Accurate structure prediction of biomolecular interactions with AlphaFold 3.

The introduction of AlphaFold 21 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design2-6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.37,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.

The Set1 complex is dimeric and acts with Jhd2 demethylation to convey symmetrical H3K4 trimethylation.

Epigenetic modifications can maintain or alter the inherent symmetry of the nucleosome. However, the mechanisms that deposit and/or propagate symmetry or asymmetry are not understood. Here we report that yeast Set1C/COMPASS (complex of proteins associated with Set1) is dimeric and, consequently, symmetrically trimethylates histone 3 Lys4 (H3K4me3) on promoter nucleosomes. Mutation of the dimer interface to make Set1C monomeric abolished H3K4me3 on most promoters. The most active promoters, particularly those involved in the oxidative phase of the yeast metabolic cycle, displayed H3K4me2, which is normally excluded from active promoters, and a subset of these also displayed H3K4me3. In wild-type yeast, deletion of the sole H3K4 demethylase, Jhd2, has no effect. However, in monomeric Set1C yeast, Jhd2 deletion increased H3K4me3 levels on the H3K4me2 promoters. Notably, the association of Set1C with the elongating polymerase was not perturbed by monomerization. These results imply that symmetrical H3K4 methylation is an embedded consequence of Set1C dimerism and that Jhd2 demethylates asymmetric H3K4me3. Consequently, rather than methylation and demethylation acting in opposition as logic would suggest, a dimeric methyltransferase and monomeric demethylase cooperate to eliminate asymmetry and focus symmetrical H3K4me3 onto selected nucleosomes. This presents a new paradigm for the establishment of epigenetic detail.

Novel Asymmetric Y Design of Fascial Sling for Restoration of Oral Competence and Adequate Mouth Opening in Oral Commissure Defects Post-Malignancy Resection.

Reconstruction of through-and-through defects of cheek and commissure resulting from cancer resection are challenging. The specialized function of oral competence that the oral commissure and lip play is difficult to replicate with flap only reconstruction. Static slings play an important role in improving the functional and aesthetic outcome. The asymmetric "y" fascial sling helps in achieving the goals of oral competence along with adequate mouth opening. A total of 10 patients were operated by this technique. The results were satisfactory in terms of functional and aesthetic outcome postsurgery and were maintained 6 months postradiation.

Meldrum's Acid Furfural Conjugate MAFC: A New Entry as Chromogenic Sensor for Specific Amine Identification.

Bioactive amines are highly relevant for clinical and industrial application to ensure the metabolic status of a biological process. Apart from this, generally, amine identification is a key step in various bioorganic processes ranging from protein chemistry to biomaterial fabrication. However, many amines have a negative impact on the environment and the excess intake of amines can have tremendous adverse health effects. Thus, easy, fast, sensitive, and reliable sensing methods for amine identification are strongly searched for. In the past few years, Meldrum's acid furfural conjugate (MAFC) has been extensively explored as a starting material for the synthesis of photoswitchable donor-acceptor Stenhouse adducts (DASA). DASA formation hereby results from the rapid reaction of MAFC with primary and secondary amines, which has so far been demonstrated through numerous publications for different applications. The linear form of the MAFC-based DASA exhibits intense pink coloration due to its linear conjugated triene-2-ol conformation, which has inspired researchers to use this easy synthesizable molecule as an optical sensor for primary, secondary, and biogenic amines. Due to its new entry into amine identification, a collection of the literature exclusively on MAFC is demanded. In this mini review, we intend to present the state-of-the-art of MAFC as an optical molecular sensor in hopes to motivate researchers to find even more applications of MAFC-based sensors and methods that pave the way to their usage in medicinal applications.

Papillon Flap-Design Modification of ALT Flap for Circumferential Laryngopharyngeal Defect.

Anterolateral thigh (ALT) free flap is a commonly used flap for reconstruction of circumferential laryngopharyngeal defects. The flap is harvested as an ellipse and tubed along its length. We would like to present a design modification of the ALT flap where the tubing of the flap is done along the width of the flap. This design has advantages as it allows for a two-layered closure without the harvest of additional tissue and provides skin for neck coverage also. After inset, the flap resembles a butterfly, hence the name "Papillon Flap."

Non-COVID-19 Cutaneous Mucormycosis from a Plastic Surgical Perspective.

Background Cutaneous mucormycosis is a rare and fulminant infection associated with high mortality. Plastic surgeons come across this infection in the settings of road traffic accidents, surgical site infections, and as a secondary infection with underlying bacterial soft tissue infections. Due to this infection's rarity and aggressive course, it is essential to initiate prompt multidisciplinary management at the first presentation. With this study, we aim to present a protocol for managing the condition. Methods This is a retrospective observational study of patients with cutaneous mucormycosis managed at a tertiary care hospital from January 1, 2016 to November 30, 2022 excluding patients with mucormycosis who tested positive for coronavirus disease 2019. Results Of 24 patients, 22 were males, and most were in the age group of 41 to 60 years. Sixteen patients survived and five out of eight deceased had comorbidities, six presented primarily without prior debridement, and six had trunk involvement. Conclusion A high index of clinical suspicion is necessary for early diagnosis and management of patients with invasive cutaneous mucormycosis. A multidisciplinary approach with appropriate medical and surgical management can improve outcomes in cases that otherwise carry a high mortality rate.

Midterm clinical outcome of a case of aortic arch aneurysm treated with a novel arch stentgraft system.

INTRODUCTION: Open surgery is the gold standard treatment for aortic arch disease. However, due to its complexity, open arch replacement is associated with considerable risk of mortality and morbidity. METHOD: We report a case of a 71-year-old gentleman with multiple comorbidities and symptomatic 7 cm aortic arch aneurysm who was treated with a single-stage carotid-carotid and left carotid-axillary bypass followed by zone 0 aortic arch stenting with bimodular Nexus™ stent graft. RESULTS: Post-operatively, the patient suffered from a minor stroke with full neurological recovery. Follow-up computed tomography of the aorta 3 years post-stenting showed excellent stent position with no endoleak and complete resolution of the saccular aneurysm. DISCUSSION: The midterm result of our patient who was successfully treated with an off-the-shelf single branch, bimodular stent graft system is excellent with complete resolution of the arch saccular aneurysm at 3-year after the operation.

Atraumatic Bilateral Renal Subcapsular Urinomas in a Young, Healthy Female.

BACKGROUND: Urinomas are rare and generally result from trauma to any part of the urinary collecting system. Appropriate imaging is crucial in the timely diagnosis and management of urinomas and for ruling out other etiologies such as subcapsular renal hematomas and perinephric abscesses. CASE REPORT: A 31-year-old woman with no past medical history or known trauma presented to the Emergency Department (ED) with a week of right flank pain, abdominal pain, and intermittent fevers. On point-of-care ultrasound (POCUS), she was found to have a complex right perinephric collection, later confirmed with computed tomography (CT) imaging. She was treated with intravenous (IV) antibiotics and discharged after a 3-day hospital admission with instructions to follow up with Urology. A day later, she was readmitted with worsening bilateral flank pain and persistent fevers. Image-guided percutaneous aspirations of her bilateral perinephric fluid collections revealed both urine and blood. A right ureteral stent was then placed with ultimate resolution of her symptoms. Why Should an Emergency Physician Be Aware of This? Urinomas without history of trauma are rare and should be on the differential for patients presenting with flank pain and infectious symptoms. Urinomas or other expanding perinephric fluid collections can result in superimposed infection, rupture, secondary hypertension, and renal failure. Here, we present an atypical case of atraumatic bilateral renal subcapsular urinomas with hemorrhagic components in a young and healthy woman. Our case further outlines the utility of POCUS in the ED for the timely diagnosis and management of this disease process.

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters.

The mammalian male germline is sustained by a pool of spermatogonial stem cells (SSCs) that can transmit both genetic and epigenetic information to offspring. However, the mechanisms underlying epigenetic transmission remain unclear. The histone methyltransferase Kmt2b is highly expressed in SSCs and is required for the SSC-to-progenitor transition. At the stem-cell stage, Kmt2b catalyzes H3K4me3 at bivalent H3K27me3-marked promoters as well as at promoters of a new class of genes lacking H3K27me3, which we call monovalent. Monovalent genes are mainly activated in late spermatogenesis, whereas most bivalent genes are mainly not expressed until embryonic development. These data suggest that SSCs are epigenetically primed by Kmt2b in two distinguishable ways for the upregulation of gene expression both during the spermatogenic program and through the male germline into the embryo. Because Kmt2b is also the major H3K4 methyltransferase for bivalent promoters in embryonic stem cells, we also propose that Kmt2b has the capacity to prime stem cells epigenetically.

Large Cerebellar Stroke in a Young COVID-19-Positive Patient: Case Report.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), most frequently presents with respiratory symptoms, such as fever, dyspnea, shortness of breath, cough, or myalgias. There is now a growing body of evidence that demonstrates that severe SARS-CoV-2 infections can develop clinically significant coagulopathy, inflammation, and cardiomyopathy, which have been implicated in COVID-19-associated cerebrovascular accidents (CVAs). CASE REPORT: We report an uncommon presentation of a 32-year-old man who sustained a large vessel cerebellar stroke associated with a severe COVID-19 infection. He presented with a headache, worse than his usual migraine, dizziness, rotary nystagmus, and dysmetria on examination, but had no respiratory symptoms initially. He was not a candidate for thrombolytic therapy or endovascular therapy and was managed with clopidogrel, aspirin, and atorvastatin. During hospital admission he developed COVID-19-related hypoxia and pneumonia, but ultimately he was discharged to home rehabilitation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We present this case to increase awareness among emergency physicians of the growing number of reports of neurologic and vascular complications, such as ischemic CVAs, in otherwise healthy individuals who are diagnosed with SARS-CoV-2 infection. A brief review of the current literature will help elucidate possible mechanisms, risk factors, and current treatments for CVA associated with SARS-CoV-2.

Feasibility of Customised Polymethyl Methacrylate Implants Fabricated Using 3D Printed Flexible Moulds for Correction of Facial Skeletal Deformities.

INTRODUCTION: Use of patient specific Polymethyl methacrylate (PMMA) implants for the reconstruction of cranial defects has become a standard practice with excellent long-term results. However, for the reconstruction of midface and mandibular osseous defects other alloplastic materials are preferred but their use is limited due to high cost. This is a report of our experience with the use of low-cost patient specific PMMA implants fabricated using 3D printed moulds in the reconstruction of osseous defects involving different areas of the facial skeleton not limited to cranium. METHODS: The 25 consecutive patients with craniofacial osseous defects who underwent reconstruction using customized PMMA implants were analyzed. All PMMA implants were fabricated intraoperatively with the use of 3D printed flexible moulds or templates. RESULTS: A total of 34 implants were used in 25 consecutive patients. Out of 34 implants 25 were used for midface and mandibular osseous defects. Most common etiology was post-traumatic deformity (n = 19) followed by tumor (n = 3), craniofacial anomalies (n = 2) and post-craniotomy (n = 1). One patient out of 25 (n = 1) had postoperative implant exposure. The follow-up was ranged from 3 to 19 months with an average of 12 months. The aesthetic outcome was found to be good to excellent with mean visual analogue score of 4.08. CONCLUSIONS: Polymethyl methacrylate implants fabricated intraoperatively using 3D printed moulds provide accurate and precise reconstruction at an exceptionally low cost. PMMA has an excellent moulding property with low infection rates. As shown in our study its application may be easily extended to all areas of the craniofacial skeleton.

Remote sensing and GIS based analysis of temporal land use/land cover and water quality changes in Harike wetland ecosystem, Punjab, India.

Wetlands help in maintaining ecological balance in an area, but are shrinking fast all over the world. A study was conducted on the Harike wetland in Punjab state of India to analyze temporal changes in land use/land cover (LULC), water spread area and water pollution by using RS and GIS techniques. The LULC map of Harike wetland ecosystem covering an area of 22213.91 ha was prepared through on-screen visual interpretation of multispectral Resourcesat 2 LISS-IV satellite data (2014 and 2018) having spatial resolution of 5.8 m. Area under agriculture, forest and built up increased and that under waste land, water bodies and wetland decreased during 2014-18. The rate of increase in agricultural land was quite high (18.87 ha/year) during 2006-2014, but reduced to 3.53 ha/year during 2014-2018. The built up land increased comparatively at low rates (0.87 and 0.90 ha/year). Areas under waste land, water bodies and wetland decreased at the rate of 4.32, 1.61 and 13.80 ha/year during 2006-2014 and 2.37, 0.34 and 1.71 ha/year during 2014-2018, respectively. The water spread area of Harike wetland which was 4073 ha and 4166 ha in year 2002 and 2006 reduced to 3918.98 ha and 3910.56 ha in the year 2014 and 2018, respectively. However, wetland ponded area shrinked at a rate of 30.37 ha/year during 2006-2014 and 2.11 ha/year during the period 2014-2018. The area under low and medium turbidity increased by 22.02% and 15.2%, respectively, but decreased by 49% under high turbidity during 2014-18. Wetland water was observed to be rich in macro and micronutrients. The pH, BOD and COD of wetland water increased by 0.51, 9.7 mg/l and 24 mg/l, respectively, during 2002-14 and by 0.03, 2.0 mg/l and 5.92 mg/l, respectively during 2014-18. Interaction between land use, water quality, water inflow, ground water and wetland area has also been studied. Intensive cultivation and declining groundwater levels in the area are negatively affecting the wetland. This necessitates regular monitoring of wetland structural components and water quality along with an urgent plan in place for conservation, rehabilitation and management of Harike wetland ecosystem in participatory mode.

Single Stage Nasal Reconstruction in a Near Total Nasal Defect.

Reconstruction of nasal defect is difficult and challenging. A full-thickness defect of nose requires reconstruction of thin inner lining, middle skeletal (bony/cartilaginous) support, and outer skin layer cover. Large full-thickness defects of nose require complex multistage reconstruction to achieve good functional and aesthetic result. We present here a case of 12-year-old boy, a known case of xeroderma pigmentosa, who underwent wide local excision for squamous cell carcinoma of the nose, leaving a near total defect of the external nose. The reconstruction was done with a suprafascial, thin radial artery forearm free-flap for the external cover as well as the inner lining along with the septal cartilage graft for skeletal support in a single stage.

Concomitant severe carotid and coronary artery diseases: a separate management or concomitant approach.

OBJECTIVE: To systematically compare outcomes between patients with asymptomatic carotid artery diseases (>80% stenosis) that had undergone staged carotid endarterectomy (CEA) before coronary artery bypass grafting (CABG) vs simultaneous CEA and CABG. METHODS: A comprehensive electronic search of MEDLINE, Scopus, EMBASE, and Ovid from their inception up till August 2018 was performed to identify all studies comparing staged CEA followed by CABG to simultaneous CEA and CABG. Primary outcome measure was postoperative stroke, and secondary measures were myocardial infarction (MI) and 30-day mortality rates. RESULTS: A total of 67 953 patients were analyzed from 11 articles. There was higher rate of previous stroke in the staged cohort (2.64% vs 2.32%; odds ratio [OR], 0.81; 95% confidence interval [CI; 0.66, 0.99]; P = .040). There was no difference in previous MI (P = .57) or unstable angina (P = .08) among both cohorts. Postoperatively, there were higher stroke rates (3.64% vs 2.83%; OR, 0.72; 95% CI [0.62-0.89]; P < .0001), operative mortality (4.32% vs 3.58%; OR, 0.90; 95% CI [0.83-0.98]; P = .02), and 30-day mortality (4.40% vs 3.58%; OR, 0.86; 95% CI [0.78-0.96]; P = .006) in the simultaneous cohort. However, length of stay was significantly shorter in the simultaneous cohort (11.9 days vs 12.6 days; weighted mean difference 3.14 [0.77-5.51]; P = .009). There were no significant differences in 1-year mortality (P = .33), MI rates (P = .08), and rates of transient neurological deficits (P = .06). CONCLUSION: The results from this study favors staged CEA with CABG with lower incidence of postoperative stroke, operative, and 30-day mortality. A larger study, ideally a randomized controlled trial, is required to address the superiority of each technique.