It is generally believed that sedentary behavior (SB) increases the risk of falls among older adults, but the evidence for it remains inconsistent and scarce.Our study aims to provide a systematic review and meta-analysis of available evidence regarding the association of SB with falls in older adults.A comprehensive search strategy was conducted using several online databases from 1906 to March 2022. Cohort studies both concerning the association between SB and falls and involving participants over 60 years old were regarded as eligible for inclusion. Evidence was pooled by a random-effects meta-analysis. Quality assessment for individual studies was performed with the Newcastle–Ottawa Scale (NOS).I2 = 46.90%, Pheterogeneity = 0.07, random model]. Subgroup analyses that stratified the studies according to NOS score showed significant differences between groups. Subgroup analysis stratified by SB measurement, sample size, region, publication year, and follow-up duration showed no significant differences between groups.Altogether seven publications were identified, and the age of the 24,750 individuals involved ranging from 60 to 99 years old. Overall quality of the included studies was rated as moderate-to-high quality. We found that SB was significantly associated with increased risk of falls compared with non-SB among older adults [Odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.07–1.28; The findings provide reliable support for the hypothesis that sedentary lifestyles are strong predictors of falls among older adults, offering critical indications to develop strategies for fall prevention. The incidence of falls increases with age, usually due to age-related issues . Falls and fall-related injuries are common for older adults , and areSince the outbreak of the COVID-19, people's range of motion has been more restricted, especially for the elderly, who are even less active than before, which leads to more frequent sedentary behavior , 7. SedeDespite the growing interest in the association between SB and fall risks , problemThis meta-analysis was conducted following the Cochrane Collaboration Handbook recommendations . We use via PubMed), EMBASE, Web of Science, Chinese BioMedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure and WanFang Database (search strategy conducted from their 1906 to March 2022). After combining medical subject heading terms and keywords, Boolean logic operators were used to widen the scope of literature search. The items and their combinations used are as follows: “sedentary behavior,” “physical inactivity,” “older adults,” “falls,” and “sedentary lifestyle.” All specific search strategies are provided in the supplementary search strategy in production forum  was used to import and manage all citations, and a third specialist got involved when different opinions between the two investigators emerged. Duplicates were deleted automatically and evaluation of the titles and abstracts was carried out respectively by the two authors. Subsequently, a further full-text evaluation was made to ensure the studies' accuracy and integrity.The following criteria were used to select studies: (1) The study design involved only cohort studies; (2) PICOS principles were used for inclusion and exclusion of literature; (3) the study population was older adults (≥60 years old); (4) The exposure factors included any type of SB, such as mobility limitation, physical inactivity, screen time, reclining, mobility limitation, seated position, watching TV, card-playing, and sitting. We chose the SB group with the highest level as a reference category when studies reported multiple categories of SB levels; (5) The measurement strategies of SB were either subjective measurement  or objective measurement .All the basic information extracted from the included studies is as follows: publication year, name of the first author, follow-up time, age, sample size, gender ratio, measurement of falls, study design, definition of sedentary factor and covariates of physical activity. When publications did not report essential data, we contacted the first author to obtain detailed data.We assessed the quality of cohort studies by the Newcastle-Ottawa Scale (NOS) , which iP-value  and I2 statistic with values of 25, 50, and 75% representing low, moderate, and high heterogeneity, separately . Additionally, a sensitivity analysis was conducted to exclude the studies with a higher risk of bias. A subgroup analysis was performed to identify potential sources of heterogeneity or to explore statistically significant differences across studies. The items of subgroup analyses were as follows: SB measurement (accelerometer vs. non-accelerometer), total sample size , region , year of publication (publication year ≥2013 vs. publication year <2013), NOS quality of included studies (score ≥6 points vs. score <6 points), follow-up duration (>1 vs. ≤ 1 year) (Table 2). All the data analyses mentioned above were conducted using STATA software version 14.0 .For all comparisons, we performed a conventional pairwise meta-analysis using random effects . For theparately . The pube < 0.05  ] was significantly lower than that of the female . The follow-up time ranged from 1 to 6 years, with a median follow-up time of 2 years. SB was measured by the accelerometer and various questionnaires such as the international physical activity questionnaire (IPAQ) and women's health initiative physical activity questionnaire (WHIPAQ). Further characteristics of the included studies were summarized in Quality assessment of the included studies was done by NOS in I2 = 46.90%, P = 0.07, random model)  were analyzed to discover the association between SB and falls among older adults. The pooled effect size (OR) was 1.17 (95% CI: 1.07–1.28), with moderate heterogeneity (m model) , which r = 0.11) . PA was  = 0.11) , 32 and  = 0.11) , 28–31.I2 = 55.10%, P < 0.05, random model) saw a notable increase of heterogeneity compared with the NOS score <6 . Details of pooled effect size for subgroup analyses were based on the random model, respectively, as shown in Based on the primary outcome, the subgroup analyses were conducted with different variables  of interest to explore the possible source of heterogeneity, and most of them yielded consistency that failed to reveal the source of heterogeneity. Nevertheless, when the items of NOS quality were taken into consideration, the NOS score ≥6  and 1.22 (95% CI: 1.09–1.36). It showed that the association between SB and falls changed after the exclusion of three studies –32, indiOur study found that older adults with SB present with a higher risk of fall compared to those without, which was consistent with the results of previous studies. We also found that the effect of sedentary behavior on falls in the elderly was not influenced by regional divisions.n = 11,761) focusing on SB and falls of postmenopausal women, a logistic regression model was conducted to determine the odds of falling based on the baseline of sedentary time, physical activity duration, and change of physical activity category within 6 years, which showed that SB (0-3METs) was associated with odds of falling (P = 0.04), but increasing activity up to ≥9 MET-h/week can also increase the risk of falling . Recent studies also revealed consistent results with ours , 32. A l falling . Some me falling , which c falling  and then falling , resulti falling , a commo falling . Some st falling , 37, whi falling , reducti falling , and dec falling , thereby falling , and the falling , both ofI2 fluctuated especially in groups of stratification by SB measurement and region. The focus of future studies can be assessment technology to measure SB objectively, such as an accelerometer, a wearable device that enables continuous and precise monitoring of the multiaxial accelerations of body movement in patients. With the help of it, a higher level of reliability can be achieved compared with traditional self-report questionnaires  does not always mean low physical activity . Typically, for older adults, a cut point of ≤ 1.5 METs is used to distinguish sedentary behavior from light physical activity . Low phyIt is found that there is a positive association between SB and falls among older adults, which serves as an important step forward for considering SB as a modifiable risk factor for falls in older adults. Reducing SB can help reduce the level of falls and improve the quality of life of older adults. Therefore, older adults should be encouraged to reduce sedentary behavior and engage in appropriate physical activity. Considering the quantity and quality of the included studies, our conclusion needs to be interpreted with caution. In addition, given the rising prevalence of falls and universal SB in modern society, the results of our study provide valuable insights into promoting clinical and public health. In the future, more longitudinal studies should be conducted to better demonstrate the relationship between sedentary behavior and falls in older adults.The original contributions presented in the study are included in the article/YJ served as the principal author and had full access to all the data in the study, taking responsibility for the analysis and interpretation of data, and the acquisition of the data analysis. XY contributed to the study's conception and design. SL and GD contributed to data acquisition of data. MW contributed to the draft of the manuscript. ZW contributed to the critical revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Arabidopsis, the expression of the mercuric ion-binding protein in Bacillus megaterium improves the metal accumulation capacity. The phytoremediation efficiency of plants is also enhanced when assisted with microorganisms, biochar, and/or chemicals. Removing heavy metals from agricultural land without challenging food security is almost impossible. As a result, crop selections with the ability to sequester heavy metals and provide food security are in high demand. This paper summarizes the role of plant proteins and plant–microbe interaction in remediating soils contaminated with heavy metals. Biotechnological approaches or genetic engineering can also be used to tackle the problem of heavy metal contamination.The contamination of soils with heavy metals and its associated hazardous effects are a thrust area of today’s research. Rapid industrialization, emissions from automobiles, agricultural inputs, improper disposal of waste, etc., are the major causes of soil contamination with heavy metals. These contaminants not only contaminate soil but also groundwater, reducing agricultural land and hence food quality. These contaminants enter the food chain and have a severe effect on human health. It is important to remove these contaminants from the soil. Various economic and ecological strategies are required to restore the soils contaminated with heavy metals. Phytoremediation is an emerging technology that is non-invasive, cost-effective, and aesthetically pleasing. Many metal-binding proteins (MBPs) of the plants are significantly involved in the phytoremediation of heavy metals; the MBPs include metallothioneins; phytochelatins; metalloenzymes; metal-activated enzymes; and many metal storage proteins, carrier proteins, and channel proteins. Plants are genetically modified to enhance their phytoremediation capacity. In  Some common technologies are chemical reduction, electrophoresis, excavation, pneumatic fracturing, soil washing, soil flushing, solidification, and nitrification  are now hazardous to the environment globally and lead to a negative impact on human health. Due to their persistence in the environment for very long periods, such as for many hundreds to thousands of years, they negatively impact human and animal health . Long-tefication . All of fication .The conventional methods of removing pollutants from the environment are associated with numerous issues, such as partial removal, needing high energy, producing a significant amount of toxic sludge, being limited to a small area, and being costly . The ecoOver the last 10 years, a rapidly emerging, economically sound, and environmentally supportive alternative to traditional remediation practices has gained attention. This technique, known as “phytoremediation,” uses plants to clean up the environment as they can extract, accumulate, and depollute the substrate  from the contaminants through physical, chemical, or biological processes.Several soil and plant factors influence phytoremediation efficiency, including chemical and physical soil properties, exudates from plants and microbes, metal bioavailability, and the plant ability to “uptake, accumulate, translocate, sequester, and detoxify metals” . BioremeUnderstanding the mechanisms of how plants tolerate a specific metal is critical for increasing the number of plants that can be used for the phytoremediation of heavy metal–polluted sites. Various metal-binding proteins (MBPs) in the plants are involved in the absorption, accumulation, translocation, and detoxification of heavy metals and hence provide tolerance to the plants . The MBPThe selection criteria for the plants used in phytoremediation are that they should be highly metal tolerant and have a short life cycle, broad distribution, large biomass, and a translocation factor (TF) greater than 1 . Some plThe phytoremediation of heavy metal–contaminated soil includes any one mechanism or a combination of two or more phytoremediation mechanisms. The phytoremediation mechanisms mainly involved phytoextraction, phytostabilization, phytovolatilization, and rhizofiltration Figure 1in situ, collect the heavy metal–containing biomass, and treat it to minimize its mass and size, which can be achieved through composting, compressing, dehydrating, and thermal decomposition. The resultant heavy metal–enriched biomass contains high levels of metal contaminants and, if economically feasible, is utilized for trace element reextraction or disposed of as carefully hazardous waste  of Cr(VI), can accumulate 82.8% of Cr(VI) and 40.4% of As(III) of the initial amount of 3 and 6 ppm, respectively (Zea mays L.). This potential was also increased with the addition of the metal chelating agent EDTA, which enhances more than 13-fold extraction of Pb and more than 3-fold extraction of Cd. Phytoaccumulation capacity for Cu contamination by three different lettuces  was investigated by −1, while, in shoot tissue, it was 0.71 mg kg−1, which is relatively high among these three lettuces.Plants uptake pollutants from soil, water, or sediments by their roots and transfer them to the aboveground biomass where they accumulate, such as in shoots or other harvestable parts of the plant. This is known as phytoextraction . Plants us waste . Lemna ved water . Bixa orectively . Suthar Scariola orientalis can be used as an efficient plant species in the phytoremediation (phytostabilization) of soils polluted with Zn and Fe. The level of heavy metal Cd in the rice grain can be reduced to improve the food quality. Cd levels in harvested rice (Oryza sativa L.) grains dramatically decreased in the Cd-contaminated fields when rice was intercropped with the alligator flag . This reduction was accomplished because the fine roots of the alligator flag absorb a high quantity of Cd from the rice’s rhizosphere soil, lowering the rice’s Cd intake , Indian mustard (Brassica juncea), and Arabidopsis thaliana, have been shown to absorb heavy metals and transform them to gaseous forms within the plant before releasing them into the environment . Approximately 25% remained in the sand, and only approximately 0.15% accumulated in the plant (+3) and arsenate (As+5). Formerly, it was believed that the microorganisms and enzymes reduced and methylated the arsenite and arsenate within the plants. Two As species, trimethylated and dimethylated As, were easily evaporated from the plants’ aerial parts (3)2Se (3)2Se], dimethyl selenone [(CH3)2SeO2], dimethyl selenylsulfide [(CH3)2SeS], and methaneselenol (CH3Se) are also released by plants from the soil 2Se . Dimethythe soil . The phythe soil . Plants ile form .Z. mays L. was evaluated , Pistia (water lettuce), and Eichhornia (water hyacinth) have different phytoremediation properties. Pistia has a good capacity for the phytoextraction and phytostabilization of As, Pb, and F, while, Eichhornia and Azolla effectively absorb Ni and Cu from the contaminated water. The TF of Pistia for fluoride is 5.0, making it an excellent hyperaccumulator of fluoride  is possible . Long-rovaluated  and repoediation . Three vfluoride .Several MBPs have been reported in plants, which include MTs; PCs; metalloenzymes (MEs); metal-activated enzymes; and many metal storage proteins, carrier proteins, and channel proteins . AdditioL. minor, was evaluated for its phytoremediation capacity. PC species with a higher degree of polymerization  accumulated more Cd than PC species with a lower degree of polymerization (PC2 and PC3)  .Cicer arietinum is part of the P1 subfamily, together with MT1a and MT1c from A. thaliana. On the other hand, the MT2 gene from C. arietinum is part of the P2 subfamily, along with MT2a and MT2b from A. thaliana. Musa acuminate and A. thaliana MT3 are both members of the P3 subfamily. Members of the ‘pec’ subfamily include A. thaliana MT4a (Ec-2) and MT4b (Ec-1), in addition to Ec-1 from T. aestivum. There are four different kinds of MT-encoding genes, and these genes may be found in Arabidopsis, rice, and sugarcane  , metal tolerance proteins (MTPs), and natural resistance–associated macrophage proteins (NRAMPs) . The HMAs (CAXs) .A. thaliana and rice. In the present review, literature available on the other crops is also reviewed.Literature on the phytoremediation ability of cereal crops is sparingly available, although studies are mainly focused on the model plant The elevated level of the heavy metal in the contaminated soil induced the expression of glutathione S-transferases (GSTs) and GSH in rice, which quenches the reactive molecules that induce the biosynthesis of the PCs. The PCs make a complex with the As, and the complex is sequestered into the vacuoles by ABCC1/ABCC2 transporters. Therefore, GST is involved in arsenic detoxification . LocalizZmMTs gene under heavy metal stresses  regulated by the hormones and MT synthesis improves the growth and development of the maize plants  was inoculated under As stress and enhanced the As-phytoremediation ability of both plants  gene under Cd stress and Pb stress , high porosity (0.0–1.32 cm3 g1), and a specific surface area that ranges from 10 to 400 m2 g1. The COOH, –CO–, –OH, and ester groups are all found on the surface of biochar, and their presence boosts the CEC and adsorption while simultaneously lowering the leachability of nutrients  to Amaranthus hypochondriacus under different Cd stress conditions reduces the cell membrane damage and provides tolerance to Cd toxicity. The application of ‘rutin’ can immobilize the Cd in the cell wall, and a less amount of Cd is transported to the vacuole; it also enhances the synthesis of GSH and conversion of GSH to PCs. The rutin enhances the phytoextraction capacity of Cd in A. hypochondriacus (219%–260%) (Tagetes patula L. improves the plant biomass and accumulation of cadmium (Cd). Plants can withstand Cd stress as well as can remediate contaminated soil; T. patula L. removes 12.9% of Cd from the contaminated agricultural land when GLDA is applied to the soil  . The appthe soil .via genetic engineering. Plant species can be developed by gene transfer and gene editing focusing on metal absorption and transport processes involving PC and MT proteins  of Bacillus megaterium and reported the excellent metal-accumulating capability of Arabidopsis. Genetically modified rice plants were reported to accumulate more Cd in their root than shoot under the overexpression of the rice V-PPase  under particular stress conditions is required for further study for effective remediation of contaminated soil.The tolerance of heavy metal stress in plants is a defining characteristic of both their capacity to protect themselves and their efficient remediation systems. Utilizing model crops has provided several benefits in recent years for a better understanding of the biosynthesis, function, expression, and regulation of MT and PC. Even though several studies have shown that plant MTs play a significant role, we still have a long way to go before we can determine all of the tasks that MTs do. Their capacity to connect with a wide variety of metals, which results in a wide variety of functions, is shown by the enormous diversity that exists in the areas of metal binding in plant MTs compared to those in animal MTs. In via the use of genome sequencing might pave the way for the construction of transgenics with desirable characteristics that can be employed in phytoextraction technology. These findings, in association with considerable evolutionary research conducted across putative genes related to heavy metal tolerance, could provide some encouraging outcomes.An emerging field of study and one with significant potential for commercial use is the creation of transgenic plants with an outstanding capacity to chelate certain metals and prevent the deleterious effects of these metals. In the future, the bioremediation of polluted places may benefit from the coordinated use of traditional breeding techniques in combination with molecular biology. Additionally, the identification of genes associated with metal tolerance All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Plant polyphenols have many potential applications, for example, in the fields of chemical ecology and human and animal health and nutrition. These biological benefits are related to their bioavailability, bioaccessibility and interactions with other biomolecules, such as proteins, lipids, fibers and amino acids. Polyphenol–protein interactions are well-studied, but less is known about their interactions with lipids and cell membranes. However, the affinity of polyphenols for lipid bilayers partially determines their biological activity and is also important from the usability perspective. The polyphenol–lipid interactions can be studied with several chemical tools including, among others, partition coefficient measurements, calorimetric methods, spectroscopic techniques and molecular dynamics simulation. Polyphenols can variably interact with and penetrate lipid bilayers depending on the structures and concentrations of the polyphenols, the compositions of the lipids and the ambient conditions and factors. Polyphenol penetrating the lipid bilayer can perturb and cause changes in its structure and biophysical properties. The current studies have used structurally different polyphenols, diverse model lipids and various measuring techniques. This approach provides detailed information on polyphenol–lipid interactions, but there is much variability, and the results may even be contradictory, for example, in relation to the locations and orientations of the polyphenols in the lipid bilayers. Nevertheless, by using well-characterized model polyphenols and lipids systematically and combining the results obtained with several techniques within a study, it is possible to create a good overall picture of these fascinating interactions. Polyphenols are plant specialized metabolites  having antioxidant, anticarcinogenic, antitumoral, antiviral, antimicrobial, anti-inflammatory and anti-fibrillogenic properties; they derive exclusively from the shikimate-derived phenylpropanoid or polyketide pathways, feature more than one phenolic ring and are devoid of any nitrogen-based functional group . PolyphePlant polyphenols have been intensively investigated due to their potential positive health effects and the possibility of using them in animal nutrition and health ,7,8,9,10Polyphenols are known to have interactions with all macromolecules: proteins, carbohydrates, lipids and amino acids. The polyphenol–protein interactions, especially tannin–protein interactions, are well-known . The intLipids are molecules that are classically thought to comprise a hydrophilic head and two hydrophobic tails . HoweverE. coli [The size of vesicles can be confirmed by dynamic light scattering (DLS) analysis ,29 or byE. coli ,34; the E. coli ; egg L-αE. coli ,35 and cE. coli . LiposomE. coli , and theE. coli .As mentioned above, the interactions between polyphenols, especially tannins, and proteins are very well studied, and the interactions of polyphenols with membrane lipids in vitro and the related challenges are also known ,27; howeThe methods used to study polyphenol–lipid interactions vary from simple partition coefficient measurements to more detailed calorimetric, spectroscopic and computational techniques. There are also less commonly used techniques, such as noncovalent immobilized artificial membrane chromatography  and elecn-octanol-water (owK), have been traditionally used to study the physicochemical properties of polyphenols [owK coefficients, tend to be more easily absorbed into tissues [Partition coefficient measurements in biphasic solvent systems, such as yphenols . Hydrophyphenols . The samyphenols . The com tissues ,44.owK method is relatively simple as the polyphenol studied is dissolved in an octanol–water system and allowed to equilibrate, after which both phases are analyzed by high- or ultrahigh-performance liquid chromatography with UV detection [owK coefficients can be calculated from the ratio of the peak area in the water-saturated octanol phase to the peak area in the octanol-saturated water phase. In some cases, owK measurements have been performed so that the concentration of the analyte was analyzed in only one of the phases (either octanol or water) and in the initial stock solution before the analyte concentration in the unanalyzed phase was calculated as their difference. This approach might ignore the recovery of the analyte due to poor solubility or other issues. Therefore, the initial sample and the samples from both the water and octanol phases should be analyzed in order to determine the recovery rate of the polyphenol studied and transition to both phases accurately [owK can also be measured using simple 1H nuclear magnetic resonance (NMR), where the partitioning between water and octanol is performed in an NMR tube and the aqueous phase is then analyzed by NMR provided that the analyte is sufficiently soluble in water [p values can be determined by in silico predictions using structure-based computational tools such as AlogP, Molinspiration and COSMOtherm [The traditional etection ,44,45. Kcurately ,45. Kow in water . In addiSMOtherm . These mSMOtherm . In geneSMOtherm .owK coefficients seem to vary between studies [owK than polar flavonoid glycosides, and PA gallates are more hydrophobic than PAs [Published  studies . This is studies ,48. In gthan PAs ,44. The than PAs ,48. Howethan PAs ,49. The than PAs .pK [The partition coefficients of polyphenols can also be evaluated in membrane models by determining the partition of polyphenols between the model lipid membranes and the aqueous phase as Kp ,50,51. TKp ,50. The Kp . In thisKp ,52. In aowK model [The octanol–water and liposome–water partitioning models have been compared using 66 drugs . For theow model . Similarow model . These cn; the binding constant aK; and the enthalpy of the binding ΔH, thereby also allowing for determining the entropy ΔS, the Gibbs free energy change ΔG, and the heat capacity change ΔCp [Escherichia coli [The thermodynamics of the polyphenol–lipid interaction can be studied and the related thermodynamic binding parameters determined by calorimetric techniques. Isothermal titration calorimetry ITC, A is a teange ΔCp ,55. ITC ange ΔCp ,60,61,62hia coli . In thishia coli .n, aK and ΔH. However, these are not always easy to obtain, and experimental compromises are needed that can cause challenges in later data interpretation and fits. In any case, for correct results, the concentrations of ligand and macromolecules need to be accurately known [In a typical ITC measurement, the lipid solution is placed in the sample cell of the calorimeter, and the polyphenol solution is titrated into the lipid incrementally ,54,64. Tly known , althougc/Lα transitions [Differential scanning calorimetry (DSC), like ITC, is used for the identification of the physical and chemical changes and thermal transitions of polymeric molecules, such as for peptides and lipids . Thermoansitions ,75,76, mm and the transition enthalpy ΔH when the lipid bilayer undergoes thermally induced phase transitions [m), whereas the other compounds caused a slight reduction in Tm [DSC can notably be used to determine the phase transition temperature Tnsitions . In the nsitions . In thison in Tm . In the on in Tm . In geneon in Tm .Spectroscopic techniques can be used to obtain detailed structural information but also to study interactions at the molecular scale. There are many spectroscopic techniques available, but in this section, the most used techniques related to polyphenol–lipid interactions are discussed.−1 for both liquid and solid samples [–1) is strongly affected [The penetration and distribution of polyphenols into lipid bilayers and the related forces can be studied by the changes in infrared absorption spectra obtained by Fourier transform infrared (FTIR) spectrophotometer, which can provide spectra in the common range of 4000 to 400 cm samples . For exaaffected .2 and CH3 of alkyl groups in the range of 3000–2800 cm−1, the vibrations of the carbonyl groups (C=O) in the range of 1780–1700, the vibrations of the phosphate groups (PO2) in the range of 1300–1200 cm–1, and the vibrations of choline groups (N-CH3) in the range of 1000–900 cm–1 [2 antisymmetric stretching vibration, indicating an increase in the fluidity of the membranes. The advantages of FTIR are the minimal sample preparation needed and the good reproducibility of the measurements. Most commonly, ATR–FTIR is applied for MLVs [3 with DMPC membranes studied by fluorescence, DSC and FTIR obtained using an oriented flat multilamellar membrane and liposomes [The best method for solid samples is to use an attenuated total reflectance (ATR) accessory, which has facilitated the IR analysis of solids and today is offered along with the typical transmittance module . With th900 cm–1 . ATR–FTI900 cm–1 . In thisfor MLVs ,77, whicN,N-dimethyl-6-propionyl-2-naphthylamine (prodan) [Another spectroscopic technique used to study polyphenol–lipid interactions and the locations of polyphenols is fluorescence anisotropy, which utilizes a polarized fluorescence excitation light beam to excite fluorescent probes embedded in the lipid regions of the membrane samples ,82. The (prodan) . The flu(prodan) ,84,86, 1(prodan)  and tran(prodan) . Typical(prodan) ,84. Pruc(prodan) . It was (prodan) ,89. In g(prodan) ,82. In t(prodan) . In gene(prodan) ,91, but (prodan) ,93.13C NMR, 31P and 2H spectroscopy utilizing a cross-polarization magic angle spinning (CP-MAS) probe. The solid-state 31P NMR tells about the interactions between polyphenols and the head group region of lipids. 31P has a wide chemical shift range, making it a sensitive probe for changes in its magnetic environment; therefore, the lipid phosphate group expresses well the changes in the water–lipid surfaces [2H is another interesting nucleus in biological solid-state NMR. In solid-state 2H NMR, the long lipid chain can be perdeuterated to report on the hydrophobic interior [NMR spectroscopic techniques are powerful and versatile methods for studying polyphenol–lipid interactions. Solid-state NMR spectroscopy can be used to study the structural and dynamic properties of polyphenols incorporating into membrane lipid bilayers and to elucidate the locations and interactions of small molecules in lipid bilayers ,95,96. T1H, 13C and 2D spectra, similar to solution-state NMR [2O and subsequently handling it via freeze–thaw in order to form the lipid bilayers. Then, the emulsion is transferred into an specific HR–MAS insert that is placed into the HR–MAS rotor and then in the instrument [1H MAS NMR can be used to measure ring current-induced chemical shift changes: for example, the interactions between flavonoids and phospholipid bilayers cause the lipid signals to slightly shift upfield [E.coli [β and H-G1 (see High-resolution magic angle spinning (HR–MAS) is a newer approach to study biological interactions, and HR–MAS NMR has been used for the investigation of the locations and distributions of flavonoids with lipid membranes . By spintate NMR ,96,97. Ttate NMR  by dissostrument . 1H MAS  upfield ,97. In t [E.coli . In thesAnother interesting method of studying polyphenol–lipid interactions is nuclear Overhauser effect spectra (NOESY) to see the spatial proton–proton correlations. The cross-relaxation between nuclei is formed during the mixing time. In general, the cross-relaxation is formed faster for large molecules than for small molecules, and for that reason, shorter mixing times are better for large molecules. The distance between the nuclei also affects the cross-relaxation formation. Therefore, different mixing times, for example 0.1 s and 0.3 s , are typThe other option is to measure the NOESY spectra at various mixing times, integrate the volumes of the respective diagonal and cross-peaks and then fit the results according to the spin pair model yielding more accurate cross-relaxation rates ,100. Bas1H NMR spectra and the correlation signals in NOESY spectra can be supported by the diffusion measurements by pulsed field gradient (PFG) NMR [The results obtained from the shifts in the lipid signals in PFG) NMR . PFG–NMRPFG) NMR ,101,102 PFG) NMR .n database with the words “polyphenol” and “molecular dynamics simulation” yields a trend of yearly increasing number of publications, with a most recent total of 147,073 references, indicating that the simulational approaches are growing rapidly [Molecular dynamics simulations have become a standard tool for studies of biomolecules in recent years . A searc rapidly . This pr rapidly . In gene rapidly ,103,106. rapidly . For pol rapidly ,108,109  rapidly .The basic idea of molecular dynamics simulation is rather straightforward: to create the molecular system, assign force field parameters and then predict how the particles move. However, this all requires a solid understanding of both the biological system and the theoretical basis of molecular dynamics simulations . First, The investigation and understanding of the polyphenol–lipid interactions is a complex process including different model polyphenols, lipids and chemical methods. The intensity of the interactions, the affinity of polyphenols to lipids and the forces included are related to the structure of the polyphenols but also to their locations and orientations in the lipid bilayers. Polyphenols penetrating the lipid bilayer can cause changes in its structure and physicochemical properties.Polyphenols show a large distribution along the lipid membrane depending on the structures of both the polyphenols and the lipid. It is widely accepted that the deeper the permeation of ligand into the lipid bilayer, the higher the affinity between the ligand and the lipid bilayer ,115. In Flavonoids show a large distribution along the membrane, but as the number of OH groups in flavonoids increases; thereby, the hydrophobicity of the flavonoids decreases, and the maximum of this distribution bends toward the lipid headgroups . For exaThe forces stabilizing the location and orientation of polyphenol in the lipid bilayer are mainly hydrogen bonds. Polyphenols have the ability to form hydrogen bonds between their hydroxyl groups (H-bond-donating moieties) and the C=O and phosphate groups of polar lipid headgroups (H-bond-accepting group) ,125,126.The ability of polyphenols to permeate the lipid bilayer depends on their physicochemical and structural properties . The hydThe galloyl group seems to be vital in the membrane interactions of polyphenols: the more galloyl groups there are in the structure, the more lipophilic is the polyphenol and the deeper it is in the lipid bilayer . Flavan-Similar observation has been made for galloylated PAs: Zhu et al. showed that the galloylated A-type procyanidin and prodelphinidin dimers have much higher affinities to the lipid bilayer with lower binding free energies in comparison with nongalloylated PA dimers, indicating that the gallates also play a vital role in the membrane interactions of PA dimers . There asn-glycero-3-phosphocholine have shown that these flavonoids increase the lipid order [When polyphenols penetrate the membrane lipids, they can perturb the lipid bilayers and their properties in many different ways. They can, for example, increase or decrease the acyl chain order, fluidity or rigidity of the lipid membrane. The changes detected in the lipid order vary depending on the polyphenol and lipid studied. For example, the studies on the interactions of kaempferol and quercetin with the membranes of EPC:sphingomyelin (2.4:1) and of 1,2-dipalmitoyl-id order . For hesid order . In a stid order . On the id order ,106. EGCid order .Cell membrane fluidity has an important role in cell physiology. Several polyphenols have been reported to affect the cell membrane fluidity and thereby contribute to the cell homeostasis ,130,131.Polyphenol–lipid interactions are of great importance as the affinity of polyphenols for lipid membranes affects their biological activity. Generally speaking, for high affinity to lipids, two factors are important: First, the hydrophobicity of the polyphenol matters: More hydrophobic polyphenols can penetrate more deeply into the lipid bilayers, and second, the forces stabilizing the location and orientation of the polyphenol in the lipid bilayer are important. These two things are dependent on the structures of the polyphenols and the compositions of the membrane lipids. The polyphenol–lipid interactions can be studied in detail at the molecular level using the state-of-the-art techniques such as HR–MAS NMR spectroscopy and molecular dynamics simulation. These techniques provide comprehensive information about the locations, orientations, mobility and lateral diffusion of polyphenols within the lipid bilayers. However, these techniques are not readily available for everyone, and their usage requires a notable amount of prior knowledge and expertise. Therefore, in some applications, partition coefficient measurements using octanol–water or membrane models provide feasible results for evaluating these interactions: in general, the hydrophobicity of the polyphenol predicts its ability penetrate the lipid bilayers. However, as discussed above, the hydrophobicity of the polyphenol does not fully determine its affinity to lipids.In general, there is still room for improvements in chemical methodology. Future computational chemistry can offer even better possibilities for studying these interactions. Multiple models with various force fields can be utilized in order to make sure that most of the physicochemical characteristics are correct; for example, the conformational flexibility and steric effects of tannins make their analysis challenging. There exists a risk that the computational methods produce unnecessary data without in-depth knowledge. However, this risk can be reduced by producing a considerable amount of specific, high-quality experimental data, for example by HR–MAS NMR, to support the calculations. Polyphenol–lipid interactions are complex and challenging to study, and the complexity is increased even further if the other macromolecules and components in the biological system are considered. The interactions of all components might be, for instance, distinct, synergistic, antagonistic or competing. There seem to be similar structural features of polyphenols affecting their interactions with proteins and with lipids; for example, the molecular size, conformational mobility and flexibility of tannins are important in their macromolecule interactions. Similarly, the methylation of flavonoids increases their hydrophobicity but also their affinities for proteins, and different polyphenols have different affinities for proteins, carbohydrates and lipids. Can we in the end conclude an affinity order of polyphenols for different macromolecules? What are the combined effects resulting from the different interactions between polyphenols and macromolecules? Can we even generalize the interactions or are they so highly specific that the overall view is not possible? With systematic further studies using well-known model substances and several different methods, we can find answers to these questions and better understand the biological context of these interactions.


The assessment process of elderly people considers all aspects of an individual’s life, including physical, mental, and social aspects. Frailty refers to a decline in physiological functions or strengths leading to increased vulnerability to stressors and decreased ability to cope with them. Comprehensive Geriatric Assessment (CGA) is a validated and useful tool in this context to holistically study elderly people. The primary aim of this study was to determine the prevalence of impaired health status in a large geriatric population turning to outpatient service, based on the components of the CGA, and thus to describe its usefulness in real-life clinical practice. The secondary aim of this study was the evaluation of the association between nutritional status, assessed with Mini Nutritional Assessment (MNA)—within the CGA—and cognitive-affective and functional capacities, and multimorbidity.This real-life, retrospective cross-sectional study included subjects consecutively evaluated from January 2009 to December 2020 at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy. A sum of 3,260 patients were subjected to CGA.p < 0.0001), Barthel Index of Independence in Activities of Daily Living (ADL) , Instrumental Activities of Daily Living (IADL) , and Performance-Oriented Mobility Assessment . A multiple regression also highlighted these variables as significant regressors of MNA. Finally, malnutrition showed a significant association with depression (odds ratio [OR]: 4.97), dependence on ADL (OR: 19.8) and IADL (OR: 7.04), and falling risk (OR: 5.16).Only a small proportion of the sample (2.24%) showed an absence of impairment in cognitive-affective, functional, and nutritional domains. Moderate correlations were found between MNA and several other CGA variables, namely, Geriatric Depression Scale (GDS; ϱ = −0.41, This study has figured out the complex situation in which geriatric care finds itself the complexity and severe impairment of elderly people. The possibilities of intervention are often limited, but the literature confirms the benefits of good nutritional status on the general health status. The data that emerged from our study fit into this assumption, highlighting the close association between the nutritional domain and the other CGA domains. With a higher life expectancy, and general health awareness on the rise, the world is witnessing an increase in geriatric patients . MoreoveMoreover, recent studies suggest that malnutrition is associated with cognitive decline and the degree of impairment in daily functioning in patients with dementia . The aboThe primary aim of this study was to determine the prevalence of impaired health status in a large geriatric population turning to outpatient service, based on the components of the CGA, and thus to describe its usefulness in real-life clinical practice.The secondary aim of this study was the evaluation of the association between nutritional status, assessed with MNA—within the CGA—and cognitive-affective and functional capacities, and multimorbidity.This study fits into a thriving field of study, contributing to explain the growing burden of multimorbidity and demand for care.This real-life, retrospective cross-sectional study included subjects consecutively evaluated from January 2009 to December 2020 at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy.Inclusion criteria: It includes those with the age of ≥65 years and has been subjected to CGA from January 2009 to December 2020.Exclusion criteria: It includes those with the age of <65 years and has not been subjected to CGA.A total of 3,260 subjects met the inclusion criteria.The enrolled subjects were evaluated with a validated battery of tools, includingMini-Mental State Examination (MMSE), which is a screening test to detect severity and changes in time of cognitive impairment. The total score, given by the sum of the exact answers in each item, corrected for age and education, with scores from 30 (absence of cognitive impairment) to 0 (maximum cognitive impairment). A score of <24 is suggestive of cognitive impairment , 21.Geriatric Depression Scale (GDS): It is a screening tool designed to evaluate the presence of depression in elderly subjects with MMSE > 14. This test is made up of 15 Yes/No questions, each of which is translated into a relative score of “0” or “1” as a result of the absence/presence of the investigated depressive symptom. The score ranges from 0 (absence of depression) to 15. A score of >5 is suggestive of depression .Barthel Index of Independence in Activities of Daily Living (ADL): It is used to assess the ability to perform tasks such as taking a bath, using the toilet, walking, maintaining urinary and fecal continence, dressing up, and feeding. The total score ranges from 100 (independence) to 0 (complete dependence) . In its Instrumental Activities of Daily Living (IADL): It is used to assess the ability to perform tasks such as using a telephone, doing laundry, and handling finances. The score ranges from 8 (independence) to 0 (complete dependence). A score of <6 is suggesting of dependence .Mini Nutritional Assessment (MNA): It is a tool to assess malnutrition or its risk. The total score is obtained from the sum of the scores assigned to the answers of the 18 questions, which can be divided into four sections . The total score classifies the subject as follows: malnourished (<17), risk of malnutrition (17–23.5), and well-nourished (≥24) .Performance-Oriented Mobility Assessment (POMA): It is a tool for the evaluation of balance and gait in the elderly without cognitive impairment or affected by mild-to-moderate dementia. It identifies subjects at falling risk. The total score (0–28) is obtained by adding the resulting partial scores of two sections, namely, Balance and Gait. The total score classifies the subject in the following way: not able to walk (<2); high fall risk (2–19); moderate fall risk (20–23); and not increased fall risk (≥24) .Cumulative Illness Rating Scale (CIRS): It is a tool to measure the elderly state of health. It evaluates 14 categories of pathologies concerning some organs and systems , hypertension, and psychiatric and behavioral aspects. Every item is evaluated on an ordinal scale with increasing severity levels, from 1 (absence of pathology) to 5 (severe pathology). Using this tool, we can evaluate the total score (CIRS Tot.), the Severity Index (CIRS ISC), which is obtained from the average of the 13 categories scores—excluding psychiatric and behavioral problems—, and the Comorbidity Index Score (CIRS ICC), which corresponds to the number of categories with a score of ≥3 .post-hoc analysis. Multivariate analysis was performed with a stepwise multiple regression : MNA scores were considered as “dependent variable”; the remaining CGA scores , age, and gender were considered “independent variables”.Quantitative variables were expressed as median and interquartile ranges (IQRs). The Mann–Whitney test for continuous variables was used to study gender differences in CGA variables. Spearman’s rank correlation coefficient (ϱ) and, since this is a retrospective study, odds ratios (ORs) were used to study the relationship between the variables. The Kruskal–Wallis test was used to compare the three groups deriving from MNA scores. The Conover test was performed for p-values in reference to 95% confidence intervals.The results are reported that indicate The MedCalc software  was used for the statistical analysis.This retrospective cross-sectional study included 3,260 participants, of whom 2,350 (72.1%) were women. The characteristics of the enrolled subjects are shown in p < 0.0001), while no gender-related differences were found in age, MMSE, and CIRS ICC.Only 73 (2.24%) subjects have proved good performances in MMSE, GDS, ADL, IADL, and MNA.A sum of 1,819 (55.8%) people were revealed dependent on ADL  and IADL, but only 495 (27.2% of them) could be considered cognitively intact.p < 0.0001), ADL and POMA , and MMSE and IADL ; moderate correlation (0.4 < ϱ < 0.59) was found between MNA and ADL , MNA and IADL , MNA and POMA , and MNA and GDS . The other correlations were weak or very weak (ϱ < 0.4) or not statistically significant.The correlation between the variables has been studied using Spearman’s rank correlation coefficient (ϱ), and the results are shown in p < 0.000001) were found among the three groups , MNA2 (24–17), and MNA3 (<17). The Kruskal–Wallis test was conducted to examine the differences in CGA scores according to the nutritional status. Significant differences (e groups . Post-hovs. MNA1 .p < 0.0001), and CIRS Tot. (p = 0.0332) as regressors of MNA; the other variables were not included in the model  with cognitive impairment , depression , dependence on ADL  and IADL , and risk of fall .For the purpose of further examining the role of the nutritional status in influencing the other CGA domains, We collected and examined data from a sample of 3,260 subjects referred from January 2009 to December 2020. The primary aim of this study was to examine the performance status presented by geriatric patients who turn to outpatient service, based on the components of the CGA. Understanding this aspect is fundamental to be able to build appropriate assistance and care plans. In our population, only 15.5% of the patients showed intact cognitive function, and 25.4% showed adequate mood; the percentages of the subjects that considered independent in performing basic and IADL were 15.2 and 10.9%, respectively. Low or absent increased risk of fall was found in 23.9% of the patients, and adequate nutritional status was found in 19.5%. These data denounce that too often, the people come to the attention of the specialist clinician when their status is compromised, leaving less room for maneuver to interventions, whether pharmacological or not. To confirm this thesis, it can be seen that only 2.24% of the study population could be considered “fit” in one of the CGA areas, such as cognitive, affective, functional, and nutritional areas; moreover, unfortunately, only 27.2% of functional-dependent people showed adequate cognitive performances.p = 0.0003, does not evidence any variation from the point of view of real dependence in performing daily living activities. On the other way, as mentioned earlier, GDS scores were higher, highlighting a more deflected mood, in women (median: 9 vs. 7), and this difference cannot fail to be considered relevant also from the clinical point of view, as well as pharmacological. Nevertheless, this data are consistent with the literature  emerged between malnutrition and cognitive impairment: although it is confirmed that a poor nutritional status impacts cognitive function, MMSE was excluded by stepwise multiple regression (variable removed by the model if p > 0.1) and also showed poor correlation with MNA , our data have not been able to clearly comply with this evidence , MNA2 , and MNA3 . Every variable showed the same pattern that is a worsening of the performed results to the worsening of the nutritional status. To better explain this trend, the multiple regression highlighted GDS, ADL, IADL, POMA, and CIRS Tot. as significant regressors of MNA. The strength of the association between the malnutrition and the various outcomes suggested by CGA was measured through ORs. The most powerful associations emerged with ADL, IADL, and POMA: it is intuitive, as well as confirmed in clinical studies –39, thatevidence .This real-life, cross-sectional study analyzed the performances of geriatric people evaluated in an outpatient setting. We have sadly become aware of the delay for patients to undergo a holistic geriatric assessment for the first time: this delay can strongly limit every area of intervention.One of the fields more correlated to the others, and in which it is easier to intervene, is the nutritional one, which is also strongly associated with the other CGA domains: our data seem to suggest that maintaining an adequate nutritional status is strongly associated with a maintenance of affective and functional status, and also of the general health of the elderly people.The strengths of the study are represented by the size of the sample, as well as its design: the real-life approach allows to have an effective idea of the conditions of multimorbidity and demand for care of the elderly population. The main limitation of the study is represented by the fact it is single-center and did not prospectively examine the patients: in this sense, by longitudinally monitoring the patients, it would also be possible to establish causal associations between the variables.The raw data supporting the conclusions of this article will be made available by the authors, upon reasonable request.The studies involving human participants were reviewed and approved by the Ethics Committee of the University of Cagliari (certification NP/2022/1382). The patients/participants provided their written informed consent to participate in this study.FS, SL, and AM were principal investigators and contributed to the study design, data analyses, interpretation of the findings, and wrote the manuscript. FZ and LS contributed to the data collection. MP carried out the data analyses. All authors have read and approved the final version of the manuscript.


Operative cholangiography, the gold standard for the diagnosis of biliary atresia (BA), is being challenged due to an increase in the studies of misdiagnosis. A previous study has shown that the laparoscopic hepatic subcapsular spider-like telangiectasis (HSST) sign was accurate for diagnosing BA. This study aims to compare the performance of the HSST sign with cholangiography in the identification of BA.We prospectively screened consecutive infants with cholestasis who underwent laparoscopic exploration in this multicenter study. Demographics, intraoperative findings (videos and images), and outcomes were retrospectively analyzed. The data of the HSST sign and cholangiography were compared according to the final diagnosis. Then, the diagnostic accuracy of the BA using the HSST sign and cholangiography was validated in other independent cohorts.p < 0.001). Moreover, to realize the early diagnosis of BA, the accuracy of the HSST sign in identifying BA was better than cholangiography in the subgroup of neonates . Interestingly, 92 non-BA patients without the HSST sign had positive cholangiography. Among them, 28 infants had negative cholangiography when the common bile duct was compressed and 39 patients displayed visible bile ducts due to repeated postoperative biliary irrigation. The other 25 patients  had consistently positive cholangiography. In the independent validation cohort, the diagnostic accuracy of the HSST sign (99.2%) was higher than cholangiography .A total of 2,216 patients were enrolled in this study. The sensitivity and negative predictive values were both 100% for diagnosing BA based on the HSST sign and cholangiography. The specificity, negative predictive value, and accuracy of the HSST sign  in discriminating BA were significantly higher than operative cholangiography (81.6, 94.9, 95.8; The laparoscopic HSST sign is superior to cholangiography in the diagnosis of BA in the infants with cholestasis and has advantages in early diagnosis. This method is expected to become a novel shift for diagnosing BA during ongoing laparoscopy. Biliary atresia (BA) is characterized by progressive obliteration of the intrahepatic and extrahepatic bile ducts within a few weeks of birth, and it leads to death if not treated before the patient is at the age of 2 years , 2. For Even now, histological, or anatomical diagnostic tests that can precisely distinguish BA are still needed. Intraoperative cholangiography  was considered a definitive and gold standard for diagnosing BA until the twenty-first century –9. This We previously found that laparoscopic hepatic subcapsular spider-like telangiectasis (HSST) sign, a prominent pathological change on the liver surface, was accurate in the diagnosis of BA . AlthougTherefore, in this multicenter study, a large sample comparative study was used to further evaluate the accuracy of the two diagnostic methods for differentiating BA in infants with cholestasis. To identify neonatal BA, because early diagnosis correlates with the outcome.This study was approved by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (IORG003571-1). The patients with suspected BA who presented to undergo laparoscopic exploration were prospectively screened in three large tertiary medical centers between January 2005 and December 2018 . The evaThe typical HSST sign was defined as enlarged tortuous spider-like vascular plexuses with four to eight branches that were distributed all over the liver surface under laparoscopy, and these showed either a centralized vascular plexus or scattered type . These vLaparoscopic procedures were performed under general anesthesia. A 5-mm umbilical camera port and a working port with 3-mm forceps  above the umbilicus were placed separately to assess the gallbladder, to determine if there was liver cirrhosis, and to examine the extrahepatic bile ducts . If the To test the reproducibility of the HSST sign, we performed the assay in other independent cohorts. We enrolled a series of 120 BA and age-matched 120 non-BA patients in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2019 and December 2020. The HSST sign was used to identify BA. Then the LAC was recorded and compared. All enrolled patients were diagnosed according to postoperative liver pathology and follow-up.t-test or ANOVA for continuous data and chi-square test or Fisher’s exact test for categorical data was applied to assess the differences between groups, respectively. A receiver operating characteristic (ROC) curve analysis, that reported the area under the curve (AUC) with a 95% confidence interval (CI), was performed to illustrate the predictive performance. All data were presented as mean ± SD and percentage, a p-value < 0.05 was considered statistically significant.The data were analyzed by SPSS software version 22.0. The Student’s All 1,782 BA patients (including 67 patients who could not undergo cholangiography) had the HSST sign, of which 1,715 had positive LAC . A totalp < 0.001), positive predictive value (PPV) , and accuracy  in discriminating BA than LAC. The AUC for the HSST sign in BA was 0.986 .A typical HSST sign was observed in all the patients who were eventually diagnosed with BA. Therefore, regarding the diagnostic ability of the HSST sign and LAC , 2, bothp = 0.012).In the validation cohort, a typical HSST sign was observed in all 120 BA patients; 118 non-BA patients had no HSST sign and two patients  had atypical HSST sign. All BA patients had positive LAC; 108 non-BA patients had negative LAC. Twelve non-BA patients  had positive LAC and were misdiagnosed with BA. Therefore, the diagnostic accuracy of the HSST sign (99.2%) was higher than cholangiography . Therefore, we considered that the virus activated the notch3 pathway and regulated VSMCs, leading to vascular remodeling and abnormal resistance, and this resulted in small artery dilation (p < 0.001). Moreover, the diagnostic accuracy of the HSST sign (99.3%) was higher than cholangiography  in the independent cohort.The HSST sign was not isolated in the BA patients, but spread all over the surface of the liver, including the diaphragmatic surface and the visceral surface. The distribution characteristics of the HSST sign have no relationship with age. We initially thought the HSST sign was secondary to liver fibrosis of BA , 23. Howdilation . Thus, tdilation , 23. Ultdilation . El-Guindilation  found thdilation . In thisp = 0.032).It is generally accepted that the earlier the hepatoportoenterostomy is performed, the better the clinical outcomes. Therefore, for infants with conjugated hyperbilirubinemia, an early and accurate diagnosis of BA is mandatory . Our resIntraoperative cholangiography has been regarded as the gold standard and a definitive investigative test in the diagnosis of BA –29. Howen = 14) false-positive results for BA, and this prevented 5.1% (n = 92) needless operations, which was superior to cholangiography.The atypical HSST sign was recorded in 14 non-BA cases  in the negative-LAC group. This feature was validated as dilated capillaries rather than dilated arterioles according to pathologic examination. Furthermore, to verify the sensitivity of the HSST sign, patients who did not undergo cholangiography due to cystic atresia were also reviewed. The HSST sign was discovered in all BA patients under laparoscopy, with a sensitivity of 100%. Typical HSST sign was absent in 5.1% (92/1807) of the patients whose LAC images failed to reveal intrahepatic bile ducts, and BA was eventually excluded in these patients. Deleterious interventions could be avoided in these infants. High-serum metalloproteinase-7 level was a predictive biomarker of BA among infants with cholestasis , 36. TheThe HSST sign is associated with the following advantages. First, laparoscopy is widespread in almost all hospitals, which makes a diagnosis through simple laparoscopic observation available, and this reduces the degree of the diagnostic difficulty. Images are acquired with a RGB camera and spectral separation is amplified by adapted color processing algorithms, enhancing the interface between vascularized and non-vascularized tissues through Spectra A and Spectra B of Storz Professional Image Enhancement System . Especially, the HSST sign is highlighted with Spectra B mode , as it iIn conclusion, the present study further investigates the power of the HSST sign for diagnosing BA by comparing it with cholangiography. The absence of intrahepatic bile ducts by cholangiography was not always a “must” for defining BA. The laparoscopic HSST sign is a minimally invasive, radiation-free, and time-saving method to accurately differentiate BA. Additionally, the HSST sign, given its simplicity, stability, and intuitive amplification under laparoscopy, is particularly suitable for primary hospitals with a minimal number of specialists. A future prospective randomized study is needed to identify the diagnostic ability of the HSST sign.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.ST and SC designed the study, reviewed, and revised the manuscript. YL, LR, and JT performed the search, analysis, and wrote the manuscript. HN, ZJ, and YZ collected the data. GC and XZ rechecked the data. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To assess the lateralization of cerebral blood flow (CBF) in the auditory cortex of idiopathic tinnitus patients and healthy controls (HCs) using 3D pseudocontinuous arterial spin labeling (pcASL).Thirty-six patients with idiopathic tinnitus and 43 sex- and age-matched HCs underwent 3D-pcASL scanning using a 3.0 T MRI system. For both groups, region of interest analysis was performed on the primary auditory cortex (PAC), auditory associative cortex (AAC), and secondary auditory cortex (SAC). The clinical data of all subjects were analyzed.P = 0.02; patients: P = 0.043), but CBF of the right AAC and SAC was significantly higher than that of the left . Compared with HCs, tinnitus patients exhibited significantly higher CBF in the bilateral PAC . CBF in the left PAC was positively correlated with tinnitus severity .In both tinnitus patients and HCs, CBF of the left PAC was significantly higher than that of the right (HCs: This study confirms the asymmetry of the auditory cortex and investigates the underlying neuropathology of idiopathic tinnitus in terms of CBF. Idiopathic tinnitus is a subjective auditory perception that occurs in the absence of external sound stimuli. In adults, the incidence of idiopathic tinnitus is as high as 15% and increases with age; consequently, idiopathic tinnitus has become a major health issue worldwide . This coThe etiology of idiopathic tinnitus remains unclear. It is considered to originate from abnormal neuronal activity in the auditory cortex (AC) . In animCurrently, the lateralization of the AC in idiopathic tinnitus patients remains unclear. Neuronal activity is closely coupled to cerebral blood flow (CBF), and increased neuronal activity leads to increased CBF . ArteriaThus, the aim of this study was to assess the lateralization of CBF in the AC in idiopathic tinnitus patients and healthy controls (HCs) using 3D-pcASL. In addition, we explored the differences in CBF in the AC between patients with tinnitus and HCs, and the correlation of altered CBF with clinical data.This research was approved by the Medical Research Ethics Committees. Written informed consent was acquired from each participant in accordance with the Declaration of Helsinki.In this study, 36 bilateral tinnitus patients and 43 sex- and age-matched HCs were enrolled from Kailuan community. Patients were included if the following criteria were met: persistent idiopathic tinnitus, self-reported normal audiology, no prior history of central nervous system disorders or head trauma, and no MRI contraindications. Subjects were excluded if they had pulsatile tinnitus, hyperacusis, prior stroke, systemic diseases, or a history of drug or alcohol abuse in the previous 3 months. Tinnitus is divided into 6 grades according to its severity: grade 1, in which tinnitus is seemingly non-existent; grade 2, in which tinnitus is only experienced in quiet environments; grade 3, in which tinnitus is experienced in daily environments and does not affect quality of life; grade 4, in which tinnitus is experienced in noisy environments and affects sleep; grade 5, in which tinnitus seriously affects sleep and work; and grade 6, in which tinnitus leads to anxiety and depression.All subjects were scanned on a GE 750W 3.0 T MR scanner . We used earplugs and foam padding to reduce scanner noise and head motion, respectively. All participants were instructed to close their eyes and avoid thinking of anything. Structural images were obtained using a brain volume sequence (echo time (TE) = 2.8 ms; inversion time (TI) = 450 ms; repetition time (TR) = 7.5 ms; flip angle (FA) = 15°; slice thickness = 1 mm; matrix = 256 × 256; and field of view (FOV) = 256 mm × 256 mm). Perfusion data were acquired by a 3D-pcASL sequence , 2525 ms; and FA = 111°; FOV, 240 mm × 240 mm; and in-plane resolution, 3.37 × 3.37 mm). The acquisition time of ASL was 4 min and 45 s.In the AW4.6 workstation, the ASL difference images were derived by pairwise subtraction of the control and label images; subsequently, the CBF map was obtained from the ASL difference images. Details of the processing procedures were described in a previous study . The CBFTinnitus has been confirmed to originate from abnormal neuronal activity in the AC . Thus, wThe lateralization index (LI), which was calculated as: (left–right)/(left+right) , was uset-test were performed to identify group differences in demographic data. CBF differences in the bilateral AC of each group were explored using the paired samples t-test. We used one-sample t-test as the comparison point to investigate the LI difference in the AC of each group. The analysis of covariance was used to compare the difference in CBF and LI in each AC between patients and HCs, with age and sex as covariates. In addition, we analyzed the correlations of altered CBF with the duration and severity of tinnitus. All results were presented without correction for multiple comparisons.The chi-square test and two-sample The baseline information for all subjects is shown in P = 0.02; patients: 0.996 ± 0.077 vs. 0.969 ± 0.089, P = 0.043), but CBF of the right AAC and SAC was significantly higher than that of the left . In addition, compared with HCs, patients with tinnitus exhibited significantly higher CBF in the bilateral PAC .The CBF in the AC in each group of subjects is shown in t-test showed that in each group, the LI of the PAC was significantly higher than 0 , while the LI of the SAC and AAC were significantly lower than 0 . In addition, tinnitus patients had significantly lower LI in SAC than HCs (P = 0.008), and no significant LI difference was found in PAC and AAC between the two groups (P > 0.05).r = 0.399, P = 0.016)  . No signThis study investigated the lateralization of CBF in the AC of patients with idiopathic tinnitus using the 3D-pcASL technique. CBF was asymmetric in the AC in both tinnitus patients and HCs. Moreover, CBF in the bilateral PAC was significantly higher in tinnitus patients than in HCs. The higher CBF in the left PAC was positively correlated with tinnitus severity. These findings contribute toward an understanding of the neuropathological mechanisms of tinnitus in terms of CBF.The AC is responsible for processing auditory information. A previous study demonstrated that the columnar and connective structures of the AC in the left cerebral hemisphere differ anatomically from those in the right hemisphere . LantingIn the present study, we compared CBF differences in bilateral AC using the 3D-pcASL technique and found that the CBF in the right AAC and SAC was significantly higher than that in the left, while the CBF in the left PAC was significantly higher than that in the right. We also used the LI to confirm the asymmetry of CBF in the AC. These findings suggest that asymmetric CBF in the bilateral AC is a physiological feature of both tinnitus patients and HCs, regardless of the presence or absence of tinnitus.The CBF in the bilateral PAC was significantly higher in tinnitus patients than in HCs in this study. Auditory stimuli can increase neural activity in the bilateral AC. Several limitations of this study should be noted. The sample size of this study was limited, and more patients need to be enrolled in the future to further verify these results. Second, all patients in this study had bilateral tinnitus, which is the most common type of tinnitus observed in clinical practice. In future work, we will include patients with unilateral tinnitus and evaluate lateralization in the AC. Third, MRI noise may have a potential effect on the results. In this study, we used earplugs and foam pads to reduce scanner noise, thereby minimizing the impact of noise on the results. In the future, we will further explore the effect of noise on CBF in AC. In addition, we will recruit left-handed subjects to eliminate the possible effect of handedness on the results.In this study, the asymmetry of the AC in tinnitus patients and HCs was identified using the 3D-pcASL technique. CBF in the PAC was left-lateralized in all subjects, and CBF in the SAC and AAC was right-lateralized. Moreover, CBF in the bilateral PAC was higher in tinnitus patients than in HCs. In this study, we not only investigated the underlying neuropathology of tinnitus in terms of CBF but also may have implications for the rationale of tinnitus treatment protocols based on lateralized hyperactivity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Beijing Friendship Hospital. The patients/participants provided their written informed consent to participate in this study.XL, YZ, YH, QC, HS, ML, and WZ performed the experiment and collected, analyzed, or interpreted the data involved in the study. XL preprocessed image data, performed the statistical results, and drafted the manuscript. PZ, HL, XZ, and YW designed the study and ensured the questions related to all aspects of the work. JL, LC, and ZW gave critical comments on the manuscript. All authors contributed to the article and approved the submitted version.


To evaluate the value of ultrasound-based radiomics in the preoperative prediction of type I and type II epithelial ovarian cancer.A total of 154 patients with epithelial ovarian cancer were enrolled retrospectively. There were 102 unilateral lesions and 52 bilateral lesions among a total of 206 lesions. The data for the 206 lesions were randomly divided into a training set (53 type I + 71 type II) and a test set (36 type I + 46 type II) by random sampling. ITK-SNAP software was used to manually outline the boundary of the tumor, that is, the region of interest, and 4976 features were extracted. The quantitative expression values of the radiomics features were normalized by the Z-score method, and the 7 features with the most differences were screened by using the Lasso regression tenfold cross-validation method. The radiomics model was established by logistic regression. The training set was used to construct the model, and the test set was used to evaluate the predictive efficiency of the model. On the basis of multifactor logistic regression analysis, combined with the radiomics score of each patient, a comprehensive prediction model was established, the nomogram was drawn, and the prediction effect was evaluated by analyzing the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve.The AUCs of the training set and test set in the radiomics model and comprehensive model were 0.817 and 0.731 and 0.982 and 0.886, respectively. The calibration curve showed that the two models were in good agreement. The clinical decision curve showed that both methods had good clinical practicability.The radiomics model based on ultrasound images has a good predictive effect for the preoperative differential diagnosis of type I and type II epithelial ovarian cancer. The comprehensive model has higher prediction efficiency. Ovarian cancer is the deadliest cancer of the female reproductive system , 2. ApprTraditional imaging is the main means of detecting ovarian tumors , but thiRadiomics, first proposed by Lambin et al. in 2012 , has devAt present, there is a lack of ultrasound-based radiomics methods for distinguishing different subtypes of epithelial ovarian cancer before surgery ; therefoThe Ethics Committee of the First Affiliated Hospital of Guangxi Medical University approved this retrospective study . Informed consent was waived. Patients with epithelial ovarian cancer diagnosed by pathology after surgery at the First Affiliated Hospital of Guangxi Medical University from January 2017 to September 2021 were enrolled  to manually draw the tumor boundary and determine the tumor area of interest (ROI) Fig. . The ult.8 to manIntelligenceFoundry software  was used to analyze and extract radiomics features. Feature types included first-order features , shape features , wavelet features and texture features . A total of 4976 high-throughput features were extracted in this study. The feature parameters extracted by the Intelligence Foundry software were based on the algorithm provided by the pyRadiomics package, which calculates radiomics features according to the feature definition described in the Image Biomarker Standardization Initiative (IBSI) version 2016 . The medPatients with epithelial ovarian cancer were marked with different labels according to their histological types. Type I epithelial ovarian cancer was labeled "0", and type II epithelial ovarian cancer was labeled "1". Then, using the method of stratified sampling, patients with two histological types of epithelial ovarian cancer were randomly divided into two groups according to a 6:4 (training set:test set) ratio. The training set was used to build the model, and the test set was used to verify the effectiveness of the model.In this study,all patients were diagnosed with GEVolusion ultrasound and were examined under the transvaginal probe.We collected the important ultrasonic parameters of all the pictures in this study, including gain,mechanical index,depth,angle. After analysis, we found that these important parameters were not statistically significant in the two types of ovarian cancer (P > 0.05). Table .Table 1TIn this study, a total of 4976 features were extracted from ultrasound images.To increase the comparability of quantitative radiomic features, we performed Z-score normalization for quantitative features in training and test sets. In order to reduce the influence of high-dimensional features on the model, we use lasso regression method to downscale features, and select the optimal feature subset through ten-fold cross-validation. Figs. . FinallyThe seven radiomics features selected were introduced into the classifier to establish a model for evaluating two different histopathological types of epithelial ovarian cancer. We used six machine learning methods  to construct the model learning method Fig. . FinallyBasic information , menopausal status, maximum tumor diameter, serum tumor marker levels, ascites and histopathological classification were collected. Serum tumor markers included carcinoembryonic antigen, glycosyl antigen 125, glycosyl antigen 153, glycosyl antigen 199, squamous cell carcinoma-associated antigen, serum human chorionic gonadotropin, human epididymal epithelial secretory protein 4, alpha-fetoprotein, the Premenopausal ROMA index and the Postmenopausal ROMA index. The above data were detected within two weeks before the operation. The markers selected by the LASSO method were analyzed by multivariate analysis, and the markers with P < 0.05 were selected to establish the prediction model.The selected features were used to construct a radiomics model by logistic regression, and a comprehensive prediction model was obtained by combining the radiomics score with clinical parameters Fig. . The comSPSS software (version 22.0) were used for statistical analysis. For the measurement data of normal distribution, the t test of complete random design was used to compare the two samples, and the analysis of variance was used to compare several independent samples. The variables were summed as the mean ± standard deviation (SD). For the skewness distribution measurement data, the rank sum test was used for the progressive nonparametric test, and the variables were summed as M (Q1 ~ Q3). The counting data were tested by the chi-square test, and the variables are presented as percentages.R software (version 3.6.0) and At the end of this study, 154 patients with epithelial ovarian cancer were enrolled, with an average age of 50.15 ± 10.80 years, ranging from 21 to 76 years old. Seventy-three patients  were confirmed to have type I epithelial ovarian cancer by postoperative pathology; 33 of these patients had low-grade serous carcinoma, 20 had clear cell carcinoma, 9 had endometrioid carcinoma, and 11 had mucinous carcinoma. Eighty-one patients  were confirmed to have type II epithelial ovarian cancer by postoperative pathology; 80 of these patients had high-grade serous carcinoma, and 1 of these patients had undifferentiated carcinoma. Among the 154 patients, 102 had unilateral lesions, and 52 had bilateral lesions; of the 206 total lesions, 89 were type I epithelial ovarian cancer, and 117 were type II epithelial ovarian cancer.Among the 154 patients with epithelial ovarian cancer, the training set included 93 patients, with 62 unilateral lesions and 31 bilateral lesions. The total number of lesions in the training set was 124, and the number of type I and type II epithelial ovarian cancer lesions was 53 and 71, respectively. The test set included 61 patients, with 40 unilateral lesions and 21 bilateral lesions. The total number of lesions in the test set was 82, and the number of type I and type II epithelial ovarian cancer lesions was 36 and 46, respectively. The clinical parameters of the training set and the test set are shown in Table A total of 4976 features were extracted and normalized. The features with differences were screened by Lasso regression tenfold cross-validation and minimum absolute shrinkage Figs. . FinallyThe radiomics model has a high overall classification performance in identifying epithelial ovarian cancer types I and II, with AUC values of 0.817 and 0.731 in the training set and test set, respectively Fig. .Combined with the results of multivariate logistic regression analysis Table , a comprThe ultrasound images of 154 patients with epithelial ovarian cancer were included in this study. The quantitative expression values of imaging features were normalized with the Z-score method, and the 7 most different features were screened by using the Lasso regression tenfold cross-validation method. Then, six machine learning methods  were used to construct the model, and the method with the highest AUC value was selected to establish the logistic regression radiology model. The AUCs of the training group and test group were 0.817 and 0.731, respectively. In addition, combined with the clinical indexes of the patients, the data regarding serum tumor markers monitored two weeks before operation were collected and analyzed by multivariate logistic regression analysis. Finally, menopausal state,ascites, CA125, SCC, HE4 and Premenopausal and Postmenopausal ROMA were identified as independent factors. The above indexes were combined with the radiomics score to create a comprehensive prediction model, and the AUCs in the training group and test group were 0.982 and 0.886, respectively. The nomogram of this study quantifies the value of each factor of the patient and visually shows the efficiency of the comprehensive model in predicting two kinds of epithelial ovarian cancer. From the value of AUC, the efficacy of comprehensive prediction model is higher than radiomics model. After analysis, the following factors were obtained. Firstly, this study collected a lot of clinical indicators, including maximum tumor diameter,ascites,carcinoembryonic antigen, glycosyl antigen 125, glycosyl antigen 153, glycosyl antigen 199, squamous cell carcinoma-associated antigen, serum human chorionic gonadotropin, human epididymal epithelial secretory protein 4, alpha-fetoprotein, the Premenopausal ROMA index and the Postmenopausal ROMA index. The two indexes of maximum tumor diameter,ascites came from ultrasonic testing. Therefore, these indexes are not only simple blood test indexes, but also comprehensive indexes of patients' basic information, blood biochemistry and ultrasonic examination. Ultrasound has certain advantages in daily work.Ultrasonic operation is convenient, simple and non-invasive. It can also monitor the size of the mass and the presence of ascites. Therefore, ultrasound is a common method to detect ovarian tumors in clinical work. At the same time, radiomics also provides a new evaluation method for clinic, which has a certain potential value. In this study, the clinical decision curve shows that both the imaging model and the joint model are located above the None line and the All line, indicating that both models are valuable in predicting the classification of epithelial ovarian cancer, and the net return of the combined model is higher than that of the radiomics model. Because the progression of type I and type II epithelial ovarian cancer is different, it is of clinical significance to correctly predict the two types.Radiomics, first proposed by Lambin et al. in 2012 , has devHowever, our research also has some limitations. First, all the ultrasound imaging data came from a single center, and the study was retrospective, so it was necessary to conduct a multicenter prospective study. Second, our study only included epithelial ovarian cancer, excluding benign, borderline, sex cord interstitial and germ cell tumors of the ovary. We will add data on other types of ovarian tumors in future studies to optimize the universality and clinical value of the model. In addition,We are also trying to use radiomics to distinguish benign and malignant ovarian tumors, hoping that it can provide us with new ideas in differential diagnosis.In summary, we developed and validated a radiomics model based on ultrasound to distinguish different histopathological types of epithelial ovarian cancer. Thus, it provides clinicians with a new method for the noninvasive preoperative identification of type I and type II epithelial ovarian cancer.


Late-life depression is a complex phenomenon that cannot be fully understood simply as depression occurring in older adults, prompting researchers to suggest that it represents a component of geriatric syndrome. Given the inherent complexity and multifactorial nature of geriatric syndrome, understanding the interactions between the comorbid conditions involved is important for establishing appropriate preventive strategies. While sleep disturbance and malnutrition are common manifestations of geriatric syndrome, they have also been regarded as indicators of late-life depression. However, the differential effects of sleep disturbance and malnutrition on late-life depression and their interrelationships remain unclear.The objective of this study was to examine the effects of sleep disturbance and malnutrition on depression and the interactions between them among community-dwelling older adults.2 values and the Johnson–Neyman technique, respectively.Sleep disturbance and malnutrition in 1,029 community-dwelling older adults from Suwon Geriatric Mental Health Center were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Mini Nutritional Assessment (MNA), respectively. The Korean version of the Short Form of the Geriatric Depression Scale (SGDS-K) was used to evaluate depressive symptoms. Sociodemographic parameters were recorded. A multiple linear regression analysis was conducted to examine the effects of sleep and nutrition on depressive symptoms after adjusting for covariates. The effect size and conditional effects of sleep disturbance and malnutrition on late-life depression were assessed using Cohen’s fP < 0.001) and negatively associated with the MNA score . The local effect size of the associations was small for PSQI and medium for MNA. A significant interaction was observed between the PSQI and MNA scores. The result of the Johnson–Neyman technique indicated that the influence of PSQI on SGDS-K became weaker and insignificant as nutritional status worsened. However, the association between the MNA and SGDS-K scores was significant regardless of PSQI.After possible confounders were adjusted, the SGDS-K score was positively associated with the PSQI score (standardized beta = 0.166, Both sleep disturbance and malnutrition were significantly associated with late-life depression, although malnutrition may be more critically associated with depression than sleep disturbance in community-dwelling older adults. Progression of population aging has promoted an increased emphasis on the negative consequences of late-life depression, which has been associated with functional impairment, worsening of coexisting medical problems, and cognitive decline . HoweverThe prevalence of sleep disturbance in later adulthood is estimated to range from 40 to 70% and is known to increase with age , 7. OldeMalnutrition is also an important clinical condition associated with late-life depression. Malnutrition is defined as inadequate nutritional status characterized by insufficient dietary intake, poor appetite, muscle wasting, and weight loss . The preUnderstanding the interrelationships among sleep, nutritional status, and depression in later adulthood is of particular importance in the context of geriatric medicine, in which depression among older adults may present within the context of multiple age-related disorders. This phenomenon, referred to as geriatric syndrome , is defiThe objective of this study was to examine the effects of sleep disturbance and malnutrition on depression among community-dwelling older adults. The authors hypothesized that both sleep disturbance and malnutrition exhibit significant associations with late-life depression and that these conditions interact to influence depressive symptomatology.From January 2017 to April 2021, 1,029 community-dwelling older adults, aged between 60 and 90 years, who came to Suwon Geriatric Mental Health Center in the Republic of Korea for general screening of cognitive impairments, depression, and other possible mental health problems were analyzed for this study. The exclusion criteria were as follows: severe cognitive impairment based on a global deterioration score > 3 points or a Mini-Mental State Examination score < 18 points; history of another psychiatric disorder ; history of neurological or medical disorders, such as traumatic brain injury, brain tumor, and hemiparalysis; and participants who had missing values on independent, dependent, and covariates. This study was approved by the Institutional Review Board of Ajou University Hospital (AJIRB-SBR-SUR-16-122). All participants provided written informed consent.The Korean version of the Pittsburgh Sleep Quality Index (PSQI) was used to examine sleep disturbance. The PSQI is a widely used and validated tool for evaluating sleep quality. The PSQI consists of a self-report questionnaire on sleep quality during the past month. The PSQI has seven sub-scores, each with a score of up to three points . The totThe Korean version of the MNA was used to assess nutritional status. The MNA is a well-validated test to measure the nutritional status of older adults, and it requires a short time to complete. The MNA consists of the following four groups of questions: anthropometric measurements, global assessment, dietary questionnaire, and subjective assessment . The MNAThe Geriatric Depression Scale (GDS) consists of a self-reported yes–no questionnaire, and it is widely used in assessing depression in older adults due to simplicity. GDS has also been shown to be a useful screening tool for depressive symptoms in patients with mild cognitive impairment . The shoVariables known to be associated with depression, sleep, and nutrition were included in the analysis. Sociodemographic parameters, including age, sex, education, living status, and body mass index, were recorded . The lin2 of each variable was calculated, and f2 ≥ 0.02, f2 ≥ 0.15, and f2 ≥ 0.35 were interpreted as small, medium, and large effect sizes, respectively  or the R Statistical Software, version 4.1.0 .To calculate the minimum required number of samples, G*power 3.1.9.7 software was used. Assuming a significance level of 0.05, small effect size, power of 0.8, and number of variables as 10, the analysis indicated that the minimum number of participants required was 822; thus, an adequate number of study participants were included . Numericectively . In Modeectively , 38. P-vDemographic characteristics of the participants are presented in R2 = 0.045 and P < 0.001), and age, sex, education, and living status were significantly associated with depression. While adjusting for all the same variables included and in Model 1, the MNA and PSQI scores were added to Model 2, which demonstrated a considerable increase in adjusted R2 value compared with Model 1 (adjusted R2 = 0.313 and P < 0.001). In Model 2, higher SGDS-K scores were significantly associated with lower MNA scores  and higher PSQI scores . Partial regression plots after adjusting for possible covariates are shown in 2: 0.270) and small for PSQI (Cohen’s f2: 0.035).The results of the multiple linear regression are shown in F-test suggested a significant interaction effect of MNA and PSQI scores . The conditional effect of MNA was significant at the mean PSQI value . The conditional effect of PSQI was also significant at the mean MNA value . To assess and visualize the conditional effects of sleep disturbance and malnutrition on late-life depression, the authors applied the Johnson–Neyman technique. The analysis indicated that the association between sleep disturbance and depression became weaker as nutritional status worsened, even becoming non-significant at a certain level (MNA < 14.028). However, the association between nutritional status and depression was significant regardless of the severity of sleep disturbance  and malnutrition  with depression was observed.There are some limitations to this study. First, as this was a cross-sectional study, it is difficult to determine the causal relationships among depression, sleep disturbance, and malnutrition. Further longitudinal studies are required to verify the current results. Second, the results may not be generalizable to the entire population given that participants were recruited from a mental health center, implying that the rate of coexisting psychiatric or physical illnesses may have been higher. For instance, the prevalence of depression in this study was higher than that reported in a previous nationwide study of older adults in Korea . HoweverIn conclusion, the current results demonstrated that both sleep disturbance and malnutrition were significantly associated with late-life depression. A comparison of effect sizes indicated that malnutrition exerted a greater effect than sleep disturbance, although the interaction between the two was significant. In particular, the effect of sleep disturbance on depression was not significant in patients with severe malnutrition. This study highlights the potential importance of nutritional interventions when developing treatment strategies for community-dwelling older adults with depression.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was approved by the Institutional Review Board of Ajou University Hospital (AJIRB-SBR-SUR-16-122). The patients/participants provided their written informed consent to participate in this study.GH: conceptualization, writing—original draft, and formal analysis. CH and SS: writing—review, editing, methodology, funding acquisition, and supervision. HR: conceptualization, methodology, investigation, writing—original draft, and formal analysis. All authors have approved the final article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.