Phase Of Cycle Research Articles

DNA repair is efficient in irradiated M phase zygotes.

In somatic cells, DNA repair is attenuated during mitosis to prevent the formation of anaphase bridges and facilitate the proper segregation of sister chromatids. Irradiation-induced γH2AX foci persist for hours in M phase somatic cells. However, we observed that anaphase bridges formed in a significant fraction of mouse zygotes irradiated during mitosis. Additionally, γH2AX signals in M phase zygotes peaked 30 min after irradiation and subsequently reduced with a half-life within 1-2 h. These results suggest that the DNA repair system may operate efficiently in M phase zygotes following irradiation, leading to the frequent formation of anaphase bridges. The absence of H2AX promoted the successful segregation of sister chromatids and enhanced the development of embryos to the blastocyst stage. The DNA repair system may be differentially regulated during the M phase of the first cell cycle to ensure the immediate elimination of damaged zygotes, thereby efficiently preventing transmission of mutations to subsequent generations.

Effects of Solar Variability on Tropical Cyclone Activity

AbstractThe current study explores the relationship between solar variability and tropical cyclone (TC) activity using sunspot number (SSN) and TC best‐track data as respective proxies. We have considered six regions of the globe, for example, EP: Eastern Pacific, NA: North Atlantic, NI: North Indian, SI: South Indian, SP: South Pacific, and WP: Western Pacific. The results show strong anti‐correlation between yearly TC activity and yearly SSN while considering their 11‐year moving averages. This behavior is consistent for TC counts as well as accumulated cyclone energy. However, this is true only for the North Atlantic region. Overall, when we consider all regions together, more TCs (in terms of counts) are observed during lower solar activity periods (SSN < 50) as compared to higher solar activity conditions (SSN > 100). However, the yearly rates remain more or less similar. On the other hand, extreme TC events with a maximum wind speed of 137 knots and higher (category 5) are most likely to occur during the declining phase of a solar cycle and least likely to occur during the ascending phase or the maximum phase. Although solar activity levels are similar during the declining and ascending phases, the yearly occurrence rate is nearly double in the declining phase (1.123) as compared to that in the ascending phase (0.625).

An anti-mitotic compound, (+)-6-tuliposide a, isolated from the Canadian glacier lily, Erythronium grandiflorum

The Canadian prairie ecosystem is subjected to abiotic and biotic conditions that induce plants to produce secondary metabolites that affect mammalian physiology. Extracts prepared from certain plant species native to Canadian prairie and montane cordillera ecosystems have previously been shown to have anti-mitotic activity on human cancer cell lines. In this study, we investigated the glacier lily, Erythronium grandiflorum (Liliaceae), in which the species was the most taxonomically distant from Asteraceae and had anti-mitotic activity. When added to cell lines, E. grandiflorum extracts induced rounded cell morphology and arrested cells in the G2/M phase of the cell cycle. Of the cells that displayed a rounded phenotype, all were positive for phospho-histone H3 and contained a distorted mitotic spindle. This anti-mitotic activity was distinct from that of the compound colchicine, which has been previously isolated from the Liliaceae family. By biology-guided fractionation, we isolated the natural product (+)-6-tuliposide A and are the first to report its anti-mitotic activity. These results reveal a chemical motif in secondary metabolites and expand the range of Canadian prairie plants with anti-mitotic activity that can become new scientific tools or used in the development of anti-proliferative medicines.

Effect of neratinib on HER2 mRNA stability via hsa-miR-23a-5p and efficacy of CDK4/6 inhibitors in HER2-low breast cancer.

e12550 Background: Traditional HER2-negative breast cancer sometimes includes HER2-low components, and CDK4/6 inhibitors are the first- and second-line treatments for advanced HER2-low breast cancer. Nonetheless, little is understood about how the stability of HER2 mRNA in HER2-low breast cancer affects the effectiveness of CDK4/6 inhibitor therapy and the associated intervention techniques. Methods: In order to investigate the impact of HER2-low on the effectiveness of CDK4/6 inhibitor in treating breast cancer, we first used HER2-0 and HER2-low breast cancer cells/mice as the study object and assessed the anti-proliferation effect of CDK4/6 inhibitor using CCK8 technique and monoclonal formation experiment. Second, we increased the treatment of anti-HER2 inhibitor neratinib and assessed its impact on the efficacy of HER2 low breast cancer CDK4/6 inhibitors. By reducing the expression of HER2 in HER2 low breast cancer cells, we analyzed and determined whether HER2 is the primary pathway that influences the poor efficacy of HER2 low breast cancer CDK4/6 inhibitors; At last, actinomycin D was used to detect the mRNA stability of HER2 in the treatment of HER2-low breast cancer by neratinib against CDK4/6 inhibitors, and then microRNA sequencing and luciferase reporter gene detection technology were used. To investigate the specific mechanism of action of neratinib on the mRNA stability of HER2 in the treatment of HER2-low breast cancer by CDK4/6 inhibitors. Results: Our study found that treatment with CDK4/6 inhibitors was significantly less effective against HER2-low breast cancer compared to HER2-0 subtype (P=0.005). Notably, in HER2-low subtype cells, HER2 knockdown significantly inhibited cell proliferation (P<0.001), G1 phase cell cycle arrest (P=0.001), and downregulated cyclin D1 expression and CDK4 protein levels (P=0.007, P=0.003). Second, it was found that in the cell and animal models of HER2-low breast cancer, the addition of the CDK4/6 inhibitor drug neratinib effectively reduced the stability of HER2 mRNA (P=0.001), inhibited the cell cycle of G1 phase (P=0.005). In addition, we observed that lowering the dose of neratinib to 1/2 (20 mg/kg) remained effective and well tolerated (P=0.002). Finally, we found that neratinib can reduce the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3'UTR region of HER2 (P<0.001), thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. Conclusions: We found that low expression of HER2 reduced the efficacy of CDK4/6 inhibitors in HER2-low breast cancer; Neratinib reduces the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3 'UTR region of HER2, thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. These findings provide a tolerable and effective two-drug combination regimen for patients with clinical HER2-low breast cancer.

Real world tebentafusp-tebn experience at a tertiary care referral center.

e21526 Background: Tebentafusp-tebn is an FDA approved therapy specifically for patients with metastatic uveal melanoma (MUM). The major challenge of this treatment is the weekly infusion schedule and potentially significant toxicity during the dose escalation and induction phase (Cycle 1). To overcome this challenge, we developed a treatment model consisting of an induction phase at a tertiary center of MUM and subsequent treatments at a local cancer center. Methods: This retrospective cohort study included patients who received Cycle 1 at our institution since FDA approval. Patients who received initial induction doses at other health systems were excluded. Data was collected by chart review. Cytokine release syndrome (CRS) was graded by ASTCT consensus guidelines. Results: From 3/14/2022-11/7/23, 26 patients received at least one dose of tebentafusp-tebn at our institution. 14/26 were female and median age was 69 (range 51-80). 24/26 patients had metastatic disease to the liver, followed by bone (6/26), lung (3/26), and others (5/26). Patients underwent a median of 2 (range 0-5) lines of therapy prior to tebentafusp-tebn initiation. Major side effects during Cycle 1 included CRS (22/26), rash/itching (24/26), and nausea (3/26). One patient developed grade 4 liver enzyme elevations. Of the patients who developed CRS, 77.3% (17/22) were grade 1, 13.7% (3/22) were grade 2, and 9.1% (2/22) were grade 3. 5/26 (19.2%) patients required at least one dose of steroid for management of CRS. The median number of hospitalizations for Cycle 1 was 3 (range 3-6). After Cycle 1, 21/26 (80.8%) patients were successfully transitioned to local health systems to continue outpatient weekly tebentafusp-tebn infusions, including 2 patients who went were able to continue of therapy in their home countries. 1 patient is in the process of transferring, 1 patient discontinued after dose escalation due to disease progression, and 3 patients decided to continue treatment at our institution. 19 patients who were transitioned to their local cancer centers in the US traveled a median of 107 miles (range 30-298 miles) for Cycle 1 at our institution, and a median of 23 miles (range 4-58 miles) after transition to local health systems. The median number of days patients received therapy was 203 days (range 22-610 days). Median time to progression was 12.6 weeks (range 5.8-65.6). 6/26 (23.1%) patients have received additional therapy upon progression while continuing tebentafusp-tebn. 12/26 patients are currently receiving therapy and 2 patients were lost to follow up after transferring to a local site. At time of review 19/26 patients were alive. Conclusions: This hybrid model of treatment (Cycle 1 at a tertiary center followed by continuation at a local cancer center) made weekly tebentafusp-tebn treatment safe and feasible for patients with MUM. Our single center experience demonstrates side effects and outcomes similar to what has been reported in the clinical trial.

Unfolding the role of cell state on stress granule heterogeneity and function in pancreatic cancer.

e16357 Background: A major impediment to cancer therapy is the reality that cancer is a heterogeneous disease. A single tumor can consist of many genotypic or phenotypic profiles, which are marked by degrees of sensitivity to different therapeutics. Identifying and targeting origins of cancer cell heterogeneity is critical for predicting patient outcome and enhancing treatment efficacy. We observe a novel source of cancer cell heterogeneity that involves one of the largest stress-sensing platforms described to date: the stress granule (SG). Stress granules are non-membranous, cytoplasmic organelles that assemble in response to stress, and promote cell survival. Deregulation of SGs has been linked to several pathological conditions, including cancer, neurodegeneration, ischemia, and viral infections. SGs have been shown to promote tumor growth and metastasis, as well as contribute to mechanisms of chemo-resistance. Thus, these signaling hubs are emerging as a potential target in cancer. Methods: To induce SG formation, human pancreatic ductal adenocarcinoma (PDAC) cell lines were treated with sodium arsenite, thapsigargin, or exposed to hypoxic conditions. Immunoflourescent staining of core SG proteins was then conducted. To investigate cell cycle-driven mechanisms of SG heterogeneity, cell cycle stage was identified by expression of a Fluorescent ubiquitination-based cell cycle indicator (Fucci) lentiviral system. To investigate cPLA2’s role in SG formation, the chemical inhibitor Pyrrophenone, an shRNA targeting cPLA2, and an exogenous full-length or cleaved form of cPLA2, were used. In vivo, ES149 cells expressing Luciferase and the Fucci system were orthotopically implanted into C57BL/6 mice. Established tumors were treated every 3 days with Vehicle, Oxaliplatin, Pyrrophenone, or a combination of the latter. Tumor size was tracked via IVIS Spectrum. Fucci flourescence was used to identify cell cycle phase. SGs and cell death were assessed by immunoflourescent staining of tumors. Results: Cancer cells show a high degree of heterogeneity in their production of SGs. Cell cycle phase dictates SG heterogeneity. G2 phase cells have significantly higher levels of SG formation as compared cells in G1/S. This process is regulated by cleavage of the cPLA2 protein. Oxaliplatin administration increases G2 phase content in tumors. Co-treatment with Oxaliplatin and Pyrrophenone significantly decreases SG formation, increases cell death, and leads to tumor regressions in vivo. Conclusions: G2 phase cancer cells develop higher levels of SGs when exposed to stressful stimuli, as compared to G1/S phase counterparts. The cPLA2 protein is cleaved into a catalytically dead form that is present in G1/S phases, but absent in G2 phase. Oxaliplatin treatment in vivo leads to an increase in G2 phase tumor cells. When paired with cPLA2 inhibition, this results in increased cancer cell death and decreased tumor growth.

Influence of the Menstrual Cycle and Training on the Performance of a Perturbed Single-Leg Squatting Task in Female Collegiate Athletes.

Anterior cruciate ligament (ACL) injuries often occur when an athlete experiences an unexpected disruption, or perturbation, during sports. ACL injury rates may also be influenced by the menstrual cycle. To determine whether training adaptations to knee control and muscle activity during a perturbed single-leg squatting (SLS) task depend on menstrual cycle phase in female athletes. Controlled laboratory study. A total of 21 healthy female collegiate athletes (current or former [<3 years]) who competed in 9 different sports performed an SLS task in which they attempted to match their knee position (user signal) to a target signal. The protocol consisted of a 9-condition pretest, 5 sets of 3 training trials, and a 9-condition posttest. One perturbation was delivered in each condition by altering the resistance of the device. Sagittal knee control (absolute error between the target signal and user signal) was assessed using a potentiometer. Muscle activity during perturbed squat cycles was normalized to maximal activation and to corresponding muscle activity during unperturbed squat cycles (%unperturbed) within the same test condition. Athletes performed the protocol during a distinct menstrual cycle phase (early follicular [EF], late follicular [LF], midluteal [ML]). Two-way mixed analysis of variance was used to determine the effects of the menstrual cycle and training on knee control and muscle activity during task performance. Venous blood was collected for hormonal analysis, and a series of health questionnaires and anthropometric measures were also assessed to determine differences among the menstrual cycle groups. After training, athletes demonstrated better knee control during the perturbed squat cycles (lower absolute error, P < .001) and greater soleus feedback responses to the perturbation (%unperturbed, P = .035). Better knee control was demonstrated in the ML phase versus the EF phase during unperturbed and perturbed squat cycles (P < .039 for both). Quadriceps activation was greater in the ML phase compared with the EF and LF phases, both immediately before and after the perturbation (P < .001 for all). Athletes learned to improve knee control during the perturbed performance regardless of menstrual cycle phase. The best knee control and greatest quadriceps activation during the perturbed squatting task was found in the ML phase. These findings may correspond to a lower incidence of ACL injury in the luteal phase and alterations in exercise performance across the menstrual cycle.

Unfolding the role of cell state on stress granule heterogeneity and function in pancreatic cancer.

e16357 Background: A major impediment to cancer therapy is the reality that cancer is a heterogeneous disease. A single tumor can consist of many genotypic or phenotypic profiles, which are marked by degrees of sensitivity to different therapeutics. Identifying and targeting origins of cancer cell heterogeneity is critical for predicting patient outcome and enhancing treatment efficacy. We observe a novel source of cancer cell heterogeneity that involves one of the largest stress-sensing platforms described to date: the stress granule (SG). Stress granules are non-membranous, cytoplasmic organelles that assemble in response to stress, and promote cell survival. Deregulation of SGs has been linked to several pathological conditions, including cancer, neurodegeneration, ischemia, and viral infections. SGs have been shown to promote tumor growth and metastasis, as well as contribute to mechanisms of chemo-resistance. Thus, these signaling hubs are emerging as a potential target in cancer. Methods: To induce SG formation, human pancreatic ductal adenocarcinoma (PDAC) cell lines were treated with sodium arsenite, thapsigargin, or exposed to hypoxic conditions. Immunoflourescent staining of core SG proteins was then conducted. To investigate cell cycle-driven mechanisms of SG heterogeneity, cell cycle stage was identified by expression of a Fluorescent ubiquitination-based cell cycle indicator (Fucci) lentiviral system. To investigate cPLA2’s role in SG formation, the chemical inhibitor Pyrrophenone, an shRNA targeting cPLA2, and an exogenous full-length or cleaved form of cPLA2, were used. In vivo, ES149 cells expressing Luciferase and the Fucci system were orthotopically implanted into C57BL/6 mice. Established tumors were treated every 3 days with Vehicle, Oxaliplatin, Pyrrophenone, or a combination of the latter. Tumor size was tracked via IVIS Spectrum. Fucci flourescence was used to identify cell cycle phase. SGs and cell death were assessed by immunoflourescent staining of tumors. Results: Cancer cells show a high degree of heterogeneity in their production of SGs. Cell cycle phase dictates SG heterogeneity. G2 phase cells have significantly higher levels of SG formation as compared cells in G1/S. This process is regulated by cleavage of the cPLA2 protein. Oxaliplatin administration increases G2 phase content in tumors. Co-treatment with Oxaliplatin and Pyrrophenone significantly decreases SG formation, increases cell death, and leads to tumor regressions in vivo. Conclusions: G2 phase cancer cells develop higher levels of SGs when exposed to stressful stimuli, as compared to G1/S phase counterparts. The cPLA2 protein is cleaved into a catalytically dead form that is present in G1/S phases, but absent in G2 phase. Oxaliplatin treatment in vivo leads to an increase in G2 phase tumor cells. When paired with cPLA2 inhibition, this results in increased cancer cell death and decreased tumor growth.

Privacy Challenges and Solutions in Big Data Analytics: A Comprehensive Review

Abstract: Large data collections with a more intricate and diversified structure are referred to as "big data." These traits are typically associated with more challenges when it comes to storing, analyzing, and applying additional procedures or getting results. The technique of analyzing vast quantities of intricate data to uncover patterns or connections that are concealed is known as "big data analytics." Nonetheless, there is a clear conflict between big data's extensive use and its security and privacy. This paper examines privacy needs in big data, distinguishes between privacy and security, and focuses on privacy and security issues in large data. This study addresses the applications of privacy in business by utilizing established techniques like HybrEx, k-anonymity, T-closeness, and L-diversity. Many privacy-preserving techniques have been created for protection of privacy at various phases of the big data life cycle (such as data generation, storage, and processing). This work aims to explain the issues facing current privacy preservation strategies in big data and to give a comprehensive evaluation of them. This study also introduces new approaches to privacy preservation in big data, such as quick anonymization of massive data streams, identity-based anonymization, differential privacy, privacy preserving big data publishing, and hiding a needle in a haystack. This study discusses big data privacy and security issues in healthcare. A comparative analysis of some contemporary large data privacy approaches is also conducted. A comparative analysis of the latest big data privacy approaches is also conducted.

METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade

BackgroundRNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure.MethodsThe biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms.ResultsThe tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor.ConclusionOur study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

Organic Trace Elements Improve the Eggshell Quality via Eggshell Formation Regulation during the Late Phase of the Laying Cycle.

The quality of eggshells is critical to the egg production industry. The addition of trace elements has been shown to be involved in eggshell formation. Organic trace elements have been found to have higher biological availability than inorganic trace elements. However, the effects of organic trace elements additive doses on eggshell quality during the laying period of commercial laying hens required further investigation. This experiment aims to explore the potential mechanisms of different doses of organic trace elements replacing inorganic elements to remodel the eggshell quality of egg-laying hens during the laying period. A total of 360 healthy hens (Lohmann Pink, 45-week-old) were randomly divided into four treatments, with six replications per treatment and 15 birds per replication. The dietary treatments included a basal diet supplemented with inorganic iron, copper, zinc and manganese at commercial levels (CON), a basal diet supplemented with organic iron, copper, zinc and manganese at 20% commercial levels (LOT), a basal diet supplemented with organic iron, copper, zinc and manganese at 30% commercial levels (MOT), and a basal diet supplemented with organic iron, copper, zinc and manganese at 40% commercial levels (HOT). The trial lasted for 8 weeks. The results of the experiment showed that the replacement of organic trace elements did not significantly affect the production performance of laying hens (p > 0.05). Compared with inorganic trace elements, the MOT and HOT groups improved the structure of the eggshells, enhanced the hardness and thickness of the eggshells, increased the Haugh unit of the eggs, reduced the proportion of the mammillary layer in the eggshell, and increased the proportion of the palisade layer (p < 0.05). In addition, the MOT and HOT groups also increased the enzyme activity related to carbonate transport in the blood, the expression of uterine shell gland-related genes (CA2, OC116, and OCX32), and the calcium and phosphorus content in the eggshells (p < 0.05). We also found that the MOT group effectively reduced element discharge in the feces and enhanced the transportation of iron (p < 0.05). In conclusion, dietary supplementation with 30-40% organic micronutrients were able to improve eggshell quality in aged laying hens by modulating the activity of serum carbonate transport-related enzymes and the expression of eggshell deposition-related genes.

Premenstrual syndrome is associated with differences in heart rate variability and attentional control throughout the menstrual cycle: A pilot study

IntroductionMost persons with an active menstrual cycle suffer from a range of aversive symptoms (e.g. reduced ability to concentrate) in the days before their menstruation – the premenstrual syndrome (PMS). Biological and cognitive mechanisms of PMS are poorly understood. It has been shown that vagally mediated heart rate variability (vmHRV), a physiological marker of self-regulation, decreases during the PMS-affected cycle phase (luteal phase) only in individuals with high PMS symptomology. This study investigates the specific associations between vmHRV, PMS symptomology and cognitive self-regulation (attentional control). MethodsIn this between-subject study, participants completed an vmHRV baseline measurement through electrocardiography, a reaction time paradigm to measure attentional control (modified attention network test revised, ANT-R) and filled out a questionnaire regarding impact of PMS as well as current menstrual phase. ResultsMixed Model analysis showed interactions effects in the hypothesized direction. VmHRV was decreased during the luteal phase only in individuals with higher PMS. Analogously, performance in the Executive Functioning of the ANT-R task was reduced in the luteal compared to the follicular phase only in individuals with increased PMS symptoms. No effects were found in the Orienting Network Score. DiscussionThe results point in the direction of associations between vmHRV, PMS and self-regulation. This could hint at common underlying mechanisms. Further research, however, must be conducted to examine causal pathways to confirm these associations.

Characterization of internal jugular vein region-specific distension and flow patterns during progressive volume shifting.

Blood volume shifts during postural adjustment leads to irregular distension of the internal jugular vein (IJV). In microgravity, distension may contribute to flow stasis and thromboembolism, though the regional implications and associated risk remain unexplored. We characterized regional differences in IJV volume distension and flow complexity during progressive head-down tilt (HDT) (0°, -6°, -15°, -30°) using conventional ultrasound and vector flow imaging. We also evaluated low-pressure thigh cuffs (40 mmHg) as a fluid shifting countermeasure during -6° HDT. Total IJV volume expanded 139±95% from supine (4.6±2.7 mL) to -30° HDT (10.3±5.0 mL). Blood flow profiles had greater vector uniformity at the cranial IJV region (P<0.01) and became more dispersed with increasing tilt (P<0.01). Qualitatively, flow was more uniform throughout the IJV during its early flow cycle phase, and more disorganized during late flow phase. This disorganized flow was accentuated closer to the vessel wall, near the caudal region, and during greater HDT. Low-pressure thigh cuffs during -6° HDT decreased IJV volume at the cranial region (-12±15%; P<0.01) but not the caudal region (P=0.20), although flow uniformity was unchanged (both regions,P>0.25). We describe a distensible IJV accommodating large volume shifts along its length. Prominent flow dispersion was primarily found at the caudal region, suggesting multi-directional blood flow. Thigh cuffs appear effective for decreasing IJV volume but effects on flow complexity are minor. Flow complexity along the vessel length is likely related to IJV distension during chronic volume shifting and may be a precipitating factor for flow stasis and future thromboembolism risk.

Energy availability modulates regional blood flow via estrogen-independent pathways in regularly menstruating young women.

This study aimedto investigate the impact of short-term low energy availability (LEA) on vascular function in young, regularly menstruating women. Participants were 19 women, aged 22.9 ± 4.2years, with body mass index 18-30kg·m2. They were divided into two groups and completed two conditions in a crossover design: a 3-day control condition (CON) with an energy availability of 45kcals·kgFFM-1·day-1 and a 3-day LEA condition of 15kcals·kgFFM-1 day-1. Assessments were conducted during the early follicular phase of the menstrual cycle. Outcome measures included forearm blood flow (FBF), heart rate, blood pressure, arterial stiffness, resting energy expenditure (REE), metabolic blood markers and body composition. Significant time-by-condition interactions were found for resting FBF (p = .004), REE (p = .042), triiodothyronine (p = .006), β-hydroxybutyrate (p = .002) and body mass (p < .001). Resting FBF was 1.43 ± 1.01 and 1.31 ± 0.61 (arbitrary units) at pre and post, respectively, in LEA and 1.52 ± 0.7 and 1.76 ± 0.57 at pre and post in CON. The LEA condition led to a decrease in triiodothyronine (pre: 1.54 ± 0.28, post: 1.29 ± 0.27ng ml-1), REE (pre: 1588 ± 165, post: 1487 ± 160 kcals day-1) and body mass (pre: 61.4 ± 7.5, post: 59.6 ± 7.3kg). Changes in resting FBF were significantly correlated with changes in REE in the LEA condition (r = 0.53; p = 0.02). Short-term LEA modifies regional blood flow and this might contribute to the observed decreased in REE. Findings emphasize the need for careful management of energy availability in populations at risk of LEA.

Inhibiting HSD17B8 suppresses the cell proliferation caused by PTEN failure

Loss of the tumor suppressor PTEN homolog daf-18 in Caenorhabditis elegans (C. elegans) triggers diapause cell division during L1 arrest. While prior studies have delved into established pathways, our investigation takes an innovative route. Through forward genetic screening in C. elegans, we pinpoint a new player, F12E12.11, regulated by daf-18, impacting cell proliferation independently of PTEN's typical phosphatase activity. F12E12.11 is an ortholog of human estradiol 17-beta-dehydrogenase 8 (HSD17B8), which converts estradiol to estrone through its NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. We found that PTEN engages in a physical interplay with HSD17B8, introducing a distinctive suppression mechanism. The reduction in estrone levels and accumulation of estradiol may arrest tumor cells in the G2/M phase of the cell cycle through MAPK/ERK. Our study illuminates an unconventional protein interplay, providing insights into how PTEN modulates tumor suppression by restraining cell division through intricate molecular interactions.

Evaluation of mitral chordae tendineae length using four-dimensional computed tomography.

Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation. Achieving precise measurements of artificial chordae tendineae length (CL) is an important factor in the procedure; however, no objective index currently exists to facilitate this measurement. Therefore, preoperative assessment of CL is critical for surgical planning and support. Four-dimensional x-ray micro-computed tomography (4D-CT) may be useful for accurate CL measurement considering that it allows for dynamic three-dimensional (3D) evaluation compared to that with transthoracic echocardiography, a conventional inspection method. To investigate the behavior and length of mitral chordae tendineae during systole using 4D-CT. Eleven adults aged > 70 years without mitral valve disease were evaluated. A 64-slice CT scanner was used to capture 20 phases in the cardiac cycle in electrocardiographic synchronization. The length of the primary chordae tendineae was measured from early systole to early diastole using the 3D image. The primary chordae tendineae originating from the anterior papillary muscle and attached to the A1-2 region and those from the posterior papillary muscle and attached to the A2-3 region were designated as cA and cP, respectively. The behavior and maximum lengths [cA (ma), cP (max)] were compared, and the correlation with body surface area (BSA) was evaluated. In all cases, the mitral anterior leaflet chordae tendineae could be measured. In most cases, the cA and cP chordae tendineae could be measured visually. The mean cA (max) and cP (max) were 20.2 mm ± 1.95 mm and 23.5 mm ± 4.06 mm, respectively. cP (max) was significantly longer. The correlation coefficients (r) with BSA were 0.60 and 0.78 for cA (max) and cP (max), respectively. Both cA and cP exhibited constant variation in CL during systole, with a maximum 1.16-fold increase in cA and a 1.23-fold increase in cP from early to mid-systole. For cP, CL reached a plateau at 15% and remained elongated until end-systole, whereas for cA, after peaking at 15%, CL shortened slightly and then moved toward its peak again as end-systole approached. The study suggests that 4D-CT is a valuable tool for accurate measurement of both the length and behavior of chordae tendineae within the anterior leaflet of the mitral valve.

Habitat type modulates sharp body mass oscillations in cyclic common vole populations

Cyclic rodent populations exhibit pronounced changes in body mass associated with the population cycle phase, long-known as Chitty effect. Although Chitty effect is a common epiphenomenon in both America and Europe, there is still incomplete evidence about the generality of these patterns across the entire range of most species. Moreover, despite decades of research, the underlying factors driving Chitty effect remains poorly understood. Here, we examined the influence of intrinsic and extrinsic factors that may underlie observed patterns in vole size variation in the Iberian common vole Microtus arvalis asturianus. We weighed and measured 2816 adult voles that were captured during 6 trapping periods. Vole numbers and body mass showed strong period- and phase-related variation both in females and males, demonstrating marked Chitty effect in the studied population. Body mass of adult males correlated with body length, evidencing that heavier males are also structurally larger. Statistical models showed that probability of occurrence of large-sized vole (> 37 g) was significantly more likely in reproductive males, during increase and peak phases, and it was modulated by habitat, with crop fields and field margins between crops showing an increased likelihood. We suggest an effect of the habitat on vole body mass mediated by predation.

Sleep characteristics in underweight young females across their menstrual cycles: A sleep-monitoring survey study with preliminary results.

This study investigated the association between underweight and sleep in young females across their menstrual cycles. A lifestyle-monitoring survey was conducted among 38 female university students aged 18-24 years in Japan from January to December 2023. Sleep data from 28 participants were analysed. Participants were categorized into underweight (n = 10) and control (n = 18) groups based on a baseline body mass index cut-off of 18.5 kg m-2. Sleep parameters were assessed using a daily sleep questionnaire, sleep sensor mats, and urinary melatonin metabolites across their menstrual cycles. The results indicated no significant differences in sleep patterns between the underweight and control groups or menstrual cycle phases, as assessed using both the daily sleep questionnaire and the sleep sensor mats. However, underweight participants experienced more difficulty maintaining sleep during the follicular phase. Body mass index significantly correlated with sleep efficiency (rs = 0.52) and wake after sleep onset (rs = -0.56). While urinary melatonin metabolite levels did not differ significantly between the groups or menstrual cycle phases, decreased levels during the luteal phase were more prevalent in the underweight group (7 of 10 participants) than in the control group (3 of 13 participants). This study suggests an association between underweight and sleep quality, especially nocturnal awakening, in young females. These findings underscore the importance of considering sleep quality in the management of underweight young females to improve their overall health outcomes.

Innovating in the Detection of Depression in Young Adults: Development of a Mobile Application Based on the Enhanced Cascade Model

Depression is a disorder that usually begins in early adulthood, having a duration according to the World Health Organization (WHO) from a couple of months to a couple of years, however, in approximately 20% of cases there is a chronic evolution that results in a high mortality rate by suicide due to lack of adequate treatment. Therefore, the objective of this project is to facilitate the tools for an adequate care of depression, mainly in young adults through the development of a mobile application that monitors patients. To carry out the project, the enhanced cascade model was implemented, because the feedback between the different phases of the system development life cycle is important to make the appropriate modifications. The application of interviews and the use of brainstorming were the selected way in which all the system requirements were designed and the goals to be met by the system were adequately defined.

Increased risk of supraventricular tachycardia with polycystic ovarian syndrome

Abstract Background Many arrhythmias are known to be triggered by hormonal imbalances. Polycystic ovarian syndrome (PCOS) is a common hormonal imbalance seen in reproductive aged women. There is sparse literature linking PCOS to increased risk of atrial fibrillation (1). We hypothesise that PCOS could also be associated with Supraventricular tachycardia (SVT) Purpose To determine if PCOS is a risk factor for SVT and Atrial fibrillation/flutter (AF/AFL). Methods Utilising the National Inpatient Sample (NIS) of the years 2015-2020, We performed a multivariable logistic regression analysis to determine if PCOS was independently associated with SVT and AF/AFL. The NIS is the largest publicly available database of United States containing data on upto 7 million hospital visits per year. Results From the years 2015 to 2020, PCOS was present in 367,375 adult patients and SVT was observed in 965, 799 patients. After adjusting for relevant risk factors, PCOS was associated with increased odds of SVT (OR 1.23, 95% CI 1.12-1.36, P&amp;lt;0.001) (Table 1). However, PCOS was not associated with increased odds of atrial fibrillation and atrial flutter (OR 0.72, 95% CI 0.66-0.77, P&amp;lt;0.001) Conclusion SVTs have been clinically observed to be more frequent in the luteal phase of the menstrual cycle due to low estrogen. The high androgen/estrogen ratio seen in PCOS may result in a similar increased risk of SVT in PCOS patients. PCOS is known to increase P wave maximum duration and dispersion, indicating abnormal atrial conduction (2). The negative association between AF/AFL is likely because PCOS is seen more commonly in younger patients, and AF/AFL is a disease of older adults. We recommend further studies in PCOS women to confirm our findings and characterise the mechanisms of SVT.