A blueprint for precise and fault-tolerant analog neural networks.

Analog computing has reemerged as a promising avenue for accelerating deep neural networks (DNNs) to overcome the scalability challenges posed by traditional digital architectures. However, achieving high precision using analog technologies is challenging, as high-precision data converters are costly and impractical. In this work, we address this challenge by using the residue number system (RNS) and composing high-precision operations from multiple low-precision operations, thereby eliminating the need for high-precision data converters and information loss. Our study demonstrates that the RNS-based approach can achieve ≥99% FP32 accuracy with 6-bit integer arithmetic for DNN inference and 7-bit for DNN training. The reduced precision requirements imply that using RNS can achieve several orders of magnitude higher energy efficiency while maintaining the same throughput compared to conventional analog hardware with the same precision. We also present a fault-tolerant dataflow using redundant RNS to protect the computation against noise and errors inherent within analog hardware.

Role of surgery along with antimicrobials in refractory skull base osteomyelitis-A prospective observational study.

INTRODUCTION: Study aimed to ole of surgery along with antimicrobials to improve clinical outcomes in treating refractory cases of skull base osteomyelitis (SBO). METHODS: A prospective observational study in a tertiary care centre with 70 SBO patients meeting eligibility criteria. The study population comprised 35 patients refractory to systemic antimicrobials of at least 4 weeks duration who later underwent surgery in addition to medication (surgical group). They were compared with a medical group that responded to medications alone. The outcome variables studied were the resolution of clinical features (pain, discharge, radiology, and inflammatory markers), culture yield, and total duration of treatment. RESULTS: According to our study, relief of pain was faster in the surgical group (1.66 against 4.57 months) with statistical significance (p < 0.001). Relief of symptoms (p < 0.001), radiological improvement (p = 0.001), and normalising of inflammatory markers (p < 0.001) were better in the surgical group than in the medical group. The duration of treatment was an average of 9.2 months in the surgical group compared to 11.3 months in the medical group (p = 0.019). Microbial culture from deep tissue sampling was positive in 24 surgical patients (68.57%). CONCLUSIONS: The treatment response in selected patients of refractory SBO who underwent surgery along with antimicrobials was better than the group who responded to antimicrobials alone. Surgery provided higher microbial yield resulting in culture-specific antimicrobials. The surgical group observed faster relief of symptoms, reduced hospital stay, and total treatment duration.

Surface engineered nanodiamonds: mechanistic intervention in biomedical applications for diagnosis and treatment of cancer.

In terms of biomedical tools, nanodiamonds (ND) are a more recent innovation. Their size typically ranges between 4 to 100 nm. ND are produced via a variety of methods and are known for their physical toughness, durability, and chemical stability. Studies have revealed that surface modifications and functionalization have a significant influence on the optical and electrical properties of the nanomaterial. Consequently, surface functional groups of NDs have applications in a variety of domains, including drug administration, gene delivery, immunotherapy for cancer treatment, and bio-imaging to diagnose cancer. Additionally, their biocompatibility is a critical requisite for theirin vivoandin vitrointerventions. This review delves into these aspects and focuses on the recent advances in surface modification strategies of NDs for various biomedical applications surrounding cancer diagnosis and treatment. Furthermore, the prognosis of its clinical translation has also been discussed.

Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells.

Calcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA-GNR) conjugated glutamic acid developed in the study was used as a nano-bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA-GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.

Porphyrin and doxorubicin mediated nanoarchitectonics of copper clusters: a bimodal theranostics for cancer diagnosis and treatment in vitro.

Nanoarchitectonics, an emerging strategy, presents a promising alternative for developing highly efficient next-generation functional materials. Multifunctional materials developed using nanoarchitectonics help to mimic biological molecules. Porphyrin-based molecules can be effectively utilized to design such assemblies. Metal nanocluster is one of the functional materials that can shed more insight into developing nanoarchitectonic materials. Herein, an inherently near-infrared (NIR) fluorescing copper nanocluster (CuC)-mediated structural assembly via protoporphyrin IX (PPIX) and doxorubicin (Dox) is demonstrated as the functional material. Dox-loaded porphyrin-mediated CuC assembly shows singlet oxygen generation and 66% drug release at 15 min. Furthermore, the efficacy of this material is tested for cancer diagnosis and bimodal therapeutic strategy due to the fluorescing ability of the cluster and loading of PPIX as well as the drug, respectively. The nanoarchitecture exhibits targeted imaging and 83% cell death in HeLa cells upon laser irradiation with 10 nmoles and 20 nmoles of PPIX and Dox, respectively.

Electroconductivity, a regenerative engineering approach to reverse rotator cuff muscle degeneration.

Muscle degeneration is one the main factors that lead to the high rate of retear after a successful repair of rotator cuff (RC) tears. The current surgical practices have failed to treat patients with chronic massive rotator cuff tears (RCTs). Therefore, regenerative engineering approaches are being studied to address the challenges. Recent studies showed the promising outcomes of electroactive materials (EAMs) on the regeneration of electrically excitable tissues such as skeletal muscle. Here, we review the most important biological mechanism of RC muscle degeneration. Further, the review covers the recent studies on EAMs for muscle regeneration including RC muscle. Finally, we will discuss the future direction toward the application of EAMs for the augmentation of RCTs.

Hyaluronic acid-British anti-Lewisite as a safer chelation therapy for the treatment of arthroplasty-related metallosis.

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.

Efficacy of a Novel Electroconductive Matrix To Treat Muscle Atrophy and Fat Accumulation in Chronic Massive Rotator Cuff Tears of the Shoulder.

The high retear rate after a successful repair of the rotator cuff (RC) is a major clinical challenge. Muscle atrophy and fat accumulation of RC muscles over time adversely affect the rate of retear. Since current surgical techniques do not improve muscle degenerative conditions, new treatments are being developed to reduce muscle atrophy and fat accumulation. In the previous study, we have shown the efficacy of aligned electroconductive nanofibrous fabricated by coating poly(3,4-ethylene dioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) nanoparticles onto aligned poly(ε-caprolactone) (PCL) electrospun nanofibers (PEDOT:PSS matrix) to reduce muscle atrophy in acute and subacute models of RC tears (RCTs). In this study, we further evaluated the efficacy of the PEDOT:PSS matrix to reduce muscle atrophy and fat accumulation in a rat model of chronic massive full-thickness RCTs (MRCTs). The matrices were transplanted on the myotendinous junction to the belly of the supraspinatus and infraspinatus muscles at 16 weeks after MRCTs. The biomechanics and histological assessments showed the potential of the PEDOT:PSS matrix to suppress the progression of muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 weeks after MRCTs. We also demonstrated that the PEDOT:PSS matrix implantation significantly improved the tendon morphology and tensile properties compared with current surgical techniques.

COVID-19 vaccine immune response in patients with plasma cell dyscrasia: a systematic review.

Background: Patients with plasma cell dyscrasia are at a higher risk of developing a severe Coronavirus-2019 (COVID-19) infection. Here we present a systematic review of clinical studies focusing on the immune response to the COVID-19 vaccination in patients with plasma cell dyscrasia. Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to utilize the results to improve day-to-day practice. Design: Systematic Review. Methods: Online databases (PubMed, CINAHL, Ovid, and Cochrane) were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Out of 59 studies, nine articles (seven prospective and two retrospective studies) were included in this systematic review. Abstracts, case reports, and case series were excluded. Results: In all nine studies (N = 1429), seroconversion post-vaccination was the primary endpoint. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23% and 95.5%. Among patients on active therapy, lower seroconversion rates were seen on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially in those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S. Conclusion: Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell dyscrasias should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19. Registration: PROSPERO ID: CRD42023404989.

COVID-19 vaccine immune response in patients with plasma cell dyscrasia- a systematic review Background: Patients with plasma cell disorders are at a higher risk of developing a severe coronavirus-19 infection. Here we present a systematic review of clinical studies focusing on the immune response to the coronavirus-19 vaccination in patients with plasma cell dyscrasia. Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to transcribe the results to day-to-day practice. Design: Systematic Review Data sources: PubMed, CINAHL, Ovid, and Cochrane. Methods: Online databases were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Abstracts, case reports, and case series were excluded. Out of 59 studies, nine articles were selected for a systematic review. Results: In all 9 studies (N = 1,429), seroconversion post-vaccination was the primary endpoint that our review assessed. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23 and 95.5%. Amongst patients on active therapy, lower seroconversion rates were seen in patients on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S. Conclusion: Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell disorders should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19.

COVID-Somnia: A Multicentric Study on Sleep Disturbances During the COVID-19 Pandemic With Spatial Mapping of Hotspots.

Objective The purpose of this study was to document sleep quality and assess its sociodemographic, behavioral (i.e., tobacco use, alcohol use, and screen time), and mental-health-related indicators (i.e., anxiety and depression) in adults aged 30-59 years across three states of India, and to geo-locate state and district-level findings of sleep quality during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Methods From October 2020 to April 2021, residents (aged 30-59 years) of Kerala, Madhya Pradesh, and Delhi completed a web-based survey that included sociodemographic and behavioral factors, clinical history of COVID-19, and mental health screening instruments for anxiety and depression, namely the Generalized Anxiety Disorder 2-item (GAD-2) and Patient Health Questionnaire-2 (PHQ-2). The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the quality of sleep. Average PSQI scores were geo-mapped. Results Of the 694 participants who responded, 647 completed the PSQI. The mean (SD) global PSQI score was 5.99 (3.2), with approximately 54% of participants reporting poor sleep quality (PSQI Score>5). Eight hotspot districts with severe sleep disturbances (mean score PSQI>6.5) were identified. Multivariable logistic regression analysis showed that compared to Madhya Pradesh, participants from Kerala and Delhi had 62% and 33% lower chances of having poor sleep quality, respectively. Those who screened positive for anxiety had higher odds of having poor sleep quality (adjusted odds ratio {aOR}=2.4, P=0.006*). Conclusion Overall, sleep quality was poor during the early stages of the COVID-19 pandemic (October 2020-April 2021), especially among those who reported high levels of anxiety. Among the three included states, there were differences in sleep quality.

Correction: An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster.

Correction for 'An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster' by Lakshmi V. Nair et al., Dalton Trans., 2016, 45, 11286-11291, https://doi.org/10.1039/C6DT01753C.

Corrosion of Metals During Use in Arthroplasty.

Arthroplasty implants can undergo corrosion at the modular components, trunnion, and hinges, owing to implant material makeup, micromotion, and interaction with body fluid. In this review, various mechanisms of corrosion in arthroplasty were explored with suggestions on means of improvement. We identified 10 methods including pitting, crevice, mechanically assisted crevice corrosion, fretting, fretting initiated crevice corrosion, mechanically assisted taper corrosion, galvanic corrosion, stress/tension, fatigue corrosion, and inflammatory cell induced corrosion. The position of implants on the galvanic series, and their ability to maintain passivation contribute to their longevity in service. Due to the relative motion of arthroplastic components, bio-tribocorrosion may disrupt passive oxide films, and pitting is initiated at interfaces. Thus, corrosion in arthroplasty as an electrochemical phenomenon mainly starts on one spot and progresses in 3 steps: (1) the oxidative dissolution of metal from implant surfaces into the aqueous active environment, releasing cations, (2) the attraction of electrons to the opposite charge created at another point of the implant surface, producing current flow, and (3) the formation of oxides of metal and metal hydroxides deposited as rust at the surface of the implant. Recent innovations in material manufacturing continue to improve the efficiency of arthroplasty; however, the component parts remain susceptible to bio-tribocorrosion. Thus, a complete eradication of corrosion in arthroplasty would require futuristic materials with improvement in recent materials and designs, derived from knowledge of existing retrieved implants, and strategies to provide overall surface finishes that protect against bio-tribocorrosion.

Multi compartmental 3D breast cancer disease model-recapitulating tumor complexity in in-vitro.

Breast cancer is the most common ailment among women. In 2020, it had the highest incidence of any type of cancer. Many Phase II and III anti-cancer drugs fail due to efficacy, durability, and side effects. Thus, accelerated drug screening models must be accurate. In-vivo models have been used for a long time, but delays, inconsistent results, and a greater sense of responsibility among scientists toward wildlife have led to the search for in-vitro alternatives. Stromal components support breast cancer growth and survival. Multi-compartment Transwell models may be handy instruments. Co-culturing breast cancer cells with endothelium and fibroblasts improves modelling. The extracellular matrix (ECM) supports native 3D hydrogels in natural and polymeric forms. 3D Transwell cultured tumor spheroids mimicked in-vivo pathological conditions. Tumor invasion, migration, Trans-endothelial migration, angiogenesis, and spread are studied using comprehensive models. Transwell models can create a cancer niche and conduct high-throughput drug screening, promising future applications. Our comprehensive shows how 3D in-vitro multi compartmental models may be useful in producing breast cancer stroma in Transwell culture.

Unchartered waters: Significance of fall in Ki67 index after short-term preoperative endocrine therapy in early breast cancers.

BACKGROUND: Endocrine treatment for breast cancer acts largely by inhibiting tumor cell proliferation. The biomarker Ki67 is linked to the proliferative index of the tumour. OBJECTIVE: To identify the factors affecting the fall in Ki67 value in early-stage hormone receptor (HR) positive breast cancer patients receiving short-term preoperative endocrine therapy in an Indian cohort. METHODS: Women with hormone receptor positive, invasive, nonmetastatic, and early breast cancer (4 week) did not affect the fall in Ki67. CONCLUSION: Preoperative therapy with Letrozole resulted in a more significant fall in Ki67, as compared to therapy with Tamoxifen. Determining the fall in Ki67 value in response to preoperative endocrine therapy could provide an insight into the response to endocrine therapy in luminal breast cancer.

Ki 67: a Promising Prognostic Marker in Early Breast Cancer-a Review Article.

Ki67 index is considered to be a reliable indicator of the proliferative activity of breast cancer. Additionally, the Ki67 proliferative marker may play a role in assessing response to systemic therapeutic strategies and can act as a prognostic biomarker. But its limited reproducibility which stems from a lack of standardization of procedures, inter-observer variability, and preanalytical and analytical variabilities all have hampered the use of the Ki67 index in clinical practice. Currently, clinical trials have been evaluating Ki67 as a predictive marker for needing adjuvant chemotherapy in luminal early breast cancer patients receiving neoadjuvant endocrine therapy. But the inconsistencies existing in the estimation of the Ki67 index limit the utility of Ki67 in standard clinical practice. The purpose of this review is to evaluate the benefits and drawbacks of utilizing Ki-67 in early-stage breast cancer to prognosticate the disease and predict the risk of recurrence.

Fall in Ki67 Index After Short-Term Preoperative Letrozole: a Gateway to Assess the Response in Hormone-Positive Early Breast Cancers.

Endocrine treatment for breast cancer acts largely by inhibiting tumor cell proliferation. The study aimed to explore the fall in proliferative marker Ki67 in patients receiving preoperative endocrine therapy and the factors associated with it. A prospective series of hormone receptor-positive postmenopausal women with early N0/N1 breast cancer were enrolled. Patients were requested to take letrozole OD while they await surgery. The fall in Ki67 after the endocrine therapy was defined as the percentage of the difference between the pre-and postoperative Ki67 value with the preoperative Ki67. Sixty cases matched the criteria of which 41 (68.3%) of women showed a good response to preoperative letrozole (fall in Ki67 > 50%; p-value < 0.001). The average mean fall in Ki67 was 57.083 ± 37.97. Postoperative Ki67 after the therapy was less than 10% in 39 (65%) patients. Ten patients (16.6%) had a low Ki67 index at baseline, which continued to remain low after preoperative endocrine therapy. The duration of the therapy did not affect the percentage of Ki67 fall in our study. Short-term changes in the Ki67 index in the neoadjuvant settings may predict outcomes during adjuvant use of the same treatment. Proliferation index on residual tumor holds prognostic importance, and our results reflect that greater attention should be given to the percentage of reduction of Ki67, rather than focusing purely on a fixed value. This could help predict patients who respond well to endocrine therapy, while those who respond poorly may require further adjuvant treatment.

Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival.

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.

Infectious Complications After Tocilizumab in Patients with COVID: A Real-World Experience.

Introduction: Controversies remain regarding the safety of tocilizumab in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we seek to describe the infectious complications after tocilizumab in COVID patients and determine the related risk factors. Methods: A single-center retrospective observational study was conducted among adult patients with SARS-CoV-2 infection admitted between 06/01/2020 and 12/31/2021 who received tocilizumab at our institution. Baseline demographics and laboratory values are obtained through reviewing electronic medical records. Risk factors of infectious complications after tocilizumab are identified through regression analysis. Statistics are performed using SPSS. P-value <0.05 is considered statistically significant. Results: Out of the 52 patients identified, infectious complications after tocilizumab were documented in 30 patients (57.7%). The most common infections include pneumonia, urinary tract infections, and bacteremia of unknown sources. Overall mortality was 42.3%. Through multivariate regression analysis, age more than 65, hyperglycemia on admission, and tocilizumab administration more than 2 days after hospital admission are independent risk factors associated with developing infections. Conclusions: In real-world experience, infectious complications are not uncommon in COVID patients who receive tocilizumab. Early use of tocilizumab may be of benefit. More rigorous patient selection and monitoring should be explored in future studies.

Poly(cannabinoid)s: Hemp-Derived Biocompatible Thermoplastic Polyesters with Inherent Antioxidant Properties.

The legalization of hemp cultivation in the United States has caused the price of hemp-derived cannabinoids to decrease 10-fold within 2 years. Cannabidiol (CBD), one of many naturally occurring diols found in hemp, can be purified in high yield for low cost, making it an interesting candidate for polymer feedstock. In this study, two polyesters were synthesized from the condensation of either CBD or cannabigerol (CBG) with adipoyl chloride. Poly(CBD-Adipate) was cast into free-standing films and subjected to thermal, mechanical, and biological characterization. Poly(CBD-Adipate) films exhibited a lack of cytotoxicity toward adipose-derived stem cells while displaying an inherent antioxidant activity compared to poly(lactide) films. Additionally, this material was found to be semi-crystalline and able to be melt-processed into a plastic hemp leaf using a silicone baking mold.