A prime example of precisely delivered DNA.

Incorporating large fragments of DNA into specific genome positions is an inefficient process even when using the most cutting-edge genome-editing tools. Sun et al. recently described the prime editing-mediated recombination of opportune targets (PrimeRoot) method, which precisely and efficiently integrates large fragments of DNA into plant genomes and has enormous potential in research and agriculture.

Deciphering the differential expression patterns of yield-related negative regulators in hexaploid wheat cultivars and hybrids at different growth stages.

BACKGROUND: Hexaploid bread wheat underwent a series of polyploidization events through interspecific hybridizations that conferred adaptive plasticity and resulted in duplication and neofunctionalization of major agronomic genes. The genetic architecture of polyploid wheat not only confers adaptive plasticity but also offers huge genetic diversity. However, the contribution of different gene copies (homeologs) encoded from different subgenomes (A, B, D) at different growth stages remained unexplored. METHODS: In this study, hybrid of elite cultivars of wheat were developed via reciprocal crosses (cytoplasm swapping) and phenotypically evaluated. We assessed differential expression profiles of yield-related negative regulators in these cultivars and their F1 hybrids and identified various cis-regulatory signatures by employing bioinformatics tools. Furthermore, the preferential expression patterns of the syntenic triads encoded from A, B, and D subgenomes were assessed to decipher their functional redundancy at six different growth stages. RESULTS: Hybrid progenies showed better heterosis such as up to 17% increase in the average number of grains and up to 50% increase in average thousand grains weight as compared to mid-parents. Based on the expression profiling, our results indicated significant dynamic transcriptional expression patterns, portraying the different homeolog-dominance at the same stage in the different cultivars and their hybrids. Albeit belonging to same syntenic triads, a dynamic trend was observed in the regulatory signatures of these genes that might be influencing their expression profiles. CONCLUSION: These findings can substantially contribute and provide insights for the selective introduction of better cultivars into traditional and hybrid breeding programs which can be harnessed for the improvement of future wheat.

Arteriovenous malformation with hair collar sign.

We report the case of a newborn who was noted at birth to have an occipital scalp nodule presenting with a hair collar sign (HCS). The nodule had enlarged since birth. An MRI revealed a soft tissue mass on the occipital scalp without deep extension or cranial bone involvement. A biopsy of the nodule led to a diagnosis of arteriovenous malformation (AVM). A vascular malformation with HCS has not been reported before in North America. This case highlights the complexity of diagnosing a lesion with a hair collar sign.

Toxicological assessment of dietary exposure of polyethylene microplastics on growth, nutrient digestibility, carcass and gut histology of Nile Tilapia (Oreochromis niloticus) fingerlings.

This study was conducted to ascertain the negative effects of dietary low-density polyethylene microplastics (LDPE-MPs) exposure on growth, nutrient digestibility, body composition and gut histology of Nile tilapia (Oreochromis niloticus). Six sunflower meal-based diets (protein 30.95%; fat 8.04%) were prepared; one was the control (0%) and five were incorporated with LDPE-MPs at levels of 2, 4, 6, 8 and 10% in sunflower meal-based diets. A total of eighteen experimental tanks, each with 15 fingerlings, were used in triplicates. Fish were fed at the rate of 5% biomass twice a day for 60 days. Results revealed that best values of growth, nutrient digestibility, body composition and gut histology were observed by control diet, while 10% exposure to LDPE-MPs significantly (P < 0.05) reduced weight gain (WG%, 85.04%), specific growth rate (SGR%, 0.68%), and increased FCR (3.92%). The findings showed that higher level of LDPE-MPs (10%) exposure in the diet of O. niloticus negatively affects nutrient digestibility. Furthermore, the results revealed that the higher concentration of LDPE-MPs (10%) had a detrimental impact on crude protein (11.92%) and crude fat (8.04%). A high number of histological lesions were seen in gut of fingerlings exposed to LDPE-MPs. Hence, LDPE-MPs potentially harm the aquatic health.

Computational Studies on Diverse Characterizations of Molecular Descriptors for Graphyne Nanoribbon Structures.

Materials made of graphyne, graphyne oxide, and graphyne quantum dots have drawn a lot of interest due to their potential uses in medicinal nanotechnology. Their remarkable physical, chemical, and mechanical qualities, which make them very desirable for a variety of prospective purposes in this area, are mostly to blame for this. In the subject of mathematical chemistry, molecular topology deals with the algebraic characterization of molecules. Molecular descriptors can examine a compound's properties and describe its molecular topology. By evaluating these indices, researchers can predict a molecule's behavior including its reactivity, solubility, and toxicity. Amidst the captivating realm of carbon allotropes, γ-graphyne has emerged as a mesmerizing tool, with exquisite attention due to its extraordinary electronic, optical, and mechanical attributes. Research into its possible applications across numerous scientific and technological fields has increased due to this motivated attention. The exploration of molecular descriptors for characterizing γ-graphyne is very attractive. As a result, it is crucial to investigate and predict γ-graphyne's molecular topology in order to comprehend its physicochemical characteristics fully. In this regard, various characterizations of γ-graphyne and zigzag γ-graphyne nanoribbons, by computing and comparing distance-degree-based topological indices, leap Zagreb indices, hyper leap Zagreb indices, leap gourava indices, and hyper leap gourava indices, are investigated.

Prescription of statins after acute coronary syndrome; a single-centre observational study.

There is limited information about the current use of high-intensity statins (HIS) after acute coronary syndrome (ACS) in Pakistani patients. We studied the prescription of HIS in patients admitted with ACS to Ittefaq Hospital, Lahore, Pakistan, from February 2019 to December 2019. Among the 411 patients, 221 (53.8%) patients underwent Percutaneous Coronary Intervention (PCI), 62 (15.1%) were referred for Coronary Artery Bypass Graft (CABG), and 128 (31.1%) were treated medically. Overall 408 (99.3%) patients were prescribed statins and 198 (48.2%) received HIS, with 45 (10.9%) patients receiving maximally allowed dose (Atorvastatin 80mg or Rosuvastatin 40mg). Patients treated with PCI were more likely to be prescribed HIS (73.3% vs 26.7%, p <0.001), while older patients (>75 years of age), those treated medically, and patients with severely reduced LV systolic function were significantly less likely to receive HIS (p <0.001). Our study, therefore, identifies a gap in implementation of guidelines for HIS use, particularly among the medically treated ACS patients.

Acute myocardial infarction after a negative Dobutamine stress echocardiogram in a patient with end-stage liver disease.

Dobutamine stress echocardiogram (DSE) is generally a safe and reliable test for detection of myocardial ischaemia. We report the case of a 43-year-old male with end-stage liver disease (ESLD), who underwent DSE as part of workup for liver transplantation. Although the patient had an uneventful negative DSE, within 45 minutes he developed inferior ST-segment elevation myocardial infarction (STEMI). His coronary angiography showed severe 2-vessel coronary artery disease, which was treated with percutaneous coronary intervention (PCI) with implantation of drug-eluting stents (DES). Acute coronary syndrome (ACS) after a normal DSE has previously been reported in the literature. We describe one such case, with added complexity of managing an ACS in a patient with high bleeding risk. Our case is unique in reporting a STEMI after a negative DSE in a liver transplant recipient. Increased physician awareness of potential complications of DSE is essential to allow timely recognition and management.

Epidemiological and hematological investigation of dengue virus infection.

Dengue is a mosquito-borne viral illness that infects humans. For the past few decades, it has been declared a global public health problem. The current study, conducted at the district headquarter hospital (DHQ) Bannu between June to September 2018, was based on the seroprevalence of antibodies against dengue virus serotypes and their hematological parameters among the patients. A total of 1738 individuals suspected of having dengue were diagnosed through NS1, IgG, and IgM antibodies and RT-PCR techniques. Of all the samples, 716 (41.19%) were found to be positive for dengue. A higher infection rate was found in males (65.92%) compared with females (34.07%). The most affected age group was 16-40 years, whereas the most affected tehsil was Bannu, where the DENV-3 serotype was prevalent. The rare serotype (DENV-4) was found in 1% of cases. Symptoms including fever (100%), myalgia (100%), headache (61.31%), vomiting (34.63%), and rashes were common among the dengue patients. However, the mild cases showed fewer clinical signs compared with the severely infected cases. The study also revealed a significant association (P < 0.05) between hematological parameters and dengue infection, showing a significant decrease in TC, eosinophils, neutrophils, and platelets and a significant increase in monocytes and lymphocytes. Based on the current report, it is concluded that patients with the above symptoms and hematological changes may have an increased probability of dengue and should be kept under observation to separate dengue-positive patients and to enhance the treatment process.

Dosimetric properties of thermoluminescent NaCl pellets from Khewra Salt Mines, Pakistan.

Thermoluminescence (TL) and extended dosimetric characteristics of naturally occurring sodium chloride (NaCl) salt were studied. Pellets were prepared from mined crystalline salt obtained from Khewra Salt Mines, Pakistan and irradiated from 1 mGy to 10,000 mGy using cobalt-60 gamma source. The TL response showed two dominant peaks around 125°C and 230°C, respectively, at low doses, with an additional peak in between at doses beyond 300 mGy. A linear and supra-linear TL response was observed between 1 mGy-100 mGy and 100 mGy-10 Gy dose ranges, respectively. During the first 24 h post-irradiation, the TL intensity dropped by 20%. A maximum angular dependence of up to 50% was observed between 0° to 360°. For photon energies between 33 keV and 1.25 MeV significant energy dependence was observed for photons < 100 keV only. Sample sensitivity increased with dose a qualitatively similar behaviour to TLD-200. Effective atomic number (Zeff ) of the sample (14.6) was comparable to TLD-200 (16.3). No significant dose rate effects (deviation for a cobalt-60 source within 3.5%) on the TL sensitivity of the sample were found. The lowest detectable dose limit (LDDL) for salt sample was found to be 0.8 mGy whereas the sample reproducibility test showed a maximum of ±11% deviation from the first value.

Reconfiguring the radiology leadership team for crisis management during the COVID-19 pandemic in a large tertiary hospital in Singapore.

The coronavirus 2019 (COVID-19) outbreak poses a serious public health risk. To date, the disease has affected almost all countries in the world. The enormous scale of the outbreak and the relative lack of knowledge and information regarding a new virus, as well as the unpredictability of events, make it challenging for leadership teams to respond. This paper shares how we have reconfigured our radiology leadership team into a smaller disease outbreak task force (DOTF) to respond and coordinate all related efforts during this ongoing COVID-19 pandemic. The DOTF format is modelled after the military with domain groups looking at manpower, intelligence, operations, and logistics matters on a daily basis so that timely decisions can be made and action plans executed promptly. In managing the DOTF, discipline, flexibility, and teamwork are key principles, and these are built upon a strong foundation of focus on infection prevention and control, and patient and staff safety as well as staff well-being. The DOTF has positioned us well to confront the many challenges to date. We believe it will also help us navigate the complex issues that will arise with future surges in cases and in formulating strategies to manage exit from the present and future lockdowns. KEY POINTS: • In a pandemic, regular and directed meetings by a smaller leadership core group are required, for prompt decision making and execution of action plans. • The military format, with domain groups to look at manpower, intelligence, operations, and logistics matters, is useful in managing a pandemic. • Discipline, flexibility, and teamwork with strong focus on infection prevention and control, and patient and staff safety as well as staff well-being are key principles for leadership teams managing a pandemic.

Chronic kidney disease diagnosis using decision tree algorithms.

BACKGROUND: Chronic Kidney Disease (CKD), i.e., gradual decrease in the renal function spanning over a duration of several months to years without any major symptoms, is a life-threatening disease. It progresses in six stages according to the severity level. It is categorized into various stages based on the Glomerular Filtration Rate (GFR), which in turn utilizes several attributes, like age, sex, race and Serum Creatinine. Among multiple available models for estimating GFR value, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), which is a linear model, has been found to be quite efficient because it allows detecting all CKD stages. METHODS: Early detection and cure of CKD is extremely desirable as it can lead to the prevention of unwanted consequences. Machine learning methods are being extensively advocated for early detection of symptoms and diagnosis of several diseases recently. With the same motivation, the aim of this study is to predict the various stages of CKD using machine learning classification algorithms on the dataset obtained from the medical records of affected people. Specifically, we have used the Random Forest and J48 algorithms to obtain a sustainable and practicable model to detect various stages of CKD with comprehensive medical accuracy. RESULTS: Comparative analysis of the results revealed that J48 predicted CKD in all stages better than random forest with an accuracy of 85.5%. The study also showed that J48 shows improved performance over Random Forest. CONCLUSIONS: The study concluded that it may be used to build an automated system for the detection of severity of CKD.

Depth Hypotheses Fusion through 3D Weighted Least Squares in Shape from Focus.

In shape-from-focus (SFF) methods, a single focus measure is used to compute the focus volume. However, it seems that a single focus measure operator is not capable of computing accurate focus values for the images of diverse types of object shapes. Furthermore, most of the SFF methods try to improve the depth map without considering any additional structural or prior information. Consequently, the extracted shape of the object might lack important details. In this work, we address these problems and suggest a method in which depth hypotheses are combined for a more accurate 3D shape through 3D weighted least squares. First, depth hypotheses are obtained by applying a number of focus operators. Then, structural prior or guidance volume is extracted from the focus measure volumes. Finally, a 3D weighted least squares optimization technique is applied to the depth hypothesis volume, where weights are computed from the guidance volume. Thus, by inducing structural prior, an improved resultant depth map is obtained. The proposed method was tested using various image sequences of synthetic and microscopic real objects. Experimental results and comparative analysis demonstrated the effectiveness of the proposed method.

Nonosseous Periocular Manifestations of Langerhans Cell Histiocytosis: A Case Report and Systematic Review.

PURPOSE: Langerhans cell histiocytosis (LCH) is a disorder of dendritic cell proliferation that typically involves bone. It can be diagnostically challenging when LCH presents without bony involvement, leading to delays in diagnosis and treatment. In this study, the periocular manifestations of LCH in cases where the underlying orbital bones are not involved are described through a systematic review. METHODS: A systematic review of the literature was performed to capture all cases of LCH that involved the periocular region but not the underlying orbital bones. These included LCH cases that involved the periocular skin, the ocular surface, and the orbital tissue. The authors also highlight an additional case where LCH presented with periocular edema and multifocal, nodular conjunctival lesions. RESULT: This review illustrates that LCH rarely presents with periocular infiltration without orbital bone involvement. In these atypical cases, LCH can present as an eyelid mass, a chalazion-like lesion, generalized periocular swelling, ocular surface lesions, or infiltration of any orbital structure. Ocular surface LCH has a higher rate of recurrence than other periocular LCH. Orbital LCH can involve any tissue including extraocular muscles, the lacrimal gland, or indistinct areas within the orbit. CONCLUSIONS: LCH is a clinicopathologic diagnosis. Although most cases involve the bone, any soft tissue can be involved. Biopsy is required to confirm the diagnosis of this heterogeneous disease.

Improved anti-inflammatory effect of curcumin by designing self-emulsifying drug delivery system.

The purpose of the present study was to prepare and evaluate self-emulsifying drug delivery system (SEDDS) of curcumin (Cur) to enhance its solubility and percentage release for the evaluation of anti-inflammatory effect. Curcumin loaded SEDDS formulation was prepared, and zones of self-emulsification were recognized by dilution method for the construction of phase diagram. Lauroglycol FCC, tween 80 (surfactant), and transcutol HP (co-surfactant) were selected based on their solubility and highest emulsion region in phase diagram. Thermodynamic stability of Cur-SEDDS was calculated through globule size, zeta potential, polydispersity index (PDI), viscosity, and pH. Cur-SEDDS were also characterized by encapsulation efficiency (EE %), FT-IR, in vitro release, and in vivo anti-inflammatory effect. Results revealed that droplet size of Cur-SEDDS was 19.77 ± 0.03 nm with their PDI 0.22 ± 0.19, zeta potential -19.33 ± 0.94 and viscosity 25.68 ± 0.86 cp. EE % of Cur-SEDDS was found to be 94.99 ± 0.38%, percentage release 65.83% compared with pure Cur powder. The designed formulation possesses significant anti-inflammatory activity in paw edema when compared with positive control in carrageenan induced rat paw edema assay. Newly developed Cur-SEDDS with enhanced Cur solubility, percentage release, and better anti-inflammatory action may be an alternative source of oral delivery of Cur.

Histopathological features of iatrogenic occlusive vasculopathy caused by intra-articular hyaluronic acid injection for osteoarthritis.

Occlusive vasculopathy may rarely occur after intra-articular injection with hyaluronic acid. The associated histological changes are not well described. Herein, we would like to present representative histology of this phenomenon.

Calciphylaxis: how specific are the pathological features: avoiding false-positives and false-negatives.

Calciphylaxis is considered a critical inflammatory dermatosis with potentially devastating clinical consequences. Skin biopsies are expedited for evaluation and are often considered as a gold standard for diagnostic confirmation and exclusion of other conditions. The key histopathological features include a combination of vascular and extra-vascular calcifications, intravascular microthrombi, and changes related to resulting ischemia. The pathological diagnosis of calciphylaxis is not always a straightforward process as it can be influenced by a number of factors. The specificity of pathological diagnosis of calciphylaxis has been questioned and a systematic approach with multidisciplinary collaboration is required to avoid potential errors.

Frequency of high bleeding risk in patients undergoing percutaneous coronary intervention.

OBJECTIVE: To assess the prevalence of risk factors for bleeding and high bleeding risk in patients undergoing percutaneous coronary intervention. METHODS: The single-centre retrospective observational study was conducted at Ittefaq Hospital Lahore and comprised data of patients who underwent percutaneous coronary intervention from February 2018 to December 2019. Minor and major bleeding risk factors were identified on the basis of the consensus definition of the Academic Research Consortium. Patients with high bleeding risk were identified according to the consensus-based criteria of at least one major criterion or two minor criteria. Data was analysed using SPSS 20. RESULTS: Of the 385 patients, 280(72.7%) were males. The overall mean age was 57.9±11.9 years. The indication of procedure was acute coronary syndrome in 367(95%) patients. Of all the patients, 171(45%) had bleeding risk, with 94(24%) patients having a high bleeding risk. Of these, 60(15.6%) patients had high risk based on the presence of at least one major criterion and 34(8.8%) patients because of the presence of two or more minor criteria. Patients with high bleeding risk were more likely to be older and female with more co-morbidities (p<0.05). CONCLUSIONS: Almost half of the patients undergoing percutaneous coronary intervention were found to have at least one bleeding risk factor, and one in four patients had high bleeding risk.

Epidemiology of Influenza among patients with influenza-like illness and severe acute respiratory illness in Pakistan: A 10-year surveillance study 2008-17.

In Pakistan, the burden of influenza was largely unknown, as no formal surveillance system was in place. In 2008, an influenza surveillance system was set up in eight sentinel sites. This study describes the epidemiology of influenza virus using a 10-year surveillance data from 2008 to 2017. Nasopharyngeal/throat swabs were collected from patients with influenza-like illness (ILI) and severe acute respiratory illness (SARI) along with relevant epidemiological information. The samples were tested using real-time reverse transcriptase-polymerase chain reaction for the detection and characterization of influenza viruses. A total of 17 209 samples were tested for influenza, out of which 3552 (20.6%) were positive; 2151/11 239 (19.1%) were patients with ILI, whereas 1401/5970 (23.5%) were patients with SARI. Influenza A/H1N1pdm09 was the predominant strain with 40.6% (n = 1442) followed by influenza B (936, 26.4%). Influenza A/H1N1pdm09 was predominant among the children (5-14 years) and adults (15-64 years). Influenza B strain was predominantly found in the elderly age group (≥ 65 years) accounting for 48% of cases followed by children (2-4 years) accounting for 37% of cases. This 10-year surveillance data provides evidence of influenza activity in the country throughout the year with seasonal winter peaks. The results could be used to strengthen the epidemic preparedness and response plan.

iHyd-LysSite (EPSV): Identifying Hydroxylysine Sites in Protein Using Statistical Formulation by Extracting Enhanced Position and Sequence Variant Feature Technique.

INTRODUCTION: Hydroxylation is one of the most important post-translational modifications (PTM) in cellular functions and is linked to various diseases. The addition of one of the hydroxyl groups (OH) to the lysine sites produces hydroxylysine when undergoes chemical modification. METHODS: The method which is used in this study for identifying hydroxylysine sites based on powerful mathematical and statistical methodology incorporating the sequence-order effect and composition of each object within protein sequences. This predictor is called "iHyd-LysSite (EPSV)" (identifying hydroxylysine sites by extracting enhanced position and sequence variant technique). The prediction of hydroxylysine sites by experimental methods is difficult, laborious and highly expensive. In silico technique is an alternative approach to identify hydroxylysine sites in proteins. RESULTS: The experimental results require that the predictive model should have high sensitivity and specificity values and must be more accurate. The self-consistency, independent, 10-fold cross-validation and jackknife tests are performed for validation purposes. These tests are resulted by using three renowned classifiers, Neural Networks (NN), Random Forest (RF) and Support Vector Machine (SVM) with the demanding prediction rate. The overall predictive outcomes are extraordinarily superior to the results obtained by previous predictors. The proposed model contributed an excellent prediction rate in the system for NN, RF, and SVM classifiers. The sensitivity and specificity results using all these classifiers for jackknife test are 96.08%, 94.99%, 98.16% and 97.52%, 98.52%, 80.95%. CONCLUSION: The results obtained by the proposed tool show that this method may meet the future demand of hydroxylysine sites with a better prediction rate over the existing methods.

Diagnostic and treatment challenges of a case of primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid.

BACKGROUND: Primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid is an extremely rare but aggressive neoplasm diagnosed primarily in elderly men. Until now there are 32 published cases of signet-ring cell carcinoma or histiocytoid carcinoma of the eyelid. We report the clinical, radiographic and histological features of the 33rd reported case of PCSRCC in the eyelid of a 73-year-old male, and review diagnostic and treatment challenges of this rare entity. CASE PRESENTATION: Our case highlights a 73-year-old male who was referred for surgical correction of right eye ptosis that was present for 2 years. Upon assessment, he was noted to have an upper lateral orbital rim mass. Computed tomography (CT) noted ill-defined soft tissue thickening anterior to the right globe, predominantly pre-septal but with slight post-septal extension. The pathology revealed diffusely and deeply infiltrating tumour cells extending through the dermis, subcutis, orbicularis muscle bundles and nerve fibers; the tumour cells were noted to have a monotonous histiocytoid appearance with foamy granular eosinophilic cytoplasm. At high magnification, intracytoplasmic vacuoles and occasional intermixed signet ring cells were identified. Immunohistochemical staining revealed the tumour cells to be AE1/AE3, CK7, GCDFP-15, E-cadherin, androgen receptor stain and GATA3 positive. Final pathology report confirmed the diagnosis of primary cutaneous signet-ring cell/histiocytoid carcinoma. Further imaging failed to identify a distant primary malignancy or metastatic disease. The decision was made to attempt surgical excision of the tumor. After the bulk of the grossly apparent tumor was removed, intraoperative frozen sections were sent. Superficial biopsies of the right periorbital region were performed, which revealed extension significantly further than the gross disease. Thereafter, the patient underwent a wide orbital exenteration with reconstruction using a temporary split-thickness skin graft. Due to positive margins on final permanent sections, the patient underwent further wide resection with free muscle-skin flap reconstruction followed by adjuvant radiation treatment. CONCLUSION: Our case represents the 33rd case of primary signet-ring cell/histiocytoid carcinoma of the eyelid in a 73-year-old male, the first documented case with GATA3 positivity and the second documented case with androgen receptor stain positivity.