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BACKGROUND: Over the last three years, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a global impact. COVID-19 has led to diagnostic and treatment delays in head and neck squamous cell cancers (HNSCCs). Both cancer and COVID-19 trigger systemic inflammatory responses that can result in cytokine storms, creating a favorable tumor microenvironment that supports tumor growth. Various studies have shown a positive association between increasing neutrophil-to-lymphocyte ratio (NLR) and disease severity in COVID-19. Studies have also shown that high NLR is associated with poor survival outcomes in cancer patients. Our aim is to investigate whether an increased NLR is linked to rapid tumor progression in patients with HNSCC who have also been affected by infections like COVID-19 in the pre-operative period. METHODS: This was a retrospective analysis of patients of HNSCC who were scheduled for surgery and had contracted COVID-19 in their pre-operative period between April 2021 and May 2021. The study analyzed pre- and post-COVID NLR in relation to disease progression in HNSCC. Statistical analysis was presented as an interquartile range and numbered with the percentage. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 26.0, Armonk, NY) was utilized for the analysis. RESULTS: We evaluated 200 operable cases of which 38/200 (20%) patients with HNSCC were COVID-19 positive. Out of those COVID-19-positive patients, 27/38 (71%) patients got operated. Around, 11/38 (28.9%) patients were inoperable. And, 14/27 (53.8%) operated patients also had a change in treatment plan. The mean duration from the joint clinic treatment plan to the date of surgery was 25.18 days. Patients who had contracted COVID-19 and had a change in their treatment plan due to disease progression exhibited mean NLR values of 3.84 (pre-COVID) and 11.11 (post-COVID), with respective medians of 3.04 and 10.50. These differences showed a statistically significant p-value of 0.000. In contrast, patients who had no change in treatment plan displayed mean NLR values of 4.51 (pre-COVID) and 9.70 (post-COVID), with respective medians of 3.47 and 3.42, resulting in with a non-significant p-value of 0.082. CONCLUSION: This is a one-of-its-kind study that has evaluated the role of elevated NLR in patients with a COVID-19 virus infection and its relationship with the clinical progression of the disease. The findings suggest that elevated NLR in patients with HNSCC, along with concurrent SARS-CoV2 infection, may contribute to accelerated disease progression with an increase in tumor burden and nodal metastasis.
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Osteochondromas arising from the interosseous border of the distal tibia are rare, but cases have been reported previously in the literature. In long-standing cases, they can cause a "mass effect" resulting in the deformation of the bones around the ankle joint, mechanical restriction of joint movement, and even degenerative joint disease. Hence, they need to be resected if patients present with such impending complications. Several surgical techniques have been described previously for tumor resection including the anterior approach and the trans-fibular approach, the latter of which required a fibular osteotomy with or without fibular reconstruction. The surgical technique described here utilizes the posterolateral approach to the ankle joint for tumor excision, thus avoiding the need for any osteotomy or fibular reconstruction and reducing the risk of injury to major neurovascular structures. It also reduces the need for long-term immobilization and promotes a faster return to activity.
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Direct air capture (DAC) of CO2 with porous adsorbents such as metal-organic frameworks (MOFs) has the potential to aid large-scale decarbonization. Previous screening of MOFs for DAC relied on empirical force fields and ignored adsorbed H2O and MOF deformation. We performed quantum chemistry calculations overcoming these restrictions for thousands of MOFs. The resulting data enable efficient descriptions using machine learning.
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PURPOSE: To evaluate the demographic profile of premature infants presenting with stage 4B and stage 5 retinopathy of prematurity (ROP) at a tertiary referral center in South India. METHODS: This was a retrospective review including all premature infants with stage 4B and 5 ROP between January 1, 2015 and December 31, 2022. Parameters included the newborns born at the tertiary care nursery of various institutes, gestational age, birth weight, age at presentation to the hospital, risk factors, screening details, neonatal intensive care unit details, reason for consultation, and timing of referral to the center. RESULTS: Two hundred twenty eyes of 110 premature infants were included. Of 110 infants, 6 were born within the same city and 104 were from other districts or states. Mean birth weight was 1,125 ± 360 g and mean gestational age at birth was 28 ± 2 weeks. Mean age was 42 ± 82 weeks and median age at presentation was 17 weeks (range: 2.86 to 591 weeks). Male-to-female infant ratio was 1.34:1. Fifty (45.4%) infants had bilateral stage 5 ROP, 17 (15.4%) had stage 5 in one eye and stage 4B in the other eye, 15 (13.6%) had bilateral stage 4B and 23 (20.9%) had stage 4B in one eye and stage 4A/stage 3 in the other eye. Five (4.5%) had stage 5 in one eye and vitreous hemorrhage/stage 4A in the other eye. Among those with bilateral stage 5 ROP, 90% were from neighboring districts/states. Fifty-two (47.27%) infants underwent vitreoretinal surgery. Of 110 infants, 28 (25.45%) were self-referred (late presentation due to family-related issues), 80 (72.73%) were referred by ophthalmologists either after a few sessions of late screening or for further management, 1 (0.91%) was referred through telescreening, and 1 was referred from pediatricians directly to the hospital. CONCLUSIONS: This study highlights the importance of awareness of the disease and screening of premature infants. Lack of these two factors leads to late presentation of these infants with advanced stages and serious implications. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].
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Background: Post-operative infections are a common cause of morbidity following major surgery. Little is understood about how major surgery perturbs immune function leading to heightened risk of subsequent infection. Through analysis of paired blood samples obtained immediately before and 24 h following surgery, we evaluated changes in circulating immune cell phenotype and function across the first 24 h, to identify early immune changes associated with subsequent infection. Methods: We conducted a prospective observational study of adult patients undergoing major elective gastrointestinal, gynecological, or maxillofacial surgery requiring planned admission to the post-anesthetic care unit. Patients were followed up to hospital discharge or death. Outcome data collected included mortality, length of stay, unplanned intensive care unit admission, and post-operative infections (using the standardized endpoints in perioperative medicine-core outcome measures for perioperative and anesthetic care criteria). Peripheral blood mononuclear cells were isolated prior to and 24 h following surgery from which cellular immune traits including activation and functional status were assessed by multi-parameter flow cytometry and serum immune analytes compared by enzyme-linked immunosorbent assay (ELISA). Results: Forty-eight patients were recruited, 26 (54%) of whom developed a post-operative infection. We observed reduced baseline pre- and post-operative monocyte CXCR4 and CD80 expression (chemokine receptors and co-stimulation markers, respectively) in patients who subsequently developed an infection as well as a profound and selective post-operative increase in CD4+ lymphocyte IL-7 receptor expression in the infection group only. Higher post-operative monocyte count was significantly associated with the development of post-operative infection (false discovery rate < 1%; adjusted p-value = 0.001) with an area under the receiver operating characteristic curve of 0.84 (p < 0.0001). Conclusion: Lower monocyte chemotaxis markers, higher post-operative circulating monocyte counts, and reduced co-stimulatory signals are associated with subsequent post-operative infections. Identifying the underlying mechanisms and therapeutics to reverse defects in immune cell function requires further exploration.
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Monocitos , Humanos , Femenino , Masculino , Monocitos/inmunología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Adulto , Biomarcadores/sangreRESUMEN
The generation of spermatozoa from developing germ cells through mitotic and meiotic divisions is a highly regulated and complex process. Any defect in this process, may lead to subfertility/infertility. The role of different transcripts (mRNA/miRNA/lncRNA) in regulation of the pre-meiotic, meiotic, and post-meiotic stages of spermatogenesis are being proposed based on various multiomics based approaches. Such differential gene-expression is regulated by promoter elements that are activated in a stage specific manner. To determine the role of these differentially expressed transcripts in the process of meiosis, a robust post-meiotic germ cell specific promoter is required. In the present study, we have isolated and characterized the expression of the mouse Proacrosin, SP10, and ELP promoters for driving post-meiotic germ cell specific gene-expression. Promoter regions of all these 3 genes were isolated and cloned to generate mammalian expression vector. The transgene expression in post-meiotic germ cells was assessed in mice using the testicular electroporation method in vitro as well as in vivo, using above promoters. It was also validated in goat seminiferous tubules, in vitro. We have also carried out a comparative analysis of the strength of these promoters to confirm their robustness that indicated Proacrosin to be the most robust promoter that can be useful for diving post-meiotic germ cells specific gene-expression. These promoters can be used to alter gene-expression specifically in post-meiotic germ cells for deciphering the role(s) of germ cell genes in spermatogenic progression or for expressing various genome editing tools for engineering the germ cell genome to understand basis of subfertility/infertility.
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Células Germinativas , Infertilidad , Masculino , Ratones , Animales , Regiones Promotoras Genéticas/genética , Expresión Génica , Genómica , MamíferosRESUMEN
Generation of high-valent oxomanganese complexes through controlled removal of protons and electrons from low-valent congeners is a crucial step toward the synthesis of functional analogues of the native oxygen evolving complex (OEC). In-depth studies of the water oxidation activity of such biomimetic compounds help in understanding the mechanism of O-O bond formation presumably occurring in the last step of the photosynthetic cycle. Scarce reports of reactive high-valent oxomanganese complexes underscore the impetus for the present work, wherein we report the electrochemical generation of the non-heme oxomanganese(IV) species [(dpaq)MnIV(O)]+ (2) through a proton-coupled electron transfer (PCET) process from the hydroxomanganese complex [(dpaq)MnIII(OH)]ClO4 (1). Controlled potential spectroelectrochemical studies of 1 in wet acetonitrile at 1.45 V vs. NHE revealed quantitative formation of 2 within 10 min. The high-valent oxomanganese(IV) transient exhibited remarkable stability and could be reverted to the starting complex (1) by switching the potential to 0.25 V vs. NHE. The formation of 2via PCET oxidation of 1 demonstrates an alternate pathway for the generation of the oxomanganese(IV) transient (2) without the requirement of redox-inactive metal ions or acid additives as proposed earlier. Theoretical studies predict that one-electron oxidation of [(dpaq)MnIV(O)]+ (2) forms a manganese(V)-oxo (3) species, which can be oxidized further by one electron to a formal manganese(VI)-oxo transient (4). Theoretical analyses suggest that the first oxidation event (2 to 3) takes place at the metal-based d-orbital, whereas, in the second oxidation process (3 to 4), the electron eliminates from an orbital composed of equitable contribution from the metal and the ligand, leaving a single electron in the quinoline-dominant orbital in the doublet ground spin state of the manganese(VI)-oxo species (4). This mixed metal-ligand (quinoline)-based oxidation is proposed to generate a formal Mn(VI) species (4), a non-heme analogue of the species 'compound I', formed in the catalytic cycle of cytochrome P-450. We propose that the highly electrophilic species 4 catches water during cyclic voltammetry experiments and results in O-O bond formation leading to electrocatalytic oxidation of water to hydrogen peroxide.
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The role of boron-doped thiazoles as a Lewis acid catalyst in [4+2] cycloaddition reaction between 1,3-butadiene and acrolein has been addressed. Three different organic heterocycles were designed to study their catalytic activity. It has been observed that these heterocycles efficiently work as catalysts than the well-known Lewis acid BF3. All the reactions follow the normal electron demand process and are exothermic. Different conceptual DFT-based reactivity descriptors and electronic structure principles such as maximum hardness and minimum electrophilicity lend additional support to the feasibility of the reaction mechanism. The reaction force (RF), reaction electronic flux (REF), and its different components exhibit a detailed electronic activity throughout the reaction.
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Distraction disrupts Working Memory (WM) performance, but how the brain filters distraction is not known. One possibility is that neural activity associated with distractions is suppressed relative to a baseline/passive task (biased competition). Alternatively, distraction may be denied access to WM, with no suppression. Furthermore, behavioural work indicates separate mechanisms for ignoring distractions which occur (1) while we put information into WM (Encoding Distraction, ED) and (2) while we maintain already encoded information during the WM delay period (Delay Distraction, DD). Here we used fMRI in humans to measure category-sensitive cortical activity and probe the extent to which ED/DD mechanisms involve enhancement/suppression during a WM task. We observed significant enhancement of task-relevant activity, relative to a passive view task, which did not differ according to whether or when distractors appeared. For both ED and DD we found no evidence of suppression, but instead a robust increase in stimulus specific activity in response to additional stimuli presented during the passive view task, which was not seen for the WM task, when those additional stimuli were to be ignored. The results indicate that ED/DD resistance does not necessarily involve suppression of distractor-related activity. Rather, a rise in distractor-associated activity is prevented when distractors are presented, supporting models of input gating, and providing a potential mechanism by which input-gating might be achieved.
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Atención , Memoria a Corto Plazo , Humanos , Memoria a Corto Plazo/fisiología , Atención/fisiología , Encéfalo/fisiología , Cognición , CabezaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer and the main cause of cancer death globally. The use of medicinal herbs as chemotherapeutic agents in cancer treatment is receiving attention as they possess no or minimum side effects. Isorhamnetin (IRN), a flavonoid, has been under attention for its anti-inflammatory and anti-proliferative properties in a number of cancers, including colorectal, skin, and lung cancers. However, the in vivo mechanism of isorhamnetin to suppress liver cancer has yet to be explored. METHODS AND RESULT: HCC was induced by N-diethylnitrosamine (DEN) and carbon tetrachloride (CCL4) in Swiss albino mice. Isorhamnetin (100 mg/kg body weight) was given to examine its anti-tumor properties in HCC mice model. Histological analysis and liver function assays were performed to assess changes in liver anatomy. Probable molecular pathways were explored using immunoblot, qPCR, ELISA, and immunohistochemistry techniques. Isorhamnetin inhibited various pro-inflammatory cytokines to suppress cancer-inducing inflammation. Additionally, it regulated Akt and MAPKs to suppress Nrf2 signaling. Isorhamnetin activated PPAR-γ and autophagy while suppressing cell cycle progression in DEN + CCl4-administered mice. Additionally, isorhamnetin regulated various signaling pathways to suppress cell proliferation, metabolism, and epithelial-mesenchymal transition in HCC. CONCLUSION: Regulating diverse cellular signaling pathways makes isorhamnetin a better anti-cancer chemotherapeutic candidate in HCC. Importantly, the anti-TNF-α properties of isorhamnetin could prove it a valuable therapeutic agent in sorafenib-resistant HCC patients. Additionally, anti-TGF-ß properties of isorhamnetin could be utilized to reduce the EMT-inducing side effects of doxorubicin.
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Carcinoma Hepatocelular , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias Hepáticas , Animales , Ratones , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Quercetina/farmacología , Quercetina/uso terapéuticoRESUMEN
Aim: Inw nanoparticles-aided radiotherapy, the radiation sensitivity of tumor is increased with the infusion of nanoparticles in tumor. This therapeutic modality is capable of delivering enhanced dose to tumor, without exceeding the normal tissue tolerance dose. Further, the quantification of the enhanced dose using suitable dosimeter is important. The present study is aimed at measuring the dose enhancement factors (DEFs) using the combination of nanoparticles-embedded alginate (Alg) film and unlaminated Gafchromic EBT3 film. Materials and Methods: Gold nanoparticles (AuNPs)- and silver nanoparticles (AgNPs)-embedded Alg polymer films were synthesized and characterized using standard techniques. Further, a customized version of the Gafchromic EBT3 film, i.e., unlaminated EBT3 film, was specially fabricated. The DEFs were measured using Xoft Axxent electronic brachytherapy device. Results: The surface plasmon resonance (SPR) and particle size of AuNPs were found to be 550 and 15 ± 2 nm, respectively. In the case of AgNPs, the SPR and particle size were recorded as 400 and 13 ± 2 nm, respectively. The DEFs measured, using unlaminated EBT3 film, for Xoft Axxent electronic brachytherapy using AuNPs and AgNPs were 1.35 ± 0.02 and 1.20 ± 0.01, respectively. Conclusion: The increase in dose enhancement during nanoparticles-aided electronic brachytherapy can be attributed to dominance of photoelectric effect, due to the presence of low-energy X-rays. The investigation indicates that the Xoft Axxent electronic brachytherapy device is suitable for nanoparticles-aided brachytherapy.
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Braquiterapia , Nanopartículas del Metal , Humanos , Dosificación Radioterapéutica , Oro , Braquiterapia/métodos , Plata , ElectrónicaRESUMEN
Cervical cancer is the primary cause of mortality among women in developing countries. Preventing cervical cancer is partially possible through early vaccination against the human papillomavirus, the most common cause of the disease. Nevertheless, it is imperative to understand the genetics of the disease progression to develop new therapeutic strategies. The present study aims to identify potential genes and associated pathways associated with cervical squamous cell carcinoma progression. We used an integrative approach by combining differential expression analysis, network biology, and functional enrichment analysis with survival analysis. In the present study, differential expression analysis of the microarray-based gene expression profiles of cervical cancer resulted in identifying a total of 544 significantly differentially expressed genes (DEGs). Further, centrality and network vulnerability analysis of the protein-protein interaction network (PPIN) and not well documented in cervical cancer, resulted in seven proteins (FN1, MCM5, TRIP13, KIF11, TTK, CDC45, and BUB1B), in which four proteins were vulnerable. These genes are mostly enriched in biological processes of cell division, mitotic nuclear division, cell cycle checkpoint, and cell proliferation in gene ontology analysis. The KEGG pathway enrichment analysis of the proteins lists them as mainly associated with the cell cycle. In the survival analysis, it was found that the genes MCM5, FN1, KIF11, and CDC45 were statistically significant prognostic factors for cervical cancer. The outcome of the current study identifies and explores the key role of the candidate genes involved in the progression of cervical cancer.
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Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Humanos , Femenino , Perfilación de la Expresión Génica/métodos , Neoplasias del Cuello Uterino/genética , Biología Computacional/métodos , Transcriptoma , Carcinoma de Células Escamosas/genética , ATPasas Asociadas con Actividades Celulares Diversas/genética , Proteínas de Ciclo CelularRESUMEN
Ecosystem services (ES) are becoming a burgeoning topic presently playing a crucial role in sustaining human well-being, socioeconomic growth, and addressing environmental management and sustainability. The purpose of our review was to overview research trends of the forest ecosystem services (FES) in eastern India and the research methodologies adopted to evaluate them. To systematically study the FES literature, 127 articles pertaining to the term FES during the period 1991 to 2021 were reviewed through a quantitative analysis. The analytical outcome emphasized (1) the research aspects of FES and its types along with regional distribution, (2) the scenario of FES in eastern India with respect to other ES and India, (3) the quantitative trend of FES research over 30 years period, (4) the employed methodological approaches, and (5) the existing research gaps and prospects. Our findings suggest that the publication numbers are quite low in eastern India, as only 5 peer-reviewed articles were found on FES. The result also indicated that the majority of studies primarily focused on provisioning services (85.03%) and the survey/interview method gained more popularity as a primary data source. Most of the earlier studies employed basic assessments like product values or individual income. We also discussed the advantages as well as limitations of the employed methodologies. These findings further highlight the significance of valuing various FES collectively rather than individually and contribute to providing pertinent information for the FES literature scenario, which may help to strengthen forest management as well.
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Conservación de los Recursos Naturales , Ecosistema , Humanos , Monitoreo del Ambiente , Bosques , IndiaRESUMEN
INTRODUCTION: Pediatric rhegmatogenous retinal detachments, especially those presenting at birth or soon afterward, have a high likelihood of syndromic associations that can be confirmed by genetic testing. MATERIALS AND METHODS: A 5-month-old child was found to have high myopia in the right eye (RE) with highly tessellated fundus, opalescent vitreous, and peripheral thinning. Left eye had a shallow retinal detachment for which he underwent belt buckling. The baby had an occipital skin tag. A provisional diagnosis of Stickler syndrome was made. RESULTS: On 1-month follow-up, left eye retina was attached and 360° laser barrage was done. Fluorescein angiography was done which revealed peripheral avascular retina in both eyes. MRI and genetic testing were suggestive of syndromic association. Genetic testing revealed pathogenic mutation in COL 18A1 suggestive of Knobloch syndrome in the baby, and both parents were found to be carriers of the same mutation. However, brain MRI showed features not pathognomonic of Knobloch syndrome. CONCLUSION: Although Knobloch syndrome is associated with vitreoretinal degeneration and high risk of retinal detachment, there seems to be no recommendation for prophylaxis in the other eye and therefore we preferred to observe the RE closely. A unique feature noted in our case was the peripheral avascular zone (PAZ). The PAZ could be contributed by multiple factors such as high myopia, or due to endostatin deficiency (which is a derivative of collagen XVIII) or an underlying WNT signalling abnormality.
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Miopía , Desprendimiento de Retina , Recién Nacido , Lactante , Masculino , Humanos , Niño , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/genética , Retina , Fondo de Ojo , Miopía/genéticaRESUMEN
Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (â¼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO2@PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO2@PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO2@PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research.