Modeling measles transmission in adults and children: Implications to vaccination for eradication.

Despite the availability of successful vaccines, measles outbreaks have occurred frequently in recent years, presumably due to the lack of proper vaccination implementation. Moreover, measles cases in adult groups, albeit small in number, indicate that the previously neglected adult group may need to be brought into vaccine coverage to achieve WHO's goal of measles eradication from the globe. In this study, we develop a novel transmission dynamics model to describe measles cases in adults and children to evaluate the role of adult infection in persistent measles cases and vaccination programs for eradication. Analysis of our model, validated by measles cases from outbreaks in Nepal, provides the vaccination reproduction number (conditions for measles eradication or persistence) and the role of contact network size. Our results highlight that while children are primary targets for measles outbreaks, a small number of infections in adults may act as a reservoir for measles, causing obstacles to eradication. Furthermore, our model analysis shows that while impactful controls can be achieved by children-focused vaccines, a combined adult-child vaccination program may help assert eradication of the disease.

Hearing Loss and Cognitive Decline in the Aging Population: Emerging Perspectives in Audiology.

In this perspective article, the author explores the connections between hearing loss, central auditory processing, and cognitive decline, offering insights into the complex dynamics at play. Drawing upon a range of studies, the relationship between age-related central auditory processing disorders and Alzheimer's disease is discussed, with the aim of enhancing our understanding of these interconnected conditions. Highlighting the evolving significance of audiologists in the dual management of cognitive health and hearing impairments, the author focuses on their role in identifying early signs of cognitive impairment and evaluates various cognitive screening tools used in this context. The discussion extends to adaptations of hearing assessments for older adults, especially those diagnosed with dementia, and highlights the significance of objective auditory electrophysiological tests. These tests are presented as vital in assessing the influence of aging and Alzheimer's disease on auditory processing capabilities and to signal cognitive dysfunction. The article underscores the critical role of audiologists in addressing the challenges faced by the aging population. The perspective calls for further research to improve diagnostic and therapeutic strategies in audiology, and emphasizes the need for a multidisciplinary approach in tackling the nexus of hearing loss, auditory processing, and cognitive decline.

Primary Angiitis of the CNS: Differences in the Profile Between Subtypes and Outcomes From an Indian Cohort.

BACKGROUND AND OBJECTIVES: Primary angiitis of the CNS (PACNS) is a rare disease that has significant morbidity and mortality. Subtypes of PACNS can have different presentations that could be missed with certain diagnostic modalities, further increasing diagnostic complexity. We sought to distinguish the subtypes of PACNS and describe their outcomes in an Indian cohort. METHODS: Adult patients in this retrospective single-center cohort study were reviewed from the PACNS database between 2000 and 2019. Diagnosis was made as per Calabrese and Malleck criteria. Small and medium vessel vasculitis was defined, and their clinical and radiologic profile, treatment, and outcomes were compared. Functional outcomes were noted at 6-month, 1-year, and at last follow-up, while relapses were noted at last follow-up. A poor outcome was defined as modified Rankin Scale >2. RESULTS: Seventy-two patients fulfilled the inclusion criteria of whom 50 (69.4%) were male. The small vessel vasculitis subtype had a younger age at onset (30.5 vs 40.5 years, p = 0.014), presented less often as a stroke (22% vs 62%, p = 0.001), and had greater delay in diagnosis and treatment initiation (median of 620 days vs 118 days, p = 0.001) compared with medium vessel vasculitis subtype. Although no difference was noted at 6 months, the small vessel vasculitis group had poor outcomes at 1-year and last follow-up (57% vs 20%, p = 0.011 and 72% vs 34%, p = 0.005, respectively) and had more relapses at last follow-up (89% vs 30%, p < 0.001) when compared with the medium vessel vasculitis group. On analyzing the entire cohort, 50 of 72 (69%) and 37 of 53 (69.8%) patients had a good outcome at 6 months and 1 year, respectively. Relapse was noted in 35 of 72 (49%) at final follow-up. The choice of the treatment regimen did not predict outcomes or relapses. DISCUSSION: The small vessel vasculitis subtype of PACNS is a distinct entity that has diagnostic and treatment delays with poor long-term outcomes and more relapses. Recognizing the different subtypes of PACNS may help to expedite diagnosis and plan treatment.

Cancer Trials Ecosystem in India-Ready for Prime Time?

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

Audiovisual perception of interrupted speech by nonnative listeners.

The purpose of the present study was to examine the influence of visual cues in audiovisual perception of interrupted speech by nonnative English listeners and to identify the role of working memory, long-term memory retrieval, and vocabulary knowledge in audiovisual perception by nonnative listeners. The participants included 31 Mandarin-speaking English learners between 19 and 41 years of age. The perceptual stimuli were noise-filled periodically interrupted AzBio and QuickSIN sentences with or without visual cues that showed a male speaker uttering the sentences. In addition to sentence recognition, the listeners completed a semantic fluency task, verbal (operation span) and visuospatial (symmetry span) working memory tasks, and two vocabulary knowledge tests (Vocabulary Level Test and Lexical Test for Advanced Learners of English). The results revealed significantly better speech recognition in the audio-visual condition than the audio-only condition, but the magnitude of visual benefit was substantially attenuated for sentences that had limited semantic context. The listeners' vocabulary size in English played a key role in the restoration of missing speech information and audiovisual integration in the perception of interrupted speech. Meanwhile, the listeners' verbal working memory capacity played an important role in audiovisual integration especially for the difficult stimuli with limited semantic context.

An Unusual Case of Cryoglobulinemic Vasculitis and Acute Disseminating Encephalomyelitis in a 21-Year-Old Caucasian Male.

Cryoglobulinemic vasculitis and acute disseminated encephalomyelitis (ADEM) are characterized by damage to either blood vessels or grey matter. For both diseases, infections can be an etiology. In cryoglobulinemic vasculitis, the initial insult causes damage to the glomerulus, and in the case of ADEM, damage leads to a central nervous system demyelinating disorder. Infective endocarditis can be associated with both diseases and can be challenging to diagnose. Individuals on antibiotics may present with negative blood cultures, making underlying infective endocarditis difficult to diagnose. In this report, we describe a 21-year-old male who presented to the hospital after an assault with splenic laceration and was subsequently found to have infective endocarditis associated with cryoglobulinemic vasculitis and ADEM.

CLN-617 retains IL-2 and IL-12 in injected tumors to drive robust and systemic immune-mediated antitumor activity.

Despite clinical evidence of antitumor activity, the development of cytokine therapies has been hampered by a narrow therapeutic window and limited response rates. Two cytokines of high interest for clinical development are interleukin 2 (IL-2) and interleukin 12 (IL-12), which potently synergize to promote the activation and proliferation of T cells and natural killer (NK) cells. However, the only approved human IL-2 therapy, Proleukin, is rarely used in the clinic due to systemic toxicities, and no IL-12 product has been approved to date due to severe dose-limiting toxicities. Here, we describe CLN-617, a first-in-class therapeutic for intratumoral (IT) injection that co-delivers IL-2 and IL-12 on a single molecule in a safe and effective manner. CLN-617 is a single-chain fusion protein comprised of IL-2, leukocyte-associated immunoglobulin-like receptor 2 (LAIR2), human serum albumin (HSA), and IL-12. LAIR2 and HSA function to retain CLN-617 in the treated tumor by binding collagen and increasing molecular weight, respectively. We found that IT administration of a murine surrogate of CLN-617, mCLN-617, eradicated established treated and untreated tumors in syngeneic models, significantly improved response to anti-PD1 checkpoint therapy, and generated a robust abscopal response dependent on cellular immunity and antigen cross-presentation. CLN-617 is being evaluated in a clinical trial in patients with advanced solid tumors (NCT06035744).

Efflux transporters in drug disposition during pregnancy.

Evidence-based dose selection of drugs in pregnant women has been lacking due to challenges in studying maternal-fetal pharmacokinetics. Hence, many drugs are administered off-label during pregnancy based on data obtained from non-pregnant women. During pregnancy, drug transporters play an important role in drug disposition along with known gestational age-dependent changes in physiology and drug-metabolizing enzymes. In this review, as Dr. Qingcheng Mao's former and current lab members, we summarize the collective contributions of Dr. Mao, who lost his life to cancer, focusing on the role of drug transporters in drug disposition during pregnancy. Dr. Mao and his team initiated their research by characterizing the structure of Breast Cancer Resistance Protein [BCRP, ATP-Binding Cassette (ABC) G2]. Subsequently, they have made significant contributions to the understanding of the role of BCRP and other transporters, particularly P-glycoprotein (P-gp/ABCB1), in the exposure of pregnant women and their fetuses to various drugs, including nitrofurantoin, glyburide, buprenorphine, bupropion, tetrahydrocannabinol, and their metabolites. This review also highlights the gestation- and pregnancy-dependent transporter expression at the blood-brain and blood-placenta barriers in mice. Significance Statement Dr. Qingcheng Mao and his team have made significant contributions to the investigation of the role of efflux transporters, especially P-glycoprotein and breast cancer resistance protein, in maternal-fetal exposure to many xenobiotics: nitrofurantoin, glyburide, buprenorphine, bupropion, tetrahydrocannabinol and their metabolites. Studies of individual compounds and the expression of transporters during gestation and pregnancy have improved the understanding of maternal-fetal pharmacokinetics.

Fractional topological charge measurement through optical correlation.

The emerging field of optical vortex beams having fractional topological charges (TCs) is of high interest due to its usefulness in various applications. The efficiency of the result depends on the precise measurement of the orbital angular momentum information tied to the fractional TC. This Letter demonstrates, to our knowledge, a novel and simple technique to measure the fractional TC of optical vortex beams through a hybrid digital-optical correlator with the help of auto-correlation between fork-shaped interference patterns corresponding to integer and fractional TCs. Unlike machine learning-based approaches, the proposed method does not require a complex architecture, which lowers computational cost and enables real-time implementation.

Salt-tolerant plant growth-promoting Pseudomonas atacamensis KSS-6 in combination with organic manure enhances rice yield, improves nutrient content and soil properties under salinity stress.

In the current study salt tolerant-plant growth-promoting rhizobacteria (ST-PGPR) Pseudomonas atacamensis KSS-6, selected on the basis of prominent plant growth-promoting (PGP) and stress tolerance properties was tested as bioinoculant to improve yield of rice grown in saline soil. The ST-PGPR KSS-6 was capable of maintaining the PGP traits up to 200 mM NaCl, however, higher salt stress conditions affected these activities. The study was designed to determine the effect of developed talc-based bioformulation using KSS-6 along with organic manure (OM) on growth and yield of paddy under saline conditions. Bioformulation broadcasting was also done to examine the effect on soil properties. It was found that the combinatorial treatment showed positive impact on growth and yield of rice under saline conditions. Co-application of KSS-6 with OM showed maximum increment in growth, chlorophyll content, plant fresh weight, and dry weight as compared to untreated control plants. Furthermore, the combinatorial treatment improved the nutrient content (P, K, Zn, Fe, Mg, and Mn) by more than 35% and enhanced the biochemical parameters such as proline, flavonoids, carbohydrates, protein, dietary fiber, and antioxidant content of rice grains by more than 32%. Soil parameters including pH and electrical conductivity (EC), moisture content, total organic carbon, OM, sodium, and chloride ions were also improved upon treatment. There was significant lowering of EC from 7.43 to 4.3 dS/m when combination of OM and bacteria were applied. These findings suggest that the application of KSS-6 in the form of bioinoculant could be a promising strategy to mitigate negative impacts of salt stress and enhance the yield and nutritional properties of rice grown in degraded and saline soil.

Binary image encryption with a QR code-encoded optical beam having an array of vortices.

In recent years, optical information processing has become increasingly important due to its ability to handle large amounts of data efficiently. Amplitude, phase, spatial frequency, wavelength, and polarization are the physical dimensions used for information encoding into the light beam. Information encoding using orbital angular momentum (OAM) carried by a vortex beam is gaining interest in this regard. Such beams provide high-dimensional orthogonal states for encoding and have shown more stability in turbulent media than Gaussian beams, especially in the case of free space propagation. This study demonstrates an image encryption method utilizing an array of OAM light modes. The approach uses a non-interferometric intensity recording-based encoding scheme, which offers ease of implementation. Quick response codes have been utilized for encoding to avoid information loss from non-uniform distribution of light and aberrations. The encryption scheme is highly secure because the encrypted light beam contains only partial information about the object, preventing complete information retrieval without proper key information.

Renal Functional Reserve in Acute Kidney Injury Patients Requiring Dialysis.

The incidence of acute kidney injury (AKI) has increased in the recent past. Patients with AKI have an increased risk of mortality. They are also at increased risk of developing chronic kidney disease (CKD). AKI can lead to irreversible loss of renal function despite complete clinical recovery. Currently, no tools are available to diagnose this subclinical loss of renal function. Renal functional reserve (RFR) can serve as an essential tool for analyzing this subclinical loss of renal function, and patients with loss of RFR post-AKI may be closely followed for the development of CKD. This prospective observational study, conducted at the Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), aimed to investigate RFR in 223 patients with AKI requiring dialysis. The study excluded patients with CKD and obstructive uropathy. Methods included RFR assessment three months post-AKI recovery, utilizing technetium-99m (Tc-99m) diethylenetriaminepentaacetic acid (DTPA) plasma clearance during amino acid infusion. Statistical analyses and logistic regression were applied, receiving ethical approval. Results revealed a high in-hospital mortality rate of 78.02%, associated with elevated Sequential Organ Failure Assessment (SOFA) scores. Among 24 patients with complete AKI recovery, the RFR at three months was 10.06% (interquartile range (IQR) 5.60-20.15), with the measured GFR significantly lower than the estimated glomerular filtration rate (GFR). The study concludes that AKI requiring dialysis is linked to high mortality and emphasizes the predictive value of SOFA scores. Additionally, RFR testing at three months post-recovery provides insights into potential long-term impacts on renal function. This study contributes valuable insights into the prognosis of AKI patients requiring dialysis. It underscores the need for further research on RFR as a diagnostic tool and the lasting consequences of AKI.

Chemical- and green-precursor-derived carbon dots for photocatalytic degradation of dyes.

Rapid industrialization and untreated industrial effluents loaded with toxic and carcinogenic contaminants, especially dyes that discharge into environmental waters, have led to a rise in water pollution, with a substantial adverse impact on marine life and humankind. Photocatalytic techniques are one of the most successful methods that help in degradation and/or removal of such contaminants. In recent years, semiconductor quantum dots are being substituted by carbon dots (CDs) as photocatalysts, due to the ease of formation, cost-effectiveness, possible sustainability and scalability, much lower toxicity, and above all its high capacity to harvest sunlight (UV, visible, and near infrared) through electron transfer that enhances the lifetime of the photogenerated charge carriers. A better understanding between the properties of the CDs and their role in photocatalytic degradation of dyes and contaminants is required for the formation of controllable structures and adjustable outcomes. The focus of this review is on CDs and its composites as photocatalysts obtained from different sustainable green as well as chemical precursors. Apart from the synthesis, characterization, and properties of the CDs, the study also highlights the effect of different parameters on the photocatalytic properties of CDs and their composites for catalytic dye degradation mechanisms in detail. Besides the present research development in the field, potential challenges and future perspectives are also presented.

2D Ionic Liquid-Like State of Charged Rare-Earth Clusters on a Metal Surface.

Rare-earth complexes are vital for separation chemistry and useful in many advanced applications including emission and energy upconversion. Here, 2D rare-earth clusters having net charges are formed on a metal surface, enabling investigations of their structural and electronic properties on a one-cluster-at-a-time basis using scanning tunneling microscopy. While these ionic complexes are highly mobile on the surface at ≈100 K, their mobility is greatly reduced at 5 K and reveals stable and self-limiting clusters. In each cluster, a pair of charged rare-earth complexes formed by electrostatic and dispersive interactions act as a basic unit, and the clusters are chiral. Unlike other non-ionic molecular clusters formed on the surfaces, these rare-earth clusters show mechanical stability. Moreover, their high mobility on the surface suggests that they are in a 2D liquid-like state.

Promoting Choosing Wisely Thyroid Function Test Guidelines in a Large Pediatric Hospital System.

BACKGROUND: Free thyroxine (fT4) is often ordered when not indicated. The goal of the current study was to use quality improvement tools to identify and implement an optimal approach to reduce inappropriate fT4 testing throughout a large pediatric hospital system. METHODS: After reviewing evidence-based guidelines and best practices, a thyroid-stimulating hormone with reflex to fT4 test and an outpatient thyroid order panel with clinical decision support at order entry, along with several rounds of provider education and feedback, were implemented. Outpatient and inpatient order sets and system preference lists were reviewed with subject matter experts and revised when appropriate. Tracking metrics were identified. Automated monthly run charts and statistical process control charts were created using data retrieved from the electronic health record. Charts established baseline data, balancing measure data, monitored the impact of interventions, and identified future interventions. RESULTS: Over a 44-month period, among nonendocrinology providers, a reduction in fT4 and thyroid-stimulating hormone co-orders from 67% to 15% and an increase in reflex fT4 tests from 0% to 77% was obtained in inpatient and outpatient settings. Direct cost savings as a result of performing 5179 fewer fT4 tests over 3 years was determined to be $45 800. CONCLUSIONS: After implementation of a reflex fT4 test, a novel order panel with clinical decision support, provider education, and changes to ordering modes, a large and sustainable reduction in fT4 tests that was associated with significant cost savings was achieved among nonendocrinology providers.

Diffuse reflectance spectroscopy and digital soil mapping for assessing soil-associated off-road vehicle mobility risk.

Soil attributes such as granulometric fractions and Atterberg limits (LL: liquid limit, PL: plastic limit, and PI: plasticity index) are needed to assess off-road vehicle mobility (OVM) risks. Parameters describing these attributes are generally measured in soil samples collected from a few locations through cumbersome laboratory methods. Although diffuse reflectance spectroscopy (DRS) can rapidly yield estimates for soil attributes in samples collected from specific locations and digital soil mapping (DSM) can transform such discrete measurements into spatially-continuous inference systems, these two technologies are rarely used for assessing OVM risks. In this study, we combined the DRS and DSM approaches for deriving spatially-continuous estimates for the key vehicle mobility parameters (gravel, sand, and fine particles; Cu: coefficients of uniformity; Cc: coefficient of curvature; LL; and PI) and classified soils using the Unified Soil Classification System (USCS). A total of 204 soil samples were collected from the north-eastern Himalayan state of Sikkim for measuring these parameters along with spectral reflectance over the visible and near-infrared region. Results of the chemometric models in the DRS approach showed that the USCS parameters may be estimated with the coefficient of determination (R2) values as high as 0.72. The fine (<2 mm diameter) fraction spectra provided the best estimates for the Atterberg limits while a combination of spectra collected from fine and coarse (>2 mm diameter) fractions was effective in estimating other granulometric fractions except for sand, which was best estimated using the coarse fraction spectra. With the DSM approach allowing effective mapping of these parameters, a spatially-continuous framework to quantify soil-associated OVM risks was developed for Sikkim for the first time.

Marsogenin: a new pregnane ester from Marsdenia tenacissima.

A new pregnane, 12ß-O-acetyl-20(S)-O-N-methylanthranilyl-3ß, 8ß, 14ß, 17α-tetrol pregn-5-ene (12ß-O-acetyl-20(S)-O-N-methylanthranilyl-sarcostin) have been isolated from Marsdenia tenacissima (family: Asclepediaceae). The structure of new pregnane was elucidated by using spectroscopic techniques,1H,13C NMR, HMBC, HSQC, COSY and TOCSY and ESI-MS Mass spectrometry.

Time scale theory on stability of explicit and implicit discrete epidemic models: applications to Swine flu outbreak.

Time scales theory has been in use since the 1980s with many applications. Only very recently, it has been used to describe within-host and between-hosts dynamics of infectious diseases. In this study, we present explicit and implicit discrete epidemic models motivated by the time scales modeling approach. We use these models to formulate the basic reproduction number, which determines whether an outbreak occurs or the disease dies out. We discuss the stability of the disease-free and endemic equilibrium points using the linearization method and Lyapunov function. Furthermore, we apply our models to swine flu outbreak data to demonstrate that the discrete models can accurately describe the epidemic dynamics. Our comparison analysis shows that the implicit discrete model can best describe the data regardless of the data frequency. In addition, we perform the sensitivity analysis on the key parameters of the models to study how these parameters impact the basic reproduction number.

2-D NMR studies of geneoside, a novel pregnane pentaglycoside of 2-deoxy and 2, 6 dideoxy monosaccharides from 'Wattakaka lanceolata'.

Plants of Asclepiadaceae and Apocynaceae family are a rich source of pregnane and pregnane glycosides. They are found in nature either in free state or as their glycosides. They have shown antitumor, anticancer, and hypoglycaemic, antioxidant and antimicrobial activities. In our continued studies on the isolation of pregnane glycosides we have isolated a novel pregnane pentaglycoside comprised of 2-deoxy and 2, 6-dideoxy monosaccharides from Wattakaka lanceolata (Asclepiadaceae). The structure of the new glycoside, Geneoside was established as11α, 12ß-O-diacetyl-drevogenin-P-3-O-ß-D-cymaropyaranosyl (1→4)-ß-D-cymaropyranosyl (1→4) -ß-D-Oleandropyranosyl (1→4)-ß-D-digitalopyranosyl (1→4)-ß-D-digitalopyranoside. The stereoscopic structure was established by chemical degradation, chemical transformation and recent physicochemical techniques viz 1H,13C, 2-D NMR (COSY, TOCSY, HSQC and HMBC) and Mass spectrometry.