Notes

Studying protein-protein interactions within unusual tissues utilizing microbead-based single-molecule pulldown analysis.
Patients with cholangiocarcinoma have poor survival since the majority of patients are diagnosed at a stage precluding surgical resection, due to locally irresectable tumors and/or metastases. Optimization of diagnostic strategies, with a principal role for tissue diagnosis, is essential to detect cancers at an earlier stage amenable to curative treatment. Current barriers for a tissue diagnosis include both insufficient tissue sampling and a difficult cyto- or histopathological assessment. During endoscopic retrograde cholangiopancreatography, optimal brush sampling includes obtaining more than one brush within an individual patient to increase its diagnostic value. Currently, no significant increase of the diagnostic accuracy for the new cytology brush devices aiming to enhance the cellularity of brushings versus standard biliary brush devices has been demonstrated. Peroral cholangioscopy with bile duct biopsies appears to be a valuable tool in the diagnostic work-up of indeterminate biliary strictures, andaphy and focuses on the evolving molecular techniques on biliary tissue to improve the differentiation of benign and malignant biliary strictures.Colorectal cancers (CRCs) remain one of the most common and challenging neoplasia in the Western world. The response rate of immunotherapeutic treatment approaches in a subset of advanced CRCs is remarkable and has sustainably changed treatment regimens. Unfortunately, currently available immunotherapeutics only displayed significant antitumoral activity - in terms of progression free survival (PFS) and objective response rate (ORR) - in microsatellite instability-high (MSI-H)/DNA mismatch repair deficient (dMMR) CRCs. Subsequently, these remarkable results had led to the US Food and Drug Administration's approval of both immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab in the treatment of advanced MSI-H/dMMR CRCs. However, in microsatellite stable (MSS)/DNA mismatch repair proficient (pMMR) CRCs, ICIs have clearly failed to meet their expectations and are therefore not considered effective. As the vast majority of CRCs display a molecular MSS/pMMR profile, current treatment approaches endeavor to improve tumor immunogenicity that consecutively leads to increased proinflammatory cytokine levels as well as tumor infiltrating T-cells, which in turn may be targeted by various immunotherapeutic agents. Therefore, ongoing studies are investigating novel synergistic therapy modalities and approaches to overcome a "cold" to "hot" tumor conversion in MSS/pMMR CRCs. In this review, we summarize the efficacy and possible immune-related adverse events as well as novel therapeutic approaches of ICIs in the treatment of MSI-H/dMMR and MSS/pMMR CRCs.
Proton-pump inhibitors (PPI) are among the most prescribed drugs worldwide, and a large body of evidence raises concerns about their inappropriate use. Previous estimates of inappropriate use varied due to different definitions and study populations.

We aimed to measure the population-based incidence and time trends of PPI and potentially inappropriate PPI prescriptions (PIPPI) with a novel method, continuously assessing excessive cumulative doses based on clinical practice guidelines. We also assessed association of patient characteristics with PPI prescriptions and PIPPI.

This was an observational study based on a large insurance claims database of persons aged >18 years with continuous claims records of ⩾12 months. The observation period was January 2012 to December 2017. We assessed the incidence and time trends of PPI prescriptions and PIPPI based on doses prescribed, defining ⩾11.5 g of pantoprazole dose equivalents during any consecutive 365 days (average daily dose >31 mg) as inappropriateguideline recommendations could reduce polypharmacy and improve patient safety.In the Covid-19 pandemic, being older means being in a special focus Probabilities for severe infections and mortality rise with increasing age and protective measures for this population group have been increased. This was accompanied by public discourse that portrayed older adults stereotypically as vulnerable and frail but also highlighted the hardships younger people have to endure to protect them. Given the possibly detrimental effects of ageism on individuals and societies, we were interested in older adults' perception of ageism in the Corona-crisis and its relation to their health and well-being. Furthermore, we were interested in subjective aging variables as moderators in the ageism-health relationship. In June 2020, N = 611 independently living people aged 60 + from the Grand Duchy of Luxembourg were recruited via a survey research institute and interviewed online or by phone. They reported on perceived ageism in different contexts, their life satisfaction, subjective health, subjective age and self-perceptions of aging. Depending on context, ageism was perceived by around 20% of participants, and overall negatively related to subjective health and life satisfaction after the onset of the pandemic. Moderated hierarchical regressions showed that a younger subjective age buffered the negative effect of ageism on subjective health, while perceiving aging as social loss increased its effect on life satisfaction. We discuss the importance of addressing and reducing ageism (not only) in times of crisis and the consequences for individuals and societies.The native people of the Himalayan region use an indigenously designed watermill locally called as 'Gharat'. The 'Gharat' is made from the natural resources that are easily available in the area and operates through the water force coming from glaciers, perennial streams and rivulets. Thus, it is an environment friendly source of livelihood for the 'Gharatis' (the owner of Gharat). In the present communication, an effort was made to document the status of Gharats in the high-altitude Himalayan regions of Pangi and Tissa of district Chamba. Field surveys were conducted in a total of twenty remote villages of Pangi and Tissa regions (ten in each site). Information was collected on pre-designed semi-structured questionnaires from local people that primarily consisted of Gharatis, elderly informants and the inhabitants living in the vicinity of Gharats. All possible reasons responsible for the increase and reduction in the number of Gharats in the study areas were also documented by interviewing the informants. The study revealed that in the Pangi region number of Gharats have increased and are in good condition whereas there is a drastic decline in the number of Gharats in Tissa. The informants in Pangi gave maximum responses favouring motivational factors while in Tissa maximum responses were obtained for demotivational factors. Based on these responses, we prioritized the corrective measures for improving the efficiency of Gharats and restoration of this age-old indigenous and environment friendly technology. This will surely enhance livelihood security of the inhabitants besides optimum utilization of the natural resources in the Himalayan region.
The online version contains supplementary material available at 10.1007/s10668-021-01455-4.
The online version contains supplementary material available at 10.1007/s10668-021-01455-4.The Healthcare sector has been at the forefront of the adoption of artificial intelligence (AI) technologies. Owing to the nature of the services and the vulnerability of a large section of end-users, the topic of responsible AI has become the subject of widespread study and discussion. We conduct a mixed-method study to identify the constituents of responsible AI in the healthcare sector and investigate its role in value formation and market performance. The study context is India, where AI technologies are in the developing phase. Bay K 8644 order The results from 12 in-depth interviews enrich the more nuanced understanding of how different facets of responsible AI guide healthcare firms in evidence-based medicine and improved patient centered care. PLS-SEM analysis of 290 survey responses validates the theoretical framework and establishes responsible AI as a third-order factor. The 174 dyadic data findings also confirm the mediation mechanism of the patient's cognitive engagement with responsible AI-solutions and perceived value, which leads to market performance.The disruption of 'normal' academic studies in the wake of the COVID-19 pandemic outbreak was embodied mainly in a rapid transition from in-class teaching to online synchronous instruction. The purpose of this study was to examine the lecturer's emotions towards the change they experienced with the sudden shift to online instruction during the COVID-19 pandemic and the effect of those emotions on their willingness to teach online in the future. In the present study, 239 academic lecturers answered an online questionnaire. Four groups of emotions were examined Success, opportunity, failure, and threat. The findings indicated that the emotions lecturers experienced most strongly was that of success, followed by opportunity. The predictors of lecturer's willingness to teach online in the future were emotions related to 'opportunity' and 'failure'. Surprisingly, the dramatic event of COVID-19 lockdown evoked more positive than negative emotions among lecturers during the first semester of the crisis. The emotions of threat that might characterize this period did not affect the willingness to teach online in the future as may be expected. This study demonstrates how tracing the emotional response toward adopting technology may contribute to understanding technology acceptance. It also contributes to understanding the differences in experiencing change in the normal process of technology adoption as opposed to emergency times.The period of social distancing caused by the COVID-19 pandemic is characterized as an effective proposal to control the spread of the coronavirus (SARS-CoV-2), however, it changes the social dynamics of individuals in society. Based on this question, the present study aimed to understand how was the performance of Brazilian physical education professionals during this period. The sample consisted of 400 Physical Education professionals from Brazil, 224 women (56.0%) and 176 men (44.0%), selected at random, by filling out a questionnaire. Sports activities were predominant among professionals, followed by bodybuilding activities or functional training. Most professionals performed their activities at home (71%) and used different digital platforms as work tools, noting that distance learning was a strategy used and well regarded by professionals. However, even with the use of specific intervention strategies, professional income showed fluctuations during the pandemic, with academic degrees being one of the factors responsible for changing the workload.Colletes hederae Schmidt & Westrich, 1993 is a cryptic bee species from the C. succinctus species-group. The previous occurrence and spreading of this species were predominantly in south-western Europe. To determine if the species was spreading in Slovak territory, Hedera helix was monitored from autumn 2015. The ivy-bee was first recorded in Slovakia during autumn 2017. This species is widespread inside and around Bratislava; however, it was not recorded under this study in any sites located eastwards. In the Czech Republic, it was not recorded in the south-east part of the country in 2017-2019. In 2020, the occurrence of this species was confirmed in many localities in the south of the country and strong populations were discovered, especially in the towns Znojmo and Mikulov. The populations likely originated from neighbouring Austria, where this species was discovered in 2006 and the localities are usually less than 100 km away from Czech and Slovak localities. A further survey could map a route of the northwards spread of this species.
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