Alzheimer’s disease (AD) is a major global health challenge, especially among individuals aged 65 or older. According to population health studies, Turkey has the highest AD prevalence in the Middle East and Europe. To accurately determine the frequencies of common and rare APOE single nucleotide polymorphisms (SNPs) in the Turkish population residing in the Marmara Region, we conducted a retrospective study analyzing APOE variants in 588 individuals referred to the Bursa Uludag University Genetic Diseases Evaluation Center. Molecular genotyping, clinical exome sequencing, bioinformatics analysis, and statistical evaluation were employed to identify APOE polymorphisms and assess their distribution. The study revealed the frequencies of APOE alleles as follows: ε4 at 9.94%, ε2 at 9.18%, and ε3 at 80.68%. The gender-based analysis in our study uncovered a tendency for females to exhibit a higher prevalence of mutant genotypes across various SNPs. The most prevalent haplotype observed was ε3/ε3, while rare APOE SNPs were also identified. These findings align with global observations, underscoring the significance of genetic diversity and gender-specific characteristics in comprehending health disparities and formulating preventive strategies. Full article

Climate is a key driver shaping the distribution pattern of organisms. Cenozoic climate change has led to extensive biota turnover. Untangling the distribution dynamics of a representative lineage of flora can provide deep insights into biodiversity conservation. Diplopanax is a notable relict lineage of the Tertiary mastixioid flora with abundant fossils in the Northern Hemisphere. Diplopanax stachyanthus Hand.-Mazz. is a representative relic lineage of the mastixioid flora, which was once widespread in the Northern Hemisphere of the early Tertiary period, but with only endemic distribution in the (sub)tropical humid forests of East Asia. It offers a unique chance to understand how climatic drivers shape the Boreotropical flora. In this research, we investigated the distribution dynamics of D. stachyanthus at the last glacial maximum (LGM), mid-Holocene (MH), current, and three periods of the future (2041–2060, 2061–2080, and 2081–2100) at four shared socio-economic emissions scenarios pathways. Our results indicated that the Precipitation of the Wettest Quarter (32.6%), the Precipitation of the Driest Quarter (21.2%), and the Precipitation of the Coldest Quarter (17.3%) are the key factors affecting its distribution. The current high suitable distribution areas are primarily in southern China and northern Indo-China. The enforced winter monsoon seasons in East Asia since the late Pliocene period are the key climatic drivers reducing its once widespread distribution in the Northern Hemisphere. Under future scenarios, centroid transfer analysis suggests that its distribution center will shift southwestward, but the potentially suitable habitats in the coastal regions of southern China and northern Indo-China will be lost. These coastal populations should be prioritized for ex situ conservation. Expanding the nature reserve within its long-term stable distribution range in southwest China is an effective strategy for the in situ conservation of the ancient mastixioid flora. Full article

Background: Recent research has identified alternative transcript variants of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) and insulin receptors (INSRs) as potential biomarkers for various types of cancer. The objective of this study was to assess the expression of LMNA/C and INSR transcript variants in peripheral blood mononuclear cells (PBMCs) of leukemia patients to investigate their potential as diagnostic biomarkers. Methods: Quantitative TaqMan reverse transcriptase polymerase chain reaction (RT-qPCR) was utilized to quantify the mRNA levels of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) as well as INSR (IR-A and IR-B) variants in PBMCs obtained from healthy individuals (n = 32) and patients diagnosed with primary leukemias (acute myeloid leukemia (AML): n = 17; acute lymphoblastic leukemia (ALL): n = 8; chronic myeloid leukemia (CML): n = 5; and chronic lymphocytic leukemia (CLL): n = 15). Results: Only LMNA and LMNC transcripts were notably present in PBMCs. Both exhibited significantly decreased expression levels in leukemia patients compared to the healthy control group. Particularly, the LMNC:LMNA ratio was notably higher in AML patients. Interestingly, IR-B expression was not detectable in any of the PBMC samples, precluding the calculation of the IR-A:IR-B ratio as a diagnostic marker. Despite reduced expression across all types of leukemia, IR-A levels remained detectable, indicating its potential involvement in disease progression. Conclusions: This study highlights the distinct expression patterns of LMNA/C and INSR transcript variants in PBMCs of leukemia patients. The LMNC:LMNA ratio shows promise as a potential diagnostic indicator for AML, while further research is necessary to understand the role of IR-A in leukemia pathogenesis and its potential as a therapeutic target. Full article

This current article was dedicated to the determination of the composition of phenolic compounds in extracts of four species of the genus Filipendula in order to establish a connection between the composition of polyphenols and biological effects. A chemical analysis revealed that the composition of the extracts studied depended both on the plant species and its part (leaf or flower) and on the extractant used. All four species of Filipendula were rich sources of phenolic compounds and contained hydrolyzable tannins, condensed tannins, phenolic acids and their derivatives, and flavonoids. The activities included data on those that are most important for creating functional foods with Filipendula plant components: the influence on blood coagulation measured by prothrombin and activated partial thromboplastin time, and on the activity of the digestive enzymes (pancreatic amylase and lipase). It was established that plant species, their parts, and extraction methods contribute meaningfully to biological activity. The most prominent result is as follows: the plant organ determines the selective inhibition of either amylase or lipase; thus, the anticoagulant activities of F. camtschatica and F. stepposa hold promise for health-promoting food formulations associated with general metabolic disorders. Full article

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan–Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression. Full article

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC. Full article

With the discovery of tyrosine kinase inhibitors (TKIs), overall survival in patients with chronic myeloid leukemia (CML) now approaches that of the general population. While these TKIs have proven to be lifesaving, remaining on them lifelong creates both physical and financial burdens for patients. Recently, multiple trials have begun looking into the efficacy of trialing patients off these TKIs to see if they can sustain treatment-free remission (TFR). TFR eligibility is currently limited to a small population of patients with both robust and sustained responses to TKIs. Currently, for those who attempt a trial of TFR, the average success rates are promising, with anywhere from 38 to 54% of patients experiencing sustained TFR. For those who fail to maintain sustained TFR, safety results to date are reassuring, with almost all patients successfully responding to the re-initiation of TKIs, with death and disease progression being very rare complications. Moving forward, research is being conducted to more accurately risk stratify patients at diagnosis and pair them with optimized upfront treatment regimens aimed at increasing candidacy for the trial of TFR. Full article

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver—MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis—MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C. Full article

With the continuous development of rural revitalization and urbanization in China, the sustainable transformation of traditional rural architecture has become increasingly important. This study takes the Thangka exhibition hall in rural Malkang, Sichuan Province, as the research object and proposes a Thangka exhibition hall architectural design centered around solar heating and aiming for near-zero energy consumption. The research method involves establishing a solar energy system model on the roof of the exhibition hall and utilizing solar angle and area calculation formulas along with simulation software to calculate the optimal installation angle and area of solar panels, with the aim of achieving indoor temperatures that meet Thangka protection requirements while achieving zero-energy heating. Preliminary results indicate that this solar-centric near-zero energy architectural design can effectively promote the increase in indoor temperature through solar thermal conversion. Additionally, through calculation and simulation, the optimal installation angle for the solar panels achieving zero-energy heating is determined to be 24.25 with an azimuth angle of −1.2. The optimum installation area for solar panels is 8.2 square meters in the showroom and 2.7 square meters in the storeroom. Among these, the solar panel area for the Thangka exhibition hall constitutes 4.12% of the total area and is required for maintaining Thangka protection temperature requirements throughout the year, while the solar panel area for the storage room constitutes 1.88% and is also needed for the same purpose. Studying the optimal installation angle and area of solar panels can transform the exhibition hall into a near-zero-energy building, meeting the temperature requirements for Thangka preservation and human thermal comfort, while also achieving optimal economic benefits. This provides guidance and a reference for promoting near-zero-energy buildings in rural areas. Full article

Plant extracts can be a valuable source of biologically active compounds in many cosmetic preparations. Their effect depends on the phytochemicals they contain and their ability to penetrate the skin. Therefore, in this study, the possibility of skin penetration by phenolic acids contained in dogwood extracts of different fruit colors (yellow, red, and dark ruby red) prepared using different extractants was investigated. These analyses were performed using a Franz chamber and HPLC-UV chromatography. Moreover, the antioxidant properties of the tested extracts were compared and their impact on the intracellular level of free radicals in skin cells was assessed. The cytotoxicity of these extracts towards keratinocytes and fibroblasts was also analyzed and their anti-inflammatory properties were assessed using the enzyme-linked immunosorbent assay (ELISA). The analyses showed differences in the penetration of individual phenolic acids into the skin and different biological activities of the tested extracts. None of the extracts had cytotoxic effects on skin cells in vitro, and the strongest antioxidant and anti-inflammatory properties were found in dogwood extracts with dark ruby red fruits. Full article

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 μg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin’s bioactivity mirrored the extract’s effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low μM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract’s biological activities. This study is the first to explore ellagitannins’ potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies. Full article

This research work is based on a previous study by the authors that characterized the behavior of FBG sensors with a polyimide coating in a structural monitoring system. Sensors applied to structural health monitoring are affected by the presence of simultaneous multidirectional strains. The previous study observed the influence of the transverse strain (${\epsilon }_y$) while keeping the longitudinal strain constant (${\epsilon }_x$), where the x direction is the direction of the optical fiber. The present study develops an experimental methodology consisting of a biaxial test plan on cruciform specimens with three embedded FBG sensors coated with polyimide, acrylate, and ORMOCER^®. Applying the Strain–Optic Theory as a reference, a comparison of the experimental values obtained with the different coatings was studied. This experimental work made it possible to study the influence of the transverse strain (${\epsilon }_y$) on the longitudinal measurements of each FBGS and the influence of the coating material. Finally, the calibration procedure was defined as well as $K$ (strain sensitivity factor) for each sensor. Full article

China faces severe water resource shortages due to the uneven distribution of water resources and ever-increasing water demand driven by rapid industrialization and urbanization. The virtual water trade (VWT) is a potential solution to conserve water resources by transferring water from water-abundant/water-productive regions to water-scarce/less water-productive regions. Based on the inter-provincial input-output model, the provincial VWT of China was estimated at the sectoral level. The relationship of VWT with water resources in 30 provinces was analyzed in relation to the water stress index (WSI). It was found that (1) total inter-provincial VW trade showed a downward trend during the study period, with 363.91 km³ in 2002, 283.72 km³ in 2007, and 285.23 km³ in 2012. Overall, the primary industry dominated the VWT for most provinces. (2) China’s virtual water flowed from the relatively underdeveloped central and western regions to the east with a relatively developed economy from the inter-provincial level. This trend became increasingly prominent. (3) In many instances, VW was transferred from water-poor to water-rich areas. These results imply that China needs to improve its water use efficiency and optimize its regional industrial structure. Additionally, establishing an ecological compensation mechanism is considered a valuable measure for China to alleviate regional water resource pressure. Full article

Background: Sleep quality is known to affect automatic and executive brain functions such as gait control and cognitive processing. This study aimed to investigate the effect of dual tasks on gait spatiotemporal parameters among young adults with good and poor sleep quality. Methods: In total, 65 young adults with a mean age of 21.1 ± 2.5 were assessed for gait analysis during single-task and dual-task conditions. The participants’ sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and gait was assessed using the BTS Gaitlab System. The participants were asked to walk at natural speed as a single-task condition, followed by walking while performing a cognitive task as a dual-task condition. The parameters assessed included the gait velocity (m/s), cadence (steps/min), step width (m), and stride length (m). The dual-task cost (DTC) on each gait parameter was calculated. The Mann–Whitney U test was used to compare the differences in the DTC on gait variables between the good and poor sleep quality groups and the Spearman correlation test was used to assess the correlation between total PSQI scores and the DTC. Results: At a significance level of p < 0.05, a significant difference in cadence between the two sleep quality groups was observed, in addition to a positive correlation between sleep quality and the DTC effect on gait mean velocity, cadence, and stride length. Our findings also revealed a greater DTC in participants with poorer sleep quality. Conclusions: These findings contribute to our perception of the significance of sleep quality in gait performance while multitasking in younger populations. Full article

Science has been an incredibly powerful and revolutionary force. However, it is not clear whether science is suited to performance under pressure; generally, science achieves best in its usual comfort zone of patience, caution, and slowness. But, if science is organized knowledge and acts as a guiding force for making informed decisions, it is important to understand how science and scientists perform as a reliable and valuable institution in a global crisis. This paper provides insights and reflections based on the experience of the COVID-19 pandemic and from an analytical perspective. In particular, we analyze aspects such as speed, transparency, trust, data sharing, scientists in the political arena, and the psychology of scientists—all of which are areas inviting more detailed investigations by future studies conducting systematic empirical studies. Full article

The binary nature of life is deeply ingrained in daily experiences, evident in the stark distinctions between life and death and the living and the inert. While this binary perspective aligns with disciplines like medicine and much of biology, uncertainties emerge in fields such as microbiology, virology, synthetic biology, and systems chemistry, where intermediate entities challenge straightforward classification as living or non-living. This contribution explores the motivations behind both binary and non-binary conceptualizations of life. Despite the perceived necessity to unequivocally define life, especially in the context of origin of life research and astrobiology, mounting evidence indicates a gray area between what is intuitively clearly alive and what is distinctly not alive. This prompts consideration of a gradualist perspective, depicting life as a spectrum with varying degrees of “lifeness”. Given the current state of science, the existence or not of a definite threshold remains open. Nevertheless, shifts in epistemic granularity and epistemic perspective influence the framing of the question, and scientific advancements narrow down possible answers: if a threshold exists, it can only be at a finer level than what is intuitively taken as living or non-living. This underscores the need for a more refined distinction between the inanimate and the living. Full article

In the field of maritime traffic management, overcoming the challenges of low prediction accuracy and computational inefficiency in ship trajectory prediction is crucial for collision avoidance. This paper presents an advanced solution using a deep bidirectional long- and short-term memory network (BILSTM) and the Optuna hyperparameter automatic optimized framework. Utilizing automatic identification system (AIS) data to analyze ship navigation patterns, the study applies Optuna to fine-tune the hyperparameters of the BILSTM network to improve prediction accuracy and efficiency. The developed Optuna–BILSTM model shows a remarkable 7% increase in prediction accuracy over traditional back propagation (BP) neural networks and standard BILSTM models. These results not only improve ship navigation and safety but also have significant implications for the development of autonomous ship collision avoidance systems, marking a significant step toward safer and more efficient maritime traffic management. Full article

Lactic acid bacteria Ligilactobacillus salivarius has been shown to be a substitute for antibiotics in the treatment of bacterial disease in high animals. However, its beneficial mechanism in fish farming is still unclear. This study evaluated the antagonistic effects of the Ligilactobacillus salivarius GX118 strain on Aeromonas salmonicida and its regulation of rainbow trout growth in vivo and in vitro. The results found that GX118 produces an antibacterial substance that can directly destroy the cell wall of A. salmonicida. Whole-genome sequencing of GX118 revealed that Enterolysin A is a type III bacteriocin with antibacterial properties. An in vivo experiment showed that the supplementation of GX118 in diet competitively inhibited the colonization of A. salmonicida in the intestine. In addition, it was able to improve the growth performance of rainbow trout within a 21-day feeding experiment. The supplementation of GX118 increased the diversity of gut microbiota, in which the abundance of Bacteroidota, Blautia, and Rhodobacteraceae increased. In addition, the use of GX118 activated the expression of IFN-γ and NF-κB genes and reduced the expression level of IL-6 and IL-8, thus exhibiting a certain effect on activating the immunity of rainbow trout. This study provides a scientific basis for the development of antibacterial probiotics in the healthy farming of rainbow trout. Full article

Background: The advancement of multidisciplinary treatment has increased the need to develop tests to monitor tumor burden during treatment. We herein analyzed urinary microRNAs within extracellular vesicles from patients with esophageal squamous cell carcinoma (ESCC) and normal individuals using a microarray. Methods: Patients with advanced ESCC who underwent esophagectomy (A), endoscopic submucosal resection (ESD) (B), and healthy donors (C) were included. Based on microRNA expression among the groups (Analysis 1), microRNAs with significant differences between groups A and C were selected (Analysis 2). Of these candidates, microRNAs in which the change between A and C was consistent with the change between B and C were selected for downstream analysis (Analysis 3). Finally, microRNA expression was validated in patients with recurrence from A (exploratory analysis). Results: For analysis 1, 205 microRNAs were selected. For Analyses 2 and 3, the changes in 18 microRNAs were consistent with changes in tumor burden as determined by clinical imaging and pathological findings. The AUC for the detection of ESCC using 18 microRNAs was 0.72. In exploratory analysis, three of eighteen microRNAs exhibited a concordant trend with recurrence. Conclusions: The current study identified the urinary microRNAs which were significantly expressed in ESCC patients. Validation study is warranted to evaluate whether these microRNAs could reflect tumor burden during multidisciplinary treatment for ESCC. Full article

Diacylhydrazine is thermally and chemically stable, and it remains inert to oxygen even at high temperatures. However, it is rapidly oxidized by sodium hypochlorite, leading to its decomposition into carboxylic acid and nitrogen gas. In the synthesis of a novel poly(diacylhydrazine) as an oxidatively degradable polymer, L-leucine methyl ester is acylated by terephthaloyl chloride. Subsequent hydrazination yields a bishydrazide monomer. The oxidative coupling polymerization of this monomer produces poly(diacylhydrazine). The molecular structures of the products are confirmed by an ¹H NMR analysis. A polymodal molecular weight distribution and a large polydispersity index are observed by GPC in all cases. A 10% weight loss temperature is noted at 286 °C in air by TGA. The obtained polymer is not oxidized by oxygen. No glass transition is observed below the decomposition temperature. Upon the treatment of the poly(diacylhydrazine) with sodium hypochlorite solution, decomposition occurs rapidly, resulting in monomeric carboxylic acid and nitrogen gas. The L-leucine-based poly(diacylhydrazine) serves as a novel on-demand degradable polymer with high levels of thermal and chemical stability during usage. Full article

In this paper, the global distribution of precipitation for 2023, in terms of global totals and regional anomaly patterns, is analyzed using information from the new Global Precipitation Climatology Project (GPCP) V3.2 Monthly product, including how the precipitation amounts and patterns from 2023 fit into the longer record from 1983–2023. The tropical pattern of anomalies for 2023 is dominated by the effect of the El Nino which began during the Northern Hemisphere spring, after three plus years of La Nina conditions. The transition from La Nina conditions through 2022 shows the rapid change in many regional features from positive to negative anomalies or the reverse. Comparison of the observed regional trend maps with climate model results indicates similarity between the observations and the model results forced by observed SSTs, while the “free-running” model ensemble shows only a broad general agreement over large regions. Global total precipitation shows about a 3% range over the span of data, with El Nino and La Nina years prominent as positive and negative features, with 2023 showing a small positive global anomaly. The ITCZ (Inter-Tropical Convergence Zone) latitude band, 0–10° N, sets a record high mean rain rate in 2023 after a steady upward trend over the decades, probably a response related to global warming. Full article

Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition. Full article