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Topology Bench is a comprehensive topology dataset designed to accelerate benchmarking studies in optical networks. The dataset, focusing on core optical networks, comprises publicly accessible and ready-to-use topologies, including (a) 105 georeferenced real-world optical networks and (b) 270,900 validated synthetic topologies. Prior research on real-world core optical networks has been characterized by fragmented open data sources and disparate individual studies. Moreover, previous efforts have notably failed to provide synthetic data at a scale comparable to our present study. Topology Bench addresses this limitation, offering a unified resource, and represents a 61.5% increase in spatially referenced real-world optical networks. To benchmark and identify the fundamental nature of optical network topologies through the lens of graph-theoretical analysis, we analyze both real and synthetic networks using structural, spatial, and spectral metrics. Our comparative analysis identifies constraints in real optical network diversity and illustrates how synthetic networks can complement and expand the range of topologies available for use. Currently, topologies are selected based on subjective criteria, such as preference, data availability, or perceived suitability, leading to potential biases and limited representativeness. Our framework enhances the generalizability of optical network research by providing a more objective and systematic approach to topology selection. A statistical and correlation analysis reveals the quantitative range of all of these graph metrics and the relationships between them. Finally, we apply unsupervised machine learning to cluster real-world topologies into distinctive groups based on nine optimal graph metrics using K-means. It employs a two-step optimization process: optimal features are selected by maximizing feature uniqueness through principal component analysis, and the optimal number of clusters is determined by maximizing decision boundary distances via support vector machines. We conclude the analysis by providing guidance on how to use such clusters to select a diverse set of topologies for future studies. Topology Bench, openly available via Dataset 1 (https://zenodo.org/records/13921775) and Code 1 (https://github.com/TopologyBench), promotes accessibility, consistency, and reproducibility.

Supplemental Digital Content is Available in the Text.The clinical effect of drug–drug interactions (DDIs) between antiplatelets and antiretroviral therapy (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with HIV (PLWH) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. Ninety-three PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n = 84, 71%), followed by ticagrelor (n = 9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown whether DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or whether underlying platelet reactivity in PLWH is associated with these events.

Soft tissue tumors are complex neoplasms requiring accurate diagnosis, often through fine needle aspiration (FNA). The World Health Organization (WHO) classification system aims to standardize cytopathological diagnoses and assess the risk of malignancy (ROM) for these tumors.

Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.

Densities, speeds of sound, and viscosity values have been experimentally measured at temperature ranges from (298.15 to 308.15 K) and a pressure of 0.1 MPa for the whole compositions for the binary mixtures of tetrahydrofuran with methyl acetate, propyl acetate, and pentyl acetate. Excess molar volume (VmE), excess molar isentropic compressibility (ΔKS,mE), viscosity deviation (Δη), excess Gibb’s free energy of activation for viscous flow (ΔG*E), and partial molar volume (V̅m,i) have been derived with the help of experimental results and fitted to an extended Redlich–Kister equation by the least-squares approach that simultaneously considers the dependency on composition and temperature. For the calculated and experimental data, the standard deviations are estimated. The magnitude and sign of these excess properties have been utilized to explain the results in terms of structural and intermolecular interactions. Various semiempirical viscosity relations were tested using the data of viscosity of binary mixtures.

Free space optical (FSO) communication system is a promising candidate for today's era of intelligent networks for the reason that it has potential advantages such as, high data rates, large bandwidth, non-licensed spectrum, line-of-sight communication and many more. Relay-assisted communication provides an additional boost to system's performance by expanding its capacity, coverage range, enhancing data rates and mitigating the effect of turbulence. In this manuscript, three dual-hop systems are considered i.e., FSO-FSO, radio frequency (RF)-FSO and FSO-RF systems employing decode and forward (DF) relaying protocol. Furthermore, chaotic signals are incorporated in these systems to enhance their confidentiality using differential chaos shift keying (DCSK). This is demonstrated by performing secrecy analysis on the system. Here, it is assumed that RF link experiences Nakagami-m fading while the affect of fading in FSO channel is caused by Gamma-Gamma turbulence along with pointing errors. The average bit error rate (BER) of three proposed systems is analyzed, and the results indicated that the FSO-RF-DCSK system outperformed the other three in terms of performance. Finally, secrecy performance is accomplished using secrecy outage probability (SOP) as a metric for the proposed systems. The findings are noteworthy as FSO-FSO-DCSK system demonstrates superior performance as compared to FSO-RF-DCSK and RF-FSO-DCSK systems in terms of secrecy. As compared to other counterparts, FSO-FSO-DCSK system shows an improvement of more than 10 order of magnitude in terms of signal-to-noise (SNR) ratio.

Lignocellulosic biomass is one of the biggest renewable reservoirs for organic carbon that can be exploited as feed for various value-added products like fuel, nutraceuticals enzymes, and proteins. Biofuel is not only valuable but also a top priority target to address the energy crisis. Hence the current work was planned to valorize the cellulose-rich residual biomass (CRB), left after xylitol production for ethanol fermentation by yeast. Xylose-rich hydrolysate was prepared with dilute acid pretreatment (0.1 M H2SO4, 145 ℃, and 90 min) for xylitol production and CRB was further processed for enzymatic hydrolysis (crude cellulase). Acid hydrolysis offered maximum reducing sugars of 0.33±0.01 g⋅g−1biomasscomprised of xylose 0.31±0.01 g⋅g−1biomass. Besides sugar, biomass hydrolysis also produced 0.21 ±0.01 g.L−1furans and 0.34±0.11 g.L−1acetic acid. Pichia guilliermondiiRLV-04 (MH588234.1) have shown 0.90±0.02 gxylitol.g−1xyloseconversion of xylose to xylitol. The primary process has left more than 50–55 % biomass that was rich in cellulose. Enzymatic hydrolysis of the CRB using crude cellulase showed maximum glucose recovery of 0.56±0.02 g⋅g−1available celluloseat 15 FPU at 50 ℃, after 12 h. In addition, yeast biomass recovered from xylitol production was hydrolysed and used as a nitrogen source. Under an anaerobic environment, a maximum ethanol yield of 0.36±0.01 g.g−1glucosewas achieved with commercial baker’s yeast while the addition of yeast biomass hydrolysate improved the alcohol yield to 0.48±0.02 g.g−1glucose. Reutilization of biocatalysts as nitrogen source not only upgraded fermentation processes but also lowered process waste and improved process economics.

Purpose To identify predictive factors associated with US adolescents’ transition through the stages of change for potentially quitting e-cigarettes using the Trans-theoretical model of behavior change.Design Prospective cohort study.Setting United States.Subjects We utilized data from adolescents (12-17 years) in Wave 3 of the Population Assessment of Tobacco and Health study who used e-cigarettes exclusively over the past 30 days (n = 177) and were followed up with in Wave 4.Measures Outcome variables were 3 transition categories: those who remained stagnant, those who progressed, and those who regressed in their stage of quitting e-cigarettes. Predictor variables were socio-demographics, e-cigarette harm perception, e-cigarette use at home or by important people, social norms, e-cigarette and anti-tobacco advertisements, and e-cigarette health warnings.Analysis Weighted-adjusted multinomial regression analysis was performed to determine the association between predictor and outcome variables.Results From Wave 3 to Wave 4, 19% of adolescents remained stagnant; 73.3% progressed; and 7.7% regressed. Adolescents were less likely to progress in their stage of change if they perceived nicotine in e-cigarettes to be “not at all/slightly harmful” (AOR = .26 [95% CI: .25, .27], P< .001); reported important people’s use of e-cigarettes (AOR = .18 [95% CI: .05, .65, P= .009); and “rarely” noticed e-cigarette health warnings (AOR = .28 [95% CI: .08, .98, P= .054).Conclusion Intervention efforts must target specific predictive factors that may help adolescents quit e-cigarettes.

Herein, we report the application of a benzyloxy-functionalized malonic acid half thioester as an activated ester equivalent in a highly enantioselective decarboxylative glycolate aldol reaction. This robust method operates at ambient temperature, tolerates air and moisture, and generates CO2as the only byproduct. The synthetic applicability of the method is demonstrated by the large-scale enantiodivergent synthesis of α-benzyloxy-β-hydroxybutyric acid thioester and its subsequent conversion to diverse polyoxygenated building blocks, deoxy-sugars, and (−)-angiopterlactone B.

Secondary metabolites are generally produced by enzymes encoded by genes within a biosynthetic gene cluster. Transcription factor genes are frequently located within these gene clusters. These transcription factors often drive expression of the other genes of the biosynthetic gene cluster, and overexpression of the transcription factor provides a facile approach to express all genes within a gene cluster, resulting in production of downstream metabolite(s). Unfortunately this approach is not always successful, leading us to engineer more effective hybrid transcription factors. Herein, we attempted to activate a putative cryptic biosynthetic gene cluster in Aspergillus nidulansusing a combination of transcription factor engineering and overexpression approaches. This resulted in the discovery of a novel secondary metabolite we term triorsellinaldehyde. Surprisingly, deletion of the polyketide synthase gene within the gene cluster did not prevent triorsellinaldehyde production. However, targeted deletion of a polyketide synthase gene elsewhere in the genome revealed its role in triorsellinaldehyde biosynthesis.

We examined the differences in neurocognitive functions in individuals dependent on heroin (n= 120), pharmaceutical (n= 52), and natural opioids (n= 66) and compared with healthy controls (HC, n= 94). We estimated independent effects of the opioid groups on cognitive tests, adjusted for effect modifiers. Pharmaceutical opioid dependent group performed worse than HC in Wisconsin Card Sorting Test in conceptual level response and trials to complete first category. Pharmaceutical and heroin groups had higher error scores than HC in verbal and visual N-Back Tests (NBTs). There was no significant difference between pharmaceutical and heroin groups, but both had higher error scores than the natural opioid users in NBTs. Time to complete Trail Making- A test was higher in pharmaceutical than in natural opioid group. The natural opioid group required more trials than HC to complete the first category. Pharmaceutical opioid group had worst cognitive impairment. Cognitive functions are relatively spared in natural opioid-dependent group.

Castleman disease, a rare lymphoproliferative disorder characterized by non-neoplastic lymph node enlargement, typically presents as nodal involvement, while extranodal manifestations are uncommon. We present a unique case of unicentric Castleman disease localized to the gluteal region in a 27-year-old female. Initially mistaken for a neurogenic or vascular tumour, fine needle aspiration cytology (FNAC) revealed a polymorphous population of lymphoid cells with numerous traversing capillaries suggestive of reactive hyperplasia, possibly Castleman disease, which was later confirmed by histopathology. This case highlights the diagnostic challenges posed by rare extranodal presentations of Castleman disease and underscores the importance of interdisciplinary collaboration in accurate diagnosis and management.

Objective: In this study on patients with Cushing disease, post-transsphenoidal surgery (TSS), we attempt to predict the probability of remaining in remission, at least for a year and relapse after that, using Bayes’ theorem and the equation of conditional probability. The number of parameters, as well as the weightage of each, is incorporated in this equation. Design and methods: The study design was a single-centre ambispective study. Ten clinical, biochemical, radiological and histopathological parameters capable of predicting Cushing disease remission were identified. The presence or absence of each parameter was entered as binary numbers. Bayes’ theorem was applied, and each patient’s probability of remission and relapse was calculated. Results: A total of 145 patients were included in the study. ROC plot showed a cut-off value of the probability of 0.68, with a sensitivity of 82% (range 73–89%) and a specificity of 94% (range 83–99%) to predict the probability of remission. Eighty-one patients who were in remission at 1 year were followed up for relapse and 23 patients developed relapse of the disease. The Bayes’ equation was able to predict relapse in only 3 out of 23 patients. Conclusions: Using various parameters, remission of Cushing disease can be predicted by applying Bayes’ theorem of conditional probability with a sensitivity and a specificity of 82% and 94%, respectively. This study provided an objective way of predicting remission after TSS and relapse in patients with Cushing disease giving a weightage advantage to every parameter.

ABSTRACTStates view protests as disruptive and police them. Scholarship points to selective policing of protests that endanger law and order as well as those organized by minority groups. A common form of protest policing in cities is requiring protestors to obtain permits in advance. We use interviews with protestors and the police in New Delhi to examine their perception of protest policing. We test these perceptions empirically using an original dataset of 4,921 protest applications submitted to the Delhi police between 2016 and 2019. We find that the rejection of protest applications is driven by the disruptive threat that they pose rather than the identity of the protesting group. However, the police disproportionately flag protest applications by religious minorities for threat assessment. A postcolonial police force, which privileges preservation of order over its other functions, regularly curtails the democratic freedom to protest.

Determine if a new teaching bundle targeting developmental dysplasia of the hip screening improved interns’ examination skills across multiple pediatric residency programs.This multicenter prospective cohort study included interns across 6 pediatric residency sites within the Academic Pediatric Association’s Better Outcomes through Research for Newborns Network in 2022. Participants underwent a baseline hip examination assessment on models using a checklist derived from textbook descriptions of Galeazzi, Ortolani, and Barlow maneuvers before receiving a teaching bundle. Repeat testing occurred after instruction. Data were analyzed using t-test for continuous and χ2 test for categorical variables. Semistructured focus groups provided qualitative feedback regarding the teaching bundle.We enrolled 117 of 155 interns across 6 sites (76%) for participation in the teaching bundle. Only 2% of participants (n = 2) identified a positive Galeazzi sign at baseline, whereas 88% (n = 103, P < .001) did so on the postinstructional assessment. Although 27% of participants (n = 32) correctly identified a positive Barlow sign at baseline, 69% (n = 81, P < .001) did so on the postinstructional assessment. The ability to correctly detect a positive Ortolani sign increased from 22% (n = 26) to 92% (n = 108, P < .001). Fifteen interns participated in the semistructured focus groups, with resultant themes reinforcing the limited experience of the infant hip examination before this intervention and the positive impact of the teaching bundle.Most participants in this study did not have strong infant hip examination skills at entry into residency. A standardized teaching bundle significantly improved skills in examination technique and identifying abnormalities.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosisinfection status while considering tuberculosis burden of the settings.

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

Forecasting COVID-19 waves helps with public health planning and resource allocation. Cycle threshold (Ct) values obtained from positive SARS-CoV-2 nucleic acid amplification test (NAAT) results offer limited value for individual patient management, but real-time analysis of temporal trends of aggregated Ct values may provide helpful information to predict the trajectories of COVID-19 waves in the community. Ct value trends on 59,609 SARS-CoV-2 NAAT-positive results from 574,403 tests using a single testing assay system, between September 2021 and January 2023, were examined to monitor the trend of the proportion of positive NAAT with lower Ct values (≤28) in relation to changing COVID-19 case numbers over time. We applied regression with autoregressive integrated moving average errors modelling approach to study the relation between Ct values and case counts. We also developed an insight product to monitor the temporal trends with Ct values obtained from SARS-CoV-2 NAAT-positive results. In this study, the proportion of lower Ct values preceded by a range of 7–32 days the rising population COVID-19 testing rate reflecting onset of a COVID-19 wave. Monitoring population Ct values may assist in predicting increased disease activity.

Elastic optical networks (EONs) offer tremendous benefits to deal with the exponential increase of the data center traffic. The granularity offered in spectrum allocation supports efficient management of available bandwidth and accommodates multiple traffic to be routed through common links. However, this brings the inherent challenges of routing and spectrum allocation (RSA) constraints. This becomes more complex for elastic optical data center networks (EODCNs), wherein multiple requests arrive at the same time, requiring identical or different bandwidths and each request may have the same or different destination and paths. Also, data requested by different users could be of varying importance levels. Under such a scenario, maintaining the quality of service (QoS) by minimizing the probability of traffic failure and bandwidth blocking is a major task for service providers. To address these problems, we propose an enhanced methodology using path prediction and link-state analysis for efficient allocation of frequency slots and reuse of bandwidth for data centers connected through EONs. Our proposed strategy intents to minimize the number of blocked requests due to non-availability of resources and reduce the failure probability. We introduce here the concept of connectivity degree and Kuhn-Munkres multi-objective optimization for spectrum allocation. We also evaluate the call request blocking probability varying the number of data centers and traffic load. The obtained results show that the proposed algorithm is highly effective in reducing the traffic failure and blocking probability for EODCNs.

In this paper, we study a dual hop hybrid radio frequency-visible light communication (RF-VLC) system with wireless energy harvesting technique. In the proposed model the RF channel and the VLC channel are modelled by generalized-K distribution and lambertian emission model, respectively. A decode and forward relay is used as an intermediate node where power splitting relaying (PSR) protocol is employed to harvest energy from the received RF information signal. The source transmits the information signal towards the relay via RF channel. The relay then decodes the received signal and convert it into corresponding light signal. Simultaneously the energy harvesting circuit at relay harvests the energy from the received RF signal. The relay utilizes the harvested energy to aid the transmission of the light signal towards the user situated inside the building’s room at the destination. Further, the statistics of the instantaneous SNR of the hybrid RF-VLC system at the destination are derived by employing the PSR protocol to obtain an accurate closed form analytical expression for the system’s end-to-end ergodic capacity and achievable throughput in terms of Meijer’s G function. Further, with the help of numerical simulations, we analysed the end-to-end ergodic throughput performance of the hybrid system under the influence of varying channel parameters such as signal to noise ratio, power splitting factor, shadowing parameters, distance between source & relay and source transmitted power.

•EPO is crucial for maintaining RBC balance, and its dysregulation can cause conditions such as anemia and polycythemia.•This study reveals a new discovery that 2 NRs, Rev-erbα and RORα, act oppositely, suggesting a potential therapy for EPO-related disorders.

Type 2 diabetes mellitus is a long-lasting endocrine disorder characterized by persistent hyperglycaemia, which is often triggered by an entire or relative inadequacy of insulin production or insulin resistance. As a result of resistance to insulin (IR) and an overall lack of insulin in the body, type 2 diabetes mellitus (T2DM) is a metabolic illness that is characterized by hyperglycaemia. Notably, the occurrence of vascular complications of diabetes and the advancement of IR in T2DM are accompanied by dysbiosis of the gut microbiota. Due to the difficulties in managing the disease and the dangers of multiple accompanying complications, diabetes is a chronic, progressive immune-mediated condition that plays a significant clinical and health burden on patients. The frequency and incidence of diabetes among young people have been rising worldwide. The relationship between the gut microbiota composition and the physio-pathological characteristics of T2DM proposes a novel way to monitor the condition and enhance the effectiveness of therapies. Our knowledge of the microbiota of the gut and how it affects health and illness has changed over the last 20 years. Species of the genus Eubacterium, which make up a significant portion of the core animal gut microbiome, are some of the recently discovered ‘generation’ of possibly helpful bacteria. In this article, we have focused on pathogenesis and therapeutic approaches towards T2DM, with a special reference to gut bacteria from ancient times to the present day.

ABSTRACTIn the context of most small businesses, innovativeness is critical for survival. However, small businesses often lack resources and are limited in their ability to influence external constraints. Consequently, they need to innovate in unique and often limited ways. While constraints-based innovativeness is discussed in emerging economies, we know little about how it occurs in advanced economies like Canada. This study uses a case study method in the craft brewery industry to examine different paths to constraints-based innovativeness through two capabilities, namely organizational agility and organizational improvisation capability. Results indicate an important but limited role for these capabilities for constraints-based innovativeness in the context of craft brewing, but also uncover different paths for development and evolution of innovativeness. This opens future research opportunities to study innovativeness, agility and organizational improvisation capability in small businesses facing resource constraints.

A sustainable society requires high-energy storage devices characterized by lightness, compactness, a long life and superior safety, surpassing current battery and supercapacitor technologies. Single-walled carbon nanotubes (SWCNTs), which typically exhibit great toughness, have emerged as promising candidates for innovative energy storage solutions. Here we produced SWCNT ropes wrapped in thermoplastic polyurethane elastomers, and demonstrated experimentally that a twisted rope composed of these SWCNTs possesses the remarkable ability to reversibly store nanomechanical energy. Notably, the gravimetric energy density of these twisted ropes reaches up to 2.1 MJ kg−1, exceeding the energy storage capacity of mechanical steel springs by over four orders of magnitude and surpassing advanced lithium-ion batteries by a factor of three. In contrast to chemical and electrochemical energy carriers, the nanomechanical energy stored in a twisted SWCNT rope is safe even in hostile environments. This energy does not deplete over time and is accessible at temperatures ranging from −60 to +100 °C.

Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed. We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing. A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35 mg/m2 + gemcitabine 800 mg/m2 + docetaxel 35 mg/m2 intravenously on days 1 and 8 + pegfilgrastim 6 mg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate. Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and a < ypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completing > 3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint (CD274(PD-L1)), chemokine (CXCL9), and T-cell (CD8A) genes. SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications.

AbstractSARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma

The article explores the history of Indian tattoos, tracing their origins back to ancient times and examining their various uses, including as symbols of rebellion, belonging, punishment, and ornamentation. Traditional tattooing in India has declined over the past few generations due to societal changes and aspirations for modernity. The text delves into ancient literature, sculptures, and ethnographic studies to shed light on the significance and symbolism of tattoos in Indian culture. It also discusses the historiography of tattooing in India, highlighting the lack of contemporary research on the subject and the need to document and preserve traditional tattooing practices. [Extracted from the article]

Graphical Abstract

The pericardium comprises a double-walled fibrous-serosal sac that encloses the heart. Reflections of the serosal layer form sinuses and recesses. With advances in multidetector computed tomography (CT) technology, pericardial recesses are frequently detected with thin-section CT. Knowledge of pericardial anatomy on imaging is crucial to avoid misinterpretation of fluid-filled pericardial sinuses and recesses as adenopathy/pericardial metastasis or aortic dissection, which can impact patient management and treatment decisions. The authors offer a comprehensive review of pericardial anatomy and its variations observed on CT, potential pitfalls in image interpretation, and implications for the pulmonologist with respect to unnecessary diagnostic procedures or interventions.

Background and Aims: Wasp stings often result in vascular problems and local irritation. Rarely neurological difficulties result from a delayed immune response, which causes acute inflammatory demyelinating polyradiculopathy, stroke and Parkinson’s disease.Patient’s Concern: Here we are describing a young male, who presented to us with ascending paralysis a few days after being stung by multiple wasps. The patient did not have any infection or recent vaccination. Nerve conduction velocity (NCV) suggested increased latencies in peripheral nerves. Hence, a temporality between Guillain–Barré syndrome (GBS) and the wasp sting was hypothesised.Intervention: After establishing a diagnosis, the patient received standard treatment for acute inflammatory demyelinating polyneuropathy (AIDP). Intravenous immunoglobulins were given over 5 days in divided doses. The patient had gross improvement in the weakness by day 7 and fully recovered in 2 months.Conclusion: This case study highlights the possibility of acute demyelinating polyradiculopathy, a serious neurological consequence that can arise from wasp stings. Nevertheless, the pathophysiology of the same is not well recognised in the literature. This emphasises the importance of identifying uncommon causes of GBS and comprehending the mechanism and curative measures.

Background: Bee sting is a common entity during the summer season and is rarely associated with devastating complications such as myocardial infarction, pulmonary edema, bleeding, and rhabdomyolysis, neurological complications can occur after multiple stings. However, single bee venom infestation resulting in such complications is rare.Patient’s Concern: Here, we are describing a young male, who presented to us with a seizure episode, soon after bitten by a bee sting around his lips. The patient did not have hypertension, diabetes, other risk factors for seizure, or any history of trauma but the patient’s computed tomography head showed cerebral hematoma.Intervention: The patient was managed immediately with an injection of antiepileptics with intravenous (IV) fluids, antihistaminics, and IV steroids. The patient had gross improvement in the sensorium and was seizure free for 48 h under observation. The patient was discharged on the 4thday of admission with 100% recovery.Conclusion: This case report emphasizes the potential for severe neurological complications following bee stings in the form of cerebral hematoma which is clinically important to recognize early and further research is required to better understand the mechanism and management strategies.

ABSTRACTObjectivesAppraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).MethodsNNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study (N = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs.ResultsNNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (−44 [95% CI −328; −21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue.ConclusionDaridorexant 50 mg and 25 mg have a favorable benefit–risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg.

ABSTRACTBackgroundThis article presents a strategy that a Drug Delivery Device Developer (DDDD) has adopted to support Abbreviated New Drug Application (ANDA) submissions of drug–device combination products. As per the related FDA guidance, a threshold analysis should be compiled. If ‘other differences’ between the Reference Listed Drug (RLD) and the generic drug devices are identified, a Comparative Use Human Factors (CUHF) study may be requested.MethodsThe DDDD performed task analysis and physical comparison to assess the pen injector design differences. Then, a formative CUHF study with 25 participants simulating injections using both RLD and the generic pen injectors was conducted.ResultsAfter each participant completed four simulated injections, similar type and rates of use error between the RLD (0.70) and generic (0.68) pen injectors were observed.ConclusionDDDDs can support pharmaceutical companies in the ANDA submission strategy of their drug–device combination product by initiating comparative task analysis and physical comparison of the device as inputs for the threshold analysis. If ‘other differences’ are identified, a formative CUHF study can be performed. As shown in our case study, this approach can be leveraged to support the sample size calculation and non-inferiority margin determination for a CUHF study with the final combination product.

Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients who had percutaneous coronary intervention within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event. Secondary outcomes included VerifyNow platelet reactivity units (PRUs) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42%–45%), followed by NPO status (26%–28%) and MCS alone (22%–24%). The primary outcome of major adverse cardiovascular event occurred in 1 patient (1.1%). Of 92 patients, 77% had a P2Y12 level collected within 24 hours, and 89% of the cohort was able to achieve the goal P2Y12 PRU of <194. The median P2Y12 value within 24 hours of cangrelor initation was 115 PRU (40–168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients who received a drug-eluting stent in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

IMPORTANCE: Dermatologists prescribe more oral antibiotics per clinician than clinicians in any other specialty. Despite clinical guidelines that recommend limitation of long-term oral antibiotic treatments for acne to less than 3 months, there is little evidence to guide the design and implementation of an antibiotic stewardship program in clinical practice. OBJECTIVE: To identify salient barriers and facilitators to long-term antibiotic prescriptions for acne treatment. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study assessed data collected from stakeholders (including dermatologists, infectious disease physicians, dermatology resident physicians, and nonphysician clinicians) via an online survey and semistructured video interviews between March and August 2021. Data analyses were performed from August 12, 2021, to January 20, 2024. MAIN OUTCOMES AND MEASURES: Online survey and qualitative video interviews developed with the Theoretical Domains Framework. Thematic analyses were used to identify salient themes on barriers and facilitators to long-term antibiotic prescriptions for acne treatment. RESULTS: Among 30 participants (14 [47%] males and 16 [53%] females) who completed the study requirements and were included in the analysis, knowledge of antibiotic guideline recommendations was high and antibiotic stewardship was believed to be a professional responsibility. Five salient themes were to be affecting long-term antibiotic prescriptions: perceived lack of evidence to justify change in dermatologic practice, difficulty navigating patient demands and satisfaction, discomfort with discussing contraception, iPLEDGE-related barriers, and the absence of an effective system to measure progress on antibiotic stewardship. CONCLUSIONS AND RELEVANCE: The findings of this qualitative study indicate that multiple salient factors affect long-term antibiotic prescribing practices for acne treatment. These factors should be considered in the design and implementation of any future outpatient antibiotic stewardship program for clinical dermatology.

Purpose of Study: To compare the outcomes of minimally invasive and open techniques in the surgical management of dorsolumbar and lumbar spinal tuberculosis (STB). Methods: Skeletally mature patients with active STB involving thoracolumbar and lumbar region confirmed by radiology (X-ray, MRI) and histopathological examination were included. Healed and mechanically stable STB, patients having severe hepatic and renal impairment, coexisting spinal conditions such as ankylosing spondylitis and rheumatoid arthritis, and patients unwilling to participate were excluded from the study. The patients were divided in to two groups, group A consisted of patients treated by MIS techniques and group B consisted of patients treated by open techniques. All the patients had a minimum follow-up of 24 months. Results: A total of 42 patients were included in the study. MIS techniques were used in 18 patients and open techniques were used in 24 patients. On comparison between the two groups, blood loss (234 ml vs 742 ml), and immediate post-operative VAS score (5.26 vs 7.08) were significantly better in group A, whereas kyphotic correction (16° vs 33.25°) was significantly better in group B. Rest of the parameters such as duration of surgery, VAS score, ODI score and number of instrumented levels did not show significant difference between the two groups. Conclusion: MIS stabilization when compared to open techniques is associated with significant improvement in immediate post-operative VAS scores. The MIS approaches at 2-year follow-up have functional results similar to open techniques. MIS is inferior to open techniques in kyphosis correction and may be associated with complications.

This article ponders over the applicability of EU-ETS influenced schemes in the Indian Aviation Sector. In the first three sections it discusses the various policies of the Indian government for ensuring sustainable development. While mentioning these schemes, the authors underscore that these policies are not sufficient to keep a check on the emissions from the rapidly growing aviation sector and there is a need for a policy on the lines of EU’s ‘trade and cap’ principle to ensure sustainable development of the sector. A ‘trade and cap’ policy can ensure active participation of government and private entities in the sector, whereas such a policy can increase investment in sustainability and reduction of emissions. In the following sections, the authors, while dissecting the policy governing the European Union Emissions Trading Scheme (EU ETS), highlight pros and cons of the system and how it can be applied in the Indian aviation sector. The paper also dwells into the trade and cap policies already implemented by India, such as in the chemical industry. Finally, measures will be suggested which should be included in a trade and cap policy for the Indian aviation sector in order to achieve a significant and holistic growth of the sector while keeping environmental goals in mind. Also, airlines should be incentivized to invest in sustainable techniques and contribute substantially to the reduction cumulative sectoral emissions.

The capacity of communities to develop effective obesity prevention initiatives varies and should be a focus for obesity prevention intervention planning and investment. This research aimed at engaging and consulting local community stakeholders to identify determinants, needs, strategic priorities and capacity to act on overweight and obesity prevention in North‐West (NW) Tasmania. A series of semi‐structured interviews and thematic analyses was implemented to explore the knowledge, insights, experiences and attitudes of stakeholders. Mental health and obesity were identified as major concerns and were often reported to share similar determinants. This study has identified health promotion capacity assets (existing partnerships, community capital, local leadership and some pockets of health promotion activity), and a range of capacity deficits (limited investment in health promotion, a small workforce, limited access to pertinent health information). This study has identified health promotion capacity assets (existing partnerships, community capital, local leadership and some pockets of health promotion activity), and a range of capacity deficits (limited investment in health promotion, a small workforce, limited access to pertinent health information). Broad upstream socio‐economic, cultural and environmental determinants underpin the conditions by which the local community develops overweight/obesity and/or health and wellbeing outcomes. Including stakeholder consultations as a significant technique within a comprehensive plan of action aimed at achieving a sustainable, long‐term strategy for obesity prevention and/or health promotion, should be considered in future programs.

This article ponders over the applicability of EU-ETS influenced schemes in the Indian Aviation Sector. In the first three sections it discusses the various policies of the Indian government for ensuring sustainable development. While mentioning these schemes, the authors underscore that these policies are not sufficient to keep a check on the emissions from the rapidly growing aviation sector and there is a need for a policy on the lines of EU’s ‘trade and cap’ principle to ensure sustainable development of the sector. A ‘trade and cap’ policy can ensure active participation of government and private entities in the sector, whereas such a policy can increase investment in sustainability and reduction of emissions. In the following sections, the authors, while dissecting the policy governing the European Union Emissions Trading Scheme (EU ETS), highlight pros and cons of the system and how it can be applied in the Indian aviation sector. The paper also dwells into the trade and cap policies already implemented by India, such as in the chemical industry. Finally, measures will be suggested which should be included in a trade and cap policy for the Indian aviation sector in order to achieve a significant and holistic growth of the sector while keeping environmental goals in mind. Also, airlines should be incentivized to invest in sustainable techniques and contribute substantially to the reduction cumulative sectoral emissions.