Determination of the Shortest Route on the Distribution System using Ant Colony Optimization (ACO) Algorithm (Case Study: Alfamidi Palu Branch – PT. Midi Utama Indonesia)

The distribution system of goods is one of the most important parts for every company. The company certainly has many route options to visit, and this is expected to be conducted efficiently in terms of time. In the distribution of goods by Alfamidi company in Palu City which has 51 outlets include into the category of Traveling Salesman Problem (TSP) because of many route options that can be visited. The problem can be solved by employing the Ant Colony Optimization (ACO) method which is one of the algorithms Ant Colony System (ACS). The ACS acquires principles based on the behavior of ant colonies and applies three characteristics to determine the shortest route namely status transition rules, local pheromone renewal and global pheromones. The result showed that the shortest route of the distribution of goods based on the calculation of selected iterations was ant 1 with the shortest total distance obtained 86.98 km.

Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme

Nature has evolved many supramolecular proteins assembled in certain, sometimes even seemingly oversophisticated, morphological manners. The rationale behind such evolutionary efforts is often poorly understood. Here, we provide atomic-resolution insights into how the dynamic building of a structurally complex enzyme with higher order symmetry offers amenability to intricate regulation. We have established the functional coupling between enzymatic activity and protein morphological states of glutamine synthetase (GS), an old multi-subunit enzyme essential for cellular nitrogen metabolism. Cryo-EM structure determination of GS in both the catalytically active and inactive assembly states allows us to reveal an unanticipated self-assembly-induced disorder-order transition paradigm, in which the remote interactions between two subcomplex entities significantly rigidify the otherwise structurally fluctuating active sites, thereby regulating activity. We further show in vivo evidences that how the enzyme morphology transitions could be modulated by cellular factors on demand. Collectively, our data present an example of how assembly status transition offers an avenue for activity modulation, and sharpens our mechanistic understanding of the complex functional and regulatory properties of supramolecular enzymes.

Code Status Transitions in Patients with High-Risk Acute Myeloid Leukemia (AML)

Background: Patients with high-risk AML often experience intensive medical care at the end of life (EOL) such as hospitalization and intensive care unit (ICU) admission. Despite their poor prognosis, patients with AML and their caregivers often have substantial misperceptions of their prognosis, which may lead to difficult code status transitions near the end of life. However, studies examining code status transitions in patients with AML are lacking. Methods: We conducted a mixed-methods study of 200 patients with high-risk AML enrolled in supportive care studies at Massachusetts General Hospital between 2014-2021. High-risk AML was defined as: 1) new diagnosis ≥ 60 years, or 2) relapsed/refractory AML. Two physicians used consensus-driven medical record review to characterize code status transitions from time of diagnosis to death and identify patient, family, and palliative care involvement. Code status was coded as 'full' (confirmed or presumed), 'restricted' (i.e., do not resuscitate), or 'comfort measures only' (CMO). We used logistic regression to explore whether patient factors or features of the code status discussion were associated with the time between the last code status transition and death. Results: At diagnosis of high-risk AML, 86.0% of patients were 'full code' (38.5% presumed, 47.5% confirmed) and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions (range 1-8) during their illness course. Overall, a total of 206 code status transitions were described across the cohort. Median time from diagnosis to first code status transition was 212 days (range 7-4507), and from last transition to death was 2 days (range 0-350). Most of these final code status transitions (71.1%, 81/114) were transitions to CMO near the end of life. Only 60.5% of patients (69/114) who underwent a code status transition participated in their last code status change. In contrast, patients and families participated in 87.7% (100/114) of the last code status transitions and palliative care was involved in 42.1% (48/114). A substantial minority of last code status transitions occurred in the ICU or emergency department (26.3%, 30/114). We identified three processes leading to code status transitions (Table 1): 1) pre-emptive conversations prior to any clinical change (15.6%, 32/206); 2) anticipatory conversations at the time of acute clinical deterioration (32.2%, 66/206); and 3) futility conversations after acute clinical deterioration, focused on withdrawing life-sustaining therapies (51.0%, 105/206). Older age (B = 0.07, P < 0.001), and receipt of non-intensive chemotherapy (B = 1.42, P = 0.003) were associated with a longer time from the last code status transition to death (Table 2). In contrast, futility conversations were associated with shorter time from last code status transition to death (B = -2.84, P < 0.001) compared to pre-emptive or anticipatory conversations. Conclusions: Almost half of patients were "presumed full code" at the time of diagnosis of high-risk AML and most experienced code status transitions at the end of life focused on futility of life-sustaining therapies after acute clinical deterioration. These results suggest that goals of care discussions occur too late in the typical illness course of patients with poor prognosis, high-risk AML. Interventions focused on enhancing patient engagement in timely discussions regarding their end of life care preferences are warranted. Figure 1 Figure 1. Disclosures LeBlanc: AbbVie: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding, Speakers Bureau; Pfizer: Consultancy, Other: Advisory Board; Daiichi-Sankyo: Consultancy, Honoraria, Other: Advisory board; Flatiron: Consultancy, Other: Advisory board; Astellas: Consultancy, Honoraria, Other: Advisory board; American Cancer Society: Research Funding; Jazz Pharmaceuticals: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Advisory board, Research Funding; Agios: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Duke University: Research Funding; Otsuka: Consultancy, Honoraria, Other; NINR/NIH: Research Funding; CareVive: Consultancy, Other, Research Funding; Helsinn: Consultancy, Research Funding; Heron: Consultancy, Honoraria, Other: advisory board; Amgen: Consultancy, Other: travel; UpToDate: Patents & Royalties; Seattle Genetics: Consultancy, Other: Advisory board, Research Funding.

Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme

Nature has evolved many supramolecular proteins assembled in certain morphological manners, sometimes even seemingly oversophisticated. The rationale behind such evolutionary efforts is often poorly understood. Here we provide atomic-resolution insights into how the dynamic building of a structurally complex enzyme with higher-order symmetry offers amenability to intricate allosteric regulation. We have established the functional coupling between enzymatic activity and protein morphological states of glutamine synthetase (GS), an old multi-subunit enzyme essential for cellular nitrogen metabolism. Cryo-EM structure determination of GS in both the catalytically active and inactive assembly states allows us to reveal an unanticipated self-assembly-induced dynamics-driven allosteric paradigm, in which the remote interactions between two GS rings significantly rigidify the otherwise structurally fluctuating active sites, thereby regulating activity. We further show in vivo evidences that how the GS morphology transitions could be modulated by cellular factors on demand. Collectively, our data present an example of how assembly status transition offers an avenue for allosteric modulation, and sharpens our mechanistic understanding of allostery, dynamics, cooperativity, and other complex functional and regulatory properties of supramolecular enzymes.

Morphology And Status Transition Monitoring For Mouse Embryonic Stem Cell Colonies In Virto By LSTM Networks With Progressive Training Using Fluorescence Microscopy Images

Purpose Embryonic stem (ES) cells represent as a cellular resource for basic biological studies and for their uses as medically relevant cells in in vitro studies. Fluorescence microscopy images taken during cell culture are frequently used to manually monitor time-series morphology changes and status transitions of ES cell (ESC) colonies, and to study dynamical pattern formation and heterogeneity distribution within ESC colonies, intrinsic fluctuation and cell-cell cooperativity. Therefore, tracking and furthermore predicting morphology changes and status transitions of ESC colonies is an effective method to monitor culture medium for maintaining ES cells in undifferentiated or early differentiated stage. Methods A P-LSTM (Progressive Long Short-Term Memory) structure is proposed to incorporate some new time-lapse images real-time taken from incubators for a new RNN (Recurrent Neural Networks) training. The P-LSTM can achieve adaptive long- and short- term memories to generate accurate predicted images. On the time-lapse images, entropy and bi-lateral filtering are used to extract the range of every colony to calculate colony morphology. Colony status transitions between consecutive images are calculated by mapping the calculated colony centers and ranges. Results Accuracies for the colony status transition, area and roundness for the 15 predicted (five-hour) future frames calculated from 1500-2500 colonies for respective frames show the effectiveness of the proposed method.Conclusion We proposed an efficient and automatic method to predict and monitor status transitions and morphology changes of mouse ESC colonies in culture using time-lapse fluorescence microscopy images.

The Health Status Transition and Medical Expenditure Evaluation of Elderly Population in China

(1) Background: Because of the rapid expansion of the aging population in China, their health status transition and future medical expenditure have received increasing attention. This paper analyzes the health transition of the elderly and how their health transition impacts medical expenditures. At the same time, feasible policy suggestions are provided to respond to the rising medical expenditure and the demand for social care. (2) Methods: The data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015 and analyzed using the Markov model and the Two-Part model (TPM) to forecast the size of the elderly population and their medical expenditures for the period 2020–2060. (3) Results: The study indicates that: (1) for the elderly with a mild disability, the probability of their health improvement is high; in contrast, for the elderly with a moderate or severe disability, their health deterioration is almost certain; (2) the frequency of the diagnosis and treatments of the elderly is closely related to their health status and medical expenditure; alternatively, as the health status deteriorates, the intensity of the elderly individuals’ acceptance of their diagnosis and treatment increases, and so does the medical expense; (3) the population of the elderly with mild and moderate disability demonstrates an inverted “U”-shape, which reaches a peak around 2048, whereas the elderly with severe disability show linear growth, being the target group for health care; (4) with the population increase of the elderly who have severe disability, the medical expenditure increases significantly and poses a huge threat to medical service supply. Conclusions: It is necessary to provide classified and targeted health care according to the health status of the elderly. In addition, improving the level of medical insurance, establishing a mechanism for sharing medical expenditure, and adjusting the basic demographic structure are all important policy choices.

Code status transitions in patients with high-risk acute myeloid leukemia (AML).

e19009 Background: Patients with high-risk AML often experience aggressive medical care at the end of life (EOL) such as hospitalization and intensive care unit (ICU) admission. Despite this, studies examining code status transitions in this population are lacking. Methods: We conducted a mixed methods study of 107 patients with high-risk AML enrolled in supportive care studies at Massachusetts General Hospital between 2014-2019. High-risk AML was defined as 1) new diagnosis > 60 years or 2) relapsed/refractory AML. Two physicians used consensus-driven medical record review to characterize code status transitions. Code statuses were coded as ‘full’ (confirmed or presumed), ‘restricted’ (i.e., do not resuscitate), or ‘comfort measures only’ (CMO); confirmations of presumed status were not coded as transitions. Results: At diagnosis of high-risk AML, 91.9% of patients were ‘full code’ (48.5% presumed, 43.4% confirmed) and 8.1% had restrictions on life-sustaining therapies. Overall, 55.1% (59/107) of patients experienced a code status transition, with a median of two transitions (range 1-4). Median time from first to last transition was 11 days (range 1-306) and from last transition to death was 1 day (range 0-11). Most of these transitions (79.6%; 48/59) were transitions to CMO near EOL. We identified three processes leading to code status transitions (Table): 1) pre-emptive conversations prior to any clinical change (15.3%; 9/59); 2) anticipatory conversations at the time of acute clinical deterioration (15%; 9/59); and 3) futility conversations after acute clinical deterioration, focused on withdrawing life-sustaining therapy (64.4%; 38/59). Only 55.9% (33/59) of patients participated in their last code status transition and 22.0% (13/59) of these transitions occurred in the ICU or Emergency Room. Conclusions: Most patients with high-risk AML had code status transitions at EOL, often following clinical deterioration that limited their ability to engage in EOL discussions. Interventions to promote earlier and more specific code status conversations are needed to improve patients’ ability to voice their EOL preferences.[Table: see text]

Pre-adolescence DNA methylation is associated with BMI status change from pre- to post-adolescence

Background Previous studies have shown that DNA methylation (DNAm) is associated with body mass index (BMI). However, it is unknown whether DNAm at pre-adolescence is associated with BMI status transition from pre- to post-adolescence. In the Isle of Wight (IoW) birth cohort, genome-wide DNA methylation in whole blood was measured using Illumina Infinium Human450 and EPIC BeadChip arrays in n = 325 subjects, and pre- to post-adolescence BMI transition was classified into four groups: (1) normal to normal, (2) normal to overweight or obese, (3) overweight or obese to normal, and (4) persistent overweight or obese. We used recursive random forest to screen genome-wide Cytosine-phosphate-Guanine (CpG) sites with DNAm potentially associated with BMI transition for each gender, and the association of BMI status transition with DNAm at an earlier age was assessed via logistic regressions. To evaluate gender specificity, interactions between DNAm and gender were included in the model. Findings in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Results In total, 174 candidate CpGs were selected including CpGs from screening and CpGs previously associated correctionally with BMI in children and adults. Of these 174 CpGs, pre-adolescent DNAm of 38 CpGs in the IoW cohort was associated with BMI status transition, including 30 CpGs showing gender-specific associations. Thirteen CpGs showed consistent associations between the IoW cohort and the ALSPAC cohort (11 of which were gender-specific). Conclusion Pre-adolescence DNAm is associated with the change in BMI status from pre- to post-adolescence and such associations are likely to be gender-specific.