Inroads into saline-alkaline stress response in plants: unravelling morphological, physiological, biochemical, and molecular mechanisms.

MAIN CONCLUSION: This article discusses the complex network of ion transporters, genes, microRNAs, and transcription factors that regulate crop tolerance to saline-alkaline stress. The framework aids scientists produce stress-tolerant crops for smart agriculture. Salinity and alkalinity are frequently coexisting abiotic limitations that have emerged as archetypal mediators of low yield in many semi-arid and arid regions throughout the world. Saline-alkaline stress, which occurs in an environment with high concentrations of salts and a high pH, negatively impacts plant metabolism to a greater extent than either stress alone. Of late, saline stress has been the focus of the majority of investigations, and saline-alkaline mixed studies are largely lacking. Therefore, a thorough understanding and integration of how plants and crops rewire metabolic pathways to repair damage caused by saline-alkaline stress is of particular interest. This review discusses the multitude of resistance mechanisms that plants develop to cope with saline-alkaline stress, including morphological and physiological adaptations as well as molecular regulation. We examine the role of various ion transporters, transcription factors (TFs), differentially expressed genes (DEGs), microRNAs (miRNAs), or quantitative trait loci (QTLs) activated under saline-alkaline stress in achieving opportunistic modes of growth, development, and survival. The review provides a background for understanding the transport of micronutrients, specifically iron (Fe), in conditions of iron deficiency produced by high pH. Additionally, it discusses the role of calcium in enhancing stress tolerance. The review highlights that to encourage biomolecular architects to reconsider molecular responses as auxiliary for developing tolerant crops and raising crop production, it is essential to (a) close the major gaps in our understanding of saline-alkaline resistance genes, (b) identify and take into account crop-specific responses, and (c) target stress-tolerant genes to specific crops.

SARS-CoV-2 ORF6 protein targets TRIM25 for proteasomal degradation to diminish K63-linked RIG-I ubiquitination and type-I interferon induction.

Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection provide replication advantage to the virus and contribute to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host's innate immune system and found that the ORF6 protein mitigated type-I Interferon (IFN) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction and signaling. Here we show that ORF6 directly interacts with RIG-I and blocks downstream type-I IFN induction and signaling by reducing the levels of K63-linked ubiquitinated RIG-I. This involves ORF6-mediated targeting of E3 ligase TRIM25 for proteasomal degradation, which was also observed during SARS-CoV-2 infection. The type-I IFN antagonistic activity of ORF6 was mapped to its C-terminal cytoplasmic tail, specifically to amino acid residues 52-61. Overall, we provide new insights into how SARS-CoV-2 inhibits type-I IFN induction and signaling through distinct actions of the viral ORF6 protein.

Acid-Functionalized Artificial Enzymes with Tunable Selectivity for Vinyl Ether Hydrolysis.

Enzymes often employ catalytic groups with a medium or low intrinsic activity for highly challenging catalytic tasks. In this work, we report nanoparticle catalysts with accurately positioned carboxylic acids through either a covalent or noncovalent imprinting technique. The rationally designed active site allows the catalysis to be highly selective or quite unselective with respect to the substrate. With the proper catalyst, the hydrolysis proceeds smoothly in neutral water or even a slightly basic solution at room temperature.

Remote at-home wearable-based gait assessments in Progressive Supranuclear Palsy compared to Parkinson's Disease.

BACKGROUND: Wearable sensors can differentiate Progressive Supranuclear Palsy (PSP) from Parkinson's Disease (PD) in laboratory settings but have not been tested in remote settings. OBJECTIVES: To compare gait and balance in PSP and PD remotely using wearable-based assessments. METHODS: Participants with probable PSP or probable/clinically established PD with reliable caregivers, still able to ambulate 10 feet unassisted, were recruited, enrolled, and consented remotely and instructed by video conference to operate a study-specific tablet solution (BioDigit Home ™) and to wear three inertial sensors (LEGSys™, BioSensics LLC, Newton, MA USA) while performing the Timed Up and Go, 5 × sit-to-stand, and 2-min walk tests. PSPRS and MDS-UPDRS scores were collected virtually or during routine clinical visits. RESULTS: Between November, 2021- November, 2022, 27 participants were screened of whom 3 were excluded because of technological difficulties. Eleven PSP and 12 PD participants enrolled, of whom 10 from each group had complete analyzable data. Demographics were well-matched (PSP mean age = 67.6 ± 1.3 years, 40% female; PD mean age = 70.3 ± 1.8 years, 40% female) while disease duration was significantly shorter in PSP (PSP 14 ± 3.5 months vs PD 87.9 ± 16.9 months). Gait parameters showed significant group differences with effect sizes ranging from d = 1.0 to 2.27. Gait speed was significantly slower in PSP: 0.45 ± 0.06 m/s vs. 0.79 ± 0.06 m/s in PD (d = 1.78, p < 0.001). CONCLUSION: Our study demonstrates the feasibility of measuring gait in PSP and PD remotely using wearable sensors. The study provides insight into digital biomarkers for both neurodegenerative diseases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04753320, first posted Febuary 15, 2021.

A Modified Progressive Supranuclear Palsy Rating Scale for Virtual Assessments.

BACKGROUND: The reliability of the Progressive Supranuclear Palsy Rating Scale (PSPRS) using teleneurology has not been assessed. OBJECTIVES: To test whether removing items inadequately assessed by video would impact measurement of PSP severity and progression. METHODS: We performed secondary analyses of two data sets: the phase 2/3 trial of Davunetide in PSP and a large single-center cohort. We examined two modifications of the PSPRS: (1) removing neck rigidity, limb rigidity, and postural stability (25 items; mPSPRS-25) and (2) also removing three ocular motor items and limb dystonia (21 items; mPSPRS-21). Proportional agreement relative to the possible total scores was measured using the intraclass correlation coefficient, compared to the original PSPRS baseline values and change over 6 and 12 months. We examined the ability of both scales to predict survival in the single-center cohort using proportional hazards models. RESULTS: The mPSPRS-25 showed excellent agreement (0.99; P < 0.001) with the original PSPRS at baseline, 0.98 (P < 0.001) agreement in measuring change over 6 months, and 0.98 (P < 0.001) over 12 months. The mPSPRS-21 showed agreement of 0.94 (P < 0.001) with the original PSPRS at baseline, 0.92 (P < 0.001) at 6 months, and 0.95 (P < 0.001) at 12 months. Baseline and 6-month change in both modified scales were highly predictive of survival in the single-center cohort. CONCLUSIONS: Modified versions of the PSPRS which can be administered remotely show excellent agreement with the original scale and predict survival in PSP. The mPSPRS-21 should facilitate clinical care and research in PSP via teleneurology. © 2022 International Parkinson and Movement Disorder Society.

EGFR detection by liquid biopsy: ripe for clinical usage.

Introduction: With the International Association for the Study of Lung Cancer (IASLC) recommendations promoting liquid biopsy as a primary detection tool, a new era of research has begun. The authors aimed to study the concordance of plasma genotyping platforms against the tissue gold standard. Methods: 184 patients with non-small cell lung cancer underwent EGFR genotyping using Cobas, droplet digital polymerase chain reaction (ddPCR) and Therascreen assays from 2019-2020. Results: Of 184 cases, 70 were positive by Cobas, 51 by ddPCR and 69 by Therascreen. The sensitivity of Cobas was 97.1% and the sensitivity of ddPCR was 71%. Receiver operating characteristic analysis showed an area under the curve of 0.977 for Cobas and 0.846 for ddPCR. Conclusion: In line with the FLAURA trial of osimertinib making its way to first-line and given the IASLC recommendations, it is important to understand the attributes of these tests to initiate appropriate treatment.

Lay abstract Lung cancer is one of the most common malignancies and has been known to have a dismal outcome. However, owing to evolution in the knowledge of disease biology and processes, many molecules have been discovered that can be used in targeted therapy. To institute this modality of treatment, detection of alterations in these specific molecules, namely: EGFR, ALK, ROS1, RET, MET, KRAS G12C, BRAF V600E, NTRK1, NTRK2, NTRK3 and ERBB2 is necessary. This has traditionally been done using single-gene assays, which require more tissue. This is a major limitation in cases of non-small cell lung carcinoma, as the biopsies are small. Hence, new technologies like next-generation sequencing have emerged that offer a one-stop solution for these cases. In cases where tissue is very scant, the use of peripheral blood has now been recommended by international guidelines for primary detection of these molecular alterations. This article describes the concordance of tissue-based detection and blood-based detection using three different assays, for the detection of EGFR alterations. Although promising results were obtained largely for blood-based assays, liquid and tissue biopsies are complementary.

Clinical Correlation Between Vertical Gaze Palsy and Midbrain Volume in Progressive Supranuclear Palsy.

BACKGROUND: Supranuclear vertical gaze palsies and slowed vertical saccades are characteristic clinic features of progressive supranuclear palsy (PSP). The "hummingbird sign," reflective of midbrain atrophy, is a classic radiographic sign of PSP. Correlation between eye movement abnormalities and radiographic findings in PSP has been reported previously. However, due to the use of clinical criteria not commonly employed in neuro-ophthalmic practice and neuroimaging techniques that are not widely available, it remains unclear whether correlation between midbrain structure and characteristic ocular-motor disturbances can be helpful to neuro-ophthalmologists seeking to adjudicate difficult or unusual diagnostic cases. METHODS: Patients with a diagnosis of probable PSP according to Movement Disorders Society criteria were studied retrospectively. A neuroradiologist calculated brainstem volumes in enrolled participants and normal controls. Spearman correlations were used to correlate the extent of eye movement limitation as assessed by 2 neuro-ophthalmologists with brainstem volumes. RESULTS: Fourteen participants with PSP and 15 healthy controls with similar age and gender distribution were enrolled and evaluated retrospectively. All 14 participants with PSP had undergone MRIs. Midbrain atrophy significantly correlated with the PSP rating scale (P < 0.001). PSP patients had significantly reduced volumes in the midbrain (P -0.0026), tegmentum (0.0001), tectum (0.0001), and medulla (P = 0.0024) compared with normal controls. Notes documenting quantified ocular motor function were available in 7 of 14 participants with PSP. Midbrain atrophy significantly correlated with in the extent of upward gaze limitation (P = 0.03). CONCLUSIONS: The severity of upward gaze limitation correlates with the severity of midbrain atrophy in patients with PSP. Recognition of this correlation may help to adjudicate diagnostic dilemmas and guide further evaluation.

Are all ALK variants created equal? Clinicopathologic features and outcomes: a propensity-matched study.

Anaplastic lymphoma kinase (ALK) rearranged NSCLC comprises a molecularly distinct subgroup occurring in 10% cases. Various EML4-ALK and non EML4 variants are known to occur which can be detected only on NGS and show differential TKI responses. 113 ALK-IHC positive cases were subjected to a custom panel-based NGS for detection of ALK variants. Clinicopathologic features and outcomes were studied and propensity-matched analysis was done. The median age of the overall cohort was 53 years. 91 (80.5%) cases were NGS positive, the most common being EML4-ALK (90, 98.9%) cases. The most common EML4 variant was Variant 1 (40, 35%) cases, Variant 3 (28, 25%) cases, and Variant 2 (17, 15%) cases. One novel EML4-ALK variant was also encountered which was found to be intrinsically resistant to crizotinib. On pre-weight-adjusted comparison, Variant 1 group had a higher occurrence of brain and extrathoracic metastases. The median OS was 44 months for the entire cohort. 49 patients received crizotinib as first-line TKI. Among these, the median OS for Variant 2 was not reached; it was 38 months and 24 months for Variant 1 and Variant 3, respectively. The median PFS for crizotinib treated patients was 8.3 months (Variant 2: 11 months, Variant 1: 8 months, and Variant 3: 9 months). On propensity-matched analyses, there was no difference in OS and PFS between Variant 1 and Variant 3, with higher HR for Variant 3. We present a large data set evaluating clinical and outcome differences between ALK variants. The unique standpoint of this study involves the propensity-weighted model to account for differences among the groups, with no prognostic differences between Variant 1 and Variant 3, which is distinct from literature.

A Flexible Coding Scheme Based on Block Krylov Subspace Approximation for Light Field Displays with Stacked Multiplicative Layers.

To create a realistic 3D perception on glasses-free displays, it is critical to support continuous motion parallax, greater depths of field, and wider fields of view. A new type of Layered or Tensor light field 3D display has attracted greater attention these days. Using only a few light-attenuating pixelized layers (e.g., LCD panels), it supports many views from different viewing directions that can be displayed simultaneously with a high resolution. This paper presents a novel flexible scheme for efficient layer-based representation and lossy compression of light fields on layered displays. The proposed scheme learns stacked multiplicative layers optimized using a convolutional neural network (CNN). The intrinsic redundancy in light field data is efficiently removed by analyzing the hidden low-rank structure of multiplicative layers on a Krylov subspace. Factorization derived from Block Krylov singular value decomposition (BK-SVD) exploits the spatial correlation in layer patterns for multiplicative layers with varying low ranks. Further, encoding with HEVC eliminates inter-frame and intra-frame redundancies in the low-rank approximated representation of layers and improves the compression efficiency. The scheme is flexible to realize multiple bitrates at the decoder by adjusting the ranks of BK-SVD representation and HEVC quantization. Thus, it would complement the generality and flexibility of a data-driven CNN-based method for coding with multiple bitrates within a single training framework for practical display applications. Extensive experiments demonstrate that the proposed coding scheme achieves substantial bitrate savings compared with pseudo-sequence-based light field compression approaches and state-of-the-art JPEG and HEVC coders.

Semiquantitative Criteria in the Eye Bank That Correlate with Cornea Guttata in Donor Corneas.

BACKGROUND: Cornea guttata may not be recognized in the eye bank and recent studies have displayed that guttae are transplanted in about 15% of cases in varying severities. The purpose of this study was to establish semiquantitative criteria for the detection of cornea guttata in donor corneas in the eye bank. METHODS: In this retrospective cohort study, preoperative endothelial pictures of donor corneas were collected and classified according to the post-penetrating keratoplasty cornea guttata grade into three distinct groups: group 1 consists of healthy corneas with no guttae (guttata grade 0); group 2 constitutes corneas with mild asymptomatic cornea guttata (guttata grade +); and group 3 comprises corneas with advanced widespread cornea guttata (guttata grade ++/+++/++++). The preoperative pictures of each group were then individually analyzed using the following five semiquantitative criteria: The number and the area of the cell-depleted surfaces, the presence of less than 50% of the cells having a hexagonal or a circular shape, the presence of cell membrane defects and interruptions, the presence of blebs in the cell membrane, and the presence of groups of cells with a distinct whitish color. RESULTS: In total, 262 patients were included in this study, with a total number of 1582 preoperative donor corneal endothelial pictures. Out of those pictures, groups 1, 2, and 3 encompassed 995 (62.9%), 411 (26.0%), and 176 (11.1%) pictures, respectively. Three out of the five eye bank criteria were found to correlate with postoperative cornea guttata with a highly significant p value of < 0.001. These three criteria are the presence of less than 50% of the cells having a hexagonal or a circular shape, the presence of cell membrane defects and interruptions and, the presence of blebs. The presence of groups of cells with a distinct whitish color was only a weak predictive factor for cornea guttata (p = 0.069). There was no statistically significant correlation between the number and the area of cell-depleted surfaces and postoperative cornea guttata with a p = 0.181. CONCLUSION: Three semiquantitative criteria that can be detected in the eye bank using inverted light microscopy seem to correlate with postoperative cornea guttata: The presence of blebs, the presence of cell membrane defects and interruptions, as well as endothelial pictures with less than 50% of the cells having a hexagonal of circular shape. The presence of groups of cells with a distinct whitish color appears to be a weak predictor of cornea guttata.

Nature of phytotoxic interference of alien weed 'Calyptocarpus vialis' against some crop plants.

Calyptocarpus vialis (syn. Synedrella vialis; Asteraceae), a native of the tropical Americas, has acquired an invasive status in the eastern Asia and Africa and, of late, in India. It is an annual herbaceous weed that forms a dominant ground cover due to its prostrate expansion and interferes with the growth of other plant species. However, the reasons for this interference are largely unknown. Therefore, we examined the allelopathic interference of C. vialis via leachation and residue degradation on the emergence, growth, and development of three crop species (Brassica nigra, Triticum aestivum, and Avena sativa). In a laboratory bioassay, the leachates (0.5-4%) of C. vialis exhibited a dose-dependent inhibitory effect on various growth parameters of the test plants. Similarly, under screenhouse, C. vialis-amended soil (1-4%) affected the growth of test species in a dose-dependent manner. Further, the phytotoxicity of the residues of C. vialis was examined using rhizospheric soil (RS) and residue-amended soil (RAS). It was observed that RAS exerted the maximum allelopathic effect on the test species accompanied by significant changes in pH, electrical conductivity, and total water-soluble phenolic content, as compared with the control soil (CS) and RS. Liquid chromatography and mass spectroscopy analyses confirmed the presence of eleven allelochemicals as the major phytotoxins. The study demonstrated that C. vialis exerts strong phytotoxic effects on other plants through the release of potent allelochemicals, both via leachation and residue degradation.

Ki-67 labeling index as a predictor of response to neoadjuvant chemotherapy in breast cancer.

AIMS: To investigate Ki-67 index with regard to its ability to predict achievement of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer patient. MATERIAL AND METHODS: It was a prospective observational study, conducted in Department of Medical Oncology, Rajiv Gandhi Cancer Institute & Research Center (RGCIRC), New Delhi from February 2014 to March 2016. A total of 134 patients with Stage II/III breast cancer who underwent NACT followed by surgery at our center were enrolled and analyzed. Before starting the treatment, clinical, tumor-related and treatment-related factors were recorded. Response evaluation was done clinically and radiologically after completion of NACT and pathologically on the surgical specimen. We calculated Ki-67 cut-off of 35% to label it as high by area under Receiver operating characteristic curve analysis for prediction of pCR. RESULTS: Clinical complete response (cCR) was observed in 35/134 (26.1%) patients while pCR was observed in 32/134 (23.9%) patients. On univariate analysis, higher grade (III), high Ki-67 index (>35%) and number of chemotherapy cycles (>3) were associated with better CCR rates. On multivariate analysis, number of chemotherapy cycles (>3) and high Ki-67 index (>35%) were independent predictive factors. For the predictive factors of pCR, univariate analysis showed grade (III), estrogen receptor/progesterone receptor negativity, HER-2 positivity, number of chemotherapy cycles (>3), TNBC and high Ki-67 index (>35%) to be associated with higher pCR rates. On multivariate analysis, Ki-67 index >35% and HER-2 positivity were the only independent predictive factors of pCR. CONCLUSIONS: We suggest 35% as best cut-off for Ki-67 expression for predicting response to NACT and achievement of pCR. Validation of this cut-off is required in larger studies.

Antimicrobial potentials of Helicteres isora silver nanoparticles against extensively drug-resistant (XDR) clinical isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a leading opportunistic pathogen and its expanding drug resistance is a growing menace to public health. Its ubiquitous nature and multiple resistance mechanisms make it a difficult target for antimicrobial chemotherapy and require a fresh approach for developing new antimicrobial agents against it. The broad-spectrum antibacterial effects of silver nanoparticles (SNPs) make them an excellent candidate for use in the medical field. However, attempts made to check their potency against extensively drug-resistant (XDR) microbes are meager. This study describes the biosynthesis and biostabilization of SNPs by Helicteres isora aqueous fruit extract and their characterization by ultraviolet-visible spectroscopy, transmission electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. Majority of SNPs synthesized were of 8--20-nm size. SNPs exhibited dose-dependent antibacterial activities against four XDR P. aeruginosa (XDR-PA) clinical isolates as revealed by growth curves, with a minimum inhibitory concentration of 300 µg/ml. The SNPs exhibited antimicrobial activity against all strains, with maximum zone of inhibition (16.4 mm) in XRD-PA-2 at 1000 µg/ml. Amongst four strains, their susceptibilities to SNPs were in the following order: XDR-PA-2 > XDR-PA-4 > XDR-PA-3 > XDR-PA-1. The exposure of bacterial cells to 300 µg/ml SNPs resulted into a substantial leakage of reducing sugars and proteins, inactivation of respiratory chain dehydrogenases, and eventual cell death. SNPs also induced lipid peroxidation, a possible underlying factor to membrane porosity. The effects were more pronounced in XDR-PA-2 which may be correlated with its higher susceptibility to SNPs. These results are indicative of SNP-induced turbulence of membranous permeability as an important causal factor in XDR-PA growth inhibition and death.

Cell-penetrating protein-recognizing polymeric nanoparticles through dynamic covalent chemistry and double imprinting.

Molecular recognition of proteins is key to their biological functions and processes such as protein-protein interactions (PPIs). The large binding interface involved and an often relatively flat binding surface make the development of selective protein-binding materials extremely challenging. A general method is reported in this work to construct protein-binding polymeric nanoparticles from cross-linked surfactant micelles. Preparation involves first dynamic covalent chemistry that encodes signature surface lysines on a protein template. A double molecular imprinting procedure fixes the binding groups on the nanoparticle for these lysine groups, meanwhile creating a binding interface complementary to the protein in size, shape, and distribution of acidic groups on the surface. These water-soluble nanoparticles possess excellent specificities for target proteins and sufficient affinities to inhibit natural PPIs such as those between cytochrome c (Cytc) and cytochrome c oxidase (CcO). With the ability to enter cells through a combination of energy-dependent and -independent pathways, they intervene apoptosis by inhibiting the PPI between Cytc and the apoptotic protease activating factor-1 (APAF1). Generality of the preparation and the excellent molecular recognition of the materials have the potential to make them powerful tools to probe protein functions in vitro and in cellulo.

Chemotherapy for Salivary Gland Malignant Carcinoma : Meta-analysis and Systemic Review.

 The primary form of treatment for salivary gland cancer is surgical resection. Radiation therapy is used as adjuvant therapy in cases of aggressive tumours, currently patients with recurrent or metastatic cancer who are not suitable for surgery or radiation are most often treated with chemotherapy. PRISMA guidelines for systematic reviews were followed to evaluate salivary gland malignancies involving cytotoxic chemotherapy and biologic agents. An electronic literature search of Medline, PubMed, Scopus, etc. was performed and relevant articles were selected based on the inclusion criteria. Cytotoxic chemotherapies and biologic drugs such as anti HER - 2, anti-EGFR and anti-C-Kit are used to treat salivary gland cancer. Although most trials have respond poorly to standard chemotherapy with short durability and significant toxicity. Most of the research has focused on ACC and the use of combination therapy with cisplastin in conjunction with other treatments has been found to improve overall survival rate. Due to the limited patient population it was difficult to assess the efficacy of chemotherapy, which achieved very modest results. There are potential molecular targets such as HER2,NTRK and targeted treatments are becoming more popular. However to further explore potential treatment alternatives SGC patients should be enrolled in clinical trials.

Outcomes of intravitreal anti-VEGF injections and panretinal photocoagulation in preretinal hemorrhage secondary to proliferative diabetic retinopathy involving the fovea.

PURPOSE: To evaluate the outcome of intravitreal anti-vascular endothelial growth factor (VEGF) injections and panretinal photocoagulation (PRP) in fovea involving preretinal hemorrhage (PRH) secondary to proliferative diabetic retinopathy (PDR). METHODS: Retrospective non-comparative cross-sectional series of patients diagnosed with fovea involving PRH secondary to PDR at our institute from March 2019 to October 2021 who were treated with combination treatments of intravitreal anti-VEGF and PRP and have completed a minimum 6-month follow-up. The primary outcome measure was serial changes in the visual acuity (VA) and PRH regression from the fovea. Secondary outcome measures were the quantitative assessment of the size of PRH, its association with VA improvement and time to regression, and the proportion of patients who underwent surgery for poor response. RESULTS: In total, 22 eyes of 21 patients showed regression of PRH from the foveal center at 33.6 days, and complete regression was seen at 140.7 days. The average number of anti-VEGF injections required for clearance of PRH from the fovea was 1.6. Mean LogMAR visual acuity improved from 0.54 at baseline to 0.32 at 4 weeks and 0.18 at 6 months ( P < 0.01). Three eyes (13.6%) required vitrectomy surgery during follow-up. The mean area of PRH as measured by Image J analysis was 14.78 mm 2 at baseline, 8.97 mm 2 at 4 weeks, and 1.25 mm 2 at 3 months ( P < 0.01). No statistically significant difference was seen between the size of PRH and PRH clearance time and VA improvement. No systemic side effects were observed following the intravitreal injections during follow-up. CONCLUSION: Intravitreal anti-VEGF injections and PRP were found to be effective and safe treatment methods for fovea involving PRH secondary to PDR. Long-term studies are warranted to assess the long-term efficacy.

Investigation of Anterior Teeth Fractures Among Students Aged Between 8 and 13 Years in Hyderabad, India.

Introduction Trauma involving anterior teeth stands as a prevalent type of dental injury among school-age children, impacting physical, psychological, and social well-being. This study aimed to assess the occurrence of fractures in anterior teeth among school children in Hyderabad and its associated risk factors. Materials and methods This research incorporated a cross-sectional analysis, involving 2046 children in the age group of 8 to 13 years from different schools in Hyderabad City. Alongside clinical evaluations, all participants completed a questionnaire regarding traumatic dental injuries.  Results Results indicated a prevalence rate of 8.5%, notably higher among younger boys. Factors such as lip competence coverage, increased overjet, and malocclusion with maxillary incisor proclination were associated with a heightened risk of such injuries. The peak incidence was observed at age 12, with fractures involving enamel and dentin being the most common type, predominantly affecting the maxillary central incisors. Conclusion The findings emphasize the significance of educational programs aimed at enhancing awareness and understanding of dental injuries among parents, students, and school staff.

COVID-19 and Cancer: A Comparison of the Two Important Pandemic Waves in an Indian Cancer Patients' Cohort.

Ullas BatraIt is well known that patients with cancer are at an increased risk of severe COVID-19. There are no reports that depict the differences in outcomes in cancer patients between the two waves of the pandemic. This is a real-world experience aimed at characterizing the differences in demographics, clinical features, treatment details, and outcomes in COVID-19-positive cancer patients between the two pandemic waves. This was a prospective study of all COVID-19-positive cancer patients attending our specialty out-patient department at Rajiv Gandhi Cancer Institute and Research Centre between March 2020 and November 2020 (1st wave) and April 2021 and June 2021 (second wave). All patients diagnosed to have COVID-19 by real-time polymerase chain reaction (RT-PCR) with a biopsy-proven solid organ malignancy attending the medical oncology out-patient department were included during both the waves. A total of 300 patients with proven SARS-CoV-2 infection by either RT-PCR or cartridge based nucleic acid amplification test were encountered, of which 123 were encountered during the first wave of the pandemic and 177 during the second wave. The case fatality rate of the first wave was 9.8%, with a 15-day case fatality rate of 5.6%, whereas for the second wave, it was 13% and 7.2%, respectively. Twelve patients succumbed to COVID-19 disease in the first wave and 23 succumbed in the second. There were no statistically significant correlations; however, the death in the second wave tended to occur more in younger male patients, with comorbidities and history of smoking. There was no relation with ongoing cancer-directed treatment or chemotherapy. Our study is unique in comparing characteristics of the two most important COVID-19 waves and treatment patterns in cancer patients from a single center. The second wave showed a higher CFR, hospital admission rate, and higher frequency of respiratory complications; however, there was no relation to cancer-directed therapy and COVID-19, thus reiterating the fact that cancer treatment should not be halted in the event of a COVID-19 infection.

AI-based pipeline for early screening of lung cancer: integrating radiology, clinical, and genomics data.

Background: The prognosis of lung carcinoma has changed since the discovery of molecular targets and their specific drugs. Somatic Epidermal Growth Factor Receptor (EGFR) mutations have been reported in lung carcinoma, and these mutant proteins act as substrates for targeted therapies. However, in a resource-constrained country like India, panel-based next-generation sequencing cannot be made available to the population at large. Additional challenges such as adequacy of tissue in case of lung core biopsies and locating suitable tumour tissues as a result of innate intratumoral heterogeneity indicate the necessity of an AI-based end-to-end pipeline capable of automatically detecting and learning more effective lung nodule features from CT images and predicting the probability of the EGFR-mutant. This will help the oncologists and patients in resource-limited settings to achieve near-optimal care and appropriate therapy. Methods: The EGFR gene sequencing and CT imaging data of 2277 patients with lung carcinoma were included from three cohorts in India and a White population cohort collected from TCIA. Another cohort LIDC-IDRI was used to train the AIPS-Nodule (AIPS-N) model for automatic detection and characterisation of lung nodules. We explored the value of combining the results of the AIPS-N with the clinical factors in the AIPS-Mutation (AIPS-M) model for predicting EGFR genotype, and it was evaluated by area under the curve (AUC). Findings: AIPS-N achieved an average AP50 of 70.19% in detecting the location of nodules within the lung region of interest during validation and predicted the score of five lung nodule properties. The AIPS-M machine learning (ML) and deep learning (DL) models achieved AUCs ranging from 0.587 to 0.910. Interpretation: The AIPS suggests that CT imaging combined with a fully automated lung-nodule analysis AI system can predict EGFR genotype and identify patients with an EGFR mutation in a cost-effective and non-invasive manner. Funding: This work was supported by a grant provided by Conquer Cancer Foundation of ASCO [2021IIG-5555960128] and Pfizer Products India Pvt. Ltd.

Modulation of Leishmania major aquaglyceroporin activity by a mitogen-activated protein kinase.

Leishmania major aquaglyceroporin (LmjAQP1) adventitiously facilitates the uptake of antimonite [Sb(III)], an active form of Pentostam® or Glucantime®, which are the first line of defence against all forms of leishmaniasis. The present paper shows that LmjAQP1 activity is modulated by the mitogen-activated protein kinase, LmjMPK2. Leishmania parasites coexpressing LmjAQP1 and LmjMPK2 show increased Sb(III) uptake and increased Sb(III) sensitivity. When subjected to a hypo-osmotic stress, these cells show faster volume recovery than cells expressing LmjAQP1 alone. LmjAQP1 is phosphorylated in vivo at Thr-197 and this phosphorylation requires LmjMPK2 activity. Lys-42 of LmjMPK2 is critical for its kinase activity. Cells expressing altered T197A LmjAQP1 or K42A LmjMPK2 showed decreased Sb(III) influx and a slower volume recovery than cells expressing wild-type proteins. Phosphorylation of LmjAQP1 led to a decrease in its turnover rate affecting LmjAQP1 activity. Although LmjAQP1 is localized to the flagellum of promastigotes, upon phosphorylation, it is relocalized to the entire surface of the parasite. Leishmania mexicana promastigotes with an MPK2 deletion showed reduced Sb(III) uptake and slower volume recovery than wild-type cells. This is the first report where a parasite aquaglyceroporin activity is post-translationally modulated by a mitogen-activated protein kinase.