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Visible light communication (VLC) has enabled the inception of a novel communication technique due to its high bandwidth and resistance to interference from various electromagnetic sources. However, in an indoor VLC system, other users (static as well as dynamic) can act as blockages to the communication link for the desired user. In this paper, we analyze the performance of an indoor VLC system with dynamic human blockages. Specifically, we use the random waypoint (RWP) model to characterize the movement of the blockages. The system performance is analyzed for a 4-LED configuration, where the blockages can pause during the movement for a specific pause time. Further, we developed a model to calculate the blockage probability in a typical indoor space, which is consequently used to calculate the power at the VLC receiver. Additionally, the analysis is extended for multiple blockage scenarios with different pause times. The second-order statistics such as level crossing rate (LCR) and average fade duration (AFD) have been examined to demonstrate the impact of both pause time and the number of blockages on this dynamic time-varying indoor VLC channel. It is observed that a blockage with a longer pause time will have a longer average outage duration (AOD). Finally, the effect of the velocity of blockages on LCR and AFD is also analyzed. We believe that the insights obtained in this paper will be useful to the operator while deploying an indoor VLC communication system in the presence of dynamic blockages.

Background: The pancreas contains Vitamin D (Vit.-D) and an enzyme that regulates insulin levels. Vitamin D deficiency is associated with several severe health conditions, such as cardiovascular disease, diabetes, various cancers, and multiple sclerosis (MS). Therefore, the objective of the current study is to investigate the correlation between Vitamin D levels and glycosylated hemoglobin (HbA1c) in both patients and controls.Materials and Methods: The study enrolled 163 T2DM (Group I) and 174 healthy (Group II) subjects to estimate the level of Vit.-D and HbA1c in the blood serum of all subjects, using radioimmunoassay and high-performance liquid chromatography, respectively.Results: The results revealed that Group I had a lower level of Vit.-D (17.82 ± 2.23 ng/mL) than Group II. Similarly, they have high HbA1c levels, showing significant (P< 0.001; Student’s t-test). Further, in Group I, Vit.-D levels were negatively correlated with HbA1c levels (P< 0.001; r2 = 0.07, linear regression). Group I and II combined analysis revealed an inverse relationship between Vit.-D levels and HbA1c (P< 0.001; r2 = 0.021).Conclusion: The study concluded a negative correlation between Vit.-D levels and HbA1c levels in T2DM. However, Vit.-D therapy can recover this correlation, which helps control glycemic levels.

Herein we report a visible-light-induced, a-aminoalkyl radical-mediated cascade reaction of 1,7-enynes that establishes a unique ring-closing enyne transformation pathway which occurs with concomitant loss of a methylene moiety. The a-aminoalkyl radical derived from N,N-dimethylaniline was demonstrated to be a traceless promoter of enyne reorganization leading to 4-alkylquinolinones. The reaction can also be extended to nitrile-substituted acrylamide systems, leading to carbostyrils. Experiments with deuterated N,N-dimethylaniline-d6(PhN(CD3)2) established the involvement of 1,5-H atom transfer in the mechanism.

The widespread deployment of white light-emitting diodes (LEDs) for lighting offers a unique opportunity to develop ubiquitous indoor communication based on visible light communication (VLC) technology and accurate localization based on visible light positioning (VLP) technology. However, the implementation of such systems in crowded indoor environments with dynamic blockages of varying sizes and shapes introduces new design challenges. These challenges also include dynamic blockage identification and accurate 3-D obstacle localization. Previous research has presented methods for precise 3-D obstacle identification and localization, but none has harnessed this information to improve communication reliability. Therefore, this article introduces a novel optimized LED power management framework that utilizes the estimated locations of obstacles to improve communication performance in VLC-enabled indoor networks. The main objective of the proposed framework is to maximize the achieved data rates and power savings in blockage-rich indoor environments by optimizing the LED power allocation while adhering to predefined bit error rate (BER), permissible localization errors, and illumination constraints. Based on the proposed optimal LED power allocation, a power-saving optimization framework with the objective of improving the energy efficiency of the system is also proposed. The simulation results indicate that the proposed optimal LED power management framework can result in significant power savings, approximately 68% for the 16-LED configuration and 72% for the 32-LED configuration, compared to the equal power allocation policy. Furthermore, the article derives closed-form expressions for the BER and localization error as a function of the operating environment parameters (e.g., number of blockages and angle of light irradiance). Furthermore, the results demonstrate that a localization error of approximately 6 and 4 cm is sufficient to achieve maximum data rates with 16 and 32 LEDs, respectively.

Solid waste generation and its accumulation is increasing at an alarming pace due to population growth and urbanization posing severe risks to health, safety, and natural ecosystems. This review strategically addresses the challenges and solutions to increasing the sustainability footprint of solid waste management (SWM) systems by revealing multipronged approaches that reduce solid waste and handling costs while generating revenue and reducing greenhouse gas and related emissions. For example, the United States sends ∼150 million tons of waste to landfills, which is composed of over 75% organic and recyclable materials having a potential to be diverted to alternative scenarios. The emergence of an automated upstream and downstream sorting process for solid waste to increase material diversion from landfills is a promising approach for creating sustainable SWM. The utilization of artificial-intelligence-enabled smart and automated systems at the home and industrial scales, comprehensive public re-education including awareness of the adverse effects of landfilled waste on the ecosystem, and more eco-friendly product development are required to significantly reduce landfills and their negative footprint.

A visible-light-mediated, haloalkyl-radical-initiated, three-component olefin difunctionalization is reported. The application of haloalkyl radicals generated via halogen atom abstraction by α-aminoalkyl radicals has been demonstrated for accessing a new halogenated chemical space. Overall, the alkylcarbofunctionalization of styrenes was accomplished by employing them as (poly)haloalkyl radical acceptors and subsequent C–C bond formation with quinoxalinones.

ABSTRACT Three novel succinimide based additives DDSA-TETA, DDSA-TEPA and DDSA-PEHA were synthesized by a simple refluxing reaction between dodecenylsuccinic anhydride (DDSA) with triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and pentaethylenehexamine (PEHA) respectively [...]

The development of excited-state palladium-catalyzed alkylative cyclization of acrylamides and the alkylation of quinoxalinones is described. The application of a variety of primary, secondary, and tertiary unactivated alkyl halides as alkyl radical precursors and the use of a simple catalyst system are the highlights of this reactivity manifold. The reactions exhibit wide scope, occur under mild conditions, and furnish the products in excellent yields.

We report a photocatalytic approach for the installation of the amide moiety onto para-quinone methides. This transformation features a net reductive approach for the generation of carbamoyl radicals from amide-substituted Hantzsch ester derivatives under transition metal-free conditions. This protocol exhibits wide scope and allows access to diarylacetamides employing a C–C bond formation approach.

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n= 17) and advanced solid tumors (NCT03291938, n= 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759. The PK, PD, and preliminary antitumor activities of IACS-010759 in patients were also evaluated as secondary endpoints in both clinical trials. IACS-010759 had a narrow therapeutic index with emergent dose-limiting toxicities, including elevated blood lactate and neurotoxicity, which obstructed efforts to maintain target exposure. Consequently no RP2D was established, only modest target inhibition and limited antitumor activity were observed at tolerated doses, and both trials were discontinued. Reverse translational studies in mice demonstrated that IACS-010759 induced behavioral and physiological changes indicative of peripheral neuropathy, which were minimized with the coadministration of a histone deacetylase 6 inhibitor. Additional studies are needed to elucidate the association between OXPHOS inhibition and neurotoxicity, and caution is warranted in the continued development of complex I inhibitors as antitumor agents.

Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism, and an exhausted phenotype at the single-cell transcriptomic and proteomic levels. In this study, we identified that this dysfunction was mediated through a cross-talk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvβ-integrin/TGF-β/SMAD pathway but, once established, was persistent because of profound epigenetic reprogramming. We identified BATF as a core transcription factor and the main mediator of this NK cell dysfunction in AML. Mechanistically, we found that BATF was directly regulated and induced by SMAD2/3 and, in turn, bound to key genes related to NK cell exhaustion, such as HAVCR2, LAG3, TIGIT, and CTLA4. BATF deletion enhanced NK cell function against AML in vitro and in vivo. Collectively, our findings reveal a previously unidentified mechanism of NK immune evasion in AML manifested by epigenetic rewiring and inactivation of NK cells by myeloid blasts. This work highlights the importance of using healthy allogeneic NK cells as an adoptive cell therapy to treat patients with myeloid malignancies combined with strategies aimed at preventing the dysfunction by targeting the TGF-β pathway or BATF.

Byline: Amar. Pujari, Ritika. Mukhija, Anand. Singh, Rohan. Chawla, Namrata. Sharma, Atul. Kumar Sir, With the increasing use of smartphones in various aspects of our daily lives, application of the [...]

ABSTRACTThe energy hunger society drives for more electrical power consumption to raise the human conveniences have put tremendous pressure on the existing power system (PS) to function uninterruptedly. The continuous addition of non-linear loads brings a heavy inrush of fault current leading to transient instability in PS. To protect the PS and its precious elements, fault current limiters (FCLs) are generally installed with a view to limit those FCs before inviting severe damage and also quickly restore the PS to its original state. Furthermore, since faults are inevitable, efforts can only be made to minimise those damages by improving the FCLs. Herein, a brief history of FCLs, concepts, working principles, developmental stages, and experimental data, along with theoretical predictions, have been systematically presented. Finally, this article elaborates on the current challenges of FCLs, future perspectives, and, most importantly, their market potential.

This work aims to characterize a new class of automaton with input as multisets. First, we introduce two finite monoids through different congruence relations on multiset associated with lattice-valued multiset finite automata and show that they are isomorphic to each other. Next, we present the quotient structure of lattice-valued multiset finite automata by defining an admissible relation on the set of states of a given lattice-valued multiset finite automata. Then we show that there is an isomorphism between lattice-valued multiset finite automata and the quotient structure of another lattice-valued multiset finite automata. Finally, we introduce the concept of reachability, observability (coreachability), and response maps of lattice-valued multiset finite recognizer. Interestingly, we show that the lattice-valued response map of a lattice-valued multiset finite recognizer leads us to provide a characterization of a lattice-valued multiset regular language.

Agoraphobia has been defined as marked fear or anxiety being in enclosed or open places, using public transportation, and being in a crowd or outside of home alone. Such individuals make active attempts to avoid those places which cause intense distress. The neuronal areas that play a significant role in agoraphobia are uncinate fasciculus, which connects the prefrontal lobe and amygdala and various alterations in anterior cingulate cortex, insula, amygdala, and lateral prefrontal cortex. Neurofeedback is a type of biofeedback which teaches self-control of brain functions by measuring brain waves with the help of electroencephalography (EEG) and providing a feedback signal. With the help of alpha and beta training protocol, neurofeedback therapy will help in enhancing the connectivity between prefrontal cortex and amygdala. The present study aims to explore the therapeutic effectiveness of neurofeedback therapy as an adjunct treatment with cognitive behavioral therapy (CBT) in patients with agoraphobia disorder. A single case study method was adopted. The patient having the symptoms of agoraphobia disorder diagnosed as per ICD-10 criteria was taken in the study. After going through detailed case history and mental status examination, the patient was assessed on psychological measures on baseline and other follow-up visits. A total of 18 therapeutic sessions of neurofeedback therapy (alpha and beta protocol) along with CBT were conducted. Intermittent assessments on Draw A Person Test (DAPT), EEG parameters, Visual Analogue Scale (VAS), and Panic and Agoraphobia Scale (PAS) were conducted to compare the pre- and post-assessment findings. The results indicated significant improvement in the symptoms of the patient after intervention. The pre- and post-assessment findings and the neurofeedback therapy along with CBT were observed to be effective in treating the symptoms of agoraphobia. Neurofeedback therapy and CBT were proven to be effective in removing the symptoms of agoraphobia disorder within the patient.

The Himalayan foothills or the Siwaliks have been considered as one of the most fragile ecosystems of India. The underlying cause of degradation includes natural settings (geological formation and climate change) and human-mediated pressures (sandstone mining, urbanisation and developmental activities). Since the Siwaliks is associated with the livelihood of about 20 million people, it becomes imperative to respond appropriately for sustaining this ecologically fragile region. Ecological principles have great potential to develop sustainable practices for the conservation and management of natural resources. These principles offer nature-based solutions to sustain the ecologically sensitive and degraded ecosystems such as the ‘Siwaliks’. However, there is a need for concerted research to develop data-driven decisions for effective management. Therefore, a systematic analysis was conducted to assess the current patterns and knowledge gaps about plant ecological studies in the Indian Siwalik region. This article analysed the available peer-reviewed literature using established guidelines and bibliometric analyses. We found an increasing trend in the scientific output, and most studies were concentrated in the Siwalik region belonging to the Indian state of Uttarakhand. Although studies have been conducted on plant ecology, landscape ecology and ecosystem ecology have been disproportionately focused. Our findings suggest a growing interest in the plant ecology of the region; however, these studies seem relatively small compared to the complexity and diversity of this ecosystem structural and functional attributes. Further, with advances in computer application and remote sensing satellite data availability, we observed a shift towards ecological modelling studies, though experimental evidence also needs to be addressed.

A cascade reaction involving arynes and 5-ethoxyoxazoles has been developed toward the synthesis of 9-alkyl/aryl tritylones. 5-Ethoxyoxazoles undergo a [4 + 2] cycloaddition reaction with arynes followed by retro-[4 + 2] cycloaddition, a second intermolecular [4 + 2] cycloaddition reaction, and hydrolytic ring cleavage to generate substituted tritylones in good yields. The conversion of tritylone products to a series of spirocyclic anthrone derivatives has been demonstrated. The reaction is expeditious, exhibits wide scope, and employs readily available starting materials.

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS—UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma—USC060.1, and 3 new models of MPNST—MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing their tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of the cell lines and corresponding xenografts was determined by subcutaneous injection or xenograft re-passaging into immunocompromised mice. USC060.1 and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Targeted sequencing analysis of a panel of genes frequently mutated in sarcomas identified TP53, RB1, and ATRXmutations in a subset of the cell lines. These new cellular models provide the scientific community with powerful tools for detailed studies of tumorigenesis and for investigating novel therapies for UPS and MPNST.

Mountain ecosystem provides numerous vital ecosystem services (ESs) to the people residing within or near the mountains worldwide. The mountains provide services such as timber, fibre, fodder, fuelwood, medicine, aesthetic, recreation, ritual, and religion, and many other services that are vital for the maintenance of the ecosystem. The mountains of Barsoo and Tai-Suru regions in Kargil District are much familiar for their ESs supply, and the residents have utilized these services for years. The present study was focused on the provisioning ESs. We used a random sample approach for household selection and data collection regarding the pre-prepared questionnaire; the number of households was obtained from government census data. The primary ESs (identified by more than 40% of the respondents) were assessed through the direct market valuation method. The direct market valuation method produced an overwhelming value, specifically for grazing and fodder services in both regions of the study area. Results showed that grazing service was valued at 482,346.43 USD/a for Barsoo region and 1,458,099.04 USD/a for Tai-Suru region. Similarly, fodder service of Barsoo and Tai-Suru regions corresponded to values of 69,833.61 and 110,886.06 USD/a, respectively. On the other hand, food service of Barsoo and Tai-Suru regions was valued at 2601.04 and 2969.90 USD/a, respectively, and medicinal service was valued at 757.39 and 4430.94 USD/a in Barsoo and Tai-Suru regions, respectively. In addition, the regions were economically backwards, and the resident's survival and well-being relied on the mountain ESs. Therefore, it is not possible for the residents to pay services replacement costs if the services need to replace by other means. Unfortunately, such mountain ecosystem is highly prone to climate change and other human activities that would negatively impact the ecosystem functions. Therefore, this study would be helpful for the policy-makers of the region to draft any developmental plan/framework by integrating the value of ESs that would be the key to achieving sustainable development.

Power conversion efficiency (PCE) of perovskite solar cells (PSCs) has reached 26.1%, but PSC devices are plagued by poor stability when exposed to light (especially ultraviolet (UV) radiation), heat, and moisture. UV stability remains a significant challenge to overcome. Luminescent down-shifting (LDS) filters have shown significant enhancement in photostability and efficiency for PSCs. However, most explored LDS materials are costly, non-biodegradable, and the resulting photostability is limited to ∼100 h. In this report, as-obtained waste filtrate from the polyaniline (PANI) synthesis is used to synthesize fluorescent PANI carbon quantum dots (PANI-CQDs) using a facile hydrothermal method. Here we report, for the first time, the use of waste-derived PANI-CQDs to fabricate UV filters that are low-cost, bio-degradable, and room-temperature processible and, importantly, impart high UV and photostability to the PSCs. PSCs with these filters retained 90% and 100% of their initial performance when exposed to UV light and AM 1.5 solar radiation, respectively, for more than 900 h, while PSCs without filters degraded to 14 and 70% of their initial performance under the same conditions. Hence, we clearly show that using a waste-derived LDS filter improves the UV stability of PSCs by six times and photostability beyond 1,000 h.

Sugar beet is a major crop for the sugar industry. With growing awareness of unsystematic use of pesticides, health problem, and environmental issues, assessment of pesticide residues in soil and crops has become necessary. Studies of subtropical conditions on dissipation and residue analysis of clopyralid have not yet been reported. Therefore, dissipation kinetics and terminal residues of clopyralid for two cropping seasons in the soil and the sugar beet crop were studied under field conditions. An experiment was laid out in a randomized block design, and a herbicide was applied as a postemergent. Clopyralid was extracted from the matrix by basic water, subjected to solid phase extraction cleanup, and quantified by high-pressure liquid chromatography–UV. The method was validated, and recovery percentage of pesticide ranged from 81 to 88, 77 to 85, 78 to 86, and 89 to 94% in the soil, sugar beet roots, sugar beet leaves, and water, respectively. After application in the soil, clopyralid dissipated rapidly following monophasic first-order kinetics, with a half-life of 13.39 days. Limits of detection and quantitation were 0.007 and 0.02 μg g−1, respectively. Clopyralid does not persist long in soil, and residues were below the European Union's maximum residue levels (0.5 mg kg−1) in the roots and leaves of sugar beet. Residues were also not detected in the groundwater. It can be concluded that clopyralid could be considered a safe herbicide from the environmental aspect due to its nonpersistence and that it would not have an adverse effect on human or animal health.

Obsessive-compulsive disorder (OCD) is a disorder that is characterized by the presence of obsessions and compulsions. OCD can occur in a wide range of subtypes, which may include sexual OCD, i.e., the occurrence of intrusive sexual thoughts. People with sexual OCD may experience unwanted obsessive sexual thoughts about a family member, dead or inanimate objects, animals, God, or children, which can range from mild to severe levels of occurrence. The psychodynamic perspective on OCD suggests that the content of obsessive thinking is commonly drawn from primitivized sexuality and aggression. It further suggests that in the absence of key relationships that include emotional proximity, mirroring and containment, and attunement, a child experiences a void-like state. Consequently, the anxiety that arises in the child leads to a form of liveliness in a “dead” inner world. However, it occurs out of a sense of abandonment and loss of good objects, and ultimately out of fear of annihilation. As a result, the child resorts to maladaptive defense mechanisms. The study attempts to explore the adverse early childhood experiences such as parental neglect, mother–father conflict, and lack of parental love and care leading to fixation in psychosexual stages of development, which further leads to the adoption of maladaptive defense mechanisms that in turn further contribute to the development of obsessional personality traits. This study aims to explain the psychodynamic perspective on the emergence of sexual obsessions by proceeding with a case study approach by taking a diagnosed case of OCD. A comprehensive psychodiagnostic assessment was conducted with the help of Draw-a-Person Test, Thematic Apperception Test, Rotter’s Incomplete Sentence Blank, and Million’s Comprehensive Multiaxial Inventory. The analysis of the assessment protocol revealed a strong relationship between the defense mechanism, personality traits, and the development of obsessive symptoms.

This article analyzes the performance of multiple-input-multiple-output indoor visible light communication (VLC) system by randomly deploying the light-emitting-diodes (LEDs) using Matern hardcore point process (MHCP). Furthermore, photodetectors (PDs) with two different field of view (FOVs) have been utilized for an imaging as well as nonimaging receiver structures. It is a widely known fact that in a conventional VLC system, signal-to-noise ratio (SNR) profile inside the room varies with respect to the LED placement and the PDs position. Consequently, the proposed work attempts to achieve uniform SNR across the room, by utilizing MHCP based LED placement at the transmitter, and a nonimaging receiver with four PDs using 1-FOV, 2-FOV, and imaging receiver configurations. Simulation results show that random deployment of LED using MHCP configuration results in a more uniform SNR profile inside the room as compared to regular LED deployment schemes. Furthermore, three different power allocation schemes for LEDs namely equal power, distance-based power, and an optimal power allocation are proposed. For the different power allocation schemes, the average SNR and the variance of the received optical power (OP) inside the room are derived and compared. In addition, the closed-form expression for the bit-error-rate (BER) probability is derived for the proposed MHCP configuration using on-off keying as a modulation scheme. Results show improvement in BER performance with the OP allocation in comparison to other power allocation schemes both for imaging and nonimaging receiver configuration.

ObjectiveEnhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described.DesignWe performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and H3K9me3 for heterochromatin.ResultsWe demonstrate that H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumour-specific enhancers for crucial oncogenes, such as ASCL2and FZD10,was required for excessive proliferation. Consistently, combination of MEK plus bromodomain inhibition was found to have synergistic effects in CRC patient-derived xenograft models. Probing intertumour heterogeneity, we identified four distinct enhancer subtypes (EPIgenome-based Classification, EpiC), three of which correlate well with previously defined transcriptomic subtypes (consensus molecular subtypes, CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, TGFβi, mTORi and SRCi) for EpiC groups.ConclusionOur data suggest that the dynamics of active enhancer underlies CRC progression and the patient-specific enhancer patterns can be leveraged for precision combination therapy.

Recent work in Natureby Khalil’s group uncovers the mystery of structural degradation in Li- and Mn-rich cathodes to be tied with the accumulated nanostrain and lattice displacement during the operation of the cell. These effects are the real culprit in driving structural and oxygen loss, leading to rapid voltage decay.

ABSTRACTBackgroundD-penicillamine (D-pen) is a copper-chelating drug and has immune-modulatory properties. D-pen is used to treat rheumatoid arthritis, Wilson’s disease, and kidney stones (cystinuria). However, associated adverse events (AEs) of D-pen treatment are frequent and often serious. Therefore, a comprehensive assessment of the safety profile of D-pen is urgently needed.Research design and methodsWe identified and analyzed AEs associated with D-pen between April-1970 to July-2020 from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) databases and calculated the reported odds ratio (ROR) with 95% confidence intervals (CI) using the disproportionality analysis.ResultsA total of 9,150,234 AEs related to drugs were reported in the FAERS database, of which 542 were related to D-Pen. We report that D-pen was associated with dystonia (ROR: 20.52; 95%CI: 12.46–33.80), drug hypersensitivity (ROR: 5.42; 95%CI: 3.72–7.90), pancytopenia (ROR: 10.20; 95%CI: 5.61–18.56), joint swelling (ROR: 9.07; 95%CI: 5.51–14.94), renal-impairment (ROR: 6.68; 95%CI: 3.67–12.15), dysphagia (ROR: 5.05; 95%CI: 2.76–8.89), aggravation of condition (ROR: 4.16; 95%CI: 2.60–6.67), congestive cardiac failure (ROR: 4.04; 95%CI: 2.22–7.35), peripheral edema (ROR: 3.77; 95%CI: 2.17–6.55), tremor (ROR: 3.46; 95%CI: 2.00–6.01), pyrexia (ROR: 3.46; 95%CI: 2.00–6.01), and gait disturbance (ROR: 2.41; 95%CI: 1.29–4.52).ConclusionsPatients taking D-pen require close monitoring of renal function, blood counts, immunity, liver, cardiac function, and neurological function. D-pen suppresses immune system which maximizes the risk of infection.

Tumours growing in a sheet-like manner on the surface of organs and tissues with complex topologies represent a difficult-to-treat clinical scenario. Their complete surgical resection is difficult due to the complicated anatomy of the diseased tissue. Residual cancer often responds poorly to systemic therapy and locoregional treatment is hindered by the limited accessibility to microscopic tumour foci. Here we engineered a peptide-based surface-fill hydrogel (SFH) that can be syringe- or spray-delivered to surface cancers during surgery or used as a primary therapy. Once applied, SFH can shape change in response to alterations in tissue morphology that may occur during surgery. Implanted SFH releases nanoparticles composed of microRNA and intrinsically disordered peptides that enter cancer cells attenuating their oncogenic signature. With a single application, SFH shows efficacy in four preclinical models of mesothelioma, demonstrating the therapeutic impact of the local application of tumour-specific microRNA, which might change the treatment paradigm for mesothelioma and possibly other surface cancers.

Nonsense‐mediated mRNA decay (NMD) is a quality‐control process that selectively degrades mRNAs having premature termination codon, upstream open reading frame, or unusually long 3′UTR. NMD detects such mRNAs and rapidly degrades them during initial rounds of translation in the eukaryotic cells. Since NMD is a translation‐dependent cytoplasmic mRNA surveillance process, the noncoding RNAs were initially believed to be NMD‐resistant. The sequence feature‐based analysis has revealed that many putative long noncoding RNAs (lncRNAs) have short open reading frames, most of which have translation potential. Subsequent transcriptome‐based molecular studies showed an association of a large set of such putative lncRNAs with translating ribosomes, and some of them produce stable and functionally active micropeptides. The translationally active lncRNAs typically have relatively longer and unprotected 3′UTR, which can induce their NMD‐dependent degradation. This review defines the mechanism and regulation of NMD‐dependent degradation of lncRNAs and its impact on biological processes related to the functions of lncRNAs or their encoded micropeptides. This article is categorized under:RNA Turnover and Surveillance > Turnover/Surveillance MechanismsRNA Turnover and Surveillance > Regulation of RNA StabilityRNA in Disease and Development > RNA in Disease The mechanism and regulation of NMD‐dependent degradation of lncRNAs and its impact on biological processes related to the functions of lncRNAs or their encoded micropeptides.

Increased levels of CO2and various greenhouse gases cause global warming and, in combination with pollutants from fossil fuel combustion and vehicular and industrial emissions, have been driving increases in noncommunicable diseases across the globe, resulting a higher mortality and morbidity. Respiratory diseases and associated allergenic manifestations have increased worldwide, with rates higher in developing countries. Pollen allergy serves as a model for studying the relationship between air pollution and respiratory disorders. Climate changes affect the quality and amount of airborne allergenic pollens, and pollutants alter their allergenicity, resulting in greater health impacts, especially in sensitized individuals.

Coronavirus disease 2019 (COVID-19) is a major public health concern currently. To date, there are no approved antiviral drugs or vaccines against this transmissible disease. This report sheds light on available information for a better understanding of clinical trials and pharmacotherapy related to COVID-19. MEDLINE, PubMed, EMBASE, Scopus databases, Web of Science, WHO, and EU clinical trial sites were used to perform comparative analysis. Information was collected on the use of therapeutic agents for human therapy in patients with COVID-19 up to May 2020. We have extracted data from 60 clinical trials. Amongst these trials, 34 were from the European Union database of clinical trials and 26 from the National Institute of Health. The data selection procedure includes active, completed, and recruitment in progress status. Most of the clinical trials are ongoing and hence, there is a lack of precise results for the treatment.There is a lack of high-quality clinical evidence. The protocol to be developed requires large randomized clinical trials with a combination of available drugs and prospective therapies. We propose the usage of a large number of cases and different statistical analyses to conduct systematic clinical trials. This could provide comprehensive information about the clinical trial and potential therapeutic progress.

Often referred to as the custodians of nature, the Bishnois have been taking initiatives to curb the illegal hunting/poaching of animals such as the blackbuck and the chinkara that are fully covered under the provisions of the Indian Wildlife Protection Act (WLPA, 1972). From within the realms of their philosophical engagement with nature, the Bishnois imagine the law offenders from hunting communities, such as Ban Bawri and Bhil, and those who come to be defined exclusively as poachers as the ‘violent’ other. While the hunting tribes heavily contest such a viewpoint, the contours of a grass-roots debate as well as Bishnoi activism against destruction of natural resources continue to fortify in western Rajasthan. The growth of an organised protest movement of the Bishnois, spearheaded by the Bishnoi Tiger Force (BTF), since the past two decades has also coincided with an embodiment of the community’s general preparedness to die in defence of the wildlife. What fuels the spirit and the sentiment behind this rising defence of the endangered wildlife, amidst other creatures of the desert? How do Bishnoi repertoires of protest influence the discourses of other involved communities and manage to keep the democracy of India on constant alertness in the great Indian Thar?

Migraine is acknowledged as an intricate and incapacitating neurological malady, profoundly exerting a potent influence on the health-related quality of life of patients causing disability, and augmented burden on families, and entire communities. Notwithstanding the strides made in the field of headache disorder management, there remains a cohort of migraine-afflicted patients who do not encounter satisfactory alleviation. This emphasizes the need for alternative systems in addressing the issue and there is a growing interest in exploring Indian system of medicine to address migraine symptoms. Due to the dearth of prospective, high-quality randomized controlled trials, this protocol aims to conduct a scientific study of the polyherbal formulation ‘Ayush M3’ to assess its safety and efficacy in patients suffering with Migraine.

An unusual strategy toward novel substituted benzo[b]thiophenes has been developed. The generation of arynes in the presence of acyl ketene dithioacetals resulted in a cascade reaction involving [3 + 2] cycloaddition, and a dealkylative arylation of a thioether moiety to afford 2,3-disubstuted benzo[b]thiophenes. This route represents an expeditious approach to benzothiophenes that employs acyl ketene dithioacetals as dipoles.

Computer-aided detection is gradually gaining acceptance in radiology and has become a major research focus in the past few years. The development of CAD with multislice CT has reached the [...]

Malignant pleural mesothelioma (MPM) is an incurable, aggressive neoplasm with distinctive features, including preservation of wild-type p53, irrespective of histologic subtype. We posited that this consistent molecular characteristic represents an underexploited therapeutic target that can be approached by leveraging biologic effects of microRNA (miRNA). The Cancer Genome Atlas was surveyed to identify p53-responsive prognostic miRNA(s) in MPM. Using patient samples, in vitroMPM cell lines, and murine tumor xenograft models, we verified specific gene pathways targeted by these miRNAs, and we examined their therapeutic effects. miR-215-5p is a poor prognosis miRNA downregulated in MPM tissues, which has not been recognized previously. When miR-215-5p was ectopically re-expressed in MPM cells and delivered in vivoto tumor xenografts, it exerted significant cell killing by activating p53 function and inducing apoptosis. The mechanistic basis for this effect is due to combinatorial effects of a positive feedback loop of miR-215-MDM2-p53 signaling, additional mouse double minute 2 (MDM2)-p53 positive feedback loop(s) with other miRNAs such as miR-145-5p, and suppression of diverse gene targets associated with cell cycle dynamics not previously drug treatable in MPM clinical studies. Our results suggest a potential pathophysiologic role for and therapeutic significance of miR-215-5p in MPM.

Therapies against malignant pleural mesothelioma (MPM) have yielded disappointing results, in part, because pathologic mechanisms remain obscure. In searching for rational molecular targets, we identified metadherin (MTDH), a multifunctional gene associated with several tumor types but previously unrecognized in MPM. Cox proportional hazards regression analysis delineated associations between higher MTDHexpression and lower patient survival from three independent MPM cohorts (n = 349 patients). Through in vitroassays with overexpression and downregulation constructs in MPM cells, we characterized the role of MTDH. We confirmed in vivothe phenotype of altered MTDHexpression in a murine xenograft model. Transcriptional regulators of MTDHwere identified by chromatin immunoprecipitation. Overexpression of both MTDHmRNA (12-fold increased) and protein levels was observed in tumor tissues. MTDH stable overexpression significantly augmented proliferation, invasiveness, colony formation, chemoresistance, and an antiapoptosis phenotype, while its suppression showed opposite effects in MPM cells. Interestingly, NF-κBand c-Myc(in a feed-forward loop motif) contributed to modulating MTDHexpression. Knockdown of MTDHexpression profoundly retarded xenograft tumor growth. Thus, our findings support the notion that MTDHintegrates upstream signals from certain transcription factors and mediates pathogenic interactions contributing to MPM traits. MTDH represents a new MPM-associated gene that can contribute to insights of MPM biology and, as such, suggest other treatment strategies.

A synthetic method for the radical trifluoromethylation of enol acetates using trifluoroacetic anhydride (TFAA) is reported. This photochemical reaction is operationally simple and employs economical reagents and readily accessible enol acetate precursors. The mild conditions and good scope render this method a useful addition to the repertoire of reactions employing TFAA as a trifluoromethyl source. Light repertoire: A visible‐light‐mediated method for the radical trifluoromethylation of enol acetates using trifluoroacetic anhydride is reported. This photochemical reaction is operationally simple and employs economical reagents and readily accessible enol acetate precursors. The mild conditions and good scope render this method a useful addition to the repertoire of reactions employing TFAA as the trifluoromethyl source.

The article offers travel tips for India’s ancient city Varanasi which includes the Panchganga Ghat; Kashi Vishwanath Temple of Shiva; and the deer park in Sarnath is where Gautama Buddha first taught the Dharma.

In this note, we show that, in the paper [Zhong Y, Yan CH. Intuitionistic L-fuzzy rough sets, intuitionistic L-fuzzy preorders and intuitionistic L-fuzzy topologies. Fuzzy Inf Eng. 2016;8:255–279.], the conclusion regarding Proposition 3.3 of [Tiwari SP, Srivastava AK. Fuzzy rough sets, fuzzy preorders and fuzzy topologies. Fuzzy Sets Syst. 2013;210:63–68.] is not correct.

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) belong to the same spectrum of myeloid malignancies and have extremely poor outcomes in the relapsed/refractory setting. Despite advances in the understanding of the pathogenesis and molecular mechanisms of these disorders, and incremental improvements in treatment regimens, patients with MDS and AML often relapse and fail to achieve cure. These and other factors underscore the urgent need for new therapeutic alternatives that will improve the clinical outcomes of these patients. Immunotherapy using checkpoint molecule inhibitors and adoptive cell therapy using autologous immune effector cells have been mostly unsuccessful in patients with MDS and AML. This could be due to the immunosuppressive tumor microenvironment in the bone marrow niche or to intrinsic dysfunction in the immune effector cells of these patients.

The ideal management of common bile duct (CBD) stones associated with gall stones is a matter of debate. We planned a meta-analysis of randomized trials comparing single-stage laparoscopic CBD exploration and cholecystectomy (LCBDE) with two-stage preoperative endoscopic stone extraction followed by cholecystectomy (ERCP + LC). We searched the Pubmed/Medline, Web of science, Science citation index, Google scholar and Cochrane Central Register of Controlled trials electronic databases till June 2017 for all English language randomized trials comparing the two approaches. Statistical analysis was performed using Review Manager (RevMan) [Computer program], Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014 and results were expressed as odds ratio for dichotomous variables and mean difference for continuous. pvalue ≤ 0.05 was considered significant. Trial sequential analysis (TSA) was performed using TSA version 0.9.5.5 (Copenhagen: The Copenhagen Trial Unit, Centre for Clinical Intervention Research, 2016). PROSPERO trial registration number is CRD42017074673. A total of 11 trials were included in the analysis, with a total of 1513 patients (751-LCBDE; 762-ERCP + LC). LCBDE was found to have significantly lower rates of technical failure [OR 0.59, 95% CI (0.38, 0.93), p= 0.02] and shorter hospital stay [MD − 1.63, 95% CI (− 3.23, − 0.03), p= 0.05]. There was no significant difference in mortality [OR 0.37, 95% CI (0.09, 1.51), p= 0.17], morbidity [OR 0.97, 95% CI (0.70, 1.33), p= 0.84], cost [MD − 379.13, 95% CI (− 784.80, 111.2), p= 0.13] or recurrent/retained stones [OR 1.01, 95% CI (0.38, 2.73), p= 0.98]. TSA showed that although the Z-curve crossed the boundaries of conventional significance, the estimated information size is yet to be achieved. Single-stage LCBDE is superior to ERCP + LC in terms of technical success and shorter hospital stay in good-risk patients with gallstones and CBD stones, where expertise, operative time and instruments are available.

Since the discovery of perovskite based solar cells in 2009 followed by breakthroughs at Oxford in 2012, continuous efforts by the scientific community have led to tremendous developments in perovskite solar cells (PSCs) which is perhaps the most promising recent solar photovoltaic (PV) and energy harvesting technology. Advancements in nanotechnology and availability of better infrastructures for PSCs research have accelerated this field leading to the dramatic rise in efficiency with expectations of commercialization soon. Amongst other solar cell devices, PSCs have demonstrated record efficiencies exceeding 22% off late in just a few years establishing as the fastest growing solar PV technology. This extremely rapid progress in PSCs is not only because of unique properties of perovskite materials in the devices but also due to engineering and modification of other components as well as device architecture facilitating the conducive microstructure and interfaces to result in higher power conversion efficiencies. These other components such as electron transport materials (ETMs) and hole transport materials (HTMs) not only play a vital role in determining the device efficiency but also the stability of PSCs. This review focuses on the recent investigations carried out to achieve high performance and long term stability of PSCs, with primarily focus on doping or composition engineering of various components of PSCs devices (perovskite, ETM and HTM) resulting in enhanced properties with respect to their role in delivering high performance PSCs. Although, a great deal of research has been carried out and reviewed on PSCs, investigations correlating material compositions and properties vis-à-vis increase in the efficiency and enhancement in the stability, although very interesting, are rarely reviewed. Hence, this review focuses on the recent developments and critical issues related to microstructure, properties and stability of the devices resulting from doping or composition engineering. In this article, first a basic introduction to PSCs and perovskite as materials for PV devices is followed by the role and importance of ETM and HTM. The article further reviews in-detail about doping and compositional engineering in ETM, HTM and perovskite material in order to improve the PSC device performance. Finally, the article will provide an outlook towards various issues requiring further attention which can help in eventually facilitating technological promise of PSCs.