Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation (preprint)

In the realm of antibody therapeutics development, increasing the binding affinity of an antibody to its target antigen is a crucial task. This paper presents GearBind, a pretrainable deep neural network designed to be effective for in silico affinity maturation. Leveraging multi-level geometric message passing alongside contrastive pretraining on protein structural data, GearBind capably models the complex interplay of atom-level interactions within protein complexes, surpassing previous state-of-the-art approaches on SKEMPI v2 in terms of Pearson correlation, mean absolute error (MAE) and root mean square error (RMSE). In silico experiments elucidate that pretraining helps GearBind become sensitive to mutation-induced binding affinity changes and reflective of amino acid substitution tendency. Using an ensemble model based on pretrained GearBind, we successfully optimize the affinity of CR3022 to the spike (S) protein of the SARS-CoV-2 Omicron strain. Our strategy yields a high success rate with up to 17-fold affinity increase. GearBind proves to be an effective tool in narrowing the search space for in vitro antibody affinity maturation, underscoring the utility of geometric deep learning and adept pre-training in macromolecule interaction modeling.

Lyme radiculopathy in a septuagenarian.

A man in his 70s presented to hospital in early summer with a 5-week history of progressive lower back and right thigh pain, sensory deficit and right leg weakness. There had been limited response to analgesics in the community. Primary investigations on admission revealed no cause for his symptoms. Five days into admission, history emerged of a possible tick bite with subsequent rash sustained 3 months earlier, raising the possibility of neuroborreliosis leading to radiculopathy. Cerebrospinal fluid demonstrated a lymphocytic pleocytosis. An elevated Borrelia burgdorferi antibody index confirmed a diagnosis of Lyme neuroborreliosis. The patient was treated successfully with 28 days of intravenous ceftriaxone, analgesia and physiotherapy. Within the literature, Lyme radiculopathy is a common presentation of neuroborreliosis and should be considered and investigated in patients without radiological evidence of a mechanical cause of worsening lower back pain in settings with endemic Lyme disease.

Modeling and real-time prediction of irrigation water quality index using Graphical User Interface (App), a case study of Oued-Hammam North-East Algeria (preprint)

The quality of water for irrigation purposes hasnot been taken into serious consideration in many places around the Globe. The present case study at Oued-Hammam watershed aims to investigate the use of an artificial neural network in the prediction of irrigation water quality indicators of Sodium absorption ratio and Electrical Conductivity and deployment of the models using graphical user interface (App).Fourteen water quality parameters were collected at Zit Emba reservoir from 2010 to 2014.Pearson correlation matrix was used to select input parameters with respect with the output parameter. The back-propagation neural networks learning algorithm was used in modeling of irrigation water quality index (IWQI) for both SAR and EC. The performances of models were evaluated using statistical criteria of correlation coefficient (R) and root mean square error (RMSE). Back propagation neural network learning algorithm maximum correlation coefficient for SAR and EC were 0.98077 and 0.97762 respectively, also with minimum RMSE of 0.037 for SAR and 101.8 for EC. Thus current study suggests that artificial neural network (ANN) models are most effective tools for prediction of water quality prediction and their outcome can be used as effective method in management and real-time control of water pollution around the watershed.

Aerial roots elevate indoor plant health: physiological and morphological responses of three high-humidity adapted Araceae species to indoor humidity levels (preprint)

Heightened by the COVID-19 pandemic there has been a global increase in urban greenspace appreciation. Indoor plants are equally important for improving mental health and air quality but despite evolving in humid (sub)tropical environments with aerial root types, planting systems ignore aerial resource supply. This study directly compared nutrient uptake preferences of aerial and soil-formed roots of three common houseplant species under high and ambient relative humidities. Growth and physiology parameters were measured weekly for Anthurium andreanum, Epipremnum aureum and Philodendron scandens grown in custom made growth chambers. Both aerial and soil-formed roots were then fed mixtures of nitrate, ammonium and glycine, with one source labelled with N to determine uptake rates and maximum capacities.Aerial roots were consistently better at nitrogen uptake than soil roots but no species, root type or humidity condition showed a preference for a particular nitrogen source. All three species grew more in high humidity, with aerial roots demonstrating the greatest biomass increase. Higher humidities for indoor niches, together with fertiliser application to aerial roots will support indoor plant growth. We discuss how these conditions and growth outcomes will further improve air pollution reductions and human comfort, mental and physical health.

COVID-19 Worsens Chronic Lumbosacral Radicular Pain-Case Series Report.

The knowledge of the COVID-19 symptomatology has increased since the beginning of the SARS-CoV-2 pandemic. The symptoms of nervous system involvement have been observed across the spectrum of COVID-19 severity. Reports describing difficulties of nerve roots are rare; the affection of brain and spinal cord by SARS-CoV-2 is of leading interest. Our aim therefore is to describe the radicular pain deterioration in the group of nine chronic lumbosacral radicular syndrome sufferers in acute COVID-19. The intensity of radicular pain was evaluated by the Visual Analogue Scale (VAS). The VAS score in acute infection increased from 5.6 ± 1.1 to 8.0 ± 1.3 (Cohen's d = 1.99) over the course of COVID-19, indicating dramatic aggravation of pain intensity. However, the VAS score decreased spontaneously to pre-infection levels after 4 weeks of COVID-19 recovery (5.8 ± 1.1). The acute SARS-CoV-2 infection worsened the pre-existing neural root irritation symptomatology, which may be ascribed to SARS-CoV-2 radiculitis of neural roots already compressed by the previous disc herniation. These findings based on clinical observations indicate that the neurotropism of novel coronavirus infection can play an important role in the neural root irritation symptomatology deterioration in patients with chronic pre-existing lumbosacral radicular syndrome.

Acute herpes zoster radiculopathy mimicking cervical radiculopathy after ChAdOx1 nCoV-19/AZD1222 vaccination.

This case report describes an 84-year-old man who presented with 3 weeks of gradually worsening right arm weakness associated with a painful vesicular rash across his arm. This occurred 3 days after his first dose of the ChAdOx1 nCoV-19/AZD1222 (University of Oxford, AstraZeneca and the Serum Institute of India) vaccine. The diagnosis was complicated by the presence of right C5-C6 foraminal stenosis compressing on the C6 nerve root sheath on non-contrast MRI, leading to an initial diagnosis of cervical radiculopathy. However, a positive varicella zoster virus-PCR test and findings of abnormal contrast enhancement of his right C5-C7 nerve roots on gadolinium-enhanced MRI resulted in a revision of his diagnosis to zoster radiculopathy. He was subsequently commenced on oral valacilovir and made significant recovery. This report aims to highlight the diagnostic dilemma between cervical radiculopathy secondary to spondylosis and zoster radiculopathy and how an erroneous diagnosis could result in inappropriate, aggressive surgical intervention and delayed treatment with antiviral therapy.

Acute Cauda Equina Syndrome Due to Spondylolisthesis in the Midst of a Pandemic: A Case Report.

CASE: A 54-year-old woman with chronic lumbar radiculopathy due to grade II spondylolisthesis at lumbar 4 to 5 developed acute cauda equina syndrome (CES) after an elective lumbar decompression, and fusion was delayed because of statewide bans on elective procedures during the pandemic. The diagnosis was made largely through telehealth consultation and eventually prompted urgent neurosurgical intervention. CONCLUSION: This case report illustrates a rare presentation of acute CES and highlights some of the challenges of practicing clinical medicine in the midst of a pandemic.

Vertebral Algic Syndrome Treatment in Long COVID-Cases Reports.

Though pain is a frequent symptom of long COVID-19, little attention has been paid to vertebral algic syndrome. Therefore, we present the cases reports of two precisely selected physically active patients where vertebral algic syndrome and radiculopathy dramatically worsened in acute SARS-CoV-2 infections. The vertebral pain with radicular irritation was resistant to conservative treatment in chronic post-COVID syndrome. The neurological difficulties corresponded to the radiologic imaging presented on MRI scans. Due to the absence of standard therapeutic guidelines in literature sources, it was decided to provide routine therapeutic procedures. Spinal surgery with radicular decompression was performed within 6 months after acute SARS-CoV-2 infection. This led to the improvement of their neurological status and was in corroboration with decreases of VAS (from 9 to 0 in Patient 1 and from 7 to 1 in Patient 2). Our experience indicates that these patients benefited from the standard neurosurgical radicular decompression, and sufficient pain relief was achieved; nevertheless, the initial trigger of neurological worsening was acute SARS-CoV-2 infection.

Guillain-Barré syndrome associated with COVID-19 disease.

Clinical manifestations of COVID-19 are known to be variable with growing evidence of nervous system involvement. In this case report, we describe the symptoms of a patient infected with SARS-CoV-2 whose clinical course was complicated with Guillain-Barré syndrome (GBS). We present a case of a 58-year-old woman who was initially diagnosed with COVID-19 pneumonia due to symptoms of fever and cough. Two weeks later, after the resolution of upper respiratory tract symptoms, she developed symmetric ascending quadriparesis and paresthesias. The diagnosis of GBS was made through cerebrospinal fluid analysis and she was successfully treated with intravenous immunoglobulin administration.

Trigeminal and cervical radiculitis after tozinameran vaccination against COVID-19.

In this report, we describe a patient who developed an acute trigeminal neuritis and cervical radiculitis after receiving a Pfizer-BioNtech vaccination (tozinameran) against SARS-CoV-2.

A Case of Elsberg Syndrome in the Setting of Asymptomatic SARS-CoV-2 Infection.

ABSTRACT: Elsberg syndrome is a rare cause of lumbosacral radiculitis with concomitant thoracic and lumbosacral myelitis that can be seen after an acute or reactivated viral infection. After the initial coronavirus surge in New York City, a 68-year-old man developed progressive lower extremity weakness and a defined sensory level at the lower abdomen. He had highly elevated SARS-CoV-2 IgG antibodies despite an absence of preceding COVID-19 symptoms. Serial electrodiagnostic testing revealed absent lower extremity late responses, with otherwise normal distal sensorimotor conductions. Electromyography revealed active neurogenic changes and reduced motor unit recruitment in the L3-L4 myotomes. Treatment with methylprednisolone and intravenous immunoglobulin was followed by minimal clinical improvement but re-emergence of the lower extremity late responses on electrodiagnostic testing. We report here, to the best of our knowledge, the first case of suspected COVID-19-associated Elsberg syndrome, which expands the spectrum of neuromuscular manifestations associated with SARS-CoV-2 infection and sheds light on ways to approach diagnostic and treatment options for these patients.

COVID-19 associated with encephalomyeloradiculitis and positive anti-aquaporin-4 antibodies: Cause or coincidence?

Neurologic complications are being recognized as important outcomes of coronavirus disease 2019 (COVID-19). Pathogenesis is varied and incompletely understood, and may include neuroinvasion, indirect post-infectious neuroinflammation, and cerebrovascular pathologies. We present a case of COVID-19-related encephalomyeloradiculitis with clinical and magnetic resonance imaging characteristics of neuromyelitis optica spectrum disorders that was associated with anti-aquaporin-4 antibodies. Our case suggests post-infectious autoimmunity as a mechanism in at least a subset of patients with COVID-19-related neurologic disease.

Quantitative analysis of image quality in low-dose CT imaging for Covid-19 patients (preprint)

We set out to simulate four reduced dose-levels (60%-dose, 40%-dose, 20%-dose, and 10%-dose) of standard CT imaging using Beer-Lambert's law across 49 patients infected with COVID-19. Then, three denoising filters, namely Gaussian, Bilateral, and Median, were applied to the different low-dose CT images, the quality of which was assessed prior to and after the application of the various filters via calculation of peak signal-to-noise ratio (PSNR), root mean square error (RMSE), structural similarity index measure (SSIM), and relative CT-value bias, separately for the lung tissue and whole-body. The quantitative evaluation indicated that 10%-dose CT images have inferior quality (with RMSE=322.1-+104.0 HU and bias=11.44-+4.49% in the lung) even after the application of the denoising filters. The bilateral filter exhibited superior performance to suppress the noise and recover the underlying signals in low-dose CT images compared to the other denoising techniques. The bilateral filter led to RMSE and bias of 100.21-+16.47 HU, -0.21-+1.20%, respectively in the lung regions for 20%-dose CT images compared to the Gaussian filter with RMSE=103.46-+15.70 HU and bias=1.02-+1.68%, median filter with RMSE=129.60-+18.09 HU and bias=-6.15-+2.24%, and the nonfiltered 20%-dose CT with RMSE=217.37-+64.66 HU and bias=4.30-+1.85%. In conclusion, the 20%-dose CT imaging followed by the bilateral filtering introduced a reasonable compromise between image quality and patient dose reduction.

Elsberg Syndrome in the Setting of Asymptomatic SARS-CoV-2 infection: Case Report (preprint)

Background: Elsberg syndrome is a rare cause of lumbosacral radiculitis with concomitant thoracic or lumbosacral myelitis that can be seen following an acute or reactivated viral infection. COVID-19 disease, caused by the SARS-CoV-2 virus, has quickly spread to a global pandemic since its first discovery in the winter of 2019. During this time, there has been an increasing number of case reports describing SARS-CoV-2 associated neuroinflammatory disease.Case Presentation: A 68-year-old man presented in June 2020 with a fall due to progressive lower extremity weakness and numbness, occurring shortly after the initial coronavirus surge in New York City. He developed ascending numbness to the level of the lower abdomen over the preceding month. He subsequently experienced low back pain, and gastrointestinal and genitourinary dysfunction. An extensive laboratory and radiologic evaluation ensued which was notable for elevated SARS-CoV-2 IgG antibodies despite an absence of preceding COVID-19 symptoms. Initial electrodiagnostic testing was notable for absent late responses in the lower extremity nerve conductions with normal distal sensorimotor conductions, and incomplete muscle activation with otherwise normal motor unit morphology and recruitment on electromyography. Repeat testing two weeks later revealed similar nerve conductions, but also the interval development of active neurogenic changes and reduced motor unit recruitment in the L3-L4 myotomes. This was suggestive of a lower thoracic and lumbosacral myelopathy and lumbosacral polyradiculopathy without peripheral neuropathy. A diagnosis of Elsberg syndrome was made and treatment with intravenous methylprednisolone yielded mild clinical improvement and the electrodiagnostic re-emergence of the lower extremity late responses.Conclusions: We report here, to our knowledge, the first case of suspected COVID-19 associated Elsberg syndrome, which may help to shed light on ways in which to approach diagnostic and treatment options in COVID-19 patients presenting with uncommon neurological and autonomic manifestations.

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients.

BACKGROUND: Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations. METHODS: Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated. RESULTS: Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients. CONCLUSIONS: In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

Potential Phytochemical Inhibitors of the Coronavirus RNA Dependent RNA Polymerase: A Molecular Docking Study (preprint)

The COVID-19 disease that originated in China by the end of 2019 has now become a pandemic and has affected 216 countries as on 08 June 2020. RNA dependent RNA polymerase (RdRp), the core enzyme in the multiprotein replicase-transcriptase complex of coronaviruses, serves as a classical target for inhibiting the coronavirus infectivity. In this study we performed molecular docking of sixty-nine different phytochemical compounds from various herbs with RdRp of both SARS-CoV-2 and its predecessor SARS-CoV. Our results show that various phytochemical constituents from Withania somnifera root extract, Hyssopus officinalis and Camellia sinensis leaf extract have high binding affinity towards RdRps and are comparable to the small molecule drug remdesivir. Their binding interactions reveal that they bind to the amino acid residues involved in nucleoside triphosphate (NTP) entry and recognition site and metal ion cofactor chelating site of both SARS-CoV-2 and SARS-CoV. Hence they are different from the classical nucleotide analog inhibitors of RdRp. This study paves a quick platform for development of targeted therapy using phytochemicals for COVID-19 and other potential SARS coronavirus related outbreaks in future.

Acute Symptomatic Seizures in Critically Ill Patients with COVID-19: Is There an Association?

BACKGROUND: The coronavirus disease of 2019 (COVID-19) emerged as a global pandemic. Historically, the group of human coronaviruses can also affect the central nervous system leading to neurological symptoms; however, the causative mechanisms of the neurological manifestations of COVID-19 disease are not well known. Seizures have not been directly reported as a part of COVID-19 outside of patients with previously known brain injury or epilepsy. We report two cases of acute symptomatic seizures, in non-epileptic patients, associated with severe COVID-19 disease. CASE PRESENTATIONS: Two advanced-age, non-epileptic, male patients presented to our northeast Ohio-based health system with concern for infection in Mid-March 2020. Both had a history of lung disease and during their hospitalization tested positive for SARS-CoV-2. They developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures. Resolution of seizures was achieved with levetiracetam. DISCUSSION: Patients with COVID-19 disease are at an elevated risk for seizures, and the mechanism of these seizures is likely multifactorial. Clinical (motor) seizures may not be readily detected in this population due to the expansive utilization of sedatives and paralytics for respiratory optimization strategies. Many of these patients are also not electrographically monitored for seizures due to limited resources, multifactorial risk for acute encephalopathy, and the risk of cross-contamination. Previously, several neurological symptoms were seen in patients with more advanced COVID-19 disease, and these were thought to be secondary to multi-system organ failure and/or disseminated intravascular coagulopathy-related brain injury. However, these patients may also have an advanced breakdown of the blood-brain barrier precipitated by pro-inflammatory cytokine reactions. The neurotropic effect and neuroinvasiveness of SARS-Coronavirus-2 have not been directly established. CONCLUSIONS: Acute symptomatic seizures are possible in patients with COVID-19 disease. These seizures are likely multifactorial in origin, including cortical irritation due to blood-brain barrier breakdown, precipitated by the cytokine reaction as a part of the viral infection. Patients with clinical signs of seizures or otherwise unexplained encephalopathy may benefit from electroencephalography monitoring and/or empiric anti-epileptic therapy. Further studies are needed to elucidate the risk of seizures and benefit of monitoring in this population.