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Impact of functional re-education and environmental adaptation in cancer patients with respiratory pathology: Study protocol
Background In recent years, cancer survival rates have increased exponentially. However, this rise in survival comes with a significant drawback. As the number of treatment lines has grown, so too have the side effects, which can severely impact patients’ functionality and quality of life. One of the most concerning effects is dyspnoea, a serious health issue that imposes substantial limitations on individuals. While traditional clinical approaches, primarily focused on pharmacological interventions, are commonly employed to manage dyspnoea, we argue that these methods may not always provide optimal symptomatic relief. Therefore, we propose a study protocol to implement an interdisciplinary intervention for these patients. This protocol aims to enhance standard clinical practice by introducing a program of functional re-education and environmental adaptation. We believe this intervention is essential for the follow-up care of patients with respiratory conditions after hospital discharge. Methods A two-arm, randomized, parallel, controlled clinical trial will be conducted by the University of Salamanca, Spain, in collaboration with the Medical Oncology Service of the University Health Care Complex of Salamanca. The trial aims to recruit 80 oncology patients who exhibit symptoms of dyspnoea during hospital admission. Participants will be randomly assigned to one of two groups: the control group, which will receive a health education program, and the experimental group, which will receive both the health education program and a functional re-education and environmental adaptation program. Assessments will be conducted at three time points: baseline (prior to hospital discharge), follow-up (15 days after discharge), and the end of the intervention (1 month after discharge). During these assessments, sociodemographic data will be collected, and the following scales will be administered: Barthel Index, Medical Research Council Dyspnoea Scale (mMRC), EuroQol 5-D questionnaire (EQ-5D), Visual Analogue Scale (VAS), Short Physical Performance Battery (SPPB), Tampa Scale for Kinesiophobia (TSK), and the Zarit Reduced Caregiver Burden Scale. Discussion The findings of this research can be easily implemented in clinical settings by introducing a targeted intervention to improve the quality of life for this patient population. This study aims to advance traditional clinical approaches by facilitating the recovery or adaptation of cancer patients in their daily routines, in relation to the severity of their symptoms. Our primary goal is to enhance independence and functionality, ultimately improving their overall standard of living. Trial registration ClinicalTrials.gov; ID: NCT06035263. Registered on: September 19, 2023. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000DM2U&selectaction=Edit&uid=U0004OJ7&ts=6&cx=f7qqxo.
See the Harm
The Psu protein of phage satellite P4 inhibits transcription termination factor ρ by forced hyper-oligomerization
AbstractMany bacteriophages modulate host transcription to favor expression of their own genomes. Phage satellite P4 polarity suppression protein, Psu, a building block of the viral capsid, inhibits hexameric transcription termination factor, ρ, by presently unknown mechanisms. Our cryogenic electron microscopy structures of ρ-Psu complexes show that Psu dimers clamp two inactive, open ρ rings and promote their expansion to higher-oligomeric states. ATPase, nucleotide binding and nucleic acid binding studies revealed that Psu hinders ρ ring closure and traps nucleotides in their binding pockets on ρ. Structure-guided mutagenesis in combination with growth, pull-down, and termination assays further delineated the functional ρ-Psu interfaces in vivo. Bioinformatic analyses revealed that Psu is associated with a wide variety of phage defense systems across Enterobacteriaceae, suggesting that Psu may regulate expression of anti-phage genes. Our findings show that modulation of the ρ oligomeric state via diverse strategies is a pervasive gene regulatory principle in bacteria.
Let-7b-5p sensitizes breast cancer cells to doxorubicin through Aurora Kinase B
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression level of the target genes in the cell. Breast cancer is responsible for the majority of cancer-related deaths among women globally. It has been proven that deregulated miRNAs may play an essential role in the progression of breast cancer. It has been shown in many cancers, including breast cancer, that aberrant expression of miRNAs may be associated with drug resistance. This study investigated the effect of let-7b-5p, detected by bioinformatics methods, on Dox resistance through the Aurora Kinase B (AURKB) gene. In silico analysis using publicly available miRNA expression, GEO datasets revealed that let-7b-5p significantly downregulated in BC. Further in silico studies revealed that of the genes among the potential targets of let-7b-5p, AURKB was the most negatively correlated and may be closely associated with Dox resistance. Expression analysis via quantitative PCR confirmed that let-7b-5p was downregulated and AURKB was upregulated in breast cancer tissue samples. Later, functional studies conducted with MCF-10A, MCF-7, and MDA-MB-231 cell lines demonstrated that let-7b-5p inhibits cancer cells through AURKB and sensitizes them to Dox resistance. In conclusion, it has been shown that the let-7b-5p/AURKB axis may be significant in breast cancer progression and the disruption in this axis may contribute to the trigger of Dox resistance.
Bladder Stone
Double trouble: two retrotransposons triggered a cascade of invasions in Drosophila species within the last 50 years
AbstractHorizontal transfer of genetic material in eukaryotes has rarely been documented over short evolutionary timescales. Here, we show that two retrotransposons, Shellder and Spoink, invaded the genomes of multiple species of the melanogaster subgroup within the last 50 years. Through horizontal transfer, Spoink spread in D. melanogaster during the 1980s, while both Shellder and Spoink invaded D. simulans in the 1990s. Possibly following hybridization, D. simulans infected the island endemic species D. mauritiana (Mauritius) and D. sechellia (Seychelles) with both TEs after 1995. In the same approximate time-frame, Shellder also invaded D. teissieri, a species confined to sub-Saharan Africa. We find that the donors of Shellder and Spoink are likely American Drosophila species from the willistoni, cardini, and repleta groups. Thus, the described cascade of TE invasions could only become feasible after D. melanogaster and D. simulans extended their distributions into the Americas 200 years ago, likely aided by human activity. Our work reveals that cascades of TE invasions, likely initiated by human-mediated range expansions, could have an impact on the genomic and phenotypic evolution of geographically dispersed species. Within a few decades, TEs could invade many species, including island endemics, with distributions very distant from the donor of the TE.
Impact of partial occlusion of the face on multisensory emotion perception: Comparison of pre- and post-COVID-19 pandemic
We perceive and understand others’ emotional states from multisensory information such as facial expressions and vocal cues. However, such cues are not always available or clear. Can partial loss of visual cues affect multisensory emotion perception? In addition, the COVID-19 pandemic has led to the widespread use of face masks, which can reduce some facial cues used in emotion perception. Thus, can frequent exposure to masked faces affect emotion perception? We conducted an emotion perception task using audio-visual stimuli that partially occluded the speaker’s face. Participants were simultaneously shown a face and voice that expressed either congruent or incongruent emotions and judged whether the person was happy or angry. The stimuli included videos in which the eyes or mouth were partially covered and where the whole face was visible. Our findings showed that, when facial cues were partially occluded, participants relied more on vocal cues for emotion recognition. Moreover, when the mouth was covered, participants relied less on vocal cues after the pandemic compared to before. These findings indicate that partial face masking and prolonged exposure to masked faces can affect multisensory emotion perception. In unimodal emotion perception from only facial cues, accuracy also improved after the pandemic compared to before for faces with the mouth occluded. Therefore, changes in the reliance on vocal cues in multisensory emotion perception during the pandemic period could be explained by improved facial emotion perception from the eye region.
Stereotactic Body Radiotherapy in Localized Prostate Cancer
Author Correction: Patterned electrical brain stimulation by a wireless network of implantable microdevices
The effect of nature on creativity through mental imagery
Immersion in nature has been linked to wide-ranging benefits on mental health and cognitive functions, from reducing stress to enhancing creativity. However, a walk in nature is not always feasible, and whether a proxy for nature immersion via a mental walk in nature can elicit the same benefits as a physical walk remains largely unknown. Accordingly, the current study utilized guided imagery to examine whether a mental walk in nature would improve creativity in general and when compared to a mental walk in an urban environment. We implemented a within-subjects design, wherein participants completed both mental walk conditions (in a nature and urban environment) at least five days apart in counterbalanced order on an online platform. During each session, participants (N = 97) completed two pre-walk tasks assessing convergent (measured by the Remote Associates Test) and divergent creative thinking (measured by the Alternate Uses Test), followed by a mental walk in either a nature or urban environment, then finally the identical two post-walk creativity tasks. After five days, they repeated the same procedure with a mental walk in the other environment. While comparisons of post-walk creativity scores between the nature and urban environment did not significantly differ from each other, the comparisons between the pre- and post-walk creativity scores revealed a significant improvement in convergent creative thinking in the nature environment condition, but not the urban environment condition. Our results suggest that taking a mental walk in nature can enhance at least one aspect of creativity, therefore providing preliminary evidence for the potential to access the creative benefits of mentally immersing ourselves in nature. These findings have important implications for those who wish to enjoy the benefits of nature but are unable to readily access nature physically.
Total Hip Replacement or Resistance Training for Severe Hip Osteoarthritis
Author Correction: Pharmacogenomic screening identifies and repurposes leucovorin and dyclonine as pro-oligodendrogenic compounds in brain repair
Adoption of AI writing tools among academic researchers: A Theory of Reasoned Action approach
This research explores the determinants affecting academic researchers’ acceptance of AI writing tools using the Theory of Reasoned Action (TRA). The impact of attitudes, subjective norms, and perceived barriers on researchers’ intentions to adopt these technologies is examined through a cross-sectional survey of 150 researchers. Structural Equation Modeling (SEM) is employed to evaluate the measurement and structural models. Findings confirm the positive influence of favorable attitudes and subjective norms on intentions to use AI writing tools. Interestingly, perceived barriers did not significantly impact attitudes or intentions, suggesting that in the academic context, potential benefits may outweigh perceived obstacles to AI writing tool adoption. Contrarily, perceived barriers do not significantly affect attitudes and intentions directly. The TRA model demonstrates considerable explanatory and predictive capabilities, indicating its effectiveness in understanding AI writing tool adoption among researchers. The study’s diverse sample across various disciplines and career stages provides insights that may be generalizable to similar academic contexts, though further research with larger samples is needed to confirm broader applicability. Results offer practical guidance for tool developers, academic institutions, and publishers aiming to foster responsible and efficient AI writing tool use in academia. Findings suggest strategies such as demonstrating clear productivity gains, establishing AI Writing Tool programs, and developing comprehensive training initiatives could promote responsible adoption. Strategies focusing on cultivating positive attitudes, leveraging social influence, and addressing perceived barriers could be particularly effective in promoting adoption. This pioneering study investigates researchers’ acceptance of AI writing tools using a technology acceptance model, contributing to the understanding of technology adoption in professional contexts and highlighting the importance of field-specific factors in examining adoption intentions and behaviors.
Safety of Kidney Transplantation from Donors with HIV Infection
CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer
Abstract The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation. Notably, CDK4 depletion or long-term CDK4/6 inhibition confers resistance to apoptosis in TNBC cells. Mechanistically, CDK4 enhances mitochondria-endoplasmic reticulum contact (MERCs) formation, promoting mitochondrial fission and ER-mitochondrial calcium signaling, which are crucial for TNBC metabolic flexibility. Phosphoproteomic analysis identified CDK4’s role in regulating PKA activity at MERCs. In this work, we highlight CDK4’s role in mitochondrial apoptosis inhibition and suggest that targeting MERCs-associated metabolic shifts could enhance TNBC therapy.
Recruitment, follow-up and survival in an 11-country cohort study of patients at the end of life and their relatives
Background Large, international cohort studies generate high-level evidence, but are resource intense. In end-of-life care such studies are scarce. Hence, planning for future studies in terms of data on screening, recruitment, retention and survival remains a challenge. Objectives The aim was to describe recruitment, follow-up and survival in a multinational study of patients’ and relatives’ expectations, concerns and preferences at the end of life. Methods In this 11-country cohort study with six months follow-up patients, >18 years old, were included on the basis of an adapted “surprise question” to assess patients´ end of life status. Patients were required to be aware of their limited life expectancy. We collected patient questionnaires (baseline and 1 month), and searched medical records for the date of death. One relative per patient was invited to participate. Results 26735 patients were screened for inclusion, 3065 (11%) were found eligible and were invited to participate, 1509 chose to participate, i.e. 6% of those initially screened. A total of 699 patients (49%) participated in the 1-month follow-up, with proportions varying according to survival time, from 20% if the patient died at month 2, to 75% if the patient died at month 6. Survival time was not associated with patient gender or age, but with diagnosis, country of residence and healthcare setting. Conclusion Approximately 20 times the desired cohort size had to be screened for eligibility. Prognostication was difficult, we noted a wide distribution of survival after inclusion. Patients’ ability to complete follow-up questionnaires declined well before death.
Texas Executive Order GA-46 and the Erosion of Trust in Health Care
Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells
Factors influencing chopstick use and an objective identification of traditional holding techniques in children
The acquisition of chopstick skills is considered essential for child development and etiquette in many Asian cultures. However, a decline in chopstick education has been observed in Japan, and the underlying causes of this phenomenon remain elusive. This study aims to investigate children’s chopstick skills and develop an objective method to evaluate them using a hand posture estimation model. In this study. A questionnaire survey was conducted among 165 first-grade elementary school students (aged 6–7) and their parents to investigate factors influencing chopstick proficiency. To complement this, video analyses were performed using a hand posture estimation model to assess the accuracy of chopstick grip classification. The findings showed that children’s chopstick-holding styles could be classified into four categories: four-finger prehension (64 participants), three-finger prehension (49 participants), palm prehension (20 participants), and others (32 participants). Despite the fact that over 80% of parents reported teaching their children how to use chopsticks, a mere 9.7% of children exhibited correct chopstick-holding technique. Interestingly, factors such as intergenerational cohabitation with grandparents and child’s age significantly influenced chopstick proficiency. These results indicate that a gap exists in the intergenerational transmission of chopstick skills, with parents potentially lacking sufficient knowledge to teach their children. The hand posture estimation model had a high accuracy rate of 85%, precision of 83%, and recall of 88% to identify whether children use chopsticks traditionally. While chopstick education is predominantly conducted within Japanese households, the increasing prevalence of nuclear families and dual-income households suggests a decline in intergenerational transmission of chopstick education. To address this issue, it is imperative to develop web applications that can integrate chopstick education into school curricula and promote chopstick skills among students.