The molecular reach of antibodies crucially underpins their viral neutralisation capacity.

Key functions of antibodies, such as viral neutralisation, depend on high-affinity binding. However, viral neutralisation poorly correlates with antigen affinity for reasons that have been unclear. Here, we use a new mechanistic model of bivalent binding to study  >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces.

An Unstructured Mesh Reaction-Drift-Diffusion Master Equation with Reversible Reactions.

We develop a convergent reaction-drift-diffusion master equation (CRDDME) to facilitate the study of reaction processes in which spatial transport is influenced by drift due to one-body potential fields within general domain geometries. The generalized CRDDME is obtained through two steps. We first derive an unstructured grid jump process approximation for reversible diffusions, enabling the simulation of drift-diffusion processes where the drift arises due to a conservative field that biases particle motion.

Apomorphine titration with and without anti-emetic pretreatment in patients with Parkinson's disease experiencing OFF episodes: A modified Delphi panel.

Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed.

Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment.

Self-Assembled Monolayer Transporters Enable Reagentless Analysis of Small Molecule Analytes.

The detection of small molecules beyond glucose remains an ongoing challenge in the field of biomolecular sensing owing to their small size, diverse structures, and lack of alternative non-enzymatic sensing methods. Here, we present a new reagentless electrochemical approach for small molecule detection that involves directed movement of electroactive analytes through a self-assembled monolayer to an electrode surface. Using this method, we demonstrate detection of several physiologically relevant small molecules as well as the capacity for the system to operate in several biological fluids.

Corrigendum to "Recommendations for a paradigm shift in approach to increase the recognition and treatment of sialorrhea in Parkinson's disease" [Clin. Parkinsonism Related Dis. 9 (2023) 100223].

[This corrects the article DOI: 10.1016/j.prdoa.

Retrospective analyses evaluating the mortality risk associated with pimavanserin or other atypical antipsychotics in patients with Parkinson disease psychosis.

Introduction: Parkinson's disease (PD) is associated with increased mortality risk (MR), reflecting progression of motor and nonmotor symptoms. PD psychosis (PDP), a common nonmotor symptom, increases with prolonged disease and elevates the MR of PD even further. Pimavanserin is the only FDA-approved treatment for PDP.

Long-term safety, tolerability and efficacy of apomorphine sublingual film in patients with Parkinson's disease complicated by OFF episodes: a phase 3, open-label study.

Background: Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson's disease (PD).

Objective: To assess the long-term (≥ 3 years) safety/tolerability and efficacy of SL-APO.

Methods: Study CTH-301 ( http://www.

Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies.

Importance: Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies.

Objective: To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.

Safety and efficacy of continuous subcutaneous levodopa-carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial.

Background: Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease.

Recommendations for a paradigm shift in approach to increase the recognition and treatment of sialorrhea in Parkinson's disease.

Sialorrhea, or drooling, is defined as excessive saliva accumulation and unwanted loss of saliva from the mouth or over the tongue and into the pharynx. It constitutes one of the most frequent and bothersome complaints of patients with Parkinson's disease (PD), affecting up to 84% of them. Sialorrhea is a distressing and challenging condition that may result in social isolation, embarrassment, depression, skin infections, poor oral health, and aspiration pneumonia.

Feasibility of home dose optimization of apomorphine sublingual film in Parkinson's disease patients with OFF episodes: results from the dose-optimization phase of an open-label, randomized crossover study.

Background: Dose optimization of sublingual apomorphine (SL-APO), a dopamine agonist for the treatment of OFF episodes in patients with Parkinson's disease (PD), has been performed under clinical supervision in clinical trials. SL-APO may be a candidate for home dosing optimization which would be less burdensome for patients.

Objectives: To evaluate the feasibility and safety of home optimization of SL-APO in patients with PD and OFF episodes.

Clinical benefit of transcutaneous afferent patterned stimulation (TAPS) in essential tremor patients with high unmet need: a secondary analysis of TAPS studies.

Background: Transcutaneous afferent patterned stimulation (TAPS) is a noninvasive neuromodulation therapy that improves hand tremor in essential tremor (ET) patients. The benefits of TAPS in ET patients with high unmet need (severe tremor, non-responsive to medication, age ≥65 years) and early responders (substantial TAPS tremor improvement in the first month) remains unknown.

Research Design And Methods: Literature was surveyed for TAPS studies to assess the response in the high unmet need subgroup and early responders.

Catalyst: Fast and flexible modeling of reaction networks.

We introduce Catalyst.jl, a flexible and feature-filled Julia library for modeling and high-performance simulation of chemical reaction networks (CRNs). Catalyst supports simulating stochastic chemical kinetics (jump process), chemical Langevin equation (stochastic differential equation), and reaction rate equation (ordinary differential equation) representations for CRNs.

Non-Invasive Transcutaneous Afferent Patterned Stimulation Therapy Offers Action Tremor Relief in Parkinson's Disease.

Background: Many patients with Parkinson's disease (PD) experience action tremor (including postural and kinetic tremors) that impair activities of daily living. Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive neuromodulation therapy that modulates tremorgenic activity at the ventral intermediate nucleus (VIM). Most TAPS evidence evaluated relief of action tremor associated with essential tremor (ET).

IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease: The RISE-PD Randomized Clinical Trial.

Importance: Levodopa has a short half-life and a limited window of opportunity for absorption in the proximal small intestine. IPX203 is an oral, extended-release formulation of carbidopa-levodopa developed to address these limitations.

Objective: To assess the efficacy and safety of IPX203 vs immediate-release carbidopa-levodopa in patients with Parkinson disease who are experiencing motor fluctuations.

Importance of time to ON versus wearing OFF in total daily OFF time experienced by patients with Parkinson's disease.

Most patients with Parkinson's disease (PD) receiving levodopa (LD)/DOPA decarboxylase inhibitors develop motor fluctuations with an increasing amount of OFF time, negatively impacting patient quality of life. Herein, we review the evidence supporting the substantial, yet underappreciated contribution of delays in time to ON (including delayed ON and no ON) to total daily OFF time. Most clinical studies use patient diaries that do not capture time to ON and wearing OFF separately as related to LD dosing, and consequently, most OFF time has generally been attributed to wearing OFF.

Dopamine agonists in Parkinson's disease: Impact of D1-like or D2-like dopamine receptor subtype selectivity and avenues for future treatment.

Dopamine agonists (DAs) have demonstrated efficacy for the treatment of Parkinson's disease (PD) but are limited by adverse effects (AEs). DAs can vary considerably in their receptor subtype selectivity and affinity, chemical composition, receptor occupancy, and intrinsic activity on the receptor. Most currently approved DAs for PD treatment primarily target D2/D3 (D2-like) dopamine receptors.

Ulotaront, a Trace Amine-Associated Receptor 1/Serotonin 5-HT Agonist, in Patients With Parkinson Disease Psychosis: A Pilot Study.

Background And Objectives: Ulotaront (SEP-363856) is a trace amine-associated receptor 1 agonist with 5-HT receptor agonist activity currently in phase 3 clinical development for the treatment of schizophrenia. In this exploratory, flexibly dosed study, ulotaront was evaluated for the treatment of Parkinson disease psychosis (PDP).

Methods: Patients with PDP requiring antipsychotic therapy were randomized, double-blind to ulotaront (25, 50, or 75 mg/d) or placebo.

Dose Optimization of Apomorphine Sublingual Film for OFF Episodes in Parkinson's Disease: Is the Prophylactic Use of an Antiemetic Necessary?

Background: Nausea is common upon initiating dopamine agonists in patients with Parkinson's disease (PD); however, pretreatment with an antiemetic is recommended only when initiating apomorphine formulations.

Objective: Evaluate the need for prophylactic antiemetic use during dose optimization of apomorphine sublingual film (SL-APO).

Methods: A post hoc analysis of a Phase III study evaluated nausea and vomiting treatment-emergent adverse events in patients with PD who underwent SL-APO dose optimization (10-35 mg; 5-mg increments) to achieve a tolerable FULL ON.

Corrigendum to 'Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok,' [Contemporary Clinical Trials Communication (2023)101054].

[This corrects the article DOI: 10.1016/j.conctc.

How to manage the initiation of apomorphine therapy without antiemetic pretreatment: A review of the literature.

Introduction: Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods: To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.