year follow-up prospective multicentre comparative study.

BACKGROUND: The uncemented total hip arthroplasty (THA) has become the choice for many hip surgeons. Although conventional uncemented femoral components have a proven track record, there remain concerns about the rate of thigh pain, proximal stress shielding, and consequent loss of bone stock at revision surgery. METHODS: Inclusion criteria were the following: patients between 50 and 85 years old undergoing primary THA with implant of short (group 1) or conventional (group 2) femoral stem and with femoral shape type A, according to Dorr classification. Clinical follow-up was registered using OHS, HHS, and Womac scores. The radiographic scans were evaluated in order to compare component positioning and bone remodeling at five year follow-up. RESULTS: We included in the analysis 60 subjects in group 1 and 67 in group 2. No differences were registered between the groups comparing demographic and operative data. One case in group 1 (1.7%) and three cases in group 2 (4.5%) reported an intra-operative fracture. There was a significant improvement in the functional scores in both groups with no significant difference at final follow-up. The incidence of reported thigh pain at follow-up was 14.9% in group 2 and 3.3% in group 1 (p = 0.033). Radiographic analysis documented a difference in terms of stress shielding and thinning of medial and lateral cortex in favour of group 1. Moreover, patients of group 1 showed a higher varus angle at six month follow-up. CONCLUSION: In patients with high cortical index, a short stem shows better clinical and radiological outcomes at five year follow-up.

Neck modularity in total hip arthroplasty: a retrospective study of nine hundred twenty-eight titanium neck implants with a maximum follow-up of eighteen years.

PURPOSE: Neck modularity was introduced to improve total hip arthroplasty (THA) accuracy, but it has been associated with early breakages and corrosion issues. In our hospital, modular necks have been in clinical use since the 1990s. We retrospectively analysed the occurrence of these sequelae in implants placed between January 2000 and December 2014. METHODS: Survival data from patients operated on in our hospital were obtained from the regional arthroplasty registry (Registro dell'Impiantologia Protesica Ortopedica, RIPO). The cohort comprised 928 THAs on 908 patients. The average patient age was 67.8 years. Main indications were primary osteoarthritis (71.4%), fracture (9.2%), congenital dysplasia or congenital luxation (7.8%), and idiopathic osteonecrosis (6.4%). All femoral stems were cementless, with 318 anatomically shaped (34.3%), 579 straight (62.4%), and 31 short stems (3.3%). All necks used were made of titanium alloy. The average follow-up time was 9.6 years (range, 4-18 years). RESULTS: In total, 66 revisions were reported. The main revision causes were periprosthetic fractures (33.3%), aseptic stem loosening (19.7%), luxation (18.2%), and implant breakage (12.1%). Five modular neck breakages were recorded. The overall survival rate was 87.7% at 17 years. We did not observe any component corrosion. The neck breakage rate was 0.5%, and the luxation rate was 1.3%. CONCLUSIONS: Our experience suggests that neck modularity is a safe, effective way to reconstruct the proximal femur in THA patients. We attribute the absence of corrosion to the exclusive use of titanium necks.

Management of early ankle osteoarthritis through anterior joint-preserving surgery: a retrospective evaluation at mid- to long-term follow-up.

PURPOSE: Chronic anterior ankle pain is a recognized and straightforward characteristic of anterior impingement syndrome. This retrospective study aims to evaluate outcomes, clinical and radiological results in patients affected by anterior ankle impingement, in a context of early osteoarthritis, and treated with mini-open anterior ankle arthrolysis, in the perspective to delay or avoid other demolitive surgical options, such as total ankle replacement and joint fusion. METHODS: In total, 49 patients (50 feet, mean age 45 years) undergone mini-open anterior ankle arthrolysis for anterior impingement, fulfilled inclusion criteria and gave their consent and have been enlisted in the study. Patients were retrospectively reviewed with AOFAS ankle-hindfoot score and SF-36 score at a minimum follow-up of 36 months. Statistical analysis was performed. RESULTS: A marked improvement was noticed in terms of preoperative clinical score (mean AOFAS score 47.32 ± 17.89) compared to follow-up clinical score (mean AOFAS score 70.66 ± 16.62; p < 0.005), and all of 8 SF-36 domains showed statistically improved (p < 0.05) from preoperative to follow-up. Statistical significance has been shown. CONCLUSIONS: It is possible to consider the mini-open anterior arthrolysis, thanks to the reduction of the painful symptomatology, a valid tool for procrastinating more invasive interventions such as arthrodesis or prosthetic replacement in patients with grade 1 or 2 of ankle osteoarthritis.

Correction to: Management of early ankle osteoarthritis through anterior joint-preserving surgery: a retrospective evaluation at mid- to long-term follow-up.

The original version of this article unfortunately contained a mistake. The spelling of the 'Francesco Ceccarelli' name was incorrect.

Long-Term Outcome of Mini-Open Surgical Decompression for Chronic Exertional Compartment Syndrome of the Forearm in Professional Motorcycling Riders.

OBJECTIVE: To evaluate results of mini-open fasciotomy (MOF) in high-level motorcycling or motocross riders with chronic exertional compartment syndrome (CECS) at long-term follow-up (minimum 5 years). DESIGN: Case series. LEVEL OF EVIDENCE: IV. SETTING: University Hospital/Private Practice. PATIENTS: Fifty-four professional motorcycling riders treated with MOF for a CECS of the forearm from January 2006 to June 2011. Inclusion criteria comprised: high-level motorcycling or motocross riders, clinical symptoms of CECS for at least 6 months, diagnosis confirmed using preoperative compartment hydrostatic pressure measurement and/or magnetic resonance imaging of the forearm, minimum follow-up of 5 years. INTERVENTIONS: A MOF to obtain decompression of all compartments was performed in all patients. MAIN OUTCOME MEASURES: Visual analog scale; a subjective scale to measure strength; QuickDash functional scores. Time to resume full riding capacities as short-term evaluation. RESULTS: A total of 54 patients who underwent 77 MOF procedures overall (23 bilateral) were included. The mean age was 23.6 ± 5.2 years. Mean Visual Analog Scale decreased from a preoperative value of 68.2 to a 3-month postoperative value of 26 (P < 0.001). Mean QuickDash scale was 84 at preoperative registration, falling to 20, 3 months after surgery (P < 0.001) and down to 12 at 1-year follow-up (P = 0.017). The average time to return to full riding capacities was 3.5 ± 1 week. CONCLUSIONS: Mini-open fasciotomy resulted safe and effective for the treatment of chronic exertional compartment syndrome in high-level motorcycling or motocross riders. The good outcome at follow-up resulted stable at 5 years and the incidence of complications remained low. Our data demonstrate that the resolution of symptoms is reliable and durable. Pain recovery was immediate after surgery, instead functional scores showed a more gradual recovery throughout the 12 months after surgery. CLINICAL RELEVANCE: Mini-open fasciotomy is a reliable treatment for CECS of the forearm in professional motorcycling riders. This treatment should also be considered in young riders due to the absence of tardive relapse reported in this study.

Treatment of distal tibial fractures: prospective comparative study evaluating two surgical procedures with investigation for predictive factors of unfavourable outcome.

PURPOSE: The aim of this study is to compare clinical and radiological outcome of intramedullary nailing (IMN) and locked plate (LP) in patients affected by fracture of the distal tibia (DTF). We performed also an analysis to identify predictive factors of unfavourable outcome. METHODS: Data about patients with DTF treated at our first level trauma centre between 2008 and 2017 were collected. Patients were divided in group 1 (IMN) and group 2 (LP). The inclusion criteria were age at least 18 years at the time of diagnosis and unilateral DTF (closed or Gustilo 1). Demographic variables and data related to surgical procedure and hospitalization were registered. X-ray at follow-up was reviewed to identify malunions and nonunions. Clinical outcome was evaluated using scores and registering any complication. RESULTS: One hundred two patients were included in group 1 and 81 in group 2. In group 2 were documented higher operating time and hospitalization. The mean union time was 20.2 weeks for IMN and 24.8 weeks for LP group (p = 0.271). The rate of infections and wound complications was higher in group 2 while malunion and anterior knee pain were more frequent in group 1. No difference in scores for clinical outcome was documented after six months. The full-weight bearing time was significantly longer in the LP group (p = 0.019). At multivariate analysis, no variables showed a predictive power for unfavourable outcome. CONCLUSIONS: Clinical and radiological results of LP and IMN appear similar. No predictive factors of unfavourable outcome were identified.

Red-Enhanced Photon Detection Module Featuring a 32 × 1 Single-Photon Avalanche Diode Array.

In this letter, the development and the experimental characterization of a new photon detection module, based on a 32×1 red-enhanced single-photon avalanche diode (RE-SPAD) array, are presented. A custom-developed technology has been exploited to design a detector having large-area pixels (50-µm diameter) with optimized performance. With an excess bias voltage Voυ = 15 V, a photon detection efficiency as high as 57% at 600 nm (33% at 800 nm) is achieved, along with dark count rate in the kHz range and optical crosstalk probability as low as 0.29%. The remarkable detection efficiency of the RE-SPAD array makes the module particularly suitable for all applications where high detection efficiency in the red/near-infrared range is mandatory. As an example, the performance of the array module is demonstrated to match the demanding requirements of multispot single-molecule fluorescence spectroscopy.

Gigacount/second Photon Detection Module Based on an 8 × 8 Single-Photon Avalanche Diode Array.

In this letter we present a compact photon detection module, based on an 8×8 array of single-photon avalanche diodes (SPADs). The use of a dedicated silicon technology for the fabrication of the sensors allows us to combine large active areas (50-µm diameter), high photon detection efficiency (49% at 550-nm wavelength) and low dark count rate. Thanks to a fully parallel architecture, the module provides voltage pulses synchronous to each photon detection for a maximum global count rate exceeding 1 Gcps. These properties makes the system suitable for operation in two different free-running modes. The first, suitable to acquire faint signals, allows multi-spot acquisitions and can be used to considerably reduce the measurement time in applications like single-molecule analysis. With the second it is possible to use all the pixels in a combined mode, to extend and move the dynamic range of the module to very high count rates and to attain number resolving capabilities.

Total elbow arthroplasty in distal humeral nonunion: clinical and radiographic evaluation after a minimum follow-up of three years.

BACKGROUND: Total elbow arthroplasties (TEAs) are usually indicated in chronic inflammatory arthropathies. This procedure has also recently been used in complex distal humeral fractures and nonunions in selected patients. This study analyzed the clinical and radiographic outcomes in patients treated for nonunions around the elbow region with a minimum follow-up of 3 years. METHODS: Between May 2002 and June 2012, 20 patients affected with distal humeral nonunions were treated with TEA. All patients were assessed clinically using the Mayo Elbow Performance Score and radiographically to evaluate the positioning of the prosthetic components and signs of loosening. Statistical analyses were performed to investigate the presence of clinical and radiographic variables as predictive factors of poor functional outcomes. RESULTS: The Mayo Elbow Performance Score of the affected arm improved significantly between the preoperative period and follow-up. Results were good or excellent in 90% of the patients even if a high rate of complications (30%) was encountered. The development of complications after surgery and stages II, III, and IV radiolucency, according to the Morrey criteria, were predictive factors of poor outcomes. CONCLUSIONS: According to the satisfactory results observed in this study, TEA could be indicated in selected patients aged older than 70 years with low functional demands and affected with distal humeral nonunions in which obtaining a stable fixation is difficult.