2D-3D Interlaced Transformer for Point Cloud Segmentation with Scene-Level Supervision

We present a Multimodal Interlaced Transformer (MIT) that jointly considers 2D and 3D data for weakly supervised point cloud segmentation. Research studies have shown that 2D and 3D features are complementary for point cloud segmentation. However, existing methods require extra 2D annotations to achieve 2D-3D information fusion. Considering the high annotation cost of point clouds, effective 2D and 3D feature fusion based on weakly supervised learning is in great demand. To this end, we propose a transformer model with two encoders and one decoder for weakly supervised point cloud segmentation using only scene-level class tags. Specifically, the two encoders compute the self-attended features for 3D point clouds and 2D multi-view images, respectively. The decoder implements interlaced 2D-3D cross-attention and carries out implicit 2D and 3D feature fusion. We alternately switch the roles of queries and key-value pairs in the decoder layers. It turns out that the 2D and 3D features are iteratively enriched by each other. Experiments show that it performs favorably against existing weakly supervised point cloud segmentation methods by a large margin on the S3DIS and ScanNet benchmarks. The project page will be available at https://jimmy15923.github.io/mit_web/.Comment: ICCV 2023 (main + supp). Website: https://jimmy15923.github.io/mit_web

Minimum average-case queries of q + 1 -ary search game with small sets

Given a search space S={1,2,...,n}, an unknown element x*∈S and fixed integers ℓ≥1 and q≥1, a q+1-ary ℓ-restricted query is of the following form: which one of the set {A 0,A 1,...,A q} is the x* in?, where (A 0,A 1,...,A q) is a partition of S and | Ai|≤ℓ for i=1,2,...,q. The problem of finding x* from S with q+1-ary size-restricted queries is called as a q+1-ary search game with small sets. In this paper, we consider sequential algorithms for the above problem, and establish the minimum number of average-case sequential queries when x* satisfies the uniform distribution on S. © 2011 Elsevier B.V. All rights reserved

Chinese Medicinal Herbs for Childhood Pneumonia: A Systematic Review of Effectiveness and Safety

Objective. To assess the efficacy and safety of Chinese medicinal herbs for Childhood Pneumonia. Methods. We included randomized controlled trials (RCTs). The searched electronic databases included PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, CBM, CNKI, and VIP. All studies included were assessed for quality and risk bias. Review Manager 5.1.6 software was used for data analyses, and the GRADEprofiler software was applied to classify the systematic review results. Results. Fourteen studies were identified (n=1.824). Chinese herbs may increase total effective rate (risk ratio (RR) 1.18; 95% confidence interval (CI), 1.11–1.26) and improve cough (total mean difference (MD), −2.18; 95% CI, (−2.66)–(−1.71)), fever (total MD, −1.85; 95% CI, (−2.29)–(−1.40)), rales (total MD, −1.53; 95% CI, (−1.84)–(−1.23)), and chest films (total MD, −3.10; 95% CI, (−4.11)–(−2.08)) in Childhood Pneumonia. Chinese herbs may shorten the length of hospital stay (total MD, −3.00; 95% CI, (−3.52)–(−2.48)), but no significant difference for adverse effects (RR, 0.39; 95% CI, 0.09–1.72) was identified. Conclusion. Chinese herbs may increase total effective rate and improve symptoms and signs. However, large, properly randomized, placebo-controlled, double-blind studies are required

Withania somnifera Root Extract Enhances Chemotherapy through ‘Priming’

Withania somnifera extracts are known for their anti-cancerous, anti-inflammatory and antioxidative properties. One of their mechanisms of actions is to modulate mitochondrial function through increasing oxidative stress. Recently ‘priming’ has been suggested as a potential mechanism for enhancing cancer cell death. In this study we demonstrate that ‘priming’, in HT-29 colon cells, with W. somnifera root extract increased the potency of the chemotherapeutic agent cisplatin. We have also showed the W. somnifera root extract enhanced mitochondrial dysfunction and that the underlying mechanism of ‘priming’ was selectively through increased ROS. Moreover, we showed that this effect was not seen in non-cancerous cells

Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress

Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Effects of retinoic acid and hepatocyte growth factor on intramammary cell renewal and stromal remodeling of newly dried dairy cows

維生素A酸 (retinoic acid, RA)和肝細胞生長因子 (hepatocyte growth factor, HGF)可調控細胞基質金屬分解酶 (matrix metalloproteinase, MMP)表現、細胞週期和細胞凋亡 (apoptosis) 與增生。因此，RA 及 HGF可能參與乳牛乾乳期乳腺之重組。本研究分別於乳牛乾乳當天 (d0)、乾乳後第7天 (d7)從乳頭灌流 RA 40 μg/分房及HGF 2.5 μg/分房至兩分房內(處理組)，其餘兩分房則灌流磷酸緩衝液(Phosphate-Buffered Saline, PBS) (控制組)。採集乳腺分泌物樣品分別於d0、d3、d7、d10、及d14進行，並新鮮分離體細胞和乳清。體細胞計數(microscopic somatic cell counts, MSCC)後使用流式細胞儀觀察體細胞類型、體細胞週期、體細胞apoptosis、體細胞中上皮細胞之比例，並測定體細胞HGF受器 c-Met 表現。乳清用於測定基質金屬蛋白酶(Matrix Metalloproteinase, MMP)活性。研究結果顯示，控制組於d7 - d14 時MSCC (327.6 – 464.0 x 104 cells /mL)顯著高於d0 (3.4 x 104 cells /mL) (P0.05)。利用gelatin-zymography測定乳清中pro-MMP-9 (92 kDa)、active MMP-9 (82 kDa)、pro-MMP-2 (72 kDa)和active MMP-2 (62 kDa)，結果顯示控制組乳清中各種MMP於d7 - d14均顯著高於d0 (P0.05) at d0 - d14. The result of gelatin-zymography analysis showed that pro-MMP-9 (92kDa), active MMP-9 (82kDa), pro-MMP-2 (72kDa) and active MMP-2 (62kDa) of skim milk layer, pro-MMP-9, active MMP-9, pro-MMP-2 and active MMP-2 activity of control group at d7, d10, d14 was significantly higher than those at d0 (P<0.01), active MMP activity of treatment group at d7 - d14 were also higher than those at d0 and active MMP-2 activity of treatment group at d7 was significantly higher than that of control group at the same day (P<0.05). Altogether, MSCC, macrophage ratio, G0/G1 phase ratio of somatic cells, epithelial ratio of somatic cells, and MMP activity of whey increased and S phase ratio decreased as the dry period proceeded. Apoptosis, G2/M phase, c-Met expression ratio was not significantly changed in control and treatment group. After RA and HGF infusion, MSCC was lower than control at d14, epithelial ratio of somatic cells was lower than control at d7, apoptosis ratio of somatic cells increased at d3 - d14, c-Met expression of somatic cells trend to increased at d 3, and active MMP2 activity increased at d7. The results of this study indicated that immune cells migrated quickly in mammary gland of dairy cows in dry period., Macrophages migrate the fastest among the immune cells is. At the same time, the decline of epithelial cells in mammary gland was accelerated. However, the rate of cell proliferation was palliated. The infusion of RA and HGF reduced the migration of immune cell to mammary gland and shed of epithelial cells, promoted apoptosis and c-Met expression, and increased MMP secretion. These will be helpful in intramammary cell renewal and stromal remodeling.壹、前言 1 貳、文獻探討 2 一、乳牛乳腺生理 2 (一) 乳腺結構 2 (二) 乾乳期乳腺之重組 2 (三) 乳腺上皮細胞之凋亡與增生 2 (四) 牛乳體細胞種類與功能 5 (五) 牛乳主要蛋白質成分 6 二、Retinoic acid 6 (一) Retinoic acid之生理功能與合成 6 (二) Retinoic acid在乳腺之可能角色 7 三、Hepatocyte growth factor 9 (一) Hepatocyte growth factor之生理功能與合成 9 (二) Hepatocyte growth factor在乳腺之可能角色 9 四、Flow cytometry 11 (一) 原理 11 (二) 應用 13 五、基質金屬蛋白酶(matrix metalloproteinase, MMPs) 13 (一) MMPs之結構及種類 13 (二) MMPs在生理之角色 15 (三) MMPs與TIMPs 15 参、材料與方法 19 一、乾乳牛之飼養管理 19 二、灌流試驗設計及採樣 19 三、RA 和HGF灌流液的配製 20 四、乾乳分泌物體細胞及上清液的製備 22 五、蛋白質定量的測量 22 六、SDS-PAGE 分析 23 七、Gelatin zymography 24 八、Flow cytometric somacic cell typing and cell cycle analyses 25 九、Flow cytometric somatic cell apoptosis analyses 26 十、Flow cytometric epithelial cell analyses 26 十一、RT-PCR 26 十二、統計分析 30 肆、結果 31 一、乾乳分泌物中體細胞總數及細胞種類百分比受RA和HGF處理之影響 31 (一) 體細胞總數 31 (二) 體細胞種類 33 二、乾乳分泌物中體細胞之細胞週期受RA和HGF處理之影響 36 三、乾乳分泌物中體細胞之凋亡受RA和HGF處理之影響 39 四、乾乳分泌物中體細胞之上皮細胞百分比受RA和HGF處理之影響 42 五、乾乳分泌物中體細胞上c-Met表現受RA和HGF處理之影響 48 六、乾乳分泌物中總蛋白質含量與乳清成分受RA和HGF處理之影響 50 (一) 總蛋白質含量 50 (二) 乳清成分 50 七、乾乳分泌物中MMP活性受RA和HGF處理之影響 54 八、相關性分析 58 伍、討論 60 一、乳線內灌流 RA 和 HGF 後對乳腺分泌物中 SCC 和不同種類體細胞所佔比例之影響 60 二、乳線內灌流RA和HGF後對乳腺分泌物中體細胞週期之影響 61 三、乳線內灌流RA和HGF後對乳腺分泌物中體細胞凋亡之影響 61 四、乳線內灌流RA和HGF後對體細胞中上皮細胞含量之影響 62 五、乳線內灌流RA和HGF後對乳腺分泌物中蛋白質成分改變之影響 62 六、乳線內灌流RA和HGF後對乳腺中 MMP-9 與 MMP-2 活性及對乳腺 退化過程之影響 63 七、相關性分析 64 八、總結 64 陸、結論 65 柒、參考文獻 6