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Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC. Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Abstract Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat. Resumo Guindastes são a grande e atraente criatura da natureza com um pescoço longo, pernas e vida útil. Adultos de ambos os sexos são os mesmos com padrões de cores semelhantes. Guindastes Demoiselle passam a maior parte da vida em gramíneas secas. Também se encontram ao redor do córrego, rios, lagos rasos, pântanos naturais e depressões. Para avaliar o estado atual do uso do hábitat e as principais ameaças, um estudo foi realizado no distrito de Tehsil Domel, em Bannu. Foram utilizados o método transect e testes de qualidade da água (temperatura, pH, contaminação da bactéria E. coli). Para determinar as principais ameaçasfoi utilizado o método de questionário. Todos os dados foram analisados por meio da versão SPSS 21. Com base na distribuição, foram selecionados quatro locais de estudo e quatro amostras de água de cada local de estudo. A maioria dos locais estava moderada a altamente degradada, exceto no ponto de encontro dos rios Kashoo e Kurram, que teve baixa degradação com pastagem de gado e atividades humanas. Os testes de qualidade da água mostraram variação de pH de 7-9, temperatura 6,5-8,5 e contaminação de E. coli em todas as amostras. A pesquisa do questionário revelou que a caça, a degradação do hábitat e a poluição são as principais ameaças. Efetiva conservação e gestão a longo prazo na área de estudo são necessárias para se concentrar na proteção de um hábitat livre de distúrbios.

Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h) followed by 5 days with restricted sleep (03.00-07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

A bstract Using 983.0 fb − 1 and 427.9 fb − 1 data samples collected with the Belle and Belle II detectors at the KEKB and SuperKEKB asymmetric energy e + e − colliders, respectively, we present studies of the Cabibbo-favored decays and , and the singly Cabibbo-suppressed decay . The ratios of branching fractions of and relative to that of are measured for the first time, while the ratio is also determined and improved by an order of magnitude in precision. The measured branching fraction ratios are Additionally, the ratio is measured to be 0 . 068 ± 0 . 010 ± 0 . 004. Here, the first and second uncertainties are statistical and systematic, respectively. Multiplying the ratios by the branching fraction of the normalization mode, , we obtain the following absolute branching fractions where the third uncertainties are from .

Inelastic dark matter models that have two dark matter particles and a massive dark photon can reproduce the observed relic dark matter density without violating cosmological limits. The mass splitting between the two dark matter particles \\(\\chi_{1}\\) and \\(\\chi_{2}\\), with \\(m(\\chi_{2}) > m(\\chi_{1})\\), is induced by a dark Higgs field and a corresponding dark Higgs boson \\(h^{\\prime}\\). We present a search for dark matter in events with two vertices, at least one of which must be displaced from the interaction region, and missing energy. Using a \\(365\\,\\mbox{fb}^{-1}\\) data sample collected at Belle II, which operates at the SuperKEKB \\(e^+e^-\\) collider, we observe no evidence for a signal. We set upper limits on the product of the production cross section \\(\\sigma\\left(e^+e^- \\to h^\\prime \\chi_1 \\chi_2\\right)\\), and the product of branching fractions \\(\\mathcal{B}\\left(\\chi_2\\to\\chi_1 e^+ e^-\\right)\\times\\mathcal{B}\\left(h^\\prime\\to x^+x^-\\right)\\), where \\(x^+x^-\\) indicates \\(\\mu^+\\mu^-, \\pi^+\\pi^-\\), or \\(K^+K^-\\), as functions of \\(h^{\\prime}\\) mass and lifetime at the level of \\(10^{-1}\\,\\mbox{fb}\\). We set model-dependent upper limits on the dark Higgs mixing angle at the level of \\(10^{-5}\\) and on the dark photon kinetic mixing parameter at the level of \\(10^{-3}\\). This is the first search for dark Higgs bosons in association with inelastic dark matter.

Cancer is one of the most common malignancies and the leading cause of death worldwide. As a member of the transmembrane emp24 domain (Tmed)/p24 family of proteins, TMED2 expression variations have been documented earlier in only a few subtypes of human cancers, and the multi-omics profiling of TMED2 as a shared biomarker in different other subtypes of human cancers remains to be uncovered. In the current study, TMED2 multi-omics analysis in 24 major subtypes of human cancer was performed using different authentic online databases and bioinformatics analysis including UALCAN, Kaplan-Meier (KM) plotter, Human Protein Atlas (HPA), GENT2, MEXPRESS, cBioportal, STRING, DAVID, TIMER, and CTD. In general, the TMED2 expression in 24 major subtypes of human cancers was higher relative to normal controls and was also strongly associated with the lower overall survival (OS) and relapse-free survival (RFS) duration of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. This implies that TMED2 plays a significant role in the development and progression of these cancers. Furthermore, the TMED2 overexpression was also correlated with different clinicopathological features of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. TMED2-associated genes network was involved in 3 diverse pathways, and finally, few stronger correlations were also explored between TMED2 expression and its promoter methylation level, genetic alterations, and CD8+ T immune cells level. In conclusion, via this in silico study, we have elucidated that TMED2 can serve as a shared diagnostic and prognostic biomarker in CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients of different clinicopathological features but, further in vitro and in vivo research should be carried out to confirm these findings.

ABSTRACT The intent of the present study was conducted (January, 2020 to December, 2020) to estimate the prevalence of wingless insects in dog population and to identify the potential risks factors in selected areas of Lahore, Punjab, Pakistan. Results of the study revealed an overall prevalence of wingless insects 50.16% (1204/2400) in dogs of study area. Among various insects, fleas were found predominant (28.5%; 684/2400; P<0.05) as compared to lice (21.66%; 520/2400). Among the reported species 4 were wingless insects (Ctenocepahlides (Ct.) felis, Ct, canis, Linognathus setosus and Trichodectes canis). Breed, age and sex of host were not found to be related with risk factors (P>0.05) affecting incidence of wingless insects. These inscets effect different body parts differently as highest prvelance was noted at neck (15%) and back (11.5%) followed by abdomen (10%) and ear (7.4%). Prevelence of the ectoparasites was found to be 6.2% at forelegs and 4% in congenital area, 4% around the shoulder and 6% around the hind legs, however, tail area was minimally affected (1.2%). Prevelance of Ct. felis was noted to be 35.96, Ct. canis 68.43%, Linognathus setosus 21.1% and Trichodectes canis 78.8%. Town wise incidences were found to be highest in Shalimar Town (62.91%) followed by Wagha Town (59.58%), Aziz Bhatti(59.16%), Data Ganj Bakhsh (55.41%), Nishtar Town (46.66%), Samanabad (44.3%), Iqbal Town (43.6%), Ravi Town (42%), Lahore Cantonment (41.6%) and Gulberg (40.4%). Rate of ectoparasites infestation was observed higher (P<0.05) in stray dogs (80.36%) followed by guard dogs (63.7%), hunting dogs (37.5%) and pet dogs (35.66%). Amongst the different seasons, rainy season showed higher lice prevalence (26.1%; 157/600), fleas (37.8%; 227/600), as compared to summer season and spring. Though, summer season was found to be unfavourable for the increase of almost all these insects. Comparative results of blood profile revealed significant difference (P<0.05) between non-infested and infested dogs, in the sort of lower value of infested/infected animals. To control the prevelance and ultimate effect of wingless insects on dog population applicable a well planned and control startegies as well as extension facilities should be arranged. Pet owners should be provided awareness about the significance of controlling the wingless insects to keep the pets and owner healthy.

Urinary tract infection (UTI) is a renal infection that affects the urinary tract and is global problem related to health and many people are affected each year at some points of their lives. Modern studies about urinary tract infections show that almost one third of the world's population has been suffering from this ailment. Different antibacterial medicines have been reported to have resistance against pathogens. In order to overcome the problem, exploration for new and dynamic antibacterial agents from natural sources is the emerging trend. The primary objective was to evaluate the efficacy and safety of the polyherbal test drug formulation, \"Crano-cure\", as treatment for UTIs. In the current study, clinical trials were designed to evaluate the effects of the polyherbal formulation \"Crano-cure\" compared to the standard drug Ciprofloxacin in randomized, controlled multicenter trial of 205 patients, analyzing clinical outcomes and safety profiles. Conducted across multiple centers, including Shifa-ul-Mulk Memorial Hospital at Hamdard University Karachi and three other clinics, the study involved 205 patients aged 15-60, irrespective of their socioeconomic status. Patients were classified into two groups i.e. control group (ciprofloxacin) and the test group (crane-cure). Polyherbal formulation of 500 mg Crano-cure capsules two times in a day were administered to the test group for 28 days. The control group was administered a control ciprofloxacin tablet 500 mg two times in a day for 28 days. The drug was found safe for further clinical study after observing changes or improvements in UTI symptoms, urine culture and blood complete tests. The clinical trial was dully registered on the US National Library of Medicine, ClinicalTrials.gov Identifier: NCT04575493. The trial was accompanied in the instructions of EC (Ethical Committee). The study plan and procedures were displayed to the BASR (Board of Advance Studies and Research) and board members of the Ethical Committee (EC), which was ERB-2021-9-1. Clinical study results revealed the effectiveness of Crano-cure in the management of UTIs symptoms and hematological and biochemical parameters including blood complete test, liver function tests, renal function tests and lipid profile. Moreover, the test drug Crano-cure revealed a significance level (P ≤ .05) in compliance and cost-effectiveness compared to control ciprofloxacin. In conclusion, Crano-cure is a safe and cost-effective alternate to Ciprofloxacin for treatment of UTIs.

We present a measurement of the time-dependent CP asymmetry in decays using a data set of 365 fb−1 recorded by the Belle II experiment and the final data set of 711 fb−1 recorded by the Belle experiment at the Υ(4S) resonance. The direct and mixing-induced time-dependent CP violation parameters C and S are determined along with two additional quantities, S+ and S−, defined in the two halves of the plane. The measured values are C = −0.17 ± 0.09 ± 0.04, S = −0.29 ± 0.11 ± 0.05, S+ = −0.57 ± 0.23 ± 0.10 and S− = 0.31 ± 0.24 ± 0.05, where the first uncertainty is statistical and the second systematic.

We search for the \\(e^+ e^- \\to \\gamma \\chi_{bJ}\\) (\\(J\\) = 0, 1, 2) processes at center-of-mass energies \\(\\sqrt{s}\\) = 10.653, 10.701, 10.746, and 10.804 GeV. These data were collected with the Belle II detector at the SuperKEKB collider and correspond to 3.5, 1.6, 9.8, and 4.7 fb\\(^{-1}\\) of integrated luminosity, respectively. We set upper limits at the 90\\% confidence level on the Born cross sections for \\(e^+ e^- \\to \\gamma \\chi_{bJ}\\) at each center-of-mass energy \\(\\sqrt{s}\\) near 10.746 GeV. The upper limits at 90\\% confidence level on the Born cross sections for \\(e^+ e^- \\to \\gamma \\chi_{b1}\\) are significantly smaller than the corresponding measured values for \\(e^+e^-\\to\\omega\\chi_{b1}\\) and \\(e^+e^-\\to\\pi^+\\pi^-\\Upsilon(2S)\\) at \\(\\sqrt{s}\\) = 10.746 GeV.