Advanced deep learning approaches to predict supply chain risks under COVID-19 restrictions.

The ongoing COVID-19 pandemic has created an unprecedented predicament for global supply chains (SCs). Shipments of essential and life-saving products, ranging from pharmaceuticals, agriculture, and healthcare, to manufacturing, have been significantly impacted or delayed, making the global SCs vulnerable. A better understanding of the shipment risks can substantially reduce that nervousness. Thenceforth, this paper proposes a few Deep Learning (DL) approaches to mitigate shipment risks by predicting "if a shipment can be exported from one source to another", despite the restrictions imposed by the COVID-19 pandemic. The proposed DL methodologies have four main stages: data capturing, de-noising or pre-processing, feature extraction, and classification. The feature extraction stage depends on two main variants of DL models. The first variant involves three recurrent neural networks (RNN) structures (i.e., long short-term memory (LSTM), Bidirectional long short-term memory (BiLSTM), and gated recurrent unit (GRU)), and the second variant is the temporal convolutional network (TCN). In terms of the classification stage, six different classifiers are applied to test the entire methodology. These classifiers are SoftMax, random trees (RT), random forest (RF), k-nearest neighbor (KNN), artificial neural network (ANN), and support vector machine (SVM). The performance of the proposed DL models is evaluated based on an online dataset (taken as a case study). The numerical results show that one of the proposed models (i.e., TCN) is about 100% accurate in predicting the risk of shipment to a particular destination under COVID-19 restrictions. Unarguably, the aftermath of this work will help the decision-makers to predict supply chain risks proactively to increase the resiliency of the SCs.

L-carnitine suppresses transient receptor potential vanilloid type 1 activity and myofibroblast transdifferentiation in human corneal keratocytes.

Corneal stromal wound healing is a well-balanced process promoted by overlapping phases including keratocyte proliferation, inflammatory-related events, and tissue remodeling. L-carnitine as a natural antioxidant has shown potential to reduce stromal fibrosis, yet the underlying pathway is still unknown. Since transient receptor potential vanilloid 1 (TRPV1) is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing, we investigated if L-carnitine can mediate inhibition of the fibrotic response through suppression of TRPV1 activation in human corneal keratocytes (HCK). We determined TRPV1-induced intracellular calcium transients using fluorescence calcium imaging, channel currents by planar patch-clamping, and cell migration by scratch assay for wound healing. The potential L-carnitine effect on TRPV1-induced myofibroblast transdifferentiation was evaluated by immunocytochemical detection of alpha smooth muscle actin. RT-PCR analysis confirmed TRPV1 mRNA expression in HCK. L-carnitine (1 mmol/l) inhibited either capsaicin (CAP) (10 µmol/l), hypertonic stress (450 mOsmol/l), or thermal increase (>43 °C) induced Ca2+ transients and corresponding increases in TRPV1-induced inward and outward whole-cell currents. This was accompanied by suppression of injury-induced increases in myofibroblast transdifferentiation and cell migration. In conclusion, L-carnitine contributes to inhibit stromal scarring through suppressing an injury-induced intrinsic TRPV1 activity that is linked with induction of myofibroblast transdifferentiation in HCK cells.

Effect of Bandage Contact Lens Exchange on Pain and Healing After Photorefractive Keratectomy-A Randomized Control Trial.

OBJECTIVE: To evaluate the corneal re-epithelialization and patient-perceived pain after bandage contact lens (BCL) exchange on day one, after photorefractive keratectomy (PRK). METHODS: A randomized controlled trial, of all patients who underwent bilateral transepithelial-PRK (trans-PRK) or bilateral alcohol debridement and PRK (A-PRK), between March and October 2019. One eye of each patient was randomly assigned to BCL exchange on the first postoperative day (exchange group) and the BCL was not exchanged in the fellow eye (control group). Patients were evaluated daily until healing was complete. At each visit, the corneal epithelial defect was measured, and a questionnaire was used to assess pain, photophobia, and excessive tearing. P<0.05 was statistically significant. RESULTS: The study sample was comprised of 56 patients (mean age 27.2±5.7 years). Trans-PRK was performed in 20 (34.5%) and A-PRK in 36 (64.3%) patients. At day 3, 40 (71.4%) eyes of the exchange group healed completely compared with 38 (67.9%) eyes of the control group (P=0.5). At day-1 follow-up, the pain score was 1.87±1.4 in the exchange group and 2.29±1.3 in the control group (P=0.009). The mean pain score was 1.58±1.4 among patients who underwent A-PRK and 2.35±1.2 among patients operated by trans-PRK (P=0.04). CONCLUSION: The epithelial healing did not vary when BCL was exchanged one day after refractive surgery. However, postoperative pain score after PRK was lower at day 1, when the BCL was exchanged. Compared with A-PRK, trans-PRK group demonstrated a higher pain score in the early postoperative phase.

Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts.

Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of liquefactive necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of liquefactive necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of liquefactive necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of liquefactive necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of liquefactive necrosis from surviving brain tissue.

Ruthenium-Containing Linear Helicates and Mesocates with Tuneable p53-Selective Cytotoxicity in Colorectal Cancer Cells.

The ligands L1 and L2 both form separable dinuclear double-stranded helicate and mesocate complexes with RuII . In contrast to clinically approved platinates, the helicate isomer of [Ru2 (L1 )2 ]4+ was preferentially cytotoxic to isogenic cells (HCT116 p53-/- ), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53+/+ . Other structurally similar RuII -containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be "tuned" to either genotype. In the search for compounds that can target difficult-to-treat tumours that lack the p53 tumour suppressor gene, [Ru2 (L1 )2 ]4+ is a promising compound for further development.

Preoperative embolization and microsurgical resection of a cerebellar hemangioblastoma: embolization goals and technical nuances of the approaches. Illustrative case.

BACKGROUND: Resection remains the optimal treatment for hemangioblastomas, highly vascular tumors commonly located in the cerebellum or spinal cord. Preoperative embolization can be used with caution to reduce intraoperative blood loss and promote gross-total resection while reducing neurological morbidity. OBSERVATIONS: The authors report a case of a 44-year-old male who presented with worsening dizziness, gait imbalance, and diplopia. Imaging revealed a large vascular cerebellar mass with brainstem compression and hydrocephalus, concerning for hemangioblastoma. The patient underwent preoperative embolization of the main arterial supply from the right superior cerebellar artery, which devascularized the tumor and reduced the early venous shunting, followed by gross-total resection of the tumor. Preoperative embolization helped to facilitate safe microsurgical resection because this main arterial supply was deep to the planned surgical approach, and the Onyx cast served as a landmark of the dorsal midbrain and remaining arterial supply. This resulted in minimal intraoperative blood loss. At 2-year follow-up, the patient's diplopia and vertigo had resolved, and his gait continues to improve. LESSONS: Despite controversy regarding the use of preoperative embolization for hemangioblastoma resection, the authors emphasize its safety and utility during resection of a large cerebellar hemangioblastoma. Onyx embolization provided benefit in both reducing the tumor blood supply and serving as intraoperative visual guidance.

Management of a recurrent spinal arachnoid cyst presenting as arachnoiditis in the setting of spontaneous spinal subarachnoid hemorrhage: illustrative case.

BACKGROUND: Spontaneous spinal subarachnoid hemorrhage is a rare pathological entity with a variety of presentations depending on the underlying etiology, which often remains cryptogenic. The literature is sparse regarding the most efficacious treatment or management option, and there is no consensus on follow-up time or modalities. Additionally, there are very few reports that include operative videos, which is provided herein. OBSERVATIONS: The authors present a case of spontaneous spinal subarachnoid hemorrhage without an underlying etiology in a patient with progressive myelopathy, back pain, and lower-extremity paresthesias. She presented to our institution, and because of progressive worsening of her symptoms and the development of compressive arachnoid cysts, she underwent thoracic laminectomies for evacuation of subdural fluid, fenestration of the arachnoid cysts, and lysis of significant arachnoid adhesions. Her clinical course was further complicated by the recurrence of worsening myelopathy and the development of a large compressive arachnoid cyst with further arachnoiditis. The patient underwent repeat surgical intervention for cyst decompression with an improvement in symptoms. LESSONS: This case highlights the importance of long-term follow-up for these complicated cases with an emphasis on repeat magnetic resonance imaging. Unfortunately, surgical intervention is associated with short-term relief of the symptoms and no significant nonoperative management is available for these patients.

Non-hemorrhagic cerebellar contrast enhancement on intraoperative MRI during a supratentorial glioma resection: Concerning finding of no significance.

Intraoperative magnetic resonance imaging (iMRI) is a powerful tool used to verify maximal safe resection of gliomas. However, unsuspected new or incidental findings can present difficult clinical scenarios. Here we present a case of a large supratentorial glioma resection where new, incidental bilateral cerebellar hemispheric enhancement was noted on iMRI. A 52-year-old male with a large intra-axial mass spanning the right temporal and parietal lobes underwent a craniotomy for tumor resection utilizing iMRI. Imaging displayed new, remote, bilateral cerebellar enhancement. Upon completion of surgery, the patient was extubated and was at his neurological baseline. An immediate CT scan showed no abnormalities in the cerebellum, and the duration of his hospital stay was unaffected by this finding. An MRI 24 hours after the procedure demonstrated complete resolution of the enhancement. New, remote contrast enhancement in the cerebellum raises concerns for the potentially emergent, well-defined pathology known as remote cerebellar hemorrhage (RCH). However, here we describe a case where these findings turned out to be clinically insignificant, CT-negative, and self-limiting. Therefore, here we call this finding remote non-hemorrhagic cerebellar contrast enhancement (RNHCCE) to differentiate it from RCE, and we discuss nuances and management considerations for differentiating the two.

The Role of Magnetic Resonance Imaging and Computed Tomography in Spinal Cord Injury.

Traumatic injuries of the spine are associated with long-term morbidity and mortality. Timely diagnosis and appropriate management of mechanical instability and spinal cord injury are important to prevent further neurologic deterioration. Spine surgeons require an understanding of the essential imaging techniques concerning the diagnosis, management, and prognosis of spinal cord injury. We present a review in the role of computed tomography (CT) including advancements in multidetector CT (MDCT), dual energy CT (DECT), and photon counting CT, and how it relates to spinal trauma. We also review magnetic resonance imaging (MRI) and some of the developed MRI based classifications for prognosticating the severity and outcome of spinal cord injury, such as diffusion weighted imaging (DWI), diffusion tractography (DTI), functional MRI (fMRI), and perfusion MRI.

Temporary standalone percutaneous fixation with pedicle screws for the treatment of subacute tuberculous osteomyelitis with kyphotic deformity in the lumbar spine.

Background: Tuberculous (TB) osteomyelitis is a rare, but challenging infection, that mandates antituberculosis antibiotics, and potentially surgical intervention. Per the Gulhane Askeri Tip Akademisi (GATA) classification system, corrective reconstruction is indicated in severe cases, where the kyphotic deformity is >20° (GATA Class III). Here, we describe a case of BCG vaccine-induced lumbar TB osteomyelitis at the L1-2 level in a patient presenting with mechanical pain and a focal, nonfixed kyphotic deformity of 36.1°. Surgery consisted of percutaneous fixation with pedicle screws without debridement, fusion arthrodesis, or anterior reconstruction. Case Description: A 77-year-old male presented with L1-2 TB osteomyelitis secondary to intravesical BCG application. A 36.1° focal nonfixed kyphotic deformity was evident on standing X-rays that reduced in the supine position. He underwent posterior percutaneous screw fixation with rods extending from the T12 to L3 levels, with resolution of his mechanical pain. Nine months later, the CT demonstrated reconstitution of the vertebral bodies (i.e., volume increase of 6.99 cm3 (21%) and 7.49 cm3 (27%) at L1 and L2, respectively). Standing X-rays after hardware removal demonstrated 32.7° of lumbar lordosis and a reduction of focal kyphosis to 12.9°. Conclusion: Here, we present an exceedingly rare case of BCG vaccine-induced L1-2 spinal tuberculosis with extensive vertebral body destruction and deformity. This was effectively treated with standalone temporary pedicle fixation instead of corpectomy and reconstruction.

Complex Microsurgical Reconstruction After Tumor Resection in the Trunk and Extremities.

Reconstruction of soft tissue defects following tumor ablation procedures in the trunk and extremities can challenge the microsurgeon. The goal is not just to provide adequate soft tissue coverage but also to restore form and function and minimize donor site morbidity. Although the principles of the reconstructive ladder still apply in the trunk and extremities, free tissue transfer is used in many cases to optimally restore form and function. Microsurgery has changed the practice in soft tissue tumors, and amputation is less frequently necessary.

Revisiting Bromohexitols as a Novel Class of Microenvironment-Activated Prodrugs for Cancer Therapy.

Bromohexitols represent a potent class of DNA-alkylating carbohydrate chemotherapeutics that has been largely ignored over the last decades due to safety concerns. The limited structure-activity relationship data available reveals significant changes in cytotoxicity with even subtle changes in stereochemistry. However, no attempts have been made to improve the therapeutic window by rational drug design or by using a prodrug approach to exploit differences between tumour physiology and healthy tissue, such as acidic extracellular pH and hypoxia. Herein, we report the photochemical synthesis of highly substituted endoperoxides as key precursors for dibromohexitol derivatives and investigate their use as microenvironment-activated prodrugs for targeting cancer cells. One endoperoxide was identified to have a marked increased activity under hypoxic and low pH conditions, indicating that endoperoxides may serve as microenvironment-activated prodrugs.

Management of Extracranial Blunt Cerebrovascular Injuries: Experience with an Aspirin-Based Approach.

BACKGROUND: Optimal management of patients with extracranial blunt cerebrovascular injury (BCVI) remains controversial, with both anticoagulation and antiplatelet therapy being recommended. The purpose of this study was to evaluate the efficacy and safety of using acetylsalicylic acid (ASA) in the management of BCVI. METHODS: Patients with BCVI were identified from the registry of a Level 1 trauma center between 2010 and 2017. Digital imaging and electronic medical records were reviewed for patient information including demographic characteristics, injury type, therapy, outcomes, and follow-up. RESULTS: Over the study period, 13,578 patients were admitted following blunt trauma, with 94 (0.7%) having confirmed BCVI (mean age, 42 years; 72% male). Mean Injury Severity Score and Glasgow Coma Score were 27 and 10, respectively. BCVI was identified in 130 vessels with Biffl grade I (38%) and grade II injury (29%) being most common. Twelve (13%) patients experienced an ischemic event, but only 3 events occurred after diagnosis. ASA was primary treatment for 56 (60%) patients. Thirty patients (32%) received no treatment; 21 patients died within 24 hours of primary injury. Only 4 patients had ASA contraindications. Four patients (7%) had ASA-related complications; there were 2 cases of intracranial hemorrhage progression and 2 cases of gastrointestinal bleeding. Follow-up vascular imaging at a mean of 36 days demonstrated stable or improved levels of BCVI in 94% of patients. CONCLUSIONS: An ASA-based management strategy for BCVI was efficacious and relatively safe in this study. This approach may be the preferred treatment for BCVI, but confirmation is needed.

Selective in vitro anti-cancer activity of non-alkylating minor groove binders.

Traditional cytotoxic agents which act through a DNA-alkylating mechanism are relatively non-specific, resulting in a small therapeutic window and thus limiting their effectiveness. In this study, we evaluate a panel of 24 non-alkylating Strathclyde Minor Groove Binders (S-MGBs), including 14 novel compounds, for in vitro anti-cancer activity against a human colon carcinoma cell line, a cisplatin-sensitive ovarian cancer cell line and a cisplatin-resistant ovarian cancer cell line. A human non-cancerous retinal epithelial cell line was used to measure selectivity of any response. We have identified several S-MGBs with activities comparable to cis-platin and carboplatin, but with better in vitro selectivity indices, particularly S-MGB-4, S-MGB-74 and S-MGB-317. Moreover, a comparison of the cis-platin resistant and cis-platin sensitive ovarian cancer cell lines reveals that our S-MGBs do not show cross resistance with cisplatin or carboplatin and that they likely have a different mechanism of action. Finally, we present an initial investigation into the mechanism of action of one compound from this class, S-MGB-4, demonstrating that neither DNA double strand breaks nor the DNA damage stress sensor protein p53 are induced. This indicates that our S-MGBs are unlikely to act through an alkylating or DNA damage response mechanism.

Complex Microsurgical Reconstruction After Tumor Resection in the Trunk and Extremities.

Reconstruction of soft tissue defects following tumor ablation procedures in the trunk and extremities can challenge the microsurgeon. The goal is not just to provide adequate soft tissue coverage but also to restore form and function and minimize donor site morbidity. Although the principles of the reconstructive ladder still apply in the trunk and extremities, free tissue transfer is used in many cases to optimally restore form and function. Microsurgery has changed the practice in soft tissue tumors, and amputation is less frequently necessary.

Severe Aortic Valve Stenosis Due to Alkaptonuric Ochronosis.

Alkaptonuric ochronosis is a rare cause of aortic valve stenosis. We report the case of a 61-year-old female patient with alkaptonuria who presented to our institute with the clinical picture of severe aortic valve stenosis, which was confirmed by transthoracic echocardiography. On aortotomy, she was noted to have an impressive black discoloration of ascending aorta and the aortic root complex involving the aortic valve leaflets. She underwent an uneventful aortic valve replacement. She was discharged home 10 days postoperatively.