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In some cancer patients, treatment with anti-PD-1 results in rapid progression of the disease, known as hyperprogression disease (HPD). The mathematical model can also explain how this situation arises, and it predicts that HPD may be reversed by combining anti-TGF-β to anti-PD-1. The model is used to demonstrate how the two cancer-specific parameters may serve as biomarkers in predicting the efficacy of combination therapy with PD-1 and TGF-β inhibitors.

Low back pain (LBP) is the commonest cause of disability throughout the world. This study aimed to determine the prevalence and factors associated with LBP among the construction workers in Nepal.

A community-based cross-sectional study was conducted among the construction workers working in Banepa and Panauti municipalities of Kavre district, from September 2019 to February 2020. Data was collected purposively by face-to-face interview from 402 eligible participants from the both municipalities using semi-structured questionnaire. Mobile-based data collection was done using KoboCollect. Data were exported to and analysed using R-programming software (R-3.6.2). Univariate and multivariate logistic regressions were performed. All tests were two tailed and performed at 95% confidence interval (CI).

One-year prevalence of LBP among construction workers were 52.0% (95%CI 47.0-57.0). The higher odds of LBP was reported among females [adjusted odds ratio (aOR) = 2.42; 95%CI 1.12-5.23], those living below poveent or manage LBP. Therefore, the public health professionals should set up the health promotion, education, and interventions aimed at increasing awareness on preventive techniques and predisposing factors of LBP.We recently developed 'cellular' reagents-lyophilized bacteria overexpressing proteins of interest-that can replace commercial pure enzymes in typical diagnostic and molecular biology reactions. To make cellular reagent technology widely accessible and amenable to local production with minimal instrumentation, we now report a significantly simplified method for preparing cellular reagents that requires only a common bacterial incubator to grow and subsequently dry enzyme-expressing bacteria at 37°C with the aid of inexpensive chemical desiccants. We demonstrate application of such dried cellular reagents in common molecular and synthetic biology processes, such as PCR, qPCR, reverse transcription, isothermal amplification, and Golden Gate DNA assembly, in building easy-to-use testing kits, and in rapid reagent production for meeting extraordinary diagnostic demands such as those being faced in the ongoing SARS-CoV-2 pandemic. Furthermore, we demonstrate feasibility of local production by successfully implementing this minimized procedure and preparing cellular reagents in several countries, including the United Kingdom, Cameroon, and Ghana. Our results demonstrate possibilities for readily scalable local and distributed reagent production, and further instantiate the opportunities available via synthetic biology in general.Gambling Disorder (GD) has recently been reclassified from an impulse-control disorder to a behavioural addiction and, as in other addictive disorders, the dopaminergic reward system is involved. According to neuroimaging studies, alterations within the striatal dopaminergic signalling can occur in GD. However, the findings to date are controversial and there has been no agreement yet on how the reward system is affected on a molecular basis. Within the last 20 years, there has been growing evidence for a higher risk to develop GD in response to certain dopaminergic medication. Especially the dopamine agonists pramipexole and ropinirole, and the dopamine modulator aripiprazole seem to increase the likelihood for GD. The goal of this study was to examine the association between a prescription for either of the three pharmaceuticals and a GD diagnosis in a large cross-sectional study of the Swedish population. Compared to patients with any other dopaminergic drug prescription (38.7% with GD), the diagnosis was more common in patients with a dopamine agonist prescription (69.8% with GD), resulting in an odds ratio of 3.2. A similar association was found between aripiprazole prescriptions and GD diagnoses, which were analysed within the subgroup of all patients with schizophrenia or a schizotypal, delusional, or another non-mood psychotic disorder. An aripiprazole prescription increased the likelihood of GD (88.8%) in comparison to patients without an aripiprazole prescription (71.2%) with an odds ratio of 3.4. This study contributes to the increasingly reliable evidence for an association between several dopaminergic drugs and a higher risk for developing GD. Therefore, one future research goal should be a better understanding of the neurobiology in GD to be able to design more selective dopaminergic medication with less severe side effects. Additionally, this knowledge could enable the development of pharmacotherapy in GD and other addictive disorders.

Laryngoscopy and endotracheal intubation are essential components of general anesthesia. But it is always associated with side effects called reflex cardiovascular responses. Many methods have been identified to attenuate these responses like intravenous lidocaine, deep inhalational anesthesia, vasodilators, intravenous magnesium sulphate even though therapeutic superiority remains understudied.

An institutional-based cohort study on 112 adult patients aged between 18-60 years was applied. 37 patients in the non-exposed group (Group N), 37 in the lidocaine group (Group L), and 38 in magnesium sulphate (Group M) were included. The hemodynamic parameters like heart rate, systolic, diastolic and mean arterial blood pressure at various time points up to 7 minutes post-intubation were recorded and the effect of both drugs to reduce hemodynamic responses was compared. Parametric data were analyzed using ANOVA and nonparametric data using the Kuruska-Wallis H rank test. P-value < 0.05 considered statisticallyffective in attenuating hemodynamic responses to the stress effect of laryngoscopy and intubation. find more But based on our finding prophylaxis of magnesium sulphate is associated with a more favorable hemodynamic response.Most corals acquire symbiodiniacean symbionts from the surrounding environment to initiate symbiosis. The cell densities of Symbiodiniaceae in the environment are usually low, and mechanisms may exist by which new coral generations attract suitable endosymbionts. Phototaxis of suitable symbiodiniacean cells toward green fluorescence in corals has been proposed as one such mechanism. In the present study, we observed the phototaxis action wavelength of various strains of Symbiodiniaceae and the fluorescence spectra of aposymbiotic Acropora tenuis larvae at the time of endosymbiont uptake. The phototaxis patterns varied among the Symbiodiniaceae species and "native" endosymbionts-commonly found in Acropora juveniles present in natural environments; that is, Symbiodinium microadriaticum was attracted to blue light rather than to green light. Another native endosymbiont, Durusdinium trenchii, showed no phototaxis specific to any wavelength. Although the larvae exhibited green and broad orange fluorescence under bto green fluorescence, would be required to elucidate the initial attraction mechanisms.An acceleration index is proposed as a novel indicator to track the dynamics of COVID-19 in real-time. Using data on cases and tests in France for the period between the first and second lock-downs-May 13 to October 25, 2020-our acceleration index shows that the pandemic resurgence can be dated to begin around July 7. It uncovers that the pandemic acceleration was stronger than national average for the [59-68] and especially the 69 and older age groups since early September, the latter being associated with the strongest acceleration index, as of October 25. In contrast, acceleration among the [19-28] age group was the lowest and is about half that of the [69-78]. In addition, we propose an algorithm to allocate tests among French "départements" (roughly counties), based on both the acceleration index and the feedback effect of testing. Our acceleration-based allocation differs from the actual distribution over French territories, which is population-based. We argue that both our acceleration index and our allocation algorithm are useful tools to guide public health policies as France might possibly enter a third lock-down period with indeterminate duration.Adeno-associated virus (AAV) genome replication only occurs in the presence of a co-infecting helper virus such as adenovirus type 5 (AdV5) or herpes simplex virus type 1 (HSV-1). AdV5-supported replication of the AAV genome has been described to occur in a strand-displacement rolling hairpin replication (RHR) mechanism initiated at the AAV 3' inverted terminal repeat (ITR) end. It has been assumed that the same mechanism applies to HSV-1-supported AAV genome replication. Using Southern analysis and nanopore sequencing as a novel, high-throughput approach to study viral genome replication we demonstrate the formation of double-stranded head-to-tail concatemers of AAV genomes in the presence of HSV-1, thus providing evidence for an unequivocal rolling circle replication (RCR) mechanism. This stands in contrast to the textbook model of AAV genome replication when HSV-1 is the helper virus.Living organisms are continuously under threat from a vast array of DNA-damaging agents, which impact genome DNA. DNA replication machinery stalls at damaged template DNA. The stalled replication fork is restarted via bypass replication by translesion DNA-synthesis polymerases, including the Y-family polymerases Polη, Polι, and Polκ, which possess the ability to incorporate nucleotides opposite the damaged template. To investigate the division of labor among these polymerases in vivo, we generated POLη-/-, POLι-/-, POLκ-/-, double knockout (KO), and triple knockout (TKO) mutants in all combinations from human TK6 cells. TKO cells exhibited a hypersensitivity to ultraviolet (UV), cisplatin (CDDP), and methyl methanesulfonate (MMS), confirming the pivotal role played by these polymerases in bypass replication of damaged template DNA. POLη-/- cells, but not POLι-/- or POLκ-/- cells, showed a strong sensitivity to UV and CDDP, while TKO cells showed a slightly higher sensitivity to UV and CDDP than did POLη-/- cells. On the other hand, TKO cells, but not all single KO cells, exhibited a significantly higher sensitivity to MMS than did wild-type cells. Consistently, DNA-fiber assay revealed that Polη plays a crucial role in bypassing lesions caused by UV-mimetic agent 4-nitroquinoline-1-oxide and CDDP, while all three polymerases play complementary roles in bypassing MMS-induced damage. Our findings indicate that the three Y-family polymerases play distinctly different roles in bypass replication, according to the type of DNA damage generated on the template strand.The increasingly globalized workforce and the growing need for boosting employee energy have engendered both practical and research interest in stimulating employee energy in intercultural interactions. Yet neither the culture research nor the energy literature has explored the link between cultural distance and employee relational energy-the heightened level of psychological resources in social relations. This paper presents empirical evidence of cultural distance stimulating relational energy. Further, building upon the threat-rigidity theory, I propose that cultural distance stimulates relational energy more when employees perceive high levels of psychological safety. Two studies were conducted to test these two hypotheses. One laboratory experiment on 202 international students at a Dutch university provided causal evidence of the positive relationship between cultural distance and relational energy. Next, a two-wave field study on 373 international employees was conducted to replicate this main effect of cultural distance and further investigate the moderating role of psychological safety.

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