OBJECTIVE: Our aim was to compare the PIK3CA mutation status in matched primary and recurrent tumors of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (BC) to gain insight into the optimization of patient selection and detection time for PIK3CA-targeted therapy.
METHODS: The data were from 3035 patients with BC diagnosed at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2017. Matched primary and recurrent samples were profiled using amplification-refractory mutation system-polymerase chain reaction covering 11 mutational hotspots in PIK3CA.
RESULTS: PIK3CA mutations were detected in 54.3% primary tumors and 48.6% corresponding recurrences. PIK3CA mutation was detected in 37.5% cases in the locoregional recurrent group and 40.0% of distant metastasis, without a statistical difference. Besides, PIK3CA mutations were concordant in 88.6% of the matched pairs. For patients treated with neoadjuvant chemotherapy, 100% concordance was observed. However, PIK3CA mutation was neither correlated with clinicopathological features nor associated with clinical outcomes.
CONCLUSIONS: Mutations in PIK3CA in HR+/HER2- BC generally progressed to recurrent tumors. The high concordance rate of PIK3CA mutation status between primary tumors and corresponding recurrences suggests that the detection of primary tumors could be a substitute approach when recurrent samples are not easily obtainable.

Increased mutational burden and EBV load have been revealed from normal tissues to Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs). BPLF1, encoded by EBV, is a lytic cycle protein with deubiquitinating activity has been found to participate in disrupting repair of DNA damage. We first confirmed that BPLF1 gene in gastric cancer (GC) significantly increased the DNA double strand breaks (DSBs). Ubiquitination mass spectrometry identified histones as BPLF1 interactors and potential substrates, and co-immunoprecipitation and in vitro experiments verified that BPLF1 regulates H2Bub by targeting Rad6. Over-expressing Rad6 restored H2Bub but partially reduced γ-H2AX, suggesting that other downstream DNA repair processes were affected. mRNA expression of BRCA2 were significantly down-regulated by next-generation sequencing after over-expression of BPLF1, and over-expression of p65 facilitated the repair of DSBs. We demonstrated BPLF1 may lead to the accumulation of DSBs by two pathways, reducing H2B ubiquitination (H2Bub) and blocking homologous recombination which may provide new ideas for the treatment of gastric cancer.

The autonomic nervous system (ANS) regulates the body\'s physiology, including cardiovascular function. As the ANS develops during the second to third trimester, fetal heart rate variability (HRV) increases while fetal heart rate (HR) decreases. In this way, fetal HR and HRV provide an index of fetal ANS development and future neurobehavioral regulation. Fetal HR and HRV have been associated with child language ability and psychomotor development behavior in toddlerhood. However, their associations with postbirth autonomic brain systems, such as the brainstem, hypothalamus, and dorsal anterior cingulate cortex (dACC), have yet to be investigated even though brain pathways involved in autonomic regulation are well established in older individuals. We assessed whether fetal HR and HRV were associated with the brainstem, hypothalamic, and dACC functional connectivity in newborns. Data were obtained from 60 pregnant individuals (ages 14-42) at 24-27 and 34-37 weeks of gestation using a fetal actocardiograph to generate fetal HR and HRV. During natural sleep, their infants (38 males and 22 females) underwent a fMRI scan between 40 and 46 weeks of postmenstrual age. Our findings relate fetal heart indices to brainstem, hypothalamic, and dACC connectivity and reveal connections with widespread brain regions that may support behavioral and emotional regulation. We demonstrated the basic physiologic association between fetal HR indices and lower- and higher-order brain regions involved in regulatory processes. This work provides the foundation for future behavioral or physiological regulation research in fetuses and infants.

This paper investigates the Hamiltonian energy of a modified Hindmarsh-Rose (HR) model to observe its effect on short-term memory. A Hamiltonian energy function and its variable function are given in the reduced system with a single node according to Helmholtz\'s theorem. We consider the role of the coupling strength and the links between neurons in the pattern formation to show that the coupling and cooperative neurons are necessary for generating the fire or a clear short-term memory when all the neurons are in sync. Then, we consider the effect of the degree and external stimulus from other neurons on the emergence and disappearance of short-term memory, which illustrates that generating short-term memory requires much energy, and the coupling strength could further reduce energy consumption. Finally, the dynamical mechanisms of the generation of short-term memory are concluded.

The present study investigated the potential of implicit physiological measures to provide objective measures of affective food experience in contrast to explicit self-report ratings in a cross-cultural context. Dutch and Thai participants viewed 120 food images portraying universal food image categories (regular and molded food) and cultural food image categories (typically Dutch and Thai food). The universal food images were taken as ground truth high and low valence stimuli, where we assumed no genuine difference in affective experience between nationalities. In contrast, for the cultural food images, we did expect a genuine difference between nationalities. Participants were asked to rate valence, arousal and liking of each food image. In addition, heart rate (HR) and phasic electrodermal activity (EDA) responses to the images were recorded. Typically Asian and Western response biases were found for explicit ratings of regular and molded food with an extreme response style for Dutch, and a middle response style for Thai participants. However, such bias was not observed in HR. For cultural food image categories, HR showed the hypothesized interaction between participant nationality and food image category, reflecting the expected genuine difference between nationalities in affective food experience. Besides presenting participants with images, we also asked participants to taste typically Thai and Dutch drinks. Similar to images, a significant interaction between participant nationality and cultural food category was found for HR. An interaction was also found for sip size, while this was not seen in explicit measures. We attribute this to differences in the moment that these measures were taken. In this study, phasic EDA did not appear to be a sensitive measure of affective food experience, possibly since stimuli mostly differed in valence rather than arousal. To conclude, our study constitutes an example where cultural bias negatively affected the accuracy of self-reports, and only the implicit physiological measures followed the prior expectations of genuine food experience, indicating the potential of these measures to study cross-cultural food experience.

We demonstrate here that single strand annealing (SSA) repair can be co-opted for the precise autocatalytic excision of a drive element. Although SSA is not the predominant form of DNA repair in eukaryotic organisms, we increased the likelihood of its use by engineering direct repeats at sites flanking the drive allele, and then introducing a double-strand DNA break (DSB) at a second endonuclease target site encoded within the drive allele. We have termed this technology Repeat Mediated Excision of a Drive Element (ReMEDE). Incorporation of ReMEDE into the previously described mutagenic chain reaction (MCR) gene drive, targeting the yellow gene of Drosophila melanogaster, replaced drive alleles with wild-type alleles demonstrating proof-of-principle. Although the ReMEDE system requires further research and development, the technology has a number of attractive features as a gene drive mitigation strategy, chief among these the potential to restore a wild-type population without releasing additional transgenic organisms or large-scale environmental engineering efforts.

The development of smart wearable solutions for monitoring daily life health status is increasingly popular, with chest straps and wristbands being predominant. This study introduces a novel sensorized T-shirt design with textile electrodes connected via a knitting technique to a Movesense device. We aimed to investigate the impact of stationary and movement actions on electrocardiography (ECG) and heart rate (HR) measurements using our sensorized T-shirt. Various activities of daily living (ADLs), including sitting, standing, walking, and mopping, were evaluated by comparing our T-shirt with a commercial chest strap. Our findings demonstrate measurement equivalence across ADLs, regardless of the sensing approach. By comparing ECG and HR measurements, we gained valuable insights into the influence of physical activity on sensorized T-shirt development for monitoring. Notably, the ECG signals exhibited remarkable similarity between our sensorized T-shirt and the chest strap, with closely aligned HR distributions during both stationary and movement actions. The average mean absolute percentage error was below 3%, affirming the agreement between the two solutions. These findings underscore the robustness and accuracy of our sensorized T-shirt in monitoring ECG and HR during diverse ADLs, emphasizing the significance of considering physical activity in cardiovascular monitoring research and the development of personal health applications.

BACKGROUND: A large proportion of Australians are affected by mental illness each year, and treatment gaps are well known. To meet current and future demands and enable access to treatment that is safe, effective, and acceptable, a robust and sustainable mental health workforce is required. Factors reported to attract people to work within the mental health sector include aspiring to help others, having an interest in mental health and human behavior, the desire to make a difference and do something worthwhile, personal lived experience, recognition, and value of discipline-specific roles. However, despite the various reasons people enter the public mental health workforce, recruitment and retention continue to be ongoing challenges. To date, there has been limited investigation into understanding which factors are most relevant to the current Victorian workforce. Furthermore, a comparison to health care workers outside of mental health is also needed to better understand the specific needs of staff within the mental health sector.
OBJECTIVE: This study aims to explore factors related to attraction, recruitment, and retention of the public mental health workforce in Victoria, Australia.
METHODS: The study is a multisite, mixed methods cross-sectional study to be conducted at 4 public hospital services within Victoria, Australia: 2 in metropolitan and 2 in regional or rural locations. Current, previous, and nonmental health workers will be asked to complete a 20-25-minute web-based survey, which is developed based on previous research and offered participation in an optional 30-60-minute semistructured interview to examine personal experiences and perceptions. Both aspects of the project will examine factors related to attraction, recruitment, and retention in the public mental health workforce. Differences between groups (ie, current, past, and nonmental health workers), as well as location, discipline, and health setting will be examined. Regression analyses will be performed to determine the factors most strongly associated with retention (ie, job satisfaction) and turnover intention. Qualitative data will be transcribed verbatim and thematically analyzed to identify common themes.
RESULTS: As of May 2023, we enrolled 539 participants in the web-based survey and 27 participants in the qualitative interview.
CONCLUSIONS: This project seeks to build on current knowledge from within Australia and internationally to understand role and service/system-related issues of attraction, recruitment, and retention specifically within Victoria, Australia. Seeking up-to-date information from across the health workforce may provide factors specific to mental health by illuminating any differences between mental health workers and health care workers outside of mental health. Furthermore, exploring motivators across health care disciplines and locations to enter, stay in, or leave a role in public mental health settings will provide valuable information to support how the sector plans and develops strategies that are fit for purpose.
UNASSIGNED: DERR1-10.2196/48855.

Double-strand break (DSB), a significant DNA damage brought on by ionizing radiation, acts as an initiating signal in tumor radiotherapy, causing cancer cells death. The two primary pathways for DNA DSB repair in mammalian cells are nonhomologous end joining (NHEJ) and homologous recombination (HR), which cooperate and compete with one another to achieve effective repair. The DSB repair mechanism depends on numerous regulatory variables. DSB recognition and the recruitment of DNA repair components, for instance, depend on the MRE11-RAD50-NBS1 (MRN) complex and the Ku70/80 heterodimer/DNA-PKcs (DNA-PK) complex, whose control is crucial in determining the DSB repair pathway choice and efficiency of HR and NHEJ. In-depth elucidation on the DSB repair pathway\'s molecular mechanisms has greatly facilitated for creation of repair proteins or pathways-specific inhibitors to advance precise cancer therapy and boost the effectiveness of cancer radiotherapy. The architectures, roles, molecular processes, and inhibitors of significant target proteins in the DSB repair pathways are reviewed in this article. The strategy and application in cancer therapy are also discussed based on the advancement of inhibitors targeted DSB damage response and repair proteins.

Genome integrity and maintenance are essential for the viability of all organisms. A wide variety of DNA damage types have been described, but double-strand breaks (DSBs) stand out as one of the most toxic DNA lesions. Two major pathways account for the repair of DSBs: homologous recombination (HR) and non-homologous end joining (NHEJ). Both pathways involve complex DNA transactions catalyzed by proteins that sequentially or cooperatively work to repair the damage. Single-molecule methods allow visualization of these complex transactions and characterization of the protein:DNA intermediates of DNA repair, ultimately allowing a comprehensive breakdown of the mechanisms underlying each pathway. We review current understanding of the HR and NHEJ responses to DSBs in eukaryotic cells, with a particular emphasis on recent advances through the use of single-molecule techniques.