AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Effects of rehabilitation treatment of the upper limb in multiple sclerosis patients and predictive value of neurophysiological measures

11noreservedBACKGROUND: Dysfunctions of the upper limbs occur in the 66% of multiple sclerosis (MS) patients. To date, no data, about the persistence of the effects of a rehabilitation treatment and no prognostic markers of functional improvement, have been established. AIM: The aim of this study was to define clinical data supporting the efficacy of a rehabilitation treatment in MS patients with upper limb impairment and to find prognostic factors for functional improvement. DESIGN: Pre-post comparison prospective study. SETTING: Two tertiary Italian MS centres: Rome and Siena. POPULATION: Twenty-five consecutive MS patients were tested for eligibility. METHODS: We multidimensionally evaluated 25 consecutive patients with MS-related upper limbs impairment through clinical objective, patient-oriented and neurophysiological measures pre and post a16-week rehabilitation treatment on upper limb sensorimotor function. RESULTS: We found a significant improvement in the Nine Hole Peg Test (9-HPT) at either sides, both at an immediate post-training visit (T1) (left: P=0.018, right: P=0.004) and at a 12-week postintervention assessment visit (T2) (left: P=0.033, right: P=0.022). We also found a positive correlation between the 12-week post-training changes in the 9-HPT and the N14-P20 interpeak of the somatosensory evoked potentials, (rho=0.374, P=0.008). CONCLUSIONS: Our study demonstrates that a rehabilitation treatment can lead to an improvement of the upper limb motor performance in MS patients which continues to persist even after 3 months of treatment-discontinuation suggesting a possible role of rehabilitation in neuroplasticity changes. Moreover, we found, in the latency of the N14-P20 interpeak, a possible prognostic marker for the effects of a upper limb rehabilitation treatment in MS patients. CLINICAL REHABILITATION IMPACT: The N14-P20 interpeak could be used as a prognostic marker of the effects of rehabilitation of the upper limb.mixedNociti, Viviana; Prosperini, Luca; Ulivelli, Monica; Losavio, Francesco A.; Bartalini, Simona; Caggiula, Marcella; Cioncoloni, David; Caliandro, Pietro; Minciotti, Ileana; Mirabella, Massimiliano; Padua, LucaNociti, Viviana; Prosperini, Luca; Ulivelli, Monica; Losavio, Francesco A.; Bartalini, Simona; Caggiula, Marcella; Cioncoloni, David; Caliandro, Pietro; Minciotti, Ileana; Mirabella, Massimiliano; Padua, Luc

Prevalence of bifid median nerve at wrist assessed through ultrasound

We performed a prospective study to evaluate the prevalence of bifid median nerve (BMN) and if it has a higher prevalence in carpal tunnel syndrome (CTS) patients than symptom-free subjects. We evaluated by ultrasound (US) 162 median nerves at wrist of 89 consecutive patients with symptoms suggestive of CTS and 104 of 52 consecutive symptom-free subjects. Neurophysiological evaluation confirmed CTS diagnosis. All patients underwent ultrasonographic evaluation of median nerve in the elbow-palm segment through high-frequency probe; BMN was arbitrarily classified as "complete" and "incomplete" on the basis of US results. BMN was observed in 16/104 wrists (15.4%) in control group and in 30/162 (18.5%) wrists in CTS group. Our study showed that BMN is frequent, not always bilateral, more often is "incomplete" and it has similar prevalence in CTS and control group. These findings suggest that BMN is not a risk factor of developing CTS

Levodopa effect on electromyographic activation patterns of tibialis anterior muscle during walking in Parkinson's disease

Previous studies have reported that patients with Parkinson's disease (PD) show, in the "off medication" state, a reduced activation of tibialis anterior (TA) in the late swing-early stance phase of the gait cycle. In PD patients the pathophysiological picture may cause differences among the stride cycles. Our aims were to evaluate how frequently TA activity is reduced in the late swing-early stance phase and if there is a relationship between the TA pattern and the clinical picture. Thirty PD patients were studied 2 h after Levodopa administration ("on-med") and 12 h after Levodopa wash-out ("off-med"). They were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS III) and surface electromyography of TA and gastrocnemius medialis (GM). The root mean square (RMS) of the TA activity in late swing-early stance phase (RMS-A) was normalized as a percent of the RMS of the TA activity in late stance-early swing (RMS-B). RMS-A was reduced in 30% of patients in the "off-med" condition. Within these patients, the percentage of stride cycles with reduced RMS-A, ranged between 28% and 83%. After Levodopa intake, no stride cycle showed reduced RMS-A. Patients with reduced RMS-A had a lower UPDRS III total score in the "on-med" rather than in the "off-med" condition (p=0.02). Our data confirm and extend previous observations indicating that, in "off-med" the function of TA is impaired in those patients clinically more responsive to Levodopa. TA activation is reduced in a relatively high percent of gait cycles in the "off-med" state. Since the variability of TA activation disappears after Levodopa administration, this phenomenon could be the expression of an abnormal dopaminergic drive