Machine-Guided Discovery of Acrylate Photopolymer Compositions.

Additive manufacturing (AM) can be advanced by the diverse characteristics offered by thermoplastic and thermoset polymers and the further benefits of copolymerization. However, the availability of suitable polymeric materials for AM is limited and may not always be ideal for specific applications. Additionally, the extensive number of potential monomers and their combinations make experimental determination of resin compositions extremely time-consuming and costly. To overcome these challenges, we develop an active learning (AL) approach to effectively choose compositions in a ternary monomer space ranging from rigid to elastomeric. Our AL algorithm dynamically suggests monomer composition ratios for the subsequent round of testing, allowing us to efficiently build a robust machine learning (ML) model capable of predicting polymer properties, including Young's modulus, peak stress, ultimate strain, and Shore A hardness based on composition while minimizing the number of experiments. As a demonstration of the effectiveness of our approach, we use the ML model to drive material selection for a specific property, namely, Young's modulus. The results indicate that the ML model can be used to select material compositions within at least 10% of a targeted value of Young's modulus. We then use the materials designed by the ML model to 3D print a multimaterial "hand" with soft "skin" and rigid "bones". This work presents a promising tool for enabling informed AM material selection tailored to user specifications and accelerating material discovery using a limited monomer space.

Generating new drug repurposing hypotheses using disease-specific hypergraphs.

The drug development pipeline for a new compound can last 10-20 years and cost over $10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on network graph representations, comprising a mixture of disease nodes and their interactions, have recently yielded new drug repurposing hypotheses, including suitable candidates for COVID-19. However, these interactomes remain aggregate by design and often lack disease specificity. This dilution of information may affect the relevance of drug node embeddings to a particular disease, the resulting drug-disease and drug-drug similarity scores, and therefore our ability to identify new targets or drug synergies. To address this problem, we propose constructing and learning disease-specific hypergraphs in which hyperedges encode biological pathways of various lengths. We use a modified node2vec algorithm to generate pathway embeddings. We evaluate our hypergraph's ability to find repurposing targets for an incurable but prevalent disease, Alzheimer's disease (AD), and compare our ranked-ordered recommendations to those derived from a state-of-the-art knowledge graph, the multiscale interactome. Using our method, we successfully identified 7 promising repurposing candidates for AD that were ranked as unlikely repurposing targets by the multiscale interactome but for which the existing literature provides supporting evidence. Additionally, our drug repositioning suggestions are accompanied by explanations, eliciting plausible biological pathways. In the future, we plan on scaling our proposed method to 800+ diseases, combining single-disease hypergraphs into multi-disease hypergraphs to account for subpopulations with risk factors or encode a given patient's comorbidities to formulate personalized repurposing recommendations.Supplementary materials and code: https://github.com/ayujain04/psb_supplement.

Pharmacotherapy for Treatment-Resistant Depression: Antidepressants and Atypical Antipsychotics.

Treatment-resistant depression (TRD) affects one in three patients with major depressive disorder and is associated with increased risk of all-cause mortality. Studies of real-world practices suggest that antidepressant monotherapy continues to be the most widely used treatment after inadequate response to a first-line treatment. However, rates of remission with antidepressants in TRD are suboptimal. Atypical antipsychotics are the most widely studied augmentation agent and aripiprazole, brexpiprazole, cariprazine, quetiapine extended-release, and olanzapine-fluoxetine combination are approved for depression. Benefits of using atypical antipsychotics for TRD has to be weighted against their potential adverse events, such as weight gain, akathisia, and tardive dyskinesia.

Early Results of Internal Fixation with Femoral Neck System in Young Patients with Femoral Neck Fracture.

BACKGROUND: Femoral neck fractures are intracapsular hip fractures. There are several surgical implants that have been used to treat femoral neck fractures. Depuy Synthes Products and the lower extremity expert group have developed an innovative femoral neck system (FNS) for fixing femoral neck fractures. With minimally invasive procedures, FNS can provide angular stability. MATERIALS AND METHODS: A non-randomized single centre prospective study was conducted in 30 patients of less than 60 years of age at Maharishi Markandeshwar Institute of Medical Sciences and Research between August 2020 to May 2022. All patients underwent internal fixation with FNS within 48 hours of presentation. RESULTS: Although blood loss and operative time in our operated group was more than that in conventional fixation by cannulated screws, our group had better VAS scores, better Harris scores and lower complication rates. CONCLUSIONS: 1. The Femoral Neck System resulted in better biomechanical properties and good early results in femoral neck fractures. FNS gives both angular stability and rotational stability. The last follow-up in our study showed Harris score to be significantly higher, and the incidence of complications were lower. 2. The combination of FNS bolts with anti-rotation screws avoids the "Z" effect and improves the overall stability and anti-rotation effect. 3. In addition, the novel sliding compression mechanism of FNS allows the fracture ends to come in close contact with each other, benefitting fracture healing.

Robust anti-SARS-CoV2 single domain antibodies cross neutralize multiple viruses.

We report robust SARS-CoV2 neutralizing sdAbs targeting the viral peptides encompassing the polybasic cleavage site (CSP) and in the receptor binding domain (RBD) of the spike (S) protein. Both the sdAbs inhibited infectivity of the CoV2 S protein expressing pseudoviruses (LV-CoV2S). Both anti-CSP and RBD intrabodies (IB) inhibited the output of LV(CoV2 S). Anti-CSP IB altered the proteolytic processing and targeted the viral S protein for degradation. Because of cross-reactive CSPs in the entry mediators, the anti-CSP sdAb neutralized in vitro and in vivo the infectivity of SARS-CoV2 unrelated viruses such as herpes simplex virus 1 (HSV1) and pestes des petits ruminants virus (PPRV). Conversely, anti-HSV1 and anti-PPRV sera neutralized LV(CoV2 S) owing to the presence of CSP reactive antibodies indicating that a prior infection with such pathogens could impact on the pattern of COVID-19.

Massive ovarian edema mimicking an ovarian neoplasm in a patient with IVC web.

Massive ovarian edema is an uncommon benign condition affecting young females predominantly those in the child bearing age group and preadolescent girls. Its clinical and radiologic overlap with ovarian neoplasms and torsion which require surgical intervention makes it imperative for the radiologist to consider this entity preoperatively as preserving fertility is vital in this young age group. We report a case of massive ovarian edema, a rare presentation in a patient with inferior vena cava web and consequent Budd Chiari Syndrome, an association previously unreported in literature.

MR imaging spectrum in COVID associated Rhino-Orbito-Cerebral mucormycosis with special emphasis on intracranial disease and impact on patient prognosis.

In the wake of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, a new epidemic of COVID associated mucormycosis (CAM) emerged in India. Early diagnosis and prompt treatment of this deadly disease are of paramount importance in improving patient survival. MRI is the cornerstone of diagnosis of early extrasinus disease, particularly intracranial complications which have traditionally been associated with a high mortality rate. In this review, we depict the sinonasal, perisinus, orbital and intracranial involvement in CAM. Special emphasis is laid on intracranial disease which is categorized into vascular, parenchymal, meningeal, bony involvement and perineural spread. Vascular complications are the most common form of intracranial involvement. Some unusual yet interesting imaging findings such as nerve abscesses involving the optic, trigeminal and mandibular nerves and long segment vasculitis of the internal carotid artery extending till its cervical segment are also illustrated. In our experience, patient outcome in CAM (survival rate of 88.5%) was better compared to the pre-pandemic era. Presence of intracranial disease also did not affect prognosis as poorly as traditionally expected (survival rate of 82.8%). Involvement of brain parenchyma was the only subset of intracranial involvement that was associated with higher mortality (p value 0.016). The aim of this review is to familiarise the reader with the MR imaging spectrum of CAM with special focus on intracranial complications and a brief account of their impact on patient prognosis in our experience.

Evaluation of Results of Ponseti Technique in Idiopathic Clubfoot using Clinical Evaluation and Radiological Assessment.

Background: Congenital clubfoot (congenital talipes equinovarus) occurs in approximately one in 1000 live births and is one of the most common congenital birth defects. The Ponseti method is at present a well-established method of treatment for idiopathic clubfoot deformities. Aim: The aim of the present study was to evaluate the results of serial casting in clubfoot deformity with Ponseti method on the basis of Pirani's scoring and radiological findings before and after completion of treatment. Materials and Methods: A total of 30 patients were enrolled in the study and were treated with Ponseti's casting after grading the severity of deformity clinically by Pirani's scoring and radiological assessment by calculating the talo-first metatarsal angle in anteroposterior (AP) view and talocalcaneal angle in AP and lateral views. The same clinical and radiological assessment was done at the end of treatment before putting a patient on foot abduction orthosis (FAO). Results: The average number of casts applied before full correction was 5.56 (range: 5-8). The average duration of treatment was about 6.65 weeks before the patient was put on FAO. Pirani score significantly improved from an average of 5.50 (range: 4-6) on presentation to 0.24 (range: 0-2) after correction of deformity. Conclusion: The Ponseti method is an excellent method for the correction of all four deformities associated with congenital idiopathic clubfoot, and we found that the addition of radiographic to clinical evaluation helps in the better assessment of correction. It provides statistically significant results both clinically as measured by Pirani severity score and radiologically assessed by talocalcaneal and talo-first metatarsal angle.

Deep learning via LSTM models for COVID-19 infection forecasting in India.

The COVID-19 pandemic continues to have major impact to health and medical infrastructure, economy, and agriculture. Prominent computational and mathematical models have been unreliable due to the complexity of the spread of infections. Moreover, lack of data collection and reporting makes modelling attempts difficult and unreliable. Hence, we need to re-look at the situation with reliable data sources and innovative forecasting models. Deep learning models such as recurrent neural networks are well suited for modelling spatiotemporal sequences. In this paper, we apply recurrent neural networks such as long short term memory (LSTM), bidirectional LSTM, and encoder-decoder LSTM models for multi-step (short-term) COVID-19 infection forecasting. We select Indian states with COVID-19 hotpots and capture the first (2020) and second (2021) wave of infections and provide two months ahead forecast. Our model predicts that the likelihood of another wave of infections in October and November 2021 is low; however, the authorities need to be vigilant given emerging variants of the virus. The accuracy of the predictions motivate the application of the method in other countries and regions. Nevertheless, the challenges in modelling remain due to the reliability of data and difficulties in capturing factors such as population density, logistics, and social aspects such as culture and lifestyle.

Reducing split-thickness skin grafting donor site agony; faster healing and decreased pain-role of platelet-rich plasma.

INTRODUCTION: The split-thickness skin graft harvested donor site is associated with prolonged healing, discomfort, and pain. Platelet-rich plasma (PRP) contains platelet-derived growth factors and has been widely used in chronic wounds and skin graft donor sites. PRP application is known to accelerate wound epithelialization rates, and also reduce postoperative wound site pain. MATERIALS AND METHODS: We assessed 20 patients admitted to our hospital service who underwent split-thickness skin grafting (STSGs) with proximal half of the donor site treated with PRP. The dressing was conducted on postoperative day 7, 14, and 21. The donor site healing was assessed with serial photographs and donor site pain measured by numerical rating scale. RESULTS: Complete healing of wounds (epithelialization) was present in 12 (60%) patients dressed with PRP. Pain on opening dressing was an average of 3.5 in PRP dressed wounds and 6.35 in control wounds. Patients dressed without PRP, none of them had complete epithelialization. All patients had partial healing and were less than the donor site dressed with PRP. Based on these results, skin graft donor site with PRP showed accelerated healing and reduced pain and discomfort compared to control without PRP. CONCLUSION: PRP is a beneficial adjunct for reducing donor site pain and increased healing of donor site following STSG harvest.

To Analyze the Role of Intravenous Tranexamic Acid in Hip Fracture surgeries in Orthopedic Trauma.

INTRODUCTION: Hip fractures in orthopedic trauma cases are increasing. Majority of such patients undergoing surgery require blood transfusion of one or more units. Intravenous (I. V.) Tranexamic acid (TXA) may decrease loss of blood, decrease need of blood transfusion, and improve postoperative hemoglobin (Hb) along with lesser adverse effects. Risk of thromboembolic phenomena remains a concern. A study was done to analyze the role of I. V. TXA in hip fracture surgeries in trauma cases. MATERIALS AND METHODS: Sixty patients were included in the study; in two groups (37 males and 23 females), Group A in which two doses of I. V. TXA 15 mg/kg were given and Group B in which two doses of I. V. placebo were given. RESULTS: Total number of randomized hip arthroplasty cases was 22 (11 in Group A and 11 in Group B) whereas randomized osteosynthesis cases were 38 (19 in Group A and 19 in Group B). Mean preoperative Hb value in Group A was 10.8 gm% and in Group B was 10.7 gm% (P > 0.005. Mean postoperative Hb value in Group A was Hb 9.8 gm% and in Group B 9.5 gm% (difference of 3.061%). Mean duration of surgery in Group A was 64.2 min and in Group B was 66.3 min. Mean total blood loss (intraoperative and postoperative) in Group A was 384.6 ml and in Group B was 448.7 ml (14.29% less in Group A). A total of 14 patients in Group A (17 red blood cells [RBCs] units) and 17 patients (21 RBC units) in Group B required RBC transfusion. No major vascular event, severe bacterial infections, symptomatic deep vein thrombosis, pulmonary embolism, limb ischemia, acute coronary syndrome, or immediate postoperative mortality was noted in either group. CONCLUSION: I. V. TXA has the potential to decrease risk of blood transfusion, decrease total blood loss, and to maintain a higher postoperative Hb value with no significant adverse reactions. As the number of cases of hip fractures continues to increase along with increase in age, so the use of TXA in such cases may improve clinical outcomes, lessen number of inpatient days and hence decrease overall cost.

Numb chin syndrome secondary to infiltration of inferior alveolar nerve as a presentation of relapse in treated testicular lymphoma-diagnosis on PET/CT and MR neurography.

Numb chin syndrome (NCS) is a rare presentation of primary or recurrent malignant neoplasms among other non-neoplastic causes. The syndrome is characterized by altered sensations in the distribution of the mental nerve and presents with pain and paresthesias along the distribution of the inferior alveolar nerve and its branches. The primary diagnosis is indicated while following up patients through positron emission tomography/computed tomography (PET/CT) when a hypermetabolic focus is seen in the vicinity of the angle of the mandible. Further anatomical localization is performed using magnetic resonance (MR) neurography and postcontrast MR imaging, which demonstrates neural involvement. We hereby describe a case of a 56-year-old man, a treated case of DLBCL (diffuse large B-cell lymphoma), presenting with NCS and diagnosed with perineural invasion through PET/CT and further MR evaluation. To our knowledge, there are no other reports in the literature describing the MR neurography appearance of the inferior alveolar nerve in NCS. We hereby stress on the use of MR neurography followed by postcontrast 3D sequences with multiplanar reformatting for adequate lesion detection.

A Shepherd's Crook Deformity of Proximal Femur Treated by Valgus Osteotomy and Bone Grafting.

The Shepherd's crook deformity of the proximal femur is a characteristic radiologic feature of fibrous dysplasia. It may be limited to a single bone, which is called monostotic, or may be polyostotic involving multiple bones as seen in McCune-Albright Syndrome. We report a case of a 19-year-old male patient who presented to us with pain in the right hip for one year. He had dysmorphic facies and multiple café-au-lait spots over the back, which were suggestive of McCune-Albright Syndrome. The radiographs of the hip showed varus deformity of the proximal femur. A lateral closing wedge osteotomy was done and the defect was filled with morselised femoral head allografts and fibular strut allografts. At the 14-month follow-up, the patient remained functionally active without any symptoms. The use of morselised femoral head allograft combined with strut fibular allograft ensures both stability and improved biology at the site of the lesion without any donor site morbidity.

Development and Assessment of an Artificial Intelligence-Based Tool for Skin Condition Diagnosis by Primary Care Physicians and Nurse Practitioners in Teledermatology Practices.

Importance: Most dermatologic cases are initially evaluated by nondermatologists such as primary care physicians (PCPs) or nurse practitioners (NPs). Objective: To evaluate an artificial intelligence (AI)-based tool that assists with diagnoses of dermatologic conditions. Design, Setting, and Participants: This multiple-reader, multiple-case diagnostic study developed an AI-based tool and evaluated its utility. Primary care physicians and NPs retrospectively reviewed an enriched set of cases representing 120 different skin conditions. Randomization was used to ensure each clinician reviewed each case either with or without AI assistance; each clinician alternated between batches of 50 cases in each modality. The reviews occurred from February 21 to April 28, 2020. Data were analyzed from May 26, 2020, to January 27, 2021. Exposures: An AI-based assistive tool for interpreting clinical images and associated medical history. Main Outcomes and Measures: The primary analysis evaluated agreement with reference diagnoses provided by a panel of 3 dermatologists for PCPs and NPs. Secondary analyses included diagnostic accuracy for biopsy-confirmed cases, biopsy and referral rates, review time, and diagnostic confidence. Results: Forty board-certified clinicians, including 20 PCPs (14 women [70.0%]; mean experience, 11.3 [range, 2-32] years) and 20 NPs (18 women [90.0%]; mean experience, 13.1 [range, 2-34] years) reviewed 1048 retrospective cases (672 female [64.2%]; median age, 43 [interquartile range, 30-56] years; 41 920 total reviews) from a teledermatology practice serving 11 sites and provided 0 to 5 differential diagnoses per case (mean [SD], 1.6 [0.7]). The PCPs were located across 12 states, and the NPs practiced in primary care without physician supervision across 9 states. The NPs had a mean of 13.1 (range, 2-34) years of experience and practiced in primary care without physician supervision across 9 states. Artificial intelligence assistance was significantly associated with higher agreement with reference diagnoses. For PCPs, the increase in diagnostic agreement was 10% (95% CI, 8%-11%; P < .001), from 48% to 58%; for NPs, the increase was 12% (95% CI, 10%-14%; P < .001), from 46% to 58%. In secondary analyses, agreement with biopsy-obtained diagnosis categories of maglignant, precancerous, or benign increased by 3% (95% CI, -1% to 7%) for PCPs and by 8% (95% CI, 3%-13%) for NPs. Rates of desire for biopsies decreased by 1% (95% CI, 0-3%) for PCPs and 2% (95% CI, 1%-3%) for NPs; the rate of desire for referrals decreased by 3% (95% CI, 1%-4%) for PCPs and NPs. Diagnostic agreement on cases not indicated for a dermatologist referral increased by 10% (95% CI, 8%-12%) for PCPs and 12% (95% CI, 10%-14%) for NPs, and median review time increased slightly by 5 (95% CI, 0-8) seconds for PCPs and 7 (95% CI, 5-10) seconds for NPs per case. Conclusions and Relevance: Artificial intelligence assistance was associated with improved diagnoses by PCPs and NPs for 1 in every 8 to 10 cases, indicating potential for improving the quality of dermatologic care.

Sensory Changes and Postmastectomy Pain Following Preservation of Intercostobrachial Nerve in Breast Cancer Surgery: a Prospective Randomized Study.

Surgery for breast cancer leads to sensory changes and persistent pain in about 20-60% of patients and is usually attributed to section of the intercostobrachial nerve (ICBN). However, the opinion is divided about the benefit of preservation of ICBN. Hence, this study was designed to assess the role of preservation of ICBN on sensory changes and acute and persistent pain following mastectomy. The study was conducted on patients undergoing modified radical mastectomy for breast cancer. At the time of surgery, ICBN was sacrificed in group I (N = 29), and preserved in group II (N = 24). Patients underwent sensory assessment for touch and pain in predefined areas after surgery. They were also assessed for acute post-operative pain and persistent pain (PP) on day 30 and 90 by numeric pain rating scale. PP was also evaluated by douleur neuropathique 4 questionnaire for assessment of its neuropathic character. Preservation of ICBN resulted in significantly better preserved sensation on lateral aspect of mastectomy incision, axilla, and medial aspect of the arm. Frequency and severity of acute post-operative pain were similar between the two groups. However, PP was significantly reduced in ICBN preserved group. At 3 months, 31% patients in group I and 12.5% in group II had clinically significant pain (p = 0.024). DN 4 assessment showed neuropathic character of pain in 20.6% and 8.33% in group I and II respectively. In our study, preservation of ICBN resulted in reduced rates of sensory loss and persistent neuropathic pain.

A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells.

The study was aimed at developing an accessible laboratory animal model to elucidate protective and pathological roles of immune mediators during Peste des petits ruminants virus (PPRV) infection. It is because of the critical roles of type I IFNs in anti-viral defense, we assessed the susceptibility of IFN receptor knock out (IFNR KO) mice to PPRV infection. IFNR KO mice were exceedingly susceptible to the infection but WT animals efficiently controlled PPRV. Accordingly, the PPRV infected IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days irrespective of the dose and route of infection. The lower infecting doses predominantly induced immunopathological lesions. The viral antigens as well as the replicating PPRV were abundantly present in most of the critical organs such as brain, lungs, heart and kidneys of IFNR KO mice infected with high dose of the virus. Neutrophils and macrophages transported the replicating virus to central nervous system (CNS) and contributed to pathology while the elevated NK and T cell responses directly correlated with the resolution of PPRV infection in WT animals. Using an array of fluorescently labeled H-2Kb tetramers, we discovered four immunogenic epitopes of PPRV. The PPRV-peptides interacted well with H-2Kb in acellular and cellular assay as well as expanded the virus-specific CD8+ T cells in immunized or infected mice. Adoptively transferred CD8+ T cells helped control PPRV in infected mice. Our study therefore established and employed a mouse model for investigating the pathogenesis of PPRV. The model could be useful for elucidating the contribution of immune cells in disease progression as well as to test anti-viral agents.