Explainable machine learning-based prediction model for diabetic nephropathy

The aim of this study is to analyze the effect of serum metabolites on diabetic nephropathy (DN) and predict the prevalence of DN through a machine learning approach. The dataset consists of 548 patients from April 2018 to April 2019 in Second Affiliated Hospital of Dalian Medical University (SAHDMU). We select the optimal 38 features through a Least absolute shrinkage and selection operator (LASSO) regression model and a 10-fold cross-validation. We compare four machine learning algorithms, including eXtreme Gradient Boosting (XGB), random forest, decision tree and logistic regression, by AUC-ROC curves, decision curves, calibration curves. We quantify feature importance and interaction effects in the optimal predictive model by Shapley Additive exPlanations (SHAP) method. The XGB model has the best performance to screen for DN with the highest AUC value of 0.966. The XGB model also gains more clinical net benefits than others and the fitting degree is better. In addition, there are significant interactions between serum metabolites and duration of diabetes. We develop a predictive model by XGB algorithm to screen for DN. C2, C5DC, Tyr, Ser, Met, C24, C4DC, and Cys have great contribution in the model, and can possibly be biomarkers for DN

The effect of adding a home program to weekly institutional-based therapy for children with undefined developmental delay: A pilot randomized clinical trial

AbstractBackgroundEarly rehabilitation for children with developmental delay without a defined etiology have included home and clinic programs, but no comparisons have been made and efficacy is uncertain. We compared a weekly visit for institutional-based therapy (IT) to IT plus a structured home activity program (HAP).MethodsSeventy children who were diagnosed with motor or global developmental delay (ages 6-48 months and mean developmental age 12.5 months) without defined etiology were recruited (including 45 males and 23 females). The outcomes included the comprehensive developmental inventory for infants and toddlers test and the pediatric evaluation of disability inventory.ResultsChildren who received only IT improved in developmental level by 2.11 months compared with 3.11 months for those who received a combination of IT and HAP (p = 0.000). On all domains of the comprehensive developmental inventory for infants and toddlers test, except for self-help, children who participated in HAP showed greater improvements, including in cognition (p = 0.015), language (p = 0.010), motor (p = 0.000), and social (p = 0.038) domains. Except on the subdomain of self-care with caregiver assistance, the HAP group showed greater improvement in all the pediatric evaluation of disability inventory subdomains (p < 0.05).ConclusionEarly intervention programs are helpful for these children, and the addition of structured home activity programs may augment the effects on developmental progression

Genome-Wide Association Study Reveals Candidate Genes for Growth Relevant Traits in Pigs

Improvement of the growth rate is a challenge in the pig industry, the Average Daily Gain (ADG) and Days (AGE) to 100 kg are directly related to growth performance. We performed genome-wide association study (GWAS) and genetic parameters estimation for ADG and AGE using the genomic and phonemic from four breed (Duroc, Yorkshire, Landrace, and Pietrain) populations. All analyses were performed by a multi-loci GWAS model, FarmCPU. The GWAS results of all four breeds indicate that five genome-wide significant SNPs were associated with ADG, and the nearby genomic regions explained 4.08% of the genetic variance and 1.90% of the phenotypic variance, respectively. For AGE, six genome-wide significant SNPs were detected, and the nearby genomic regions explained 8.09% of the genetic variance and 3.52% of phenotypic variance, respectively. In total, nine candidate genes were identified to be associated with growth and metabolism. Among them, TRIB3 was reported to associate with pig growth, GRP, TTR, CNR1, GLP1R, BRD2, HCRTR2, SEC11C, and ssc-mir-122 were reported to associate with growth traits in human and mouse. The newly detected candidate genes will advance the understanding of growth related traits and the identification of the novel variants will suggest a potential use in pig genomic breeding programs

Effects of Tai Chi on telomerase activity and gerotranscendence in middle aged and elderly adults in Chinese society

AbstractIntroductionTelomeres are DNA protein structures at the end of chromosomes and are linked to the physical aging process. The improvement of quality of life is closely associated with aerobic exercise, and the dynamic effects of exercise on physiology and psychology are evident with aging. Tai Chi is popularly practiced in China. However, findings on the effects of Tai Chi on telomerase activity (TA) in peripheral blood mononuclear cells, and gerotranscendence (GT), as well as the association of TA and GT with Tai Chi, have been inconsistent.PurposeThis study aims to assess TA in peripheral blood mononuclear cells, GT, and the associations between them. The associations among these variables are determined during six months of Tai Chi intervention among Chinese middle aged and elderly adults.MethodsTA assessment was obtained by TE-ELISA (human telomerase–enzyme linked immunosorbent assay), and GT was measured at the baseline level after six months of Tai Chi intervention.ResultsTA increased significantly in the Tai Chi group from 23.75 ± 3.78 u/mmol (pre-intervention) to 26.31 ± 2.93 u/mmol (after 6 months) (p < 0.05). Compared with the TA in the control group, the TA in the intervention group was statistically significant after six months (p < 0.05). Compared with the GT in the control group, the GT in the intervention group improved significantly after six months (p < 0.05). TA and GT had a positive correlation (r = 0.325, p < 0.01).ConclusionOur data illustrated that Tai Chi had a protective effect on TA and might improve the GT in Chinese middle aged and elderly adults. The TA increased with the increasing GT in Chinese middle aged and elderly adults

Autopsie d’une membrane d’osmose inverse usagée prélevée dans le Parc National du Banc d’Arguin (PNBA) en Mauritanie : cas d’étude de Teichitt

L’objectif de ce travail est d’étudier l’état de vieillissement d’une membrane d’osmose inverse (OI) usagée prélevée en Mauritanie sur une unité de dessalement installée par la coopération canarienne à Teichitt dans le parc national du banc d’Arguin et de lui appliquer une démarche d’autopsie. L’usure de la membrane est caractérisée par une augmentation significative de la perméabilité hydraulique (25 % d’augmentation) et une diminution de la rétention en sels (10 % à 30 % de diminution). Un modèle de transfert de matière de type diffusion-convection permet de montrer l’augmentation du caractère convectif du transfert, lorsque la pression transmembranaire augmente et en particulier au-delà de 15 bars. Ainsi, l’usure de la membrane d’OI induit son rapprochement vers un transfert de matière combiné de solubilisation-diffusion/convection, typique d’une opération de nanofiltration (NF). L’analyse topographique par AFM de la surface de la membrane usagée en comparaison de la membrane neuve laisse apparaître des « cavités » à plusieurs endroits de la surface usagée traduisant la dégradation physique de celle-ci. De plus, la rugosité de surface de la membrane usagée avec 74 nm est apparue supérieure à celle de la membrane neuve avec 54 nm, ce qui nous informe de la présence de matières colmatantes, dont la nature reste encore à déterminer. Par contre, l’étude de la dégradation chimique des membranes usagées et neuves par la détermination de leur point isoélectrique (PIE) à partir d’une mesure de potentiel d’écoulement transmembranaire ne montre pas de modifications significatives de ce paramètre (PIE = 2,5), preuve de la non-dégradation chimique interne de la membrane. Enfin, les résultats d’une étude statistique préliminaire sont présentés. Celle-ci consiste à évaluer l’hétérogénéité de l’usure en matière de perméabilité hydraulique et de rétention d’une solution de NaCl 0,1 M à 15 bars et 19 °C, pour six coupons différents pris sur les trois feuilles de membranes constituant le module d’osmose inverse usagé. Une tendance se dégage, elle montre en particulier que l’usure est hétérogène, non seulement au sein d’une même feuille de membrane, mais aussi au sein des différentes membranes constituant le module. En résumé, il est observé pour la première fois qu’une vieille membrane d’OI employée pendant deux années pour le dessalement d’eau de mer, dans les conditions d’utilisation sahariennes en Mauritanie (sans pré-traitements), acquiert une microporosité qui lui confère les propriétés d’une membrane de nanofiltration.Currently used reverse osmosis (RO) membranes from desalination units are burned at the end of their life as membranes for seawater desalination. In the future, a possible alternative would be to reuse the old RO membranes as nanofiltration (NF), ultrafiltration (UF) or microfiltration (MF) membranes, i.e. for wastewater treatments, but before reuse, the level of RO membrane degradation must be evaluated by autopsy studies.Our goal in the present study was to demonstrate for the first time that a used RO membrane could be used for nanofiltration. The used RO membrane was purchased from a desalination bench scale unit based in the town of Teichitt (in north-west Nouakchott, Mauritania). Membrane autopsy studies showed an increase in its hydraulic permeability (25%) and a concurrent decrease in its salt rejection behaviour (10% to 30%). We also studied the modification of mass transfer before and after ageing, and demonstrated the onset of a convective component in the mass transfer of salts and an increase in membrane hydraulic permeability. Furthermore, the determination of the isoelectric point (IEP) of the membrane, using streaming potential measurements across the membranes, showed no change in IEP, with a value of 2.5 ± 0.2 . A preliminary study, based on a statistical evaluation of membrane degradation from hydraulic permeability and salt rejection experiments, showed heterogeneous wear of the membrane (most important in the centre). Finally, we observed for the first time that after two years of use for desalination, a used RO membrane had acquired a microporosity that corresponded to the properties of a new NF membrane

香港鄉村地區長者居家養老的需要：錦田例案報告 = The needs of ageing in place in rural Hong Kong: The case of Kam Tin

香港面臨人口高齡化，政府統計處（2020）估計65 歲或以上人口會由2019年的120萬增加至2039年252 萬。長者佔總人口比例亦由18.4%上升至33.3%；而老年撫養比率（65 歲及以上人口相對每千名15 至64 歲人口的比率）將由249大幅上升至508。這意味着社會在撫養和照顧長者, 將會面對更大的壓力。另外，老年家庭人口亦不斷增加, 家庭所有成員均為長者的數目從2006年大約18萬上升至2016年超過30萬（增長67.4%）；獨居長者佔長者人口的比例亦由11.6%上升至13.1% （政府統計處，2018）。面對人口老化﹑雙老及獨居家庭等問題，社區需要有更全面的支持配套，才能使長者有良好的生活質素。 香港「社區照顧」（community care）政策源於政府於1977年發佈的《老人服務綠皮書》，強調居家安老為服務原則。該綠皮書（政府社會事務科，1977，頁5）指出，在社會及財政上而言，最可行的辦法就是提供適當的社會服務以幫助老年人能繼續與社會接觸在一起…當一個家庭在照顧老年人方面感到吃力時，政府便提供各種服務作爲對家庭一種的支持和協助。使老年人能繼續在家庭生活。 儘管政府一直強調「居家安老為本，院舍照顧為後援」，但多年來的資源分佈仍是以院舍照顧服務佔較大比例 （香港政策研究所，2017；羅致光，2018）。政府近年開始作出規劃上的調整，安老事務委員會（2017）於2017年發佈《安老服務計劃方案》建議加大社區照顧服務的比例，將社區照顧服務及院舍照顧服務的名額比率 由2016 年的1:1.3 加大至2031年的1:1.1（安老事務委員會，2017；羅致光， 2018）。因此, 加強「居家安老」政策，將會是政府其中一個安老服務規劃方向。 雖然政府及不同的社福機構在「居家安老」方面都有提供長者服務，但服務主要仍集中在城市，居住鄉村的長者因缺乏資源和渠道，較難得到協助。以居於元朗錦田 的長者為例，公營長者日間護理服務單位，全部位於元朗、天水圍或朗屏市區（社會福利署，2021），與他們的住處有一段距離。此外，針對鄉郊長者情況的「居家安老」服務規劃，亦未有在《安老服務計劃方案》中提及。因此, 本研究選取錦田區的長者作為主要訪談對象, 以了解鄉郊長者的「居家安老」情況。 錦田有悠久歷史，為最早來港定居的鄧氏族人居住地，有相當豐富的歷史建築群（陳天權，2016）。錦田面積龐大，近年開始規劃的錦田南和錦田北，佔地約1,400 公頃 （政府新聞公報，2014），佔元朗區14,430 公頃約一成面積，但人口只有 13,489，佔元朗人口約2% （政府統計處，2017；民政事務署，2021）。政府在錦 田規劃大綱中，仍保留不少地帶作「農業」、「自然保育區」或「鄉村式發展」用途（政府新聞公報，2014，2018）。因此，錦田仍然是本港主要的鄉郊地區之一。 本研究希望了解錦田長者的居家養老狀況和需求，為發展鄉郊長者服務的提供參考 資料。研究團隊探討長者於三個範疇的狀況，包括「社交支持」、「居所及社區支援 服務」和「長期護理服務的認識及意見」，並針對這三部分的發現提供相關建議

Combination of G-CSF and AMD3100 Improves the Anti-inflammatory Effect of Mesenchymal Stem Cells on Inducing M2 Polarization of Macrophages Through NF-κB-IL1RA Signaling Pathway

Mobilized peripheral blood-derived mesenchymal stem cells (PB-MSCs) mainly derived from bone marrow-derived MSCs (BM-MSCs) exert a similar anti-inflammatory effect. However, the mechanism of anti-inflammatory effect of mobilized PB-MSCs by a combination of G-CSF and AMD3100 remains unclear. Cultured rat PB-MSCs mobilized by G-CSF/AMD3100 have shown typical surface markers and potential for multiple differentiations, similar to non-mobilized BM-MSCs. In a co-culture system, rat M0-type macrophages co-cultured with PB-MSCs have shown higher expression of M2 markers including CD206, Arg-1, IL-10, and CCL-22 than BM-MSCs, indicating that PB-MSCs induced greater M0 polarization to M2. Furthermore, compared with BM-MSCs, PB-MSCs in a co-culture system with lipopolysaccharide-induced M1-type macrophages more efficiently promoted M1 polarization to M2, accompanied by increasing expression of CD206, Arg-1, IL-10, and CCL-22 while decreasing expression of M1 markers including iNOS, TNF-α, IL-1β and IL-6, indicating that PB-MSCs triggered greater M1 polarization to M2. Subsequently, polymerase chain reaction arrays showed higher expressions of both IL1rn and Tnfrsf11b in PB-MSCs versus BM-MSCs. In response to an inflammatory niche, such as TNF-α, PB-MSCs have shown higher expression and release of IL1RA, causing greater M2 polarization of macrophages, and the special effects may be almost entirely abolished through the neutralization antibody of IL1RA. Mechanistic studies determined that PB-MSCs showed higher levels NF-κBp65 and NF-κBp-p65 than BM-MSCs, which could be obviously enhanced by TNF-α. And the increased IL1RA expression by TNF-α in PB-MSCs could be markedly canceled by an NF-κB inhibitor PDTC. Interestingly, mimicking the mobilized PB-MSCs by a combination of G-CSF and AMD3100 in vivo, BM-MSCs were treated with G-CSF and/or AMD3100 in vitro, showing the increased expressions of NF-κBp65 and IL1RA, which could be prominently abolished by PDTC. Therefore, targeting IL1rn, gene modification or drug intervention for MSCs may provide a novel therapeutic strategy for human diseases, especially inflammatory diseases

Molecular determinants of plaque size as an indicator of dengue virus attenuation

The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients, and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines