UNETR++: Delving into Efficient and Accurate 3D Medical Image Segmentation.

Owing to the success of transformer models, recent works study their applicability in 3D medical segmentation tasks. Within the transformer models, the self-attention mechanism is one of the main building blocks that strives to capture long-range dependencies, compared to the local convolutional-based design. However, the self-attention operation has quadratic complexity which proves to be a computational bottleneck, especially in volumetric medical imaging, where the inputs are 3D with numerous slices. In this paper, we propose a 3D medical image segmentation approach, named UNETR++, that offers both high-quality segmentation masks as well as efficiency in terms of parameters, compute cost, and inference speed. The core of our design is the introduction of a novel efficient paired attention (EPA) block that efficiently learns spatial and channel-wise discriminative features using a pair of inter-dependent branches based on spatial and channel attention. Our spatial attention formulation is efficient and has linear complexity with respect to the input. To enable communication between spatial and channel-focused branches, we share the weights of query and key mapping functions that provide a complimentary benefit (paired attention), while also reducing the complexity. Our extensive evaluations on five benchmarks, Synapse, BTCV, ACDC, BraTS, and Decathlon-Lung, reveal the effectiveness of our contributions in terms of both efficiency and accuracy. On Synapse, our UNETR++ sets a new state-of-the-art with a Dice Score of 87.2%, while significantly reducing parameters and FLOPs by over 71%, compared to the best method in the literature. Our code and models are available at: https://tinyurl.com/2p87x5xn.

Complexities of Infective Endocarditis in a Young Patient With Hypertrophic Obstructive Cardiomyopathy: A Case of Dual Valve Involvement and Neurological Complications.

Infective endocarditis (IE) is a life-threatening infection predominantly affecting the endocardium and heart valves, commonly seen in older patients and those with pre-existing cardiac conditions. Although rare in younger individuals with intact cardiac valves, certain structural heart diseases such as hypertrophic obstructive cardiomyopathy (HOCM) can increase the risk. We present a unique case of a 39-year-old female with a known history of HOCM, a condition characterized by abnormally thickened cardiac muscle primarily affecting the left ventricle. This patient was diagnosed with group B streptococcus infective endocarditis. Notably, this case was complicated by septic emboli to the brain. This case underscores the significant risk of IE in patients with HOCM, a demographic usually less susceptible to IE. It underscores the importance of early recognition and aggressive management of IE, especially in patients with structural heart diseases.

An early force prediction control scheme using multimodal sensing of electromyography and digit force signals.

Different grasping gestures result in the change of muscular activity of the forearm muscles. Similarly, the muscular activity changes with a change in grip force while grasping the object. This change in muscular activity, measured by a technique called Electromyography (EMG) is used in the upper limb bionic devices to select the grasping gesture. Previous research studies have shown gesture classification using pattern recognition control schemes. However, the use of EMG signals for force manipulation is less focused, especially during precision grasping. In this study, an early predictive control scheme is designed for the efficient determination of grip force using EMG signals from forearm muscles and digit force signals. The optimal pattern recognition (PR) control schemes are investigated using three different inputs of two signals: EMG signals, digit force signals and a combination of EMG and digit force signals. The features extracted from EMG signals included Slope Sign Change, Willison Amplitude, Auto Regressive Coefficient and Waveform Length. The classifiers used to predict force levels are Random Forest, Gradient Boosting, Linear Discriminant Analysis, Support Vector Machines, k-nearest Neighbors and Decision Tree. The two-fold objectives of early prediction and high classification accuracy of grip force level were obtained using EMG signals and digit force signals as inputs and Random Forest as a classifier. The earliest prediction was possible at 1000 ms from the onset of the gripping of the object with a mean classification accuracy of 90 % for different grasping gestures. Using this approach to study, an early prediction will result in the determination of force level before the object is lifted from the surface. This approach will also result in better biomimetic regulation of the grip force during precision grasp, especially for a population facing vision deficiency.

Unraveling the mechanisms of Sofosbuvir resistance in HCV NS3/4A protease: Structural and molecular simulation-based insights.

Current management of HCV infection is based on Direct-Acting Antiviral Drugs (DAAs). However, resistance-associated mutations, especially in the NS3 and NS5B regions are gradually decreasing the efficacy of DAAs. Among the most effective HCV NS3/4A protease drugs, Sofosbuvir also develops resistance due to mutations in the NS3 and NS5B regions. Four mutations at positions A156Y, L36P, Q41H, and Q80K are classified as high-level resistance mutations. The resistance mechanism of HCV NS3/4A protease toward Sofosbuvir caused by these mutations is still unclear, as there is less information available regarding the structural and functional effects of the mutations against Sofosbuvir. In this work, we combined molecular dynamics simulation, molecular mechanics/Generalized-Born surface area calculation, principal component analysis, and free energy landscape analysis to explore the resistance mechanism of HCV NS3/4A protease due to these mutations, as well as compare interaction changes in wild-type. Subsequently, we identified that the mutant form of HCV NS3/4A protease affects the activity of Sofosbuvir. In this study, the resistance mechanism of Sofosbuvir at the atomic level is proposed. The proposed drug-resistance mechanism will provide valuable guidance for the design of HCV drugs.

A highly diastereoselective one-pot Ugi/radical spirocyclization/aza-Michael addition sequence.

We hereby report a highly diastereoselective synthesis of chalcogenated azaspirotricycles via a one-pot Ugi/spirocyclization/aza-Michael addition sequence. The reaction proceeds via a key visible light mediated spirocyclization step under mild, metal-free and energy efficient conditions. A variety of complex sulfenylated and selenylated azaspirotricycles were obtained in good yields. The reaction was found to be scalable and preliminary mechanistic studies indicated that the spirocyclization step proceeds via radical intermediates.

Predisposing deleterious variants in the cancer-associated human kinases in the global populations.

Human kinases play essential and diverse roles in the cellular activities of maintaining homeostasis and growth. Genetic mutations in the genes encoding the kinases (or phosphotransferases) have been linked with various types of cancers. In this study, we cataloged mutations in 500 kinases genes in >65,000 individuals of global populations from the Human Genetic Diversity Project (HGDP) and ExAC databases, and assessed their potentially deleterious impact by using the in silico tools SIFT, Polyphen2, and CADD. The analysis highlighted 35 deleterious non-synonymous SNVs in the ExAC and 5 SNVs in the HGDP project. Notably, a higher number of deleterious mutations was observed in the Non-Finnish Europeans (26 SNVs), followed by the Africans (14 SNVs), East Asians (13 SNVs), and South Asians (12 SNVs). The gene set enrichment analysis highlighted NTRK1 and FGFR3 being most significantly enriched among the kinases. The gene expression analysis revealed over-expression of NTRK1 in liver cancer, whereas, FGFR3 was found over-expressed in lung, breast, and liver cancers compared to their expression in the respective normal tissues. Also, 13 potential drugs were identified that target the NTRK1 protein, whereas 6 potential drugs for the FGFR3 target were identified. Taken together, the study provides a framework for exploring the predisposing germline mutations in kinases to suggest the underlying pathogenic mechanisms in cancers. The potential drugs are also suggested for personalized cancer management.

Women and Cardiovascular Health: Unraveling Gender-Specific Factors, Risks, and Therapeutic Approaches in Contemporary Medicine.

Background and objective Cardiovascular diseases (CVDs) constitute a significant global health challenge, causing millions of deaths annually and straining healthcare systems worldwide. This study aimed to investigate and elucidate gender-specific factors, risks, and therapeutic approaches related to cardiovascular health in women within the context of contemporary medicine. Methodology We conducted a prospective observational study spanning one year (November 2022 to October 2023) at the Peshawar Medical Complex Hospital, to meticulously explore the field of women's cardiovascular health. With a diverse cohort of 435 women (age range: 18-55 years), representing various socioeconomic backgrounds and geographic locations, our study aimed to elicit comprehensive insights. Through structured interviews covering reproductive history, lifestyle, and psychosocial aspects, coupled with clinical assessments, we gathered multifaceted data. Statistical analysis was done using SPSS Statistics version 23.0 (IBM Corp., Armonk, NY). By employing descriptive and t-tests for quantitative analysis and by thematically analyzing qualitative insights, our approach ultimately sought to provide a nuanced understanding of gender-specific factors impacting women's cardiovascular health. Results The study, involving 435 women, revealed various prevalent cardiovascular risk factors. Notable findings include a high incidence of a family history of CVD (n=213, 48.96%, p=0.013), hypertension (n=207, 47.58%), hypercholesterolemia (n=114, 26.21%), elevated triglycerides (n=162, 37.24%), and diabetes (n=64, 14.71%). Physical inactivity was also significantly more common (53.56%, p=0.004) compared to those engaging in regular activity. Women-specific risk factors comprised miscarriage (n=191, 43.91%). Therapeutic preferences varied, with a majority opting for lifestyle modifications (n=263, 60.39%) and pharmacological interventions (n=331, 76.33%). Conclusions This study provides a comprehensive understanding of prevalent cardiovascular risk factors, distinctive women-specific contributors, and diverse therapeutic preferences, highlighting the importance of personalized and targeted interventions to optimize women's cardiovascular health outcomes in contemporary medicine.

Uncommon Culprit, Familiar Foe: A Case of Septic Thrombophlebitis of the Internal Jugular Vein Triggered by Klebsiella Bacteremia.

Septic thrombophlebitis of the internal jugular vein is characterized as Lemierre syndrome. Patients typically present with sore throat and fever and may present with a tender neck mass due to thrombophlebitis of the internal jugular vein. We present the case of a 57-year-old male with neck pain, fever, chills, and headaches who was diagnosed with internal jugular vein septic thrombophlebitis associated with catheter-related introduction of bacteria.

Reaching high-hanging fruit in antimicrobial stewardship: a hospital-based intervention to withdraw inappropriately prescribed antimicrobials.

Background: Antimicrobial stewardship programs (ASPs) are responsible for addressing unnecessary antimicrobial use. We describe our experience with a unique intervention to withdraw unnecessary antimicrobials. Methods: Design, Setting, Participants: descriptive case series of adult inpatients at a single academic medical center, December 2021 to December 2022; Intervention: hospital-wide policy allowing ASP to discontinue inappropriate antimicrobials in select cases not resolved by prospective audit and feedback; Measures: count, date, and generic names of antimicrobials prescribed; reason for antimicrobial withdrawal (prolonged duration, no evidence of infection, or other); withdrawals by inpatient service (surgical or medical); time from antimicrobial start date to withdrawal intervention; days of therapy (DOT) saved; "nudge effect" defined as the prescribing team self-discontinuing withdrawn antimicrobial within 24 hours of withdrawal notice; appeals to withdrawals; ordering of alternative antimicrobials following withdrawal; incident infections, readmission, in-hospital mortality within 30 days of withdrawal intervention. Results: There were 54 antimicrobials withdrawn among 36 unique patients during the study period; piperacillin-tazobactam followed by vancomycin were the most frequently withdrawn agents; prolonged duration of therapy or prophylaxis followed by no evidence of infection were the most common reasons for withdrawal; withdrawals occurred most often on surgical services; an estimated 236 DOT (27.2 DOT per 100 patient-days) were saved; 32% of withdrawals were appealed; alternative antimicrobials were ordered following 20% of withdrawals; no incident infections, readmissions or in-hospital deaths were definitively attributed to withdrawal intervention. Conclusions: Our antimicrobial withdrawal intervention was a safe and effective addition to ASP activities to reduce inappropriate antimicrobial use and improve prescriber accountability.

Sequence based model using deep neural network and hybrid features for identification of 5-hydroxymethylcytosine modification.

RNA modifications are pivotal in the development of newly synthesized structures, showcasing a vast array of alterations across various RNA classes. Among these, 5-hydroxymethylcytosine (5HMC) stands out, playing a crucial role in gene regulation and epigenetic changes, yet its detection through conventional methods proves cumbersome and costly. To address this, we propose Deep5HMC, a robust learning model leveraging machine learning algorithms and discriminative feature extraction techniques for accurate 5HMC sample identification. Our approach integrates seven feature extraction methods and various machine learning algorithms, including Random Forest, Naive Bayes, Decision Tree, and Support Vector Machine. Through K-fold cross-validation, our model achieved a notable 84.07% accuracy rate, surpassing previous models by 7.59%, signifying its potential in early cancer and cardiovascular disease diagnosis. This study underscores the promise of Deep5HMC in offering insights for improved medical assessment and treatment protocols, marking a significant advancement in RNA modification analysis.

Learnable weight initialization for volumetric medical image segmentation.

Hybrid volumetric medical image segmentation models, combining the advantages of local convolution and global attention, have recently received considerable attention. While mainly focusing on architectural modifications, most existing hybrid approaches still use conventional data-independent weight initialization schemes which restrict their performance due to ignoring the inherent volumetric nature of the medical data. To address this issue, we propose a learnable weight initialization approach that utilizes the available medical training data to effectively learn the contextual and structural cues via the proposed self-supervised objectives. Our approach is easy to integrate into any hybrid model and requires no external training data. Experiments on multi-organ and lung cancer segmentation tasks demonstrate the effectiveness of our approach, leading to state-of-the-art segmentation performance. Our proposed data-dependent initialization approach performs favorably as compared to the Swin-UNETR model pretrained using large-scale datasets on multi-organ segmentation task. Our source code and models are available at: https://github.com/ShahinaKK/LWI-VMS.

Engineering MPC-Assisted Heterojunctional Photo-Oxidation Tailored by Interfacial Design of a P-Modulated C3N4 Heterojunction for Improved Aerobic Alcohol Oxidation.

The creation of two-dimensional van der Waals (VDW) heterostructures is a sophisticated approach to enhancing photocatalytic efficiency. However, challenges in electron transfer at the interfaces often arise in these heterostructures due to the varied structures and energy barriers of the components involved. This study presents a novel method for constructing a VDW heterostructure by inserting a phosphate group between copper phthalocyanine (CuPc) and boron-doped, nitrogen-deficient graphitic carbon nitride (BCN), referred to as Cu/PO4-BCN. This phosphate group serves as a charge mediator, enabling effective charge transfer within the heterostructure, thus facilitating electron flow from BCN to CuPc upon activation. As a result, the photogenerated electrons are effectively utilized by the catalytic Cu2+ core in CuPc, achieving a conversion efficiency of 96% for benzyl alcohol (BA) and a selectivity of 98.8% for benzyl aldehyde (BAD) in the presence of oxygen as the sole oxidant and under illumination. Notably, the production rate of BAD is almost 8 times higher than that observed with BCN alone and remains stable over five cycles. The introduction of interfacial mediators to enhance electron transfer represents a pioneering and efficient strategy in the design of photocatalysts, enabling the proficient transformation of BA into valuable derivatives.

Retrocecal Ascending Appendix Attached to the Hepatic Flexure and Right Intra-abdominal Testis Identified During Open Appendicectomy: A Case Report.

Appendicectomy, or the removal of the appendix, is an emergency procedure following symptomatic acute appendicitis. Diagnosis is made on clinical examination but can be confirmed on imaging if other abnormalities are suspected. A few variants of appendix anatomical position exist that can be difficult to manage. In addition, secondary findings during surgery can come unexpectedly. We report a case of a 14-year-old male, who presented to the emergency department at our government institution with abdominal pain and vomiting. Examination revealed an empty right scrotum, which was unnoticed by the patient and never examined previously due to residence in an area of limited healthcare access. Ultrasound done elsewhere was inconclusive. The surgical intervention showed a retrocecal appendix attached to an ascending colon terminating at hepatic flexure. The procedure was further complicated by the presence of the right intra-abdominal testis located below the cecum. Excised samples were sent for histopathology, and the patient was followed with biopsy reports. This case highlights the challenges encountered during routine appendicectomy with unusual findings.

Exploring bi-carbazole-linked triazoles as inhibitors of prolyl endo peptidase via integrated in vitro and in silico study.

A serine protease called prolyl endopeptidase (PEP) hydrolyses the peptide bonds on the carboxy side of the proline ring. The excessive PEP expression in brain results in neurodegenerative illnesses like dementia, Alzheimer's disease, and Parkinson's disease. Results of the prior studies on antioxidant activity, and the non-cytotoxic effect of bi-carbazole-linked triazoles, encouraged us to extend our studies towards its anti-diabetic potential. Hence, for this purpose all compounds 1-9 were evaluated to reveal their anti-prolyl endo peptidase activity. Fortunately, seven compounds resulted into significant inhibitory capability ranging from 26 to 63 µM. Among them six compounds 4-9 exhibited more potent inhibitory activity with IC50 values 46.10 ± 1.16, 42.30 ± 1.18, 37.14 ± 1.21, 26.29 ± 0.76, 28.31 ± 0.64 and 31.11 ± 0.84 µM respectively, while compound 3 was the least active compound in the series with IC50 value 63.10 ± 1.58 µM comparing with standard PEP inhibitor bacitracin (IC50 = 125 ± 1.50 µM). Moreover, mechanistic study was performed for the most active compounds 7 and 8 with Ki values 24.10 ± 0.0076 and 23.67 ± 0.0084 µM respectively. Further, the in silico studies suggested that the compounds exhibited potential interactions and significant molecular conformations, thereby elucidating the structural basis for their inhibitory effects.

Masseter Muscle Thickness in Relation to Facial Form in Angle's Normal Occlusion and Malocclusions: An Observational Study.

Background: Various clinical studies performed in adults have shown the relationship between craniofacial morphology and masticatory muscle function. However, the growth of the masticatory muscle has not received such attention, when compared with the volume of studies on the skeletal growth of face. With this background and considering the widespread use of ultrasonography (USG), the following study was undertaken to provide some insights into the relationship between muscle and bone and facial morphology. Methods: This was a prospective, observational study conducted over a period of three years from 2012 to 2015 to assess the correlation between the thickness of the masseter muscle in Angle's normal occlusion and the various malocclusions of the dental arch as well as the facial form. Patients with a full complement set of teeth, normal tooth morphology, Angle's normal occlusion, Angle's class I-III malocclusion, those with a history of third molar extraction, and impaction were included in the study. Those with a history of any prior orthodontic treatment, restorations, or any missing teeth (except the third molar) were exempted from the study. The greater thickness of masseter muscle in relaxed and clenched state was recorded on USG. Facial morphology was determined with the aid of facial photographs. Results: The study was conducted on 140 patients. The class I normal occlusion group had the thickest masseter muscle, while the class III malocclusion group had the thinnest masseter muscle. Facial parameters showed highly significant gender-wise differences in class I normal occlusion, class I malocclusion, and class II division II malocclusion. There was a significant negative co-relation between the thickness of masseter muscle and facial forms in all the categories of Angle's classification as indicated by a negative regression coefficient B (P < 0.05). Conclusion: The masseter muscle thickness correlated directly with male gender and normal occlusion, and inversely with the degree of malocclusion and facial form.

Fabrication and characterization of binary composite MgO/CuO nanostructures for the efficient photocatalytic ability to eliminate organic contaminants: A detailed spectroscopic analysis.

Design and eco-friendly fabrication of affordable and sustainable materials for the treatment of wastewater consisting of dyes, antibiotics, and other harmful substances has always been demanding. Untreated wastewater being released from industries imposes serious threats to our ecosystem, seeking convenient approaches to diminish this alarming issue. Here in this work, we synthesized MgO/CuO nanocomposites from a plant extract of Ammi visnaga L. and then employed these nanocomposites for the treatment of organic dye (methylene blue). We characterized the synthesized nanocomposites by dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), x-ray diffraction (XRD), and X-ray photoelectron microscopy (XPS). DLS presented information about the explicit size of nanocomposites, while the surface charge was examined by zeta potential. XRD provided detailed information about the crystalline behavior and the information regarding surface morphology and size was extracted by SEM, TEM, and AFM. Moreover, the fabricated nanocomposites were used as a photocatalyst in the treatment of methylene blue. The overall catalytic reaction took an hour to complete, and the value of percentage degradation was 98 %. Substantially, a detailed account of the kinetics, rate of reaction, and mechanism is also fostered in the context. The presented study can assist scientists and researchers around the world to reproduce the results and use them to apply them on a broader scale.

Unmasking the Enigma: Influenza Vaccine and the Rare Case of Post-Vaccination Pericarditis.

Acute pericarditis is an inflammatory condition involving the pericardium, the double-layered sac that surrounds the heart. It is characterized by chest pain, typically pleuritic and sharp, along with other clinical and laboratory findings indicative of pericardial inflammation. While acute pericarditis following influenza vaccination is rare, it has been reported in medical literature. The relationship between vaccinations, including the influenza vaccine, and pericarditis is particularly interesting, as it has implications for public health and vaccination programs. Understanding the pathophysiological mechanisms behind vaccine-induced pericarditis and recognizing the clinical presentation are essential for healthcare professionals to diagnose, manage, and educate patients appropriately.

Case of Circulating Tumor Cells Discovered in Extensive Deep Venous Thrombosis in a Patient with Known Urothelial Carcinoma.

Background: Currently, minimal data are available to explore the composition of venous thromboembolism in patients with cancer. This case report discusses a presentation of venous thromboembolism in a patient with high-grade urothelial carcinoma and highlights the pathology findings in thrombi. Case Presentation. A 55-year-old female who was diagnosed with high-grade urothelial carcinoma with multiple metastases developed an extensive deep vein thrombosis in her left lower extremity. Endovascular revascularization was indicated due to left lower extremity pain and swelling not responsive to anticoagulation. A mechanical thrombectomy was performed, and samples were sent for pathology. Pathologic examination discovered minute fragments of metastatic carcinoma, admixed with laminated blood clots (thrombus). The morphology of metastatic carcinoma and the immunostain profile were compatible with metastatic carcinoma of bladder origin. Conclusion: Cancer is a well-known risk factor for developing VTEs, and it is estimated that approximately 4-20% of cancer patients will experience VTE at some stage, the rate being the highest in the initial period following diagnosis. Annually, 0.5% of cancer patients will experience thrombosis compared with a 0.1% incidence rate in the general population (Elyamany et al., 2014). Despite knowing the increased incidence of VTEs in cancer patients, there are few studies to date that analyze the composition of thrombi in patients with cancer.