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Elderly and individuals with disabilities can greatly benefit from human activity recognition (HAR) systems, which have recently advanced significantly due to the integration of the Internet of Things (IoT) and artificial intelligence (AI). The blending of IoT and AI methodologies into HAR systems has the potential to enable these populations to lead more autonomous and comfortable lives. HAR systems are equipped with various sensors, including motion capture sensors, microcontrollers, and transceivers, which supply data to assorted AI and machine learning (ML) algorithms for subsequent analyses. Despite the substantial advantages of this integration, current frameworks encounter significant challenges related to computational overhead, which arises from the complexity of AI and ML algorithms. This article introduces a novel ensemble of gated recurrent networks (GRN) and deep extreme feedforward neural networks (DEFNN), with hyperparameters optimized through the artificial water drop optimization (AWDO) algorithm. This framework leverages GRN for effective feature extraction, subsequently utilized by DEFNN for accurately classifying HAR data. Additionally, AWDO is employed within DEFNN to adjust hyperparameters, thereby mitigating computational overhead and enhancing detection efficiency. Extensive experiments were conducted to verify the proposed methodology using real-time datasets gathered from IoT testbeds, which employ NodeMCU units interfaced with Wi-Fi transceivers. The framework's efficiency was assessed using several metrics: accuracy at 99.5%, precision at 98%, recall at 97%, specificity at 98%, and F1-score of 98.2%. These results then were benchmarked against other contemporary deep learning (DL)-based HAR systems. The experimental outcomes indicate that our model achieves near-perfect accuracy, surpassing alternative learning-based HAR systems. Moreover, our model demonstrates reduced computational demands compared to preceding algorithms, suggesting that the proposed framework may offer superior efficacy and compatibility for deployment in HAR systems designed for elderly or individuals with disabilities.

Diabetic Retinopathy (DR) is a serious eye condition that occurs due to high blood sugar levels in patients with Diabetes Mellitus. If left untreated, DR can potentially result in blindness. Using automated neural network-based methods to grade DR shows potential for early detection. However, the uneven and non-quadrilateral forms of DR lesions provide difficulties for traditional Convolutional Neural Network (CNN)-based architectures. To address this challenge and explore a novel algorithm architecture, this work delves into the usage of contrasting cluster assignments in retinal fundus images with the Swapping Assignments between multiple Views (SwAV) algorithm for DR grading. An ablation study was made where SwAV outperformed other CNN and Transformer-based models, independently and in ensemble configurations with an accuracy of 87.00% despite having fewer parameters and layers. The proposed approach outperforms existing state-of-the-art models regarding classification metrics, complexity, and prediction time. The findings offer great potential for medical practitioners, allowing for more accurate diagnosis of DR and earlier treatments to avoid visual loss.

A novel technique for electronic control unit (ECU) identification is proposed in this study to address security vulnerabilities of the controller area network (CAN) protocol. The reliable ECU identification has the potential to prevent spoofing attacks launched over the CAN due to the lack of message authentication. In this regard, we model the ECU-specific random distortion caused by the imperfections in the digital-to-analog converter and semiconductor impurities in the transmitting ECU for fingerprinting. Afterward, a 4-layered artificial neural network (ANN) is trained on the feature set to identify the transmitting ECU and the corresponding ECU pin. The ECU-pin identification is also a novel contribution of this study and can be used to prevent voltage-based attacks. We have evaluated our method using ANNs over a dataset generated from 7 ECUs with 6 pins, each having 185 records, and 40 records for each pin. The performance evaluation against state-of-the-art methods revealed that the proposed method achieved 99.4% accuracy for ECU identification and 96.7% accuracy for pin identification, which signifies the reliability of the proposed approach.

Elderly and individuals with disabilities can greatly benefit from human activity recognition (HAR) systems, which have recently advanced significantly due to the integration of the Internet of Things (IoT) and artificial intelligence (AI). The blending of IoT and AI methodologies into HAR systems has the potential to enable these populations to lead more autonomous and comfortable lives. HAR systems are equipped with various sensors, including motion capture sensors, microcontrollers, and transceivers, which supply data to assorted AI and machine learning (ML) algorithms for subsequent analyses. Despite the substantial advantages of this integration, current frameworks encounter significant challenges related to computational overhead, which arises from the complexity of AI and ML algorithms. This article introduces a novel ensemble of gated recurrent networks (GRN) and deep extreme feedforward neural networks (DEFNN), with hyperparameters optimized through the artificial water drop optimization (AWDO) algorithm. This framework leverages GRN for effective feature extraction, subsequently utilized by DEFNN for accurately classifying HAR data. Additionally, AWDO is employed within DEFNN to adjust hyperparameters, thereby mitigating computational overhead and enhancing detection efficiency. Extensive experiments were conducted to verify the proposed methodology using real-time datasets gathered from IoT testbeds, which employ NodeMCU units interfaced with Wi-Fi transceivers. The framework's efficiency was assessed using several metrics: accuracy at 99.5%, precision at 98%, recall at 97%, specificity at 98%, and F1-score of 98.2%. These results then were benchmarked against other contemporary deep learning (DL)-based HAR systems. The experimental outcomes indicate that our model achieves near-perfect accuracy, surpassing alternative learning-based HAR systems. Moreover, our model demonstrates reduced computational demands compared to preceding algorithms, suggesting that the proposed framework may offer superior efficacy and compatibility for deployment in HAR systems designed for elderly or individuals with disabilities. [ABSTRACT FROM AUTHOR]

The surface characteristics of scaffolds utilized in bone tissue engineering profoundly influence subsequent cellular response. This study investigated the efficacy of applying a gelatin coat to the surface of aminolysis surface-modified scaffolds fabricated through 3D printing with a polycaprolactone/hydroxyapatite nanocomposite, employing the hot-melt extrusion FDM technique. Initially, aminolysis surface modification using hexamethylenediamine enhanced surface hydrophilicity by introducing amine functional groups. Subsequently, gelatin solutions were applied to the scaffolds, and crosslinking with EDC/NHS was performed to increase coating strength. Contact angle measurements revealed a significantly increased surface hydrophilicity post-aminolysis. Aminolysis facilitated uniform gelatin coating formation and distribution. Subsequently, crosslinking enhanced coating durability. The addition of gelatin coating resulted in a notable 20 % increase in scaffold mechanical strength and more than 50 % rise in Young's modulus and exhibited enhancement of biodegradability and bioactivity. Gelatin coated scaffolds also demonstrated improved cell viability and adhesion and over two times higher expression of OPN and ALP genes, suggesting improved biological properties. In addition, in vivo bone formation studies verified the biological enhancement of scaffolds. Utilizing an immobilized crosslinked gelatin biomacromolecule coating effectively enhanced the biological characteristics of 3D printed scaffolds and their potential applications as bone tissue engineering scaffolds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Diabetic Retinopathy (DR) is a serious eye condition that occurs due to high blood sugar levels in patients with Diabetes Mellitus. If left untreated, DR can potentially result in blindness. Using automated neural network-based methods to grade DR shows potential for early detection. However, the uneven and non-quadrilateral forms of DR lesions provide difficulties for traditional Convolutional Neural Network (CNN)-based architectures. To address this challenge and explore a novel algorithm architecture, this work delves into the usage of contrasting cluster assignments in retinal fundus images with the Swapping Assignments between multiple Views (SwAV) algorithm for DR grading. An ablation study was made where SwAV outperformed other CNN and Transformer-based models, independently and in ensemble configurations with an accuracy of 87.00% despite having fewer parameters and layers. The proposed approach outperforms existing state-of-the-art models regarding classification metrics, complexity, and prediction time. The findings offer great potential for medical practitioners, allowing for more accurate diagnosis of DR and earlier treatments to avoid visual loss. [ABSTRACT FROM AUTHOR]

Background: Fampridine is the only drug approved by the US Food and Drug Administration (FDA) for people with multiple sclerosis (MS) to improve their movement and has exhibited a clinically significant improvement in gait function in a subset of MS patients with Expanded Disability Status Scale (ESDSS) from 4 to 7. Nevertheless, this drug has been reported to possess some adverse effects (AEs) like seizure because of its pharmacological features. The aim of this study was to evaluate the incidence rate of post-medication side effects (SEs) of fampridine in MS patients., Methods: This prospective cohort study includes MS patients aged between 18 and 65 years, referred to the neurology clinic of Kashani Hospital from April 2022 to October 2022, all with administration of fampridine (10 mg tablet twice daily according to the product specifications). Safety in these patients was monitored through monthly SEs checklist questions during 6 months of screening. SPSS version 18 was used to analyze the data of this study., Results: From 319 participants screened at baseline, 254 patients with MS, including 127 relapsing-remitting multiple sclerosis (RRMS), 101 secondary progressive multiple sclerosis (SPMS), and 26 primary progressive multiple sclerosis (PPMS), were included in the study. The most observed AEs in SPMS and RRMS patients were dry mouth (13.9% vs. 15%) and insomnia (12.9% vs. 11%), respectively. Urinary tract infection (UTI) (11.5%) and stomachache (11.5%) were the most common SEs in PPMS patients. The most severe complication of the patients was back pain, while digestive complications were less severe. Also, insomnia and UTI were the patients' most persistent SEs., Conclusions: The drug seems to be safe and well tolerated, as the SEs were mild and transient and they were consistent with most of the previous studies focusing on this medication., Competing Interests: There are no conflicts of interest., (Copyright: © 2025 International Journal of Preventive Medicine.)

This paper summarizes the information technology-related research findings after 5 years with the INTROducing Mental health through Adaptive Technology project. The aim was to improve mental healthcare by introducing new technologies for adaptive interventions in mental healthcare through interdisciplinary research and development. We focus on the challenges related to internet-delivered psychological treatments, emphasising artificial intelligence, human-computer interaction, and software engineering. We present the main research findings, the developed artefacts, and lessons learned from the project before outlining directions for future research. The main findings from this project are encapsulated in a reference architecture that is used for establishing an infrastructure for adaptive internet-delivered psychological treatment systems in clinical contexts. The infrastructure is developed by introducing an interdisciplinary design and development process inspired by domain-driven design, user-centred design, and the person based approach for intervention design. The process aligns the software development with the intervention design and illustrates their mutual dependencies. Finally, we present software artefacts produced within the project and discuss how they are related to the proposed reference architecture. Our results indicate that the proposed development process, the reference architecture and the produced software can be practical means of designing adaptive mental health care treatments in correspondence with the patients’ needs and preferences. In summary, we have created the initial version of an information technology infrastructure to support the development and deployment of Internet-delivered mental health interventions with inherent support for data sharing, data analysis, reusability of treatment content, and adaptation of intervention based on user needs and preferences.

With recent advances in the field of sensing, it has become possible to build better assistive technologies. This enables the strengthening of eldercare with regard to daily routines and the provision of personalised care to users. For instance, it is possible to detect a person’s behaviour based on wearable or ambient sensors; however, it is difficult for users to wear devices 24/7, as they would have to be recharged regularly because of their energy consumption. Similarly, although cameras have been widely used as ambient sensors, they carry the risk of breaching users’ privacy. This paper presents a novel sensing approach based on deep learning for human activity recognition using a non-wearable ultra-wideband (UWB) radar sensor. UWB sensors protect privacy better than RGB cameras because they do not collect visual data. In this study, UWB sensors were mounted on a mobile robot to monitor and observe subjects from a specific distance (namely, 1.5–2.0 m). Initially, data were collected in a lab environment for five different human activities. Subsequently, the data were used to train a model using the state-of-the-art deep learning approach, namely long short-term memory (LSTM). Conventional training approaches were also tested to validate the superiority of LSTM. As a UWB sensor collects many data points in a single frame, enhanced discriminant analysis was used to reduce the dimensions of the features through application of principal component analysis to the raw dataset, followed by linear discriminant analysis. The enhanced discriminant features were fed into the LSTMs. Finally, the trained model was tested using new inputs. The proposed LSTM-based activity recognition approach performed better than conventional approaches, with an accuracy of 99.6%. We applied 5-fold cross-validation to test our approach. We also validated our approach on publically available dataset. The proposed method can be applied in many prominent fields, including human–robot interaction for various practical applications, such as mobile robots for eldercare.

Purpose: To present to and inform the practitioner of an unusual presentation of Varicella zoster virus and Ramsay-Hunt Syndrome. Observations: A 69-year-old bedbound male with vascular dementia presented to the emergency room with a red right eye with associated tearing and mucus production. The patient could not express if he was in pain. The initial diagnosis from the emergency room was bacterial keratitis, confirmed with a positive pseudomonas culture. However, upon examination by the ophthalmologist it was noted that there was not only a large, infected epithelial defect, but also an intraocular pressure of 35 and a candy-cane hypopyon. The diagnosis of herpes neurotrophic keratitis and iridocyclitis was made and the patient was started on intravenous acyclovir along with the appropriate topical medications. A day later, it was noted that the patient developed a right sided facial palsy and vesicular lesions inside the right ear canal, as confirmed by otolaryngology. Conclusion and Importance: Ramsay-Hunt Syndrome is usually known to the ophthalmologist due to the exposure keratopathy caused by facial palsy. This case demonstrates varicella-zoster virus (VZV) neurotrophic keratitis preceding the development of facial palsy, which can further exacerbate an already neurotrophic cornea. The practitioner should be aware of these signs and symptoms and adjust their treatment with systemic acyclovir-prednisone.

Emerging highly pathogenic viruses can pose profound impacts on global health, the economy, and society. To meet that challenge, the National Institute of Allergy and Infectious Diseases (NIAID) established nine Antiviral Drug Discovery (AViDD) centers for early-stage identification and validation of novel antiviral drug candidates against viruses with pandemic potential. As part of this initiative, we established paired entry assays that simultaneously screen for inhibitors specifically targeting SARS-CoV-2 (SARS2), Lassa virus (LASV) and Machupo virus (MACV) entry. To do so we employed a dual pseudotyped virus (PV) infection system allowing us to screen ∼650,000 compounds efficiently and cost-effectively. Adaptation of these paired assays into 1536 well-plate format for ultra-high throughput screening (uHTS) resulted in the largest screening ever conducted in our facility, with over 2.4 million wells completed. The paired infection system allowed us to detect two PV infections simultaneously: LASV + MACV, MACV + SARS2, and SARS2 + LASV. Each PV contains a different luciferase reporter gene which enabled us to measure the infection of each PV exclusively, albeit in the same well. Each PV was screened at least twice utilizing different reporters, which allowed us to select the inhibitors specific to a particular PV and to exclude those that hit off targets, including cellular components or the reporter proteins. All assays were robust with an average Z' value ranging from 0.5 to 0.8. The primary screening of ∼650,000 compounds resulted in 1812, 1506, and 2586 unique hits for LASV, MACV, and SARS2, respectively. The confirmation screening narrowed this list further to 60, 40, and 90 compounds that are unique to LASV, MACV, and SARS2, respectively. Of these compounds, 8, 35, and 50 compounds showed IC 50 value < 10 μM, some of which have much greater potency and excellent antiviral activity profiles specific to LASV, MACV, and SARS2, and none are cytotoxic. These selected compounds are currently being studied for their mechanism of action and to improve their specificity and potency through chemical modification., Competing Interests: Declaration of competing interest The are no conflicts of interest amongst any of the authors and the work pertained in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Functional near-infrared spectroscopy (fNIRS) is a comparatively new noninvasive, portable, and easy-to-use brain imaging modality. However, complicated dexterous tasks such as individual finger-tapping, particularly using one hand, have been not investigated using fNIRS technology. Twenty-four healthy volunteers participated in the individual finger-tapping experiment. Data were acquired from the motor cortex using sixteen sources and sixteen detectors. In this preliminary study, we applied standard fNIRS data processing pipeline, i.e., optical densities conversation, signal processing, feature extraction, and classification algorithm implementation. Physiological and non-physiological noise is removed using 4th order band-pass Butter-worth and 3rd order Savitzky–Golay filters. Eight spatial statistical features were selected: signal-mean, peak, minimum, Skewness, Kurtosis, variance, median, and peak-to-peak form data of oxygenated haemoglobin changes. Sophisticated machine learning algorithms were applied, such as support vector machine (SVM), random forests (RF), decision trees (DT), AdaBoost, quadratic discriminant analysis (QDA), Artificial neural networks (ANN), k-nearest neighbors (kNN), and extreme gradient boosting (XGBoost). The average classification accuracies achieved were 0.75±0.04, 0.75±0.05, and 0.77±0.06 using k-nearest neighbors (kNN), Random forest (RF) and XGBoost, respectively. KNN, RF and XGBoost classifiers performed exceptionally well on such a high-class problem. The results need to be further investigated. In the future, a more in-depth analysis of the signal in both temporal and spatial domains will be conducted to investigate the underlying facts. The accuracies achieved are promising results and could open up a new research direction leading to enrichment of control commands generation for fNIRS-based brain-computer interface applications.

Many human proteins have been repurposed as biologics for clinical use. These proteins have been engineered with in vitro techniques that improve affinity for their ligands. However, these approaches do not select against properties that impair efficacy such as protease sensitivity or self-reactivity. Here we engineer the B-cell receptor of primary murine B cells to express a human protein biologic without disrupting their ability to affinity mature. Specifically, CD4 domains 1 and 2 (D1D2) of a half-life enhanced-HIV-1 entry inhibitor CD4-Ig (CD4-Ig-v0) were introduced into the heavy-chain loci of murine B cells, which were then adoptively transferred to wild-type mice. After immunization, transferred B cells proliferated, class switched, affinity matured, and efficiently produced D1D2-presenting antibodies. Somatic hypermutations found in the D1D2-encoding region of engrafted B cells improved binding affinity of CD4-Ig-v0 for the HIV-1 envelope glycoprotein (Env) and the neutralization potency of CD4-Ig-v0 by more than ten-fold across a global panel of HIV-1 isolates, without impairing its pharmacokinetic properties. Thus, affinity maturation of non-antibody protein biologics in vivo can guide development of more effective therapeutics., Competing Interests: COMPETING INTEREST A.P., W.H., T.O., Y.Y. and M.F. are inventors of a pending patent describing the in vivo affinity maturation of antibodies and biologics. C.C.B., M.D.A., and M.F. have equity stakes in Emmune, Inc., which developed CD4-Ig-v0. The authors have no other competing interests.

Ab initio quantum mechanical models can characterize and predict intermolecular binding, but only recently have models including more than a few hundred atoms gained traction. Here, we simulate the electronic structure for approximately 13 000 atoms to predict and characterize binding of SARS-CoV-2 spike variants to the human ACE2 (hACE2) receptor using the quantum mechanics complexity reduction (QM-CR) approach. We compare four spike variants in our analysis: Wuhan, Omicron, and two Omicron-based variants. To assess binding, we mechanistically characterize the energetic contribution of each amino acid involved, and predict the effect of select single amino acid mutations. We validate our computational predictions experimentally by comparing the efficacy of spike variants binding to cells expressing hACE2. At the time we performed our simulations (December 2021), the mutation A484K which our model predicted to be highly beneficial to ACE2 binding had not been identified in epidemiological surveys; only recently (August 2023) has it appeared in variant BA.2.86. We argue that our computational model, QM-CR, can identify mutations critical for intermolecular interactions and inform the engineering of high-specificity interactors.

Background: Carpal tunnel syndrome is the most common focal neuropathy that results from pressure on a nerve. The goal of this study was to assess carpal tunnel syndrome and its associated factors such as occupation, sex, and accompanying complications in a teaching general hospital. Methods: This cross-sectional study investigated 362 patients with the diagnosis of carpal tunnel syndrome admitted in the orthopedic ward of Imam Khomeini Hospital affiliated to Tehran University of Medical Sciences in Tehran, Iran during 2000-2010. Results: The difference in the mean age of men and women was statistically significant (P

Background: Syndactyly is the most common congenital malformation of the hand, with an incidence of 1 in 2000-2500 live births. In this study we evaluated the surgical outcomes and complications of patients with syndactyly.Methods : The surgical outcomes and complications of 42 patients, 27 male and 15, female, undergoing surgery for syndactyly were evaluated. The study took place in Imam Khomeini Hospital, in Tehran, Iran during 1996 to 2011. Having had the inclusion criteria, the patients were assessed for function, cosmetic outcome, sensation and occurrence of complications. The patients were followed-up for at least 3 years.Results : The mean age of patients was 4.4 years. There was a positive familial history for the disease in 8 patients. 71.4%, 90.4% and 73.8% of the participants had good results regarding cosmetic outcome, sensation and function, respectively.Conclusion: The overall results of surgery for syndactyly in this study were interpreted as good in 78.5%, moderate in 12.5% and fair in 8.4% of the patients. This study confirmed better surgical outcomes in patients older than 18 months.

"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Nerve entrapment neuropathies are relatively frequent in the upper limb. Significant costs related to resultant disability and treatment, and also simultaneous occurrence of some of these syndromes can result in alteration in the treatment approach. The aim of this study was to evaluate the frequency of these syndromes, the rate of concurrence of carpal tunnel syndrome as the most prevalent syndrome with others, related risk factors, and accordance of clinical and electrophysiological findings."n"nMethods: In a retrospective study, data of the 170 affected patients to these syndromes operated during a period of 10 years in a referral center were searched using recorded documents. Information about patient's gender, age, occupation and associated co-morbidities, clinical and surgical findings and their accordance to the EMG-NCV findings, and also concurrence of these syndromes were assessed."n"nResults: Patients' range of age was 10-91 year (mean: 48.09 year) and 74.5% of them were female. In this study carpal tunnel and cubital tunnel syndrome were the most frequent (81.7% and 15.8% respectively). In 23.5% of patients with carpal tunnel syndrome, electrophysiological findings were negative but there was no false positive result. Concurrent carpal tunnel syndrome with other syndromes were found in three cases of cubital tunnel syndrome, two cases of thoracic outlet syndrome and one case of Guyon's canal syndrome."n"nConclusion: Constellation of symptoms, physical examination and electrophysiologic-al findings altogether should be considered for correct diagnosis of nerve entrapment syndromes in the upper extremity. Simultaneous entrapment in the other regions of the same nerve or other nerves in the same extremity is a probable condition

Background: Ulnar club hand (ulnar deficiency) is a rare congenital disorder of the upper extremity. In the Flatt series among 2758 congenital disorders of upper extremity only 28 cases of ulnar deficiency were reported. Due to its rarity and variations in presentation current data in the management of the deformity is very limited. Here we present our experience and results in comparing management of ulnar deficiency.Methods: We include all of the ulnar club hand patients (five boys and one girl with seven involved extremities) from 1993 to 2006. After recognizing the type of deformity the classic management approach was performed that was splinting in corrective position until six months of age and then anlage resection. Syndactyly release was done in appropriate age according to involved rays, other operations for restoration of apposition was done after 18 months of age. Two of our patients were neglected, the first one was a 12 years old boy without any ulnar deviation but with syndactyly of the remaining rays and the other was a 32 years old male with severe ulnar deviation and partial syndactyly who is a skillful worker. We determined the effect of anlage resection on ulnar deviation of the wrist and restoration of opposition and syndactyly release on function of the limb.Results: In short term follow up, anlage resection was effective in prevention and correction of ulnar deviation, however the deformity was partially recurred later. Surprisingly, the function of the limb was not significantly affected with the extent of the deformity. On the other hand, the operations used for opposition of the thumb like first metacarpal rotational osteotomies and tendon transfers for powerful opposition, were more effective in the hand and also limb function compared with anlage resection alone. Conclusions: Due to our observation of the neglected cases, the most important factor in the function of the hand is the function of the thumb, thus we believe that restoration of opposition and syndactyly release may be more effective than anlage resection on limb function in Ulnar Club Hand patients

CRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3'-most J segments and 5' homology arms complementary to distal V segments. Cells edited in this way to express the HIV-1 broadly neutralizing antibodies 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated recipient mice. 10-1074 variants isolated from these mice bound and neutralized HIV-1 envelope glycoprotein more efficiently than wild-type 10-1074 while maintaining or improving its already low polyreactivity and long in vivo half-life. We further validated this approach by generating substantially broader and more potent variants of the anti-SARS-CoV-2 antibodies ZCB11 and S309. Thus, B cells edited at their native loci affinity mature, facilitating development of broad, potent, and bioavailable antibodies and expanding the potential applications of engineered B cells., Competing Interests: Competing interests Y.Y., W.H., T.O., and M.F. are inventors on a pending patent application describing methods for editing B cells. The other authors declare no competing interests.

During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components are distinct. Here, we compared the effect of ionizable lipids, untranslated regions (UTRs), and nucleotide composition of the two vaccines, focusing on mRNA delivery, antibody generation, and long-term stability. We found that the ionizable lipid, SM-102, in Moderna's vaccine performs better than ALC-0315 in Pfizer-BioNTech's vaccine for intramuscular delivery of mRNA and antibody production in mice and long-term stability at 4 °C. Moreover, Pfizer-BioNTech's 5' UTR and Moderna's 3' UTR outperform their counterparts in their contribution to transgene expression in mice. We further found that varying N1-methylpseudouridine content at the wobble position of mRNA has little effect on vaccine efficacy. These findings may contribute to the further improvement of nucleoside-modified mRNA-LNP vaccines and therapeutics., (© 2023. Springer Nature Limited.)

V2-glycan/apex broadly neutralizing antibodies (bnAbs) recognize a closed quaternary epitope of the HIV-1 envelope glycoprotein (Env). This closed structure is necessary to elicit apex antibodies and useful to guide the maturation of other bnAb classes. To compare antigens designed to maintain this conformation, we evaluated apex-specific responses in mice engrafted with a diverse repertoire of B cells expressing the HCDR3 of the apex bnAb VRC26.25. Engineered B cells affinity matured, guiding the improvement of VRC26.25 itself. We found that soluble Env (SOSIP) variants differed significantly in their ability to raise anti-apex responses. A transmembrane SOSIP (SOSIP-TM) delivered as an mRNA-lipid nanoparticle elicited more potent neutralizing responses than multimerized SOSIP proteins. Importantly, SOSIP-TM elicited neutralizing sera from B cells engineered with the predicted VRC26.25-HCDR3 progenitor, which also affinity matured. Our data show that HCDR3-edited B cells facilitate efficient in vivo comparisons of Env antigens and highlight the potential of an HCDR3-focused vaccine approach., Competing Interests: Declaration of interests W.H., T.O., Y.Y., and M.F. are inventors on a pending patent application describing methods for editing B cells., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Pigmented villonodular synovitis is a tumor that arises from the synovial membrane of the joint or tendon sheaths. Two main forms include a diffuse form that involves the whole synovial lining of a joint, bursa, or tendon sheath, and a less common localized form. The diffuse form typically involves the large joints, while the localized one typically occurs around the small joints of the hands and feet. Usually involving the knee joint, the occurrence of pigmented villonodular synovitis in the foot, especially in the metatarsophalangeal joint of the great toe, is very rare, and is therefore often mistaken for other foot pathologies. Although it seems histopathologically benign, it has a known tendency to recur after surgery.Case report: Here, we report a 42 year old woman who had experienced pain in the right great toe for 1.5 years. She was treated conservatively with shoe modification and NonSteroidal Anti-Inflammatory Drugs, and two injections of Corticosteroid.Results: The failure of long-term conservative therapy and the bony erosion revealed in her radiograph led us to surgically excise the lesion of the first metatarsophalangeal joint. Histopathological examination revealed the diagnosis of pigmented villonodular synovitis. For the 18 months following surgery, she had no complaint except minimal pain in her toe after activity. No sign of recurrence was observed either clinically or radiologically.Conclusion: We conclude that pigmented villonodular synovitis should be noted in the differential diagnosis of chronic monoarticular synovitis in order to provide an earlier diagnosis and more effective treatment.

Cancer has been become threatening the health and life of humans. Therefore, attempt to discovery more effective anticancer agents continue. Thiadiazole derivatives have been shown remarkable effects among chemotherapeutic agents. In this study, hybrid molecules containing thiadiazole amide derivatives -aromatic amines (anthranilic acid and 2, 5 dichloro aniline) were synthesized in multi-step reactions including Namidation and S-alkylation of thiadiazole. Synthesized compounds were assayed by MTT test against three cell lines. Molecular docking was performed on Src tyrosine kinases. Compounds 5a, 5b and 8 rendered remarkable cytotoxic properties on HeLa with IC50‹ 60 µM. Compound 5b showed significant cytotoxic effect on both cancer cell lines compared to other tested derivatives. Compound 5a with ΔG = -8.05kcal/mol was the best compound among docked compounds.The results revealed that the quiddity of the amide substitution has a definitive role in the cytotoxic activity. [ABSTRACT FROM AUTHOR]

Introduction: Subacute thyroiditis (SAT) is an inflammatory disease that has different trigger factors. Recent studies show the possible role of COVID-19 vaccine-induced thyroiditis in its initiation. Herein we report the first case of post-Sputnik V vaccination SAT., Case Presentation: A 42-year-old man without any specific disease was admitted due to tremors, palpation and sweating, and neck tenderness on the thyroid gland. Laboratory markers and radiologic assessments highlighted thyroiditis for him, and his symptoms were relieved by administering NSAIDs and corticosteroids., Discussion: There are several hypotheses for the etiology of post-COVID-19 immunization SAT; among them, immunologic reactions like the interactivity of human proteome with viral components and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are more probable than other discussed possibilities. We suggest further studies to discover the exact SAT pathophysiology to prevent the underlying causes among future vaccine candidates., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: In this study we evaluated the treatment of giant cell tumor (GCT) of long bones using cryosurgery combined with curettage and polymethylmetacrylate (PMMA) cementing. Material and methods: From January 1999 to December 2004, twenty patients (mean age at the time of surgery 29.2 years); 13 females and 7 males; were included in the study. Cortical disruption were presented in 7 patients; 4 with soft tissue extension, but none of them had intra-articular extension of tumor, 3 patients presented with pathologic fracture of distal femoral lesions. These tumors were located in distal femur in 6 patients, proximal tibia in 7, distal radius in 3, proximal femur in 2, and each of proximal humerus and distal ulna in one patient. In each case diagnostic biopsy was done and surgical procedure performed including curettage, power burr of the wall, cryosurgery with liquid nitrogen and finally filling the space with PMMA cementing. The mean follow-up was 34 months (7 to 61 ). Results: During follow-up, we observed one recurrence of GCT of proximal tibia. Secondary Aneurysmal bone cyst was reported at the site of one primary distal femoral lesion, without any finding in favor of a recurrence. Neurapraxia of the proneal nerve was occurred in one patient with proximal tibia tumor improved after 8 months. Conclusion: Cryosurgery combined with power burr and PMMA cementing in the treatment of GCT could be an effective approach in tumor eradication. This method obviates the need for extensive resections and reconstructive procedure.

Conclusion: Despite the long history of surgical treatment in syndactyly repair, this reconstructive operation has still special complexities. Materials and Methods: In order to evaluation of results of our surgical reconstructions, we studied 77 patients (40 boys and 37 girls) with hand syndactyly (mean age at operation: 5.8±4.3 years) in Imam Khomeini Hospital from 1994 to 2003. All of these patients had been operated by standard surgical methods. Post-operative complications and functional, sensational, and cosmetic results have been assessed by patient records and physical examination after an average follow-up of 4.6±2.1 years. Results: Syndactylies were simple in 71 patients (92.2%), complex in 2 (2.6%), and mixed in 4 (5.2%). In 45 patients (58.4%), surgical repair had been performed without graft. The overall results of operations were good in 81.8%, moderate in 13%, and poor in 5.2%. The most common complications were: web migration in 9.1%, scar contracture in 7.8%, infection in 5.2%, necrosis in 3.9%, and angular deformity in 2.6%. Conclusion: In this study we shown that the standard methods in our center for correction of syndactyly, at least in recent 10 years, have been efficient and with good results.

The majority of osseous tumors of the hand are benign. The surgeon who evaluates and treats osseous tumors of the hand has to be familiar with limb anatomy, tumor biology, various presentations of the tumors and the range of treatment possibilities and their limitations. Lesions in the hand more often present earlier in their course than those at other sites, just because they are more likely to superficial and easily noticed. A review of all cases of osseous tumors of the hand, seen by a hand surgeon over the last 10 years, at Imam Khomeini hospital was performed. Among 55 cases with osseous tumors of hand, 48 primary benign bone tumors, 3 primary malignant bone tumors, and 4 metastatic bone tumors were found. Enchondroma was the most common benign bone tumor followed by osteoid osteoma, osteoblastoma, aneurismal bone cyst, giant cell tumor, epidermoid cyst, and osteochondroma. There were two chondrosarcoma and one Ewing’s sarcoma as primary malignant bone tumors. Metastasis to the hand from colon, esophagus, and breast were also found. There were also two cases with Brown tumor secondary to hyperparathyroidism, we conclude that a variety of osseous tumors could occur in the hand, and usually they are benign. Although malignant neoplasms in the hand that arise from tissues other than the skin are very rare, the hand may be the site of distant breast, lung, kidney, esophagus, or colon adenocarcinoma metastases, most of which have a predilection for the distal phalanges.

Background: Osteoid osteoma is a well-known benign tumor of bone. It occurs in children and young adults and is rarely seen above the age of 40. It is uncommon in hand and wrist. If it occurs in hand and wrist, its diagnosis is difficult because of its unusual presentations both clinically and radiologically. Materials and Methods: We encountered ten patients with osteoid osteoma of hand during the last ten years in orthopedic department of Emam university hospital from 1970 to 1979. Results: The average age of ten patients with osteoid osteoma of the hand and wrist that were treated in Imam hospital from 1369 to 1378, was 22.9 years (range, 14 to 33 years). Five lesions were in proximal phalanx, one in middle phalanx, and one in distal phalanx. In the wrist, one lesion was in the capitate, one in the lunate, and one in the hamate. The average time from onset of symptoms to successful treatment was 20 months (range, 4 months to 60 months). Three of ten patients had had treatment elsewhere, all of them had had unsuccessful operative procedures related to incorrect diagnosis. All patients had a minimum follow-up of 6 months (range, 6 months to 9 years, mean: 4.6 years). The operative treatment were successful in all ten patients without any signs or symptoms of recurrence. Only limitation of proximal interphalangeal joint range of motion was remained in one patient due to 60 months delay in diagnosis and treatment. Conclusion: High index of suspicion is necessary for diagnosis of osteoid osteoma of hand because of unusual presentation of it. The most important factors for successful treatment of osteoid osteoma of hand are accurate diagnosis and exact preoperative planning.

During the last 10 years, we have had 11 cases of radioulnar (RU) synostosis, a very rare congenital amomaly of the upper extremity. Only 3 of them required surgical intervention. So we evaluated these three cases of proximal radioulnar synostosis corrected by proximal derotational osteotomy. The indication for surgery was severe pronation deformity that caused functional problem. Mean age at the time of surgery was 4.5 years (3-6 years) and mean postoperative follow up was 3.5 years(1-5 years). Forearm position after surgery was 15 supination. Anesthetic and functional results in all patients were good. In only one patient it was complicated by impending compartment syndrome that was treated by conservative measures. We recommend derotational osteotomay for correcting RU synostosis in earlier age.

Cleft hand deformity is a rare congenital anomaly of the hand with an incidence rate about 1/90,000. It has two clinical types; Typical and Atypical. In this paper we are representing ten cases of this anomaly admitted during seven years from 1992 in Emam Khomeini Hospital. Some of the patients especially those with typical cleft hand deformity achieved good functional results after surgical correction of the deformity. In the younger age group we observed better functional results.

Isolated scaphoid dislocation is a rare injury of the wrist. To our knowledger, only 22 cases of isolated scaphoid dislocation have been reported in Enghish-language literature and we could find only one case with pure radial dislocation. We present a 34-year-old man with isolated pure radial scaphoid dislocation that was treated by open reduction and repair of the scapholunate ligament and pin fixation. Because of the rarity of the injury and as few orthopedic surgeons seem to have encountered it, we present this case along with literature review stressing on treatment options and results.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses., (© 2023. Springer Nature Limited.)

Background: Rare diseases are a new global health priority, requiring evidence-based estimates of the global prevalence of diseases to inform public policymakers and provide a serious challenge to the healthcare system that must not be ignored. The purpose of this study is to investigate Iranian future healthcare professionals' knowledge and opinions about rare diseases., Results: A total of 6838 students responded to the questionnaire. Nursing and medical students had the highest participation. Almost 85% of participants rated their knowledge about rare diseases as poor or insufficient. While nearly 70 percent of participants took courses about rare diseases at university. Finally, 72.7% of future healthcare professionals did not feel ready to take care of a patient with a rare disease., Conclusion: The present study has indicated a gap in Iranian medical students' knowledge of rare diseases. The researchers believe that health science policymakers should make a joint effort to improve knowledge about rare diseases. Including courses with regard to rare diseases would be of benefit to future healthcare professionals., (© 2022. The Author(s).)

Variation of recurred branch of median nerve in relation to the median and flexor retinaculum are significant for both hand surgeons and specialists always. In this study, 64 cadaver hands (32 men) have been dissected. The median nerve was identified at the proximal edge of the flexor retinaculum, and in order to expose carpal tunnel the ligament was divided, and the above subjects were studied. The results are: 1) The relation of recurrent nerve to the flexor retinaculum was classified into 4 types: A) In (53.1%) of subjects, this branch arises from the median after the flexor retinaculum. B) In (31.3%) of subjects, it arises from the median in the carpal tunnel and the moves around the lower edge of flexor retinaculum and enters the thenar region. C) In (14.1%) of subjects, it arises from the median in the carpal tunnel and pierces the flexor retinaculum. D) In (1.56%) of subjects it arises, in the carpal tunnel and it divides into two subbranches here. One follows pattern A and the other pattern C. 2) In this step, the relation of the recurrent branch to the median nerve was studied. The results show that inspite of this image even though most often the recurrent branch arises from the lateral side of median, in (68.75%) of subjects it arises from it's anterior surface. The MC Nemar test reveals that there is no relation between manifestation of mentioned patterns with right or left hands.

Osteoid osteoma is a unique benign primary bone tumor that may present in the metaphyseal diaphyseal areas of the short tubular bones and has also been reported in the carpal bones. It occurs in the first two decades of life. The classic history is bone pain, often relieved by aspirin. The clinical appearance is local swelling and tenderness. The typical radiographic appearance is very characteristic: an eccentric area of cortical sclerosis, frequently with a radiolucent nidus. The lesion does not exceed 1 cm in diameter. The use of a bone scan may be helpful diagnostically, as are the CAT scan and tomography. Doyle et al described seven cases of osteoid osteoma with a prolonged delay in diagnosis, but reported an excellent cure rate following excision. The carpus is not unusual as a site for this tumor, especially the scaphoid. Treatment is windowing with curettage of the tumor nidus. The use of a dental drill to window the phalanx and expose the nidus is very helpful. Removal of the entire nidus is permanently curative, but if a portion of the tumor is missed, prompt recurrence of the symptoms is the rule.

Interferon-induced transmembrane protein 3 (IFITM3) has previously been identified as an endosomal protein that blocks viral infection 1-3 . Here we studied clinical cohorts of patients with B cell leukaemia and lymphoma, and identified IFITM3 as a strong predictor of poor outcome. In normal resting B cells, IFITM3 was minimally expressed and mainly localized in endosomes. However, engagement of the B cell receptor (BCR) induced both expression of IFITM3 and phosphorylation of this protein at Tyr20, which resulted in the accumulation of IFITM3 at the cell surface. In B cell leukaemia, oncogenic kinases phosphorylate IFITM3 at Tyr20, which causes constitutive localization of this protein at the plasma membrane. In a mouse model, Ifitm3 -/- naive B cells developed in normal numbers; however, the formation of germinal centres and the production of antigen-specific antibodies were compromised. Oncogenes that induce the development of leukaemia and lymphoma did not transform Ifitm3 -/- B cells. Conversely, the phosphomimetic IFITM3(Y20E) mutant induced oncogenic PI3K signalling and initiated the transformation of premalignant B cells. Mechanistic experiments revealed that IFITM3 functions as a PIP3 scaffold and central amplifier of PI3K signalling. The amplification of PI3K signals depends on IFITM3 using two lysine residues (Lys83 and Lys104) in its conserved intracellular loop as a scaffold for the accumulation of PIP3. In Ifitm3 -/- B cells, lipid rafts were depleted of PIP3, which resulted in the defective expression of over 60 lipid-raft-associated surface receptors, and impaired BCR signalling and cellular adhesion. We conclude that the phosphorylation of IFITM3 that occurs after B cells encounter antigen induces a dynamic switch from antiviral effector functions in endosomes to a PI3K amplification loop at the cell surface. IFITM3-dependent amplification of PI3K signalling, which in part acts downstream of the BCR, is critical for the rapid expansion of B cells with high affinity to antigen. In addition, multiple oncogenes depend on IFITM3 to assemble PIP3-dependent signalling complexes and amplify PI3K signalling for malignant transformation.

Cysts in bone are seen occasionally at or near its end and are filled with mucoid, glaird fluid. Typically, they have a thick fibrous wall similar to that of a "ganglion" of tendon sheath, are associated with no significant degenerative changes in the nearly near by joint, and seem appropriately considered to be collections in synovial spaces in unusual locations. Although they are rare and usually an incidental radiographic finding, intraosseous ganglions are being increasingly recognized as a source of wrist pain. Surgical treatment is best delayed, however, until all other possible etiologic factors for the patient's discomfort have been excluded. When indicated, curettage and bone grafting will adequately treat the condition. A careful exploration of the joint at the time of surgery helps rule out other undiagnosed causes for the patient's symptoms. Communications between the joint cavity and the intraosseous cyst are inconsistently demonstrated. The histologic features of intraosseous ganglions are identical to their soft tissue counterparts