Robust language-based mental health assessments in time and space through social media.

In the most comprehensive population surveys, mental health is only broadly captured through questionnaires asking about "mentally unhealthy days" or feelings of "sadness." Further, population mental health estimates are predominantly consolidated to yearly estimates at the state level, which is considerably coarser than the best estimates of physical health. Through the large-scale analysis of social media, robust estimation of population mental health is feasible at finer resolutions. In this study, we created a pipeline that used ~1 billion Tweets from 2 million geo-located users to estimate mental health levels and changes for depression and anxiety, the two leading mental health conditions. Language-based mental health assessments (LBMHAs) had substantially higher levels of reliability across space and time than available survey measures. This work presents reliable assessments of depression and anxiety down to the county-weeks level. Where surveys were available, we found moderate to strong associations between the LBMHAs and survey scores for multiple levels of granularity, from the national level down to weekly county measurements (fixed effects ß = 0.34 to 1.82; p < 0.001). LBMHAs demonstrated temporal validity, showing clear absolute increases after a list of major societal events (+23% absolute change for depression assessments). LBMHAs showed improved external validity, evidenced by stronger correlations with measures of health and socioeconomic status than population surveys. This study shows that the careful aggregation of social media data yields spatiotemporal estimates of population mental health that exceed the granularity achievable by existing population surveys, and does so with generally greater reliability and validity.

Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter.

JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.

Beyond the genome: MALAT1's role in advancing urologic cancer care.

Urologic cancers (UCs), which include bladder, kidney, and prostate tumors, account for almost a quarter of all malignancies. Long non-coding RNAs (lncRNAs) are tissue-specific RNAs that influence cell growth, death, and division. LncRNAs are dysregulated in UCs, and their abnormal expression may allow them to be used in cancer detection, outlook, and therapy. With the identification of several novel lncRNAs and significant exploration of their functions in various illnesses, particularly cancer, the study of lncRNAs has evolved into a new obsession. MALAT1 is a flexible tumor regulator implicated in an array of biological activities and disorders, resulting in an important research issue. MALAT1 appears as a hotspot, having been linked to the dysregulation of cell communication, and is intimately linked to cancer genesis, advancement, and response to treatment. MALAT1 additionally operates as a competitive endogenous RNA, binding to microRNAs and resuming downstream mRNA transcription and operation. This regulatory system influences cell growth, apoptosis, motility, penetration, and cell cycle pausing. MALAT1's evaluation and prognosis significance are highlighted, with a thorough review of its manifestation levels in several UC situations and its association with clinicopathological markers. The investigation highlights MALAT1's adaptability as a possible treatment target, providing fresh ways for therapy in UCs as we integrate existing information The article not only gathers current knowledge on MALAT1's activities but also lays the groundwork for revolutionary advances in the treatment of UCs.

Impact of miconazole nitrate ferrying cationic and anionic nanoemulsion and gels on permeation profiles of across EpiDerm, artificial membrane, and skin: Instrumental evidences.

Based on our previous report, the study was extended to investigate the impact of miconazole nitrate (MCN) loaded cationic/anionic nanoemulsions and nanoemulsion gels on permeation behaviour across artificial-membrane, EpiDerm, and rat skin. Nanoemulsions and gels were evaluated for size, charge, viscosity, size-distribution, pH, and percent entrapment efficiency (%EE). In vitro drug diffusion across artificial membrane and EpiDerm were conducted to get diffusion coefficients. Permeation profiles were studied using rat skin to investigate mechanistic insight of formulated mediated permeation followed by CLSM (confocal laser scanning microscopy), SEM (scanning electron microscopy), AFM (atomic force microscopy), and irritation studies. Results showed that MCNE11-Rh (probed cationic nanoemulsion at pH âˆ¼ 7.2) and MNE11-Rh (probed anionic nanoemulsion at pH âˆ¼ 7.2) showed size values of 158 nm and 145 nm, respectively whereas MCNE11-GR (probed cationic nanoemulsion gel at pH âˆ¼ 6.8) and MNE11-GR (probed anionic nanoemulsion gel at pH âˆ¼ 6.8) exhibited size values 257 nm and 243 nm, respectively. The %EE values were found to be as 91.5 % and 89.6 % for MCNE11-Rh and MNE11-Rh, respectively. The gels (∼6000 cP) elicited relatively high viscosity than nanoemulsions (∼3300 - 3500 cP). MCNE11-GR showed the highest values of permeation flux, diffusion rate, diffusion coefficient (D), and permeation coefficient (P) across artificial membrane, EpiDerm, and rat skin which may be attributed to three potential factors (cationic charge, composition, and hydration by the hydrophilic gel) working in tandem. Transepidermal water loss (TEWL) by the MCNE11-GR was maximum (14.4 g/m2h) than control (6.1 g/m2h) indicating augmented interaction of MCNE11-Rh with skin components. Conclusively, cationic nanoemulsion gel was promising carrier for enhanced permeation and the drug access to the dermal region to treat deep seated fungal infections.

Deciphering equity style returns: An analysis of size and value anomalies in the Pakistani stock exchange.

This study aims to identify the underlying causes of variation in the time series and cross-sectional equity style returns in the emerging stock market of Pakistan. We use asset pricing models and incorporate variables reflecting business cycle fluctuations to assess the time-varying size and value premiums. The methodology of this paper involves constructing style portfolios based on firm-specific characteristics such as market capitalization, price to earnings ratio, book-to-market equity ratio, momentum, and asset growth. We find that the style portfolios earn abnormal returns consistently which cannot be explained either through asset pricing models or business cycles variables. However, the size and value premiums are found to be subsided during the troughs of economic cycles. The results suggest that the abnormal returns for style portfolios are likely driven by firm-specific characteristics rather than macroeconomic factors. Overall, this study contributes to the literature on style investing by providing insights into the profitability of equity style portfolios in the Pakistani equity market. Our findings have implications for stock picking, investment management and risk factor analysis.

Cash flow management and its effect on firm performance: Empirical evidence on non-financial firms of China.

The main purpose of this research is to investigate the impact of changes in cash flow measures and metrics on firm financial performance. The study uses generalized estimating equations (GEEs) methodology to analyze longitudinal data for sample of 20288 listed Chinese non-financial firms from the period 2018:q2-2020:q1. The main advantage of GEEs method over other estimation techniques is its ability to robustly estimate the variances of regression coefficients for data samples that display high correlation between repeated measurements. The findings of study show that the decline in cash flow measures and metrics bring significant positive improvements in the financial performance of firms. The empirical evidence suggests that performance improvement levers (i.e. cash flow measures and metrics) are more pronounced in low leverage firms, suggesting that changes in cash flow measures and metrics bring more positive changes in low leverage firms' financial performance relatively to high leveraged firms. The results hold after mitigating endogeneity based on dynamic panel system generalized method of moments (GMM) and sensitivity analysis considering the robustness of main findings. The paper makes significant contribution to the literature related to cash flow management and working capital management. Since, this paper is among few to empirically study, how cash flow measures and metrics are related to firm performance from dynamic stand point especially from the context of Chinese non-financial firms.

Asymptomatic COVID-19 presenting with features of mixed pattern acute liver injury in a young healthy female, a case report.

COVID-19 associated severe acute liver injury in a young healthy patient has not been reported much in the literature. And currently, there are no standard management guidelines. We want to report a case of acute liver injury of mixed pattern in a young healthy female with asymptomatic COVID-19 infection. She presented with abdominal pain, nausea, vomiting and yellowish discoloration of her skin. Further laboratory investigations revealed mixed pattern liver injury with highly raised liver enzymes. She was managed with N-acetyl cysteine protocol and monitoring of her liver enzymes. Other causes of acute liver injury were ruled out. She remained stable during her hospital stay and follow up. Our aim is to highlight the significance of acute liver injury in COVID 19 patients that may lead to fatal outcomes if not managed and monitored accordingly.

Correcting Sociodemographic Selection Biases for Population Prediction from Social Media.

Social media is increasingly used for large-scale population predictions, such as estimating community health statistics. However, social media users are not typically a representative sample of the intended population - a "selection bias". Within the social sciences, such a bias is typically addressed with restratification techniques, where observations are reweighted according to how under- or over-sampled their socio-demographic groups are. Yet, restratifaction is rarely evaluated for improving prediction. In this two-part study, we first evaluate standard, "out-of-the-box" restratification techniques, finding they provide no improvement and often even degraded prediction accuracies across four tasks of esimating U.S. county population health statistics from Twitter. The core reasons for degraded performance seem to be tied to their reliance on either sparse or shrunken estimates of each population's socio-demographics. In the second part of our study, we develop and evaluate Robust Poststratification, which consists of three methods to address these problems: (1) estimator redistribution to account for shrinking, as well as (2) adaptive binning and (3) informed smoothing to handle sparse socio-demographic estimates. We show that each of these methods leads to significant improvement in prediction accuracies over the standard restratification approaches. Taken together, Robust Poststratification enables state-of-the-art prediction accuracies, yielding a 53.0% increase in variance explained (R 2) in the case of surveyed life satisfaction, and a 17.8% average increase across all tasks.

Tetravalent formulation of polymeric nanoparticle-based vaccine induces a potent immune response against dengue virus.

Dengue is a mosquito-borne disease caused by the four serotypes of the dengue virus (DENV 1-4). It is growing at an alarming rate globally, which could be partly attributed to the lack of an effective therapeutic regimen. Therefore, strategies for developing an effective vaccine have gained more significance in the given scenario. Failure of the existing live attenuated vaccine candidates to mount effective and broader protection against all the four serotypes of DENV has generated a new interest in exploring novel strategies for augmenting the efficacy of non-infectious, non-replicating subunit vaccines. In the current study, we employed a new strategy of encapsulating the immunodominant EDIII domain of Envelop protein of all the serotypes of DENV (1-4) into PLGA nanoparticles separately. All four nano formulations were physically mixed to develop a tetravalent nano formulation in combination with TLR agonists. Further, we examined its immunological efficacy using a mouse and in vitro infection model system. Interestingly, our results demonstrate that majority of EDIII protein loaded PLGA nanoparticles were polydispersed and less than 1 µm in size with optimal encapsulation efficacy. Tetravalent nanoformulation along with TLR agonists (MPLA + R837) enhanced the magnitude of antigen-specific polyfunctional T cell response. It triggered robust antibody responses in mice concurrent with the increased level of genes involved in the programming of memory B-cell formation and the maintenance and maturation of GCs, leading to the formation of long-lived plasma cells secreting antigen-specific antibodies. Further assessment revealed that tetravalent nanoformulation in combination with TLR ligands upon immunization in mice aids in the enhanced production of serotype-specific neutralizing antibodies, which can effectively neutralize all the four serotypes of DENV (DENV 1-4). The findings of this study reveal a new strategy for enhancing the immunogenicity of vaccine candidates and might pave the way for the development of a tetravalent vaccine against all the serotypes of Dengue Virus.

Clinical progress of therapeutics and vaccines: Rising hope against COVID-19 treatment.

Cases of deaths due to COVID-19 (COrona VIrus Disease-19) infection are increasing gradually worldwide. Immense research is ongoing to control this pandemic condition. Continual research outcomes are indicating that therapeutic and prophylactic agents are the possible hope to prevent the pandemic from spreading and to combat this increasing death count. Experience gained from previous coronavirus infections (eg., SARS (Severe Acute Respiratory Syndrome), MERS (Middle Ease Respiratory Syndrome), accumulated clinical knowledge during this pandemic, and research helped to identify a few therapeutic agents for emergency treatment of COVID-19. Thereby, monoclonal antibodies, antivirals, broad-spectrum antimicrobials, immunomodulators, and supplements are being suggested for treatment depending on the stage of the disease. These recommended treatments are authorized under medical supervision in emergency conditions only. Urgent need to control the pandemic condition had resulted in various approaches of repurposing the existing drugs, However, poorly designed clinical trials and associated outcomes do not provide enough evidence to fully approve treatments against COVID-19. So far, World Health Organization (WHO) authorized three vaccines as prophylactic against SARS-CoV-2. Here, we discussed about various therapeutic agents, their clinical trials, and limitations of trials for the management of COVID-19. Further, we have also spotlighted different vaccines in research in combating COVID-19.

Investigating Gender Differences in Canadian Plastic Surgery Online Patient Education.

BACKGROUND: The public interest and demand for cosmetic surgery is growing in North America. As practices continue to advertise cosmetic procedures, male consumers must also be given fair consideration in a market targeted mostly towards women. OBJECTIVES: This study investigated the advertising trends of plastic surgery clinics to assess for prevailing gender differences among online Canadian plastic surgery practice advertising. METHODS: The 2021 College of Physicians and Surgeons directory for each province and territory was utilized to identify all practicing plastic surgeons. A systematic search with Google (Mountain View, CA) was conducted to analyze the websites of Canadian plastic surgery centers in the following manner: "[physician name] [province of practice]." RESULTS: A total of 209 websites and 13,838 images were identified and analyzed. Of these images, 12,386 (90%) were female and 1452 (10%) were male patients or models. Although only 20% had a male services page, 62% of all centers offered gynecomastia procedures. The most common procedures targeting men were blepharoplasty (95%), liposuction (93%), and abdominoplasty (93%). The Prairies region had significantly fewer websites with male-only pages compared with all other Canadian regions. CONCLUSIONS: Despite the increase in cosmetic surgery procedures for males, the market for cosmetic surgery procedures targeted towards males remains insignificant. An increase in the advertising of in-demand male cosmetic procedures can allow for a broader consumer market and a subsequent increase in benefits for plastic surgeons.

The impact of crude oil prices on Chinese stock markets and selected sectors: evidence from the VAR-DCC-GARCH model.

The interaction between oil and stock market returns is one of the most important relationships that have a significant influence on the economy of any country all over the world. Therefore, this paper investigates the impact of crude oil prices on the Chinese stock market and selected industries by using the VAR-DCC-GARCH model over the period from December 26, 2001, to April 30, 2019. The empirical results show that the impact of Brent crude oil prices on the Shanghai Composite Index and selected industries is significant. However, there are some variations in these relationships and the degree of influence on each differs during different sample periods. Brent crude oil prices exert substantial influence on some specific industries, like mining, chemical, nonferrous metals, and steel. Whereas, the volatility spillover effect of Brent crude oil prices is stronger within the mining, chemical, steel, nonferrous metal, building materials, building decoration, electrical equipment, electrical equipment, textile and garment, light manufacturing, public utility, and transportation industries than within other industries. When oil prices change abruptly, the risk of spillover impacts of oil prices on stock markets will also increase. In conclusion, the impact of Brent crude oil prices on the Chinese stock market is generally positive. Furthermore, the subsequent volatility of Chinese stock market prices will, in turn, influence the volatility spillover of Brent crude oil prices on the indexes. The result is an ongoing back and forth of changes in price volatilities.

Equine immunoglobulin fragment F(ab')2 displays high neutralizing capability against multiple SARS-CoV-2 variants.

Neutralizing antibody-based passive immunotherapy could be an important therapeutic option against COVID-19. Herein, we demonstrate that equines hyper-immunized with chemically inactivated SARS-CoV-2 elicited high antibody titers with a strong virus-neutralizing potential, and F(ab')2 fragments purified from them displayed strong neutralization potential against five different SARS-CoV-2 variants. F(ab')2 fragments purified from the plasma of hyperimmunized horses showed high antigen-specific affinity. Experiments in rabbits suggested that the F(ab')2 displays a linear pharmacokinetics with approximate plasma half-life of 47 h. In vitro microneutralization assays using the purified F(ab')2 displayed high neutralization titers against five different variants of SARS-CoV-2 including the Delta variant, demonstrating its potential efficacy against the emerging viral variants. In conclusion, this study demonstrates that F(ab')2 generated against SARS-CoV-2 in equines have high neutralization titers and have broad target-range against the evolving variants, making passive immunotherapy a potential regimen against the existing and evolving SARS-CoV-2 variants in combating COVID-19.

Environmental degradation and sustainable development of economies: empirical evidence on economic performance.

The present paper aims to analyze the influence of environmental practices over the sustainable development of economies which create economic resilience for the economies classified according to different income levels. The authors aim to assess the impact of high environmental degradation (HED) on GDP growth volatility and GDP growth for economies over the long term and short term for the period of 1955-2020 in 124 countries. The findings of empirical analysis conclude that HED economies will have high growth in the long term than their counterparts. The economies of HED have a significant mean difference in volatility with their counterpart control group that implies HED economies have low volatility than the control group. Economies with HED have higher financial development relative to their control economies. The empirical analysis of robustness checks shows that economies with HED have low volatility in GDP and higher growth rates. HED economies enjoy high and sustainable financial development and high gross fixed capital formation, which signifies a high level of investment in their economy than their control counterpart.

Drug Loading and Functional Efficacy of Cow, Buffalo, and Goat Milk-Derived Exosomes: A Comparative Study.

Quite recently, milk exosomes have been recognized as efficient drug delivery systems owing to their biocompatibility and easy availability for scale-up technologies. However, there are no reports of comparative studies with regards to drug delivery by milk exosomes derived from different species. In this study, we isolated and characterized milk exosomes of cow, buffalo, and goat by various techniques and tried to understand their drug loading capacity and functional efficiency in HepG2, HCT116, and A549 cells by using doxorubicin. Doxorubicin was loaded to milk exosomes by three methods, that is, incubation, saponin treatment, and sonication. The isolated exosomes were found to be spherical with a size of <200 nm and displayed specific markers, namely, CD81, HSP70, HSC70, and miRNAs. Drug loading studies revealed that goat milk exosomes had the highest loading capacity across all three methods. Doxorubicin-encapsulated goat milk exosomes resulted in the inhibition of cell viability, with low IC50 values in HepG2, HCT-116, and A549 cells. Doxorubicin-encapsulated goat exosomes displayed better IC50 values than cow and buffalo milk-derived counterparts. In line with this, the ability of doxorubicin-encapsulated goat milk exosomes to induce apoptosis in HepG2 and HCT-116 cells was higher than that of cow and buffalo milk exosomes and free doxorubicin. Furthermore, unbound goat milk exosomes significantly reduced cell viability as compared to cow and buffalo milk exosomes. The transepithelial transport assay shows that doxorubicin-loaded milk exosomes transport doxorubicin efficiently as compared to free doxorubicin in vitro. Doxorubicin released from milk exosomes shows a biphasic release pattern, burst release followed by sustained release. These observations are important in light of the emerging importance of milk-derived exosomes as drug carriers to treat cancers.

The environmental impact of industrialization and foreign direct investment: empirical evidence from Asia-Pacific region.

Environmental degradation has been the main distress in recent years due to the drastic effect of climate change. To determine the gone thorough impact of industrialization and foreign direct investment on environmental degradation, this study utilized panel data of 55 countries of the Asia-Pacific region from 1995 to 2020 and it applies an autoregressive distributed lag (ARDL) model. The results showed that FDI, in general, has a significant negative impact on the environment and causes to increase in methane and CO2 emissions. Moreover, industrialization has a positive and significant impact on the environment. However, the size of the impact is moderate. This study also concludes that in the Asia-Pacific region, the environment Kuznets curve (EKC) and pollution heaven (PH) hypothesis are accepted. Finally, this study suggests the strict implication of environmental guidelines or the adoption of a new policy would be the key to ensuring the quality of the environment. Furthermore, the results confirmed that most of the panel countries are developing countries and do not have strict environmental management guidelines.

Role of green innovation, trade and energy to promote green economic growth: a case of South Asian Nations.

The objective of this study is to contribute to the existing debate of green economic growth by empirically investigating the role of cleaner energy production, green innovation, and green trade in green economic growth in the context of South Asian countries. For this purpose, the study collects the data of South Asian Economies for 2000-2018 from different sources such as world development indicators (WDI), International Energy Statistics (IES), and Organization for Economic Co-operation and Development (OECD) statistics. The study applied Pesaran's (2007) second-generation unit root test to test the stationarity of the data. Wasteland's (2007) test of cointegration was applied to examine the long-run association among modeled variables. The study confirmed the long-run association among modeled variables that turn to be stationary at the first differences. Moreover, the study applied fully modified least square (FMOLS) and dynamic least square (DOLS) to estimate the empirical results of the study. Results of the study show that the production of clean energy, green innovation, and green trade positively contributes to the green economic growth of South Asian Economies Graphical abstract.

The Unforeseen Diagnosis: Hyperparathyroidism-Jaw Tumour Syndrome Case Report and Review of the Literature.

Hypercalcaemia and its systemic sequelae are a relatively common finding amongst patients in the field of endocrinology. Primary hyperparathyroidism, a frequent cause of hypercalcaemia, is often seen among middle-aged female patients, typically resulting from an underlying single-gland adenoma. Although patients may present with symptoms (nephrolithiasis, musculoskeletal discomfort, dehydration, or mood disturbance, to name a few), hypercalcaemia is rather frequently identified incidentally. In younger patients, a familial form of primary hyperparathyroidism must be considered, with a positive diagnosis mandating familial screening. Hyperparathyroidism-jaw tumour syndrome is one such autosomal dominant familial disorder, characterised by a mutation in the cell division cycle 73 (CDC73; also known as HRPT-2) tumour suppressor gene. This disorder is characterised by multiple pleiotropic phenomena, including recurrent primary hyperparathyroidism (and the effects of hypercalcaemia), neoplasms (such as uterine, renal, mandibular, and maxillary), and infertility. A patient not conforming to the classic candidacy for primary hyperparathyroidism requires consideration for a familial cause. Case Description. We present a rare diagnostic entity-hyperparathyroidism-jaw tumour (HPT-JT) syndrome-in a 36-year-old female with recurrent primary hyperparathyroidism, frequent nephrolithiasis, and infertility for 18 years prior to the diagnosis. We aim to promote awareness amongst medical professionals of this rare, but nonetheless essential differential diagnosis through a case report and review of the literature. Conclusion. Medical professionals must avoid diagnostic overshadowing and display a low threshold for genetic testing in younger patients with primary hyperparathyroidism. The importance of proper identification extends beyond the patient to their relatives and offspring.