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Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT.PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/mBetween July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70-78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1-18·0). 49 (80% [95% CI 68-89]; p0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths.These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended.Juno Therapeutics, a Bristol-Myers Squibb company.

Background: Hallers cells, seen as incidental findings on radiographs, are located at the floor of the orbit and superior most aspect of the maxillary sinus. These cells are attributed to the anatomical variations in the growth and development of nose and paranasal sinuses leading to clinically significant symptoms such as headache, chronic cough, sinusitis, orofacial pain, impaired nasal breathing and various maxillofacial region associated pathologies.Therefore, the present study was carried out on hallers cells considering their clinical significance. Aims and Objectives:To determine the prevalence and radiographic characteristics of hallers cells using digital panoramic radiographs. Materials and Methods:The present retrospective study was carried out in a diagnostic setup, dental hospital, Bengaluru, Karnataka over the period of two years. Initially, the study group consists of 2376 participants, out of which 1800 met the inclusion criteria and were randomly enrolled in the studywith age range of 10 - 60 years. The digital panoramic images obtained were interpreted for presence and characteristics of hallers cells by trained oral and maxillofacial radiologists according to Ahmad M etals criteria. Results:Out of 1800 digital panoramic radiographs the hallers cells were seen in 214 radiographs of study participants, stating the prevalence rate of 11.88 %. The mean age of the study participants with hallers cells were 27.46 ± 17.93 years.Majority of cells seen on digital panoramic radiographs wereround (35.98%) and triangular (5.14%) in shape with unilocular appearance. A significant difference was observed with the shape of the hallers cells with p value of 0.001. Conclusion: The prevalence and characteristics of the hallers cells is in accordance with the various studies published in literature with highest number of panoramic radiographs taken into consideration till our knowledge. The incidental appearance of hallers cells on panoramic radiographs has its own significance in diagnosing various pathologies along with avoiding intraoperative complications in endonasal surgeries.

Ground failure is a major contributor to fatalities in underground mines in the US. Underground coal mines in the Northern Appalachian have weak roof rock composed of shale, which is prone to failure under high horizontal stress. Understanding the relationship among strength, specimen size and rock petrographic parameters is essential for developing an effective ground control plan. Size effect studies have found that rock strength varies with specimen size. This paper attempts to understand this strength variation using three specimen sizes (254-mm, 508-mm, and 762-mm). The specimen strength was measured and the major petrographic parameters affecting the strength, namely grain size, grain shape, quartz content, clay content, etc. were analyzed using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The petrographic parameters were then correlated with the strength of the three differently sized specimens. The results showed that 508-mm specimen had the lowest strength. Quartz content of the 508-mm specimen was lower than that of 254-mm and 762-mm specimens. Clay content and average grain size of the 508-mm specimen were higher than those of 254-mm and 762-mm specimens. These results clearly show that grain size, quartz content and clay content contribute to strength variation observed in differently sized shale specimens.

Coal mining activity disturbs the natural equilibrium of in situ stress state such that the induced stresses deform the surrounding rock mass. Although the installation of roof supports typically prevents rock deformation, rock mass failure may still occur in bolted roof. The erratic failure of rock mass after few days to months and years of excavation is the result of time-dependent deformation of roof rock under constant surrounding stresses. In the current research, the triaxial laboratory creep experiments proved that Marcellus shale exhibits time-dependent deformation under constant stress that was smaller than the failure strength. However, unlike conventional experimental results, the time-dependent deformation did not depend on the level of constant stress. The often-neglected initial state of specimens and intrinsic heterogeneity highly influenced the time-dependent failure of Marcellus shale.

Time is one of the often-neglected factors in the assessment of the erratic failure of shale rock. Laboratory-creep experiments showed that constant stress induces time-dependent failure in brittle shale. However, the microscopic reason for time-dependent deformation in shale is still unknown. In the current study, triaxial creep and recovery experiments showed that the brittle shale specimens exhibit viscoelastic and viscoplastic creep deformation at constant stress state. In addition, the X-ray computed tomography scan of Marcellus shale showed that the shale specimens contained significant volume of preexisting microcracks. The statistical correlation among permanent strain during the triaxial experiment and stress-induced change in the three-dimensional geometry of microcracks showed that the microcracking is the microscopic reason for viscoplastic creep deformation in shale. In addition to the time and level of constant differential stress, factors such as orientation of bedding planes and specimen heterogeneity also influence the nature of creep deformation.

In past couple of decades, scanning electron microscope and digital image correlation has been extensively used to investigate the microcrack propagation in rocks. Only recently, X-ray computed tomography (CT) scans were used for more detailed understanding of the physico-mechanical behavior of rock specimens. In current study, the deformational behavior of bedded Marcellus shale was studied through the changes in the geometry of microcracks. Quasi-static triaxial tests at three successive levels of differential stress were conducted on cylindrical-shaped shale specimens at a confining pressure of 6.89 MPa. Mineralogical analysis indicated the homogenous composition of specimen, however, triaxial tests resulted varying modulus of stiffness at similar confining pressure. The X-ray CT scanned images of specimens prior to the triaxial stress showed the significant density of pre-existing microcracks. During triaxial tests, the successive levels of differential stress influenced the geometry of pre-existing microcracks. The differential stress equivalent to 55% and 65% of the differential strength significantly closed the pre-existing microcracks. However, differential stress equivalent to 70% of the differential strength increased the density of microcracks. The orientation of the bedding plane only influenced the direction of microcrack propagation. The perpendicular-bedded specimen experienced significant microcrack propagation in the axial direction, while the parallel-bedded specimen experienced significant increase in the aperture of microcracks.

Background:Hallers cells, seen as incidental findings on radiographs, are located at the floor of the orbit and superior most aspect of the maxillary sinus. These cells are attributed to the anatomical variations in the growth and development of nose and paranasal sinuses leading to clinically significant symptoms such as headache, chronic cough, sinusitis, orofacial pain, impaired nasal breathing and various maxillofacial region associated pathologies.Therefore, the present study was carried out on hallers cells considering their clinical significance. Aims and Objectives:To determine the prevalence and radiographic characteristics of hallers cells using digital panoramic radiographs. Materials and Methods:The present retrospective study was carried out in a diagnostic setup, dental hospital, Bengaluru, Karnataka over the period of two years. Initially, the study group consists of 2376 participants, out of which 1800 met the inclusion criteria and were randomly enrolled in the studywith age range of 10 - 60 years. The digital panoramic images obtained were interpreted for presence and characteristics of hallers cells by trained oral and maxillofacial radiologists according to Ahmad M etals criteria. Results:Out of 1800 digital panoramic radiographs the hallers cells were seen in 214 radiographs of study participants, stating the prevalence rate of 11.88 %. The mean age of the study participants with hallers cells were 27.46 ± 17.93 years.Majority of cells seen on digital panoramic radiographs wereround (35.98%) and triangular (5.14%) in shape with unilocular appearance. A significant difference was observed with the shape of the hallers cells with p value of 0.001. Conclusion: The prevalence and characteristics of the hallers cells is in accordance with the various studies published in literature with highest number of panoramic radiographs taken into consideration till our knowledge. The incidental appearance of hallers cells on panoramic radiographs has its own significance in diagnosing various pathologies along with avoiding intraoperative complications in endonasal surgeries. &nbsp

As public distribution of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is underway, prevention of coronavirus disease 2019 (COVID-19) relies on minimizing spread. Toothbrushes are a potent source of infection as it harbours the microorganisms and increases the viral load as well. It also increases the chances of cross infection among family members. Therefore disinfecting toothbrushes after every use may be a viable option to decrease the total viral load as well as to limit the chances of cross - infection. This communication aims to focus on the fact that toothbrushes may be another potential source of infection in this pandemic, thereby this needs to be disinfected after every use and once person is recovered, it should be replaced with a new one.

Due to the complex structure of the brittle formations like shale, their microcracking and mechanical deformation behavior are not well known. To understand the fundamental factors at the micron scale, Marcellus shales were cored both parallel and perpendicular to the bedding orientation and mechanically tested through triaxial creep test under constant stress. The parallel-bedded shales exhibited higher level of permanent strain in the radial direction, which increased with increasing time. This also confirmed their anisotropic nature due to the bedding. Their advanced characterization via X-ray diffraction (XRD) and Raman spectroscopy techniques before and after the creep tests revealed the mineralogical heterogeneity, and the presence of an organic matter (kerogen) concentrated in the microcrack areas. Besides, the XRD peak shifts and changes in peak shape indicated that there was a certain level of macrostrain and microstrain in the shale. Further investigation of the XRD peak shape (integral breadth) changes using the Williamson-Hall method demonstrated a higher concentration of lattice defects and associated microstrain (inhomogeneous lattice strain) present in the calcite phase compared to the quartz. The parallel-bedded shales also revealed a higher level of microstrain with respect to the perpendicular-bedding. The results proved that the microcracking (initiation and propagation) and associated mechanical deformation of the Marcellus shales were mostly influenced by the presence of organic matter, microstrain level (defect concentration) in the calcite mineral, and the bedding orientation.

Due to the complex structure of the brittle formations like shale, their microcracking and mechanical deformation behavior are not well known. To understand the fundamental factors at the micron scale, Marcellus shales were cored both parallel and perpendicular to the bedding orientation and mechanically tested through triaxial creep test under constant stress. The parallel-bedded shales exhibited higher level of permanent strain in the radial direction, which increased with increasing time. This also confirmed their anisotropic nature due to the bedding. Their advanced characterization via X-ray diffraction (XRD) and Raman spectroscopy techniques before and after the creep tests revealed the mineralogical heterogeneity, and the presence of an organic matter (kerogen) concentrated in the microcrack areas. Besides, the XRD peak shifts and changes in peak shape indicated that there was a certain level of macrostrain and microstrain in the shale. Further investigation of the XRD peak shape (integral breadth) changes using the Williamson-Hall method demonstrated a higher concentration of lattice defects and associated microstrain (inhomogeneous lattice strain) present in the calcite phase compared to the quartz. The parallel-bedded shales also revealed a higher level of microstrain with respect to the perpendicular-bedding. The results proved that the microcracking (initiation and propagation) and associated mechanical deformation of the Marcellus shales were mostly influenced by the presence of organic matter, microstrain level (defect concentration) in the calcite mineral, and the bedding orientation.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

Shoulder instability encompasses a spectrum of disease ranging from subluxation to dislocation, and is typically associated with collision athletes such as wrestlers and football players. Instability, however, also can be the result of repetitive microtrauma, as seen in overhead athletes (baseball, tennis, volleyball, swimming). The presentation of instability can be subtle, and difficult to diagnose in the absence of an acute traumatic event without the proper suspicion, physical examination, and diagnostic evaluation. Overhead athletes present the unique challenge of requiring the glenohumeral joint to exceed its physiologic limits during competition; therefore, injury in this population can be devastating. Additionally, athletes who experience instability, regardless of treatment, require rehabilitation (including periscapular strengthening) to maximize strength of the surrounding musculature. Specifically they will require coordinated throwing programs, and gradual return to play protocols dependent on their sport. This article reviews the specific physiology, diagnosis, and treatment of shoulder instability in this population.

The aim of present study is prediction of blast-induced flyrock distance in opencast limestone mines using artificial intelligence techniques such as artificial neural network (ANN) and adaptive neuro fuzzy inference system (ANFIS). Blast design and geotechnical variables such as linear charge concentration, burden, stemming length, specific charge, unconfined compressive strength, and rock quality designation have been selected as independent variables and flyrock distance has been used as dependent variable. Blasts required for the study purpose have been conducted in four limestone mines in India. Out of one hundred and twenty-five (125) blasts, dataset of one hundred blasts have been used for training, testing and validation of the ANN and ANFIS based prediction model. Twenty-five (25) data have been used for evaluation of the trained ANN and ANFIS models. In order to know the relationship among the independent and dependent variables, multi-variable regression analysis (MVRA) has also been performed. The performance indices such as root mean square error (RMSE), mean absolute error (MAE) and coefficient of determination (R-2) have been evaluated for ANN, ANFIS and MVRA. RMSE as well as MAE have been found lower and R-2 has been found higher in case of ANFIS in comparison of ANN and MVRA. ANFIS has been found a superior predictive technique in comparison to ANN and MVRA. Sensitivity analysis has also been performed using ANFIS to assess the impact of independent variables on flyrock distance.

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P

Understanding the influence of gene expression on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. We have carried out whole transcriptome expression analysis on a series of eight normal human postmortem eyes by RNA sequencing. Here we present data showing that ∼80% of the transcriptome is expressed in the posterior layers of the eye and that there is significant differential expression not only between the layers of the posterior part of the eye but also between locations of a tissue layer. These differences in expression also extend to alternative splicing and splicing factors. Differentially expressed genes are enriched for genes associated with psychiatric, immune and cardiovascular disorders. Enrichment categories for gene ontology included ion transport, synaptic transmission and visual and sensory perception. Lastly, allele-specific expression was found to be significant forCFH,C3 andCFB, which are known risk genes for age-related macular degeneration. These expression differences should be useful in determining the underlying biology of associations with common diseases of the human retina, retinal pigment epithelium and choroid and in guiding the analysis of the genomic regions involved in the control of normal gene expression.