Multiple HAPS-based space-air-ground network with FSO communication: a performance analysis.

Due to the fact that the existing generation of wireless communication cannot possibly keep up with the current traffic explosion and emerging applications, research and development on next-generation (i.e., sixth generation, 6G) wireless technologies is being carried out worldwide. In this regard, it is anticipated that the space-air-ground (SAG) network with free space optics (FSO) communication can provide the terabits per second throughput necessary to sustain various potential 6G applications. However, FSO communications are susceptible to atmospheric turbulence, pointing errors, and beam scintillation effects. To remedy the severe atmospheric effects, we propose a multiple high-altitude platform station (HAPS)-based SAG network with a HAPS selection scheme. For the proposed system, we have derived the closed-form expressions for outage probability, average symbol error rate (SER), ergodic capacity, and outage capacity over Málaga distribution with pointing errors. Further, the asymptotic expressions for outage probability, average SER, and outage capacity were derived to enhance the comprehension of the system from a practical standpoint. It is observed from the numerical results that the multiple HAPS-based FSO system performs better than the existing HAPS-based FSO systems.

Design of a real-world, prospective, longitudinal, observational study to compare vortioxetine with other standard of care antidepressant treatments in patients with major depressive disorder: a PatientsLikeMe survey.

BACKGROUND: Major depressive disorder (MDD) is a recurrent psychiatric condition that presents challenges in responding to treatment and achieving long-term remission. To improve outcomes, a shared decision-making treatment approach with patient and healthcare practitioner (HCP) engagement is vital. PatientsLikeMe (PLM), a peer community of patients, provides information on MDD, symptoms, and treatment through forums and resources, helping patients stay engaged in their treatment journey. Data on PLM can be harnessed to gain insights into patient perspectives on MDD symptom management, medication switches, and treatment goals and measures. METHODS: This ongoing, decentralized, longitudinal, observational, prospective study is being conducted using the PLM platform in two parts, enrolling up to 500 patients with MDD in the United States aged ≥ 18 years to compare vortioxetine with other monotherapy antidepressants. The first qualitative component consists of a webinar and discussion forum with PLM community members with MDD, followed by a pilot for functionality testing to improve the study flow and questions in the quantitative survey. The quantitative component follows on the PLM platform, utilizing patient-reported assessments, over a 24-week period. Three surveys will be conducted at baseline and weeks 12 and 24 to collect data on patient global impression of improvement, depression severity, cognitive function, quality of life (QoL) and well-being, medication satisfaction, emotional blunting, symptoms of anhedonia and resilience, as well as goal attainment. Quantitative results will be compared between groups. The qualitative component is complete; patient recruitment is underway for the quantitative component, with results expected in late 2023. DISCUSSION: These results will help HCPs understand patient perspectives on the effectiveness of vortioxetine versus other monotherapy antidepressants in alleviating symptoms of MDD and improvements in QoL. Data from the PLM platform will support a patient goal-based treatment approach, as results can be shared by patients with their HCPs, providing them with insights on patient-centric goals, treatment management and adherence, as well as allowing them to observe changes in patient-related outcomes scores. Findings from the study will also help to optimize the PLM platform to build scalable solutions and connectivity within the community to better serve patients with MDD.

Long non-coding RNA mediated drug resistance in breast cancer.

Breast cancer is one of the most prevalent cancers in women and a leading cause of mortality. As per the GLOBCAN report of 2021, breast cancer has surpassed lung cancer which until recently was the most commonly diagnosed cancer. Despite significant efforts to improve early detection and therapeutic efficacy of breast cancer, the frequent emergence of drug resistance remains the predominant basis for the poor prognosis of cancer patients harboring various malignancies. Long non-coding RNA (lncRNAs) are known to affect a variety of components of genome function, including epigenetics, gene transcription, splicing, translation, as well as many central biological processes like cell cycle progression, cell differentiation, development, and pluripotency. LncRNAs are dysregulated in various malignancies and interact with a multitude of RNAs and proteins to impact drug resistance. LncRNAs regulate chemoresistance in cancer by employing an assortment of molecular mechanisms including multidrug efflux, suppression of apoptosis, DNA damage response, epigenetic alterations, as well as functioning as competitive endogenous RNA. When combined with other regulatory mechanisms, these pathways form a complex orchestration of signaling that ultimately lead to chemoresistance. The current review delves into the role of lncRNAs in inducing drug resistance to conventional therapeutic anti-cancer drugs used for the treatment of breast cancer. We propose that lncRNAs that provoke drug resistance could be used to develop new targeted and tailored therapeutics providing a novel approach to introduce promising personalized treatment modalities to overcome chemoresistance in breast cancer patients. Hence, lncRNAs that drive anticancer drug resistance can be potentially explored as biomarkers of disease prognosis and may provide unique opportunities to circumvent chemoresistance in breast cancer patients.

In Silico Identification of Potential Quadruplex Forming Sequences in LncRNAs of Cervical Cancer.

Long non-coding RNAs (lncRNAs) have emerged as auxiliary regulators of gene expression influencing tumor microenvironment, metastasis and radio-resistance in cancer. The presence of lncRNA in extracellular fluids makes them promising diagnostic markers. LncRNAs deploy higher-order structures to facilitate a complex range of functions. Among such structures, G-quadruplexes (G4s) can be detected or targeted by small molecular probes to drive theranostic applications. The in vitro identification of G4 formation in lncRNAs can be a tedious and expensive proposition. Bioinformatics-driven strategies can provide comprehensive and economic alternatives in conjunction with suitable experimental validation. We propose a pipeline to identify G4-forming sequences, protein partners and biological functions associated with dysregulated lncRNAs in cervical cancer. We identified 17 lncRNA clusters which possess transcripts that can fold into a G4 structure. We confirmed in vitro G4 formation in the four biologically active isoforms of SNHG20, MEG3, CRNDE and LINP1 by Circular Dichroism spectroscopy and Thioflavin-T-assisted fluorescence spectroscopy and reverse-transcriptase stop assay. Gene expression data demonstrated that these four lncRNAs can be potential prognostic biomarkers of cervical cancer. Two approaches were employed for identifying G4 specific protein partners for these lncRNAs and FMR2 was a potential interacting partner for all four clusters. We report a detailed investigation of G4 formation in lncRNAs that are dysregulated in cervical cancer. LncRNAs MEG3, CRNDE, LINP1 and SNHG20 are shown to influence cervical cancer progression and we report G4 specific protein partners for these lncRNAs. The protein partners and G4s predicted in lncRNAs can be exploited for theranostic objectives.

DECOMPOSING THE SOCIOECONOMIC INEQUALITY IN UTILIZATION OF MATERNAL HEALTH CARE SERVICES IN SELECTED COUNTRIES OF SOUTH ASIA AND SUB-SAHARAN AFRICA.

The gap in access to maternal health care services is a challenge of an unequal world. In 2015, each day about 830 women died due to complications of pregnancy and childbirth. Almost all of these deaths occurred in low-resource settings, and most could have been prevented. This study quantified the contributions of the socioeconomic determinants of inequality to the utilization of maternal health care services in four countries in diverse geographical and cultural settings: Bangladesh, Ethiopia, Nepal and Zimbabwe. Data from the 2010-11 Demographic and Health Surveys of the four countries were used, and methods developed by Wagstaff and colleagues for decomposing socioeconomic inequalities in health were applied. The results showed that although the Concentration Index (CI) was negative for the selected indicators, meaning maternal health care was poorer among lower socioeconomic status groups, the level of CI varied across the different countries for the same outcome indicator: CI of -0.1147, -0.1146, -0.2859 and -0.0638 for <3 antenatal care visits; CI of -0.1338, -0.0925, -0.1960 and -0.2531 for non-institutional delivery; and CI of -0.1153, -0.0370, -0.1817 and -0.0577 for no postnatal care within 2 days of delivery for Bangladesh, Ethiopia, Nepal and Zimbabwe, respectively. The marginal effects suggested that the strength of the association between the outcome and explanatory factors varied across the different countries. Decomposition estimates revealed that the key contributing factors for socioeconomic inequalities in maternal health care varied across the selected countries. The findings are significant for a global understanding of the various determinants of maternal health care use in high-maternal-mortality settings in different geographical and socio-cultural contexts.

A novel stop-loss mutation in NKX2-2 gene as a cause of neonatal diabetes mellitus: molecular characterization and structural analysis.

AIM: To identify the genetic etiology of neonatal diabetes in an infant and to elucidate the molecular mechanism of the identified mutation underlying the pathogenesis. METHODS: Genetic analysis was carried out by sequencing of known etiological genes associated with NDM. Molecular characterization was performed by constructing a identified mutation in NKX2-2 gene and  functional aspects was tested using transactivation, protein expression, DNA binding, nuclear localization assays. Structural analysis was performed by modeling the NKX2-2 protein structure. RESULTS: A novel homozygous frameshift mutation  c.772delC, p.Q258SFs*59 in the NKX2-2 gene was identified in a patient with neonatal diabetes. Functional studies revealed that this mutation resulted in an elongated protein sequence, affecting DNA binding activity and transcriptional function. Structural analysis suggested alterations in the protein's tertiary structure, likely contributing to its dysfunction. CONCLUSION: This study presents the first report of a stop-loss mutation in the NKX2-2 gene associated with NDM. Our findings emphasize the importance of functional and structural characterization to understand the biological consequences of such mutations. This comprehensive analysis provides insights into the molecular mechanisms underlying NDM and its clinical phenotype, which may aid in better diagnosis and management of patients with similar variants in the future.

Comparative Evaluation of Serum Levels of Vitamin B12, Folic Acid, and ESR in Chronic Periodontitis Among Smokers, Gutkha Chewers, and Type 2 Diabetic Patients: A Cross-Sectional Study.

Aim: The purpose of this research is to determine the relationship between periodontal disease severity, cigarette smoking, gutka chewing, and type 2 diabetes mellitus by estimating, correlating, and comparing blood levels of vitamin B12, folic acid, and erythrocyte sedimentation rate (ESR) in patients with chronic periodontitis. Methodology: A cross-sectional research study conducted at Rama Dental College Hospital and Research Centre in Kanpur involved 240 patients with chronic periodontitis, who also exhibited additional risk factors including smoking, gutkha chewing, and type-2 diabetes mellitus. Divided into four groups of 60 individuals each, the study aimed to estimate and correlate blood levels of vitamin B12, folic acid, and ESR. Group I served as the control with chronic periodontitis patients, while Group II comprised chronic periodontitis patients who were smokers, Group III included those who chewed gutkha, and Group IV consisted of patients with type-2 diabetes mellitus. Clinical parameters were assessed, and patients were followed up to track any changes or correlations. Result: This research confirmed that low levels of vitamin B12 and folic acid are linked to inflammatory diseases such chronic periodontitis. Conclusion: The study revealed that type-2 diabetic and gutka chewer groups exhibited statistically higher periodontal disease severity, vitamin B12, and folic acid deficiencies and elevated ESR compared to smokers and control groups.

Retrospective text and qualitative analyses of patient experience and management of vasomotor symptoms due to menopause: voices from the PatientsLikeMe community.

OBJECTIVE: Vasomotor symptoms (VMS) due to menopause cause substantial burden and distress. Some women join online communities to share experiences and treatment outcomes through peer-to-peer interactions. This study describes women's experiences with VMS and symptom management on the PatientsLikeMe online support group. METHODS: Mixed-methods research included women aged 40 to 65 years in the PatientsLikeMe community who were recruited using convenience sampling. Text from online posts by members was analyzed retrospectively using natural language processing. Relevant data, including numbers and percentages of women and frequencies of mentions, were summarized descriptively. Qualitative semistructured interviews were conducted; data, notes, and recordings were transcribed and deidentified and thematic analyses were performed. RESULTS: Demographic information was available from 1,614 accounts included in retrospective text analyses. Women had a mean age of 56.7 years; most were White (87.8%) and not Hispanic/Latino (90.2%). Hot flashes and night sweats were most commonly mentioned symptoms (n = 146). Of 16 women who were interviewed, 14 met the inclusion criteria, and their responses were included in the analysis. VMS impacted life quality in terms of physical (43%) and mental well-being (36%), social activities (21%), and productivity (14%). Symptom management included temperature regulation (43%), lifestyle changes (36%), over-the-counter Estroven (29%), hormone therapy (21%), and contraceptives (21%). Half of the women were surprised by symptom intensity and duration; many felt unheard by their healthcare providers. CONCLUSIONS: VMS have a substantial negative impact on multiple aspects of women's life. Management strategies for these symptoms vary widely, and many women feel unprepared for navigating the complex challenges of menopause.

Survey of patient experience and management of vasomotor symptoms due to menopause from the PatientsLikeMe community.

OBJECTIVE: This study aimed to describe menopause and treatment experiences of women with vasomotor symptoms due to menopause in the United States. METHODS: A cross-sectional survey was administered to women 40-65 years of age recruited from PatientsLikeMe, a dedicated online platform for patients. RESULTS: A total of 196 women (mean age 55.7 years; 81.2% White) completed the survey and were included in the analyses. The majority (87.2%) reported experiencing bothersome symptoms; 54.3% (100/184) had daytime hot flashes, and 59.2% (109/184) had nighttime sweats and hot flashes, up to 5 times per day on average. Mean postmenopause duration was 10.8 years. Although most (68.5%, 126/184) reported having vasomotor symptoms for less than 5 years, some (14.1%, 26/184) had symptoms for more than a decade. Only 35.2% (69/196) were treated for their symptoms; the most frequently reported prescription treatment was hormone therapy (58%; 40/69), which was administered for less than 3 years in most cases (67.5%, 27/40). Although women were generally satisfied with their interactions with healthcare providers, 23.0% reported inadequate support. Sleep, personal relationships, and physical, emotional, and mental well-being were the most affected by vasomotor symptoms. Healthcare professionals with training in women's health were the most valued resource for dealing with the symptoms associated with menopause. CONCLUSIONS: Not all women with symptoms were treated. In those whose concerns were addressed by providers, a reluctance to pursue treatment was still observed. A need persists to ensure that this population has the resources and support needed to effectively manage symptoms.

Cancer metastases: Tailoring the targets.

Metastasis is an intricate and formidable pathophysiological process encompassing the dissemination of cancer cells from the primary tumour body to distant organs. It stands as a profound and devastating phenomenon that constitutes the primary driver of cancer-related mortality. Despite great strides of advancements in cancer research and treatment, tailored anti-metastasis therapies are either lacking or have shown limited success, necessitating a deeper understanding of the intrinsic elements driving cancer invasiveness. This comprehensive review presents a contemporary elucidation of pivotal facets within the realm of cancer metastasis, commencing with the intricate processes of homing and invasion. The process of angiogenesis, which supports tumour growth and metastasis, is addressed, along with the pre-metastatic niche, wherein the primary tumour prepares for a favorable microenvironment at distant sites for subsequent metastatic colonization. The landscape of metastasis-related genetic and epigenetic mechanisms, involvement of metastasis genes and metastasis suppressor genes, and microRNAs (miRNA) are also discussed. Furthermore, immune modulators' impact on metastasis and their potential as therapeutic targets are addressed. The interplay between cancer cells and the immune system, including immune evasion mechanisms employed by metastatic cells, is discussed, highlighting the importance of targeting immune modulation in arresting metastatic progression. Finally, this review presents promising treatment opportunities derived from the insights gained into the mechanisms of metastasis. Identifying novel therapeutic targets and developing innovative strategies to disrupt the metastatic cascade holds excellent potential for improving patient outcomes and ultimately reducing cancer-related mortality.

Polyhydroxyalkanoate Production by Methanotrophs: Recent Updates and Perspectives.

Methanotrophs are bacteria that consume methane (CH4) as their sole carbon and energy source. These microorganisms play a crucial role in the carbon cycle by metabolizing CH4 (the greenhouse gas), into cellular biomass and carbon dioxide (CO2). Polyhydroxyalkanoates (PHAs) are biopolymers produced by various microorganisms, including methanotrophs. PHA production using methanotrophs is a promising strategy to address growing concerns regarding plastic pollution and the need for sustainable, biodegradable materials. Various factors, including nutrient availability, environmental conditions, and metabolic engineering strategies, influence methanotrophic production. Nutrient limitations, particularly those of nitrogen or phosphorus, enhance PHA production by methanotrophs. Metabolic engineering approaches, such as the overexpression of key enzymes involved in PHA biosynthesis or the disruption of competing pathways, can also enhance PHA yields by methanotrophs. Overall, PHA production by methanotrophs represents a sustainable and versatile approach for developing biomedical materials with numerous potential applications. Additionally, alternative feedstocks, such as industrial waste streams or byproducts can be explored to improve the economic feasibility of PHA production. This review briefly describes the potential of methanotrophs to produce PHAs, with recent updates and perspectives.

A Rare Case of Parotid Gland Tuberculosis.

Parotid gland tuberculosis is a very rare form of extrapulmonary tuberculosis, with less than 200 cases reported in literature. We describe a 10-year-old female who presented with a swelling in the left parotid region during the last month. CT scan neck revealed an abscess in the left parotid gland extending into the submandibular gland, muscles, and bone. Pus aspirated by FNAC showed acid fast bacilli in the ZN stain, and GeneXpert was positive for rifampicin-sensitive Mycobacterium tuberculosis. She was successfully treated with antituberculous therapy given for 6 months. Parotid gland tuberculosis, although rare, has a good prognosis with drug therapy. Surgery is rarely required.

A Strategic Target Rescues Trimethoprim Sensitivity in Escherichia coli.

Trimethoprim, a preferred treatment for urinary tract infections, is becoming obsolete owing to the rapid dissemination of resistant E. coli. Although direct resistance mechanisms such as overexpression of a mutant FolA and dfr enzymes are well characterized, associated alterations that drive or sustain resistance are unknown. We identify the repertoire of resistance-associated perturbations by constructing and interrogating a transcriptome-integrated functional interactome. From the cross talk between perturbations in stress-response and metabolic pathways, we identify the critical dependence on serine hydroxymethyltransferase (GlyA) as an emergent vulnerability. Through its deletion, we demonstrate that GlyA is necessary to sustain high levels of resistance in both laboratory-evolved resistant E. coli and a multidrug-resistant clinical isolate. Through comparative evolution, we show that the absence of GlyA activity decelerates the acquisition of resistance in E. coli. Put together, our results identify GlyA as a promising target, providing a basis for the rational design of drug combinations.

Ab initio determination of geometries and vibrational characteristics of building blocks of organic superconductors: 4,5-Ethylenedithio-1,3-dithiole-2-thione, and 4,5-ethylenedithio-1,3-dithiole-2-one.

RHF and DFT calculations were carried out to study the optimized molecular geometries and vibrational characteristics of the 4,5-ethylenedithio-1,3-dithiole-2-thione (EDT-DTT) and 4,5-ethylenedithio-1,3-dithiole-2-one (EDT-DTO) molecules and their radical cations and anions. It is found that the anionic radical of the EDT-DTO molecule is unstable. Both the neutral molecules and their radical cations have non-planar structures with C(2) symmetry while the radical anion of the EDT-DTT molecule has non-planar structure with C(1) symmetry. It is found that the most of the vibrational characteristics of the radicals are similar to their corresponding neutral molecules, however, for some of the modes significant changes are noticed. As a result of anionic radicalization of EDT-DTT, the IR intensity and Raman activity increase and Raman band becomes polarized for both the CH(2) twisting modes. Drastic enhancements in the Raman activity and reduced IR intensity are noticed for the C=S/O stretching mode in going from neutral molecules to their radical ions consistent with charge separation along this bond. The C=S and C=C stretching wavenumber changes are consistent with corresponding bond length changes in going from neutral to their radical ions.