Factors Determining Long-Term Antitumor Responses to Immune Checkpoint Blockade Therapy in Melanoma

With the increasing promise of long-term survival with immune checkpoint blockade (ICB) therapies, particularly for patients with advanced melanoma, clinicians and investigators are driven to identify prognostic and predictive factors that may help to identify individuals who are likely to experience durable benefit. Several ICB combinations are being actively developed to expand the armamentarium of treatments for patients who may not achieve long-term responses to ICB single therapies alone. Thus, negative predictive markers are also of great interest. This review seeks to deepen our understanding of the mechanisms underlying the durability of ICB treatments. We will discuss the currently available long-term data from the ICB clinical trials and real-world studies describing the survivorship of ICB-treated melanoma patients. Additionally, we explore the current treatment outcomes in patients rechallenged with ICB and the patterns of ICB resistance based on sites of disease, namely, liver or CNS metastases. Lastly, we discuss the landscape in melanoma in the context of prognostic or predictive factors as markers of long-term response to ICB.

Spatiotemporal Characteristics of Meteorological Drought During the Past Half Century in Different Climates Over Iran

The present study compares the main characteristics (intensity, duration, and frequency) of meteorological drought events in the four climates (Hyperarid, Arid, Semiarid, and Humid) of Iran. For this purpose, three drought indices, including Standardized Precipitation Index (SPI), Reconnaissance Drought Index (RDI), and Standardized Precipitation Evapotranspiration Index (SPEI), were employed at the timescales of 1-, 3-, 6-, 9- and 12-months. These indices were compared by utilizing long-term data of 41 synoptic meteorological stations for the recent half century, 1969–2019. The long-term analysis of drought indices indicates that the duration and intensity of drought events have temporally risen after the 1998–99 period. Iran has experienced the longest duration (40 months) of extreme drought during Dec 98–Mar 02 and Jan 18–Mar 18, respectively. Spatial patterns demonstrate that drought intensity uniformly increased in SPI1 to SPI12, and SPEI3 to SPEI12, from humid and semiarid to arid and hyperarid regions. The average drought duration in studied stations for SPI, SPEI and RDI indices equaled 9, 12, and 9 months, respectively. In addition, mean drought frequencies are calculated at 14, 17, and 13 percent for SPI, SPEI and RDI indices, respectively. Generally, SPEI compared to SPI and RDI shows greater duration and frequency of drought events, particularly in arid and hyperarid regions. The research shows the crucial role of climatic variables in detecting drought characteristics and the importance of selecting appropriate drought indices in various climates.

Epidemiological models based on meteorological variables to forewarn Alternaria blight of rapeseed-mustard

Alternaria blight [Alternaria brassicae (Berk.) Sacc.] is one of the most widespread and harmful maladies of rapeseed-mustard, causing yield loss up to 47 per cent. Meteorological parameters especially temperature, relative humidity and bright sunshine hours play major role in the development of Alternaria blight disease. Infection by the pathogen is highly influenced by meteorological conditions. A well-tested model based on meteorological variables is an efficient tool for forewarning this disease. Epidemiology of Alternaria blight of brassicas was investigated based on long term data during 2003-2018 crop seasons on the disease severity and meteorological variables, which was validated with data for two subsequent years. During this study, meteorological variable-based regression model of forewarning was developed for maximum severity (%) of Alternaria blight on leaves and pods for three locations viz., New Delhi, Hisar (Haryana) and Mohanpur (West Bengal)] in India. Validation of the forewarning models for maximum severity (%) of Alternaria blight proved the efficiency of the targeted forecasts.

Dental and Oral Manifestations of COVID-19 Related Mucormycosis: Diagnoses, Management Strategies and Outcomes

It has been nearly two years since the pandemic caused by the novel coronavirus disease (COVID-19) has affected the world. Several innovations and discoveries related to COVID-19 are surfacing every day and new problems associated with the COVID-19 virus are also coming to light. A similar situation is with the emergence of deep invasive fungal infections associated with severe acute respiratory syndrome 2 (SARS-CoV-2). Recent literature reported the cases of pulmonary and rhino-cerebral fungal infections appearing in patients previously infected by COVID-19. Histopathological analysis of these cases has shown that most of such infections are diagnosed as mucormycosis or aspergillosis. Rhino-orbital-cerebral mucormycosis usually affects the maxillary sinus with involvement of maxillary teeth, orbits, and ethmoidal sinuses. Diabetes mellitus is an independent risk factor for both COVID-19 as well as mucormycosis. At this point, there is scanty data on the subject and most of the published literature comprises of either case reports or case series with no long-term data available. The aim of this review paper is to present the characteristics of COVID-19 related mucormycosis and associated clinical features, outcome, diagnostic and management strategies. A prompt diagnosis and aggressive treatment planning can surely benefit these patients.

The results of the introduction of Pyracantha М. Roem. representatives in the conditions of the National Dendrological Park “Sofiyivka” of the NAS of Ukraine

Based on the analysis of long-term data, it was revealed that the weather and climatic conditions of the Right-Bank forest-steppe of Ukraine are pretty favourable for the course of seasonal rhythms of plant development studied species. P. coccinea (total points 83), P. crenatoserrata (total points 76), and P. crenulata (total score 81) are pretty promising species according to the scale for assessing the prospects of introduction of woody plants. Such species as P. × ‘Orange Charmer’ (sum of points 83) is quite promising among the varieties, and P. × ‘Red Column’ (sum of points 61), and P. × ‘Orange Glow’ (sum of points 66) are less promising. The least promising plant is P. × ‘Red Cushion’ (sum of points 42), and P. × ‘Soleil d’Оr’ (sum of points 37) is unpromising.

Spatiotemporal Variations of Aerosol Optical Depth in the Atmosphere over Baikal Region Based on MODIS Data

This paper considers spatiotemporal distribution and seasonal variability of aerosol optical depth (AOD) of the atmosphere at the 0.55 μm wavelength in the atmosphere over the Baikal region of Russia based on long-term data (2005–2019) from satellite observations (MODIS/AQUA). A comparison of satellite AOD values with the AERONET record at the Geophysical Observatory of Institute of Solar-Terrestrial Physics of Siberian Brunch of Russian Academy of Science was performed. The results show that interannual AOD variability is mainly due to forest fires. The highest atmospheric transparency was in 2010, 2013, and 2016, and the lowest was in 2008, 2012 and 2014. It is noted that AOD decreased with latitude with a gradient ΔAOD = 0.002÷0.001 per degree of latitude. The mean seasonal variations in AOD at the six satellite overpass points were characterized by spring (April) and summer (July) highs and low AOD values in autumn. From June to November, the drop in AOD monthly means was more than 60%.

Recent Progress on 3D NAND Flash Technologies

Since 3D NAND was introduced to the industry with 24 layers, the areal density has been successfully increased more than ten times, and has exceeded 10 Gb/mm2 with 176 layers. The physical scaling of XYZ dimensions including layer stacking and footprint scaling enabled the density scaling. Logical scaling has been successfully realized, too. TLC (triple-level cell, 3 bits per cell) is now the mainstream in 3D NAND, while QLC (quad-level cell, 4 bits per cell) is increasing the presence. Several attempts and partial demonstrations were made for PLC (penta-level cell, 5 bits per cell). CMOS under array (CuA) enabled the die size reduction and performance improvements. Program and erase schemes to address the technology challenges such as short-term data retention of the charge-trap cell and the large block size are being investigated.

Neuromodulation for Refractory Epilepsy

Three neuromodulation therapies, all using implanted device and electrodes, have been approved to treat adults with drug-resistant focal epilepsy, namely, the vagus nerve stimulation in 1995, deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) in 2018 (2010 in Europe), and responsive neurostimulation (RNS) in 2014. Indications for VNS have more recently extended to children down to age of 4. Limited or anecdotal data are available in other epilepsy syndromes and refractory/super-refractory status epilepticus. Overall, neuromodulation therapies are palliative, with only a minority of patients achieving long-term seizure freedom, justifying favoring such treatments in patients who are not good candidates for curative epilepsy surgery. About half of patients implanted with VNS, ANT-DBS, and RNS have 50% or greater reduction in seizures, with long-term data suggesting increased efficacy over time. Besides their impact on seizure frequency, neuromodulation therapies are associated with various benefits and drawbacks in comparison to antiseizure drugs. Yet, we lack high-level evidence to best position each neuromodulation therapy in the treatment pathways of persons with difficult-to-treat epilepsy.