[Ultrasound-guided continuous fascia iliaca compartment block for perioperative pain management in elderly patients undergoing hip fracture surgery].

OBJECTIVE: To study the effect of ultrasound-guided fascia iliaca compartment block on perioperative analgesia and postoperative complications in geriatric patients with hip fractures. METHODS: A total of 127 elderly patients undergoing hip fracture surgery from January 2021 to September 2021 were randomized to receive ultrasound-guided continuous fascia iliaca compartment block(group F) either intravenous analgesia control group(group C). There were 62 cases in group F, including 19 males and 43 females with an average age of (82.4±7.2) years old ranging from 66 to 95 years old, involving 25 femoral neck fractures and 37 femoral intertrochanteric fractures. There were 65 cases in control group, including 18 males and 47 females, with an average age of (81.4±8.7) years old ranging from 65 to 94 years old, involving 29 femoral neck fractures and 36 femoral intertrochanteric fractures. The visual analogue scale(VAS), minimental state examination (MMSE), observer's assessment of alertness/sedation(OAA/S) scale, modified Bromage score, postoperative complications and general conditions during hospitalization in two groups were observed. RESULTS: The resting and exercise VAS at 30 min after block, anesthesia placement and 6, 24 and 48 h after surgery were lower than those in group C(P<0.05). In group F, MMSE scores at 12 h before surgery, and 1, 3 d after surgery and OAA/S scores at 3 d after surgery were higher than those in group C(P<0.05). The incidence of adverse effects and the number requiring additional analgesia were lower than those in group C(P<0.05). Group F had better perioperative analgesia satisfaction and hospital stay than group C(P<0.05). But there was no significant difference regarding Bromage score and 30-day mortality between two group(P>0.05). CONCLUSION: Ultrasound-guided continuous fascia iliacus space block was safe and effective for elderly patients with hip fracture, and could significantly reduce perioperative pain, improve postoperative cognitive function, and reduce postoperative complications, thereby shortening hospital stay and improving the quality of life during hospitalization.

RNF20 is required for male fertility through regulation of H2B ubiquitination in the Sertoli cells.

BACKGROUND: Spermatogenesis depends on the supporting of the Sertoli cells and their communications with germ cells. However, the regulation of crosstalk between the Sertoli cells and germ cells remains unclear. RESULTS: In this report, we used conditional knockout technology to generate the Sertoli cells-specific knockout of Rnf20 in mice. The Amh-Rnf20-/- male mice were infertile owing to spermatogenic failure that mimic the Sertoli cell-only syndrome (SCOS) in humans. Knockout of Rnf20 resulted in the H2BK120ub loss in the Sertoli cells and impaired the transcription elongation of the Cldn11, a gene encoding a component of tight junction. Notably, RNF20 deficiency disrupted the cell adhesion, caused disorganization of the seminiferous tubules, and led to the apoptotic cell death of both spermatogonia and spermatocytes in the seminiferous tubules. CONCLUSIONS: This study describes a Rnf20 knockout mouse model that recapitulates the Sertoli cell-only syndrome in humans and demonstrates that RNF20 is required for male fertility through regulation of H2B ubiquitination in the Sertoli cells.

DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression.

Myeloproliferative neoplasms (MPNs) exhibit a propensity for transformation to secondary acute myeloid leukemia (sAML), for which the underlying mechanisms remain poorly understood, resulting in limited treatment options and dismal clinical outcomes. Here, we performed single-cell RNA sequencing on serial MPN and sAML patient stem and progenitor cells, identifying aberrantly increased expression of DUSP6 underlying disease transformation. Pharmacologic dual-specificity phosphatase (DUSP)6 targeting led to inhibition of S6 and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling while also reducing inflammatory cytokine production. DUSP6 perturbation further inhibited ribosomal S6 kinase (RSK)1, which we identified as a second indispensable candidate associated with poor clinical outcome. Ectopic expression of DUSP6 mediated JAK2-inhibitor resistance and exacerbated disease severity in patient-derived xenograft (PDX) models. Contrastingly, DUSP6 inhibition potently suppressed disease development across Jak2V617F and MPLW515L MPN mouse models and sAML PDXs without inducing toxicity in healthy controls. These findings underscore DUSP6 in driving disease transformation and highlight the DUSP6-RSK1 axis as a vulnerable, druggable pathway in myeloid malignancies.

A System for Computational Assessment of Hand Hygiene Techniques.

The World Health Organization (WHO) recommends a six-step hand hygiene technique. Although multiple studies have reported that this technique yields inadequate skin coverage outcomes, they have relied on manual labeling that provided low-resolution estimations of skin coverage outcomes. We have developed a computational system to precisely quantify hand hygiene outcomes and provide high-resolution skin coverage visualizations, thereby improving hygiene techniques. We identified frequently untreated areas located at the dorsal side of the hands around the abductor digiti minimi and the first dorsal interosseous. We also estimated that excluding Steps 3, 6R, and 6L from the six-step hand hygiene technique leads to cumulative coverage loss of less than 1%, indicating the potential redundancy of these steps. Our study demonstrates that the six-step hand hygiene technique could be improved to reduce the untreated areas and remove potentially redundant steps. Furthermore, our system can be used to computationally validate new proposed techniques, and help optimise hand hygiene procedures.

Electronic Monitoring Systems for Hand Hygiene: Systematic Review of Technology.

BACKGROUND: Hand hygiene is one of the most effective ways of preventing health care-associated infections and reducing their transmission. Owing to recent advances in sensing technologies, electronic hand hygiene monitoring systems have been integrated into the daily routines of health care workers to measure their hand hygiene compliance and quality. OBJECTIVE: This review aims to summarize the latest technologies adopted in electronic hand hygiene monitoring systems and discuss the capabilities and limitations of these systems. METHODS: A systematic search of PubMed, ACM Digital Library, and IEEE Xplore Digital Library was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were initially screened and assessed independently by the 2 authors, and disagreements between them were further summarized and resolved by discussion with the senior author. RESULTS: In total, 1035 publications were retrieved by the search queries; of the 1035 papers, 89 (8.60%) fulfilled the eligibility criteria and were retained for review. In summary, 73 studies used electronic monitoring systems to monitor hand hygiene compliance, including application-assisted direct observation (5/73, 7%), camera-assisted observation (10/73, 14%), sensor-assisted observation (29/73, 40%), and real-time locating system (32/73, 44%). A total of 21 studies evaluated hand hygiene quality, consisting of compliance with the World Health Organization 6-step hand hygiene techniques (14/21, 67%) and surface coverage or illumination reduction of fluorescent substances (7/21, 33%). CONCLUSIONS: Electronic hand hygiene monitoring systems face issues of accuracy, data integration, privacy and confidentiality, usability, associated costs, and infrastructure improvements. Moreover, this review found that standardized measurement tools to evaluate system performance are lacking; thus, future research is needed to establish standardized metrics to measure system performance differences among electronic hand hygiene monitoring systems. Furthermore, with sensing technologies and algorithms continually advancing, more research is needed on their implementation to improve system performance and address other hand hygiene-related issues.

SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria.

Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets of ovarian and lung cancers. Concomitant loss of these key subunits of SWI/SNF chromatin remodeling complexes in both cancers is associated with chemotherapy resistance and poor prognosis. Here, we discover that SMARCA4/2 loss inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca2+) release in these cancers. By restricting chromatin accessibility to ITPR3, encoding Ca2+ channel IP3R3, SMARCA4/2 deficiency causes reduced IP3R3 expression leading to impaired Ca2+ transfer from the endoplasmic reticulum to mitochondria required for apoptosis induction. Reactivation of SMARCA2 by a histone deacetylase inhibitor rescues IP3R3 expression and enhances cisplatin response in SMARCA4/2-deficient cancer cells both in vitro and in vivo. Our findings elucidate the contribution of SMARCA4/2 to Ca2+-dependent apoptosis induction, which may be exploited to enhance chemotherapy response in SMARCA4/2-deficient cancers.

Anchoring Water Soluble Phosphotungstic Acid by Hybrid Fillers to Construct Three-Dimensional Proton Transport Networks.

Phosphotungstic acid (HPW)-filled composite proton exchange membranes possess high proton conductivity under low relative humidity (RH). However, the leaching of HPW limits their wide application. Herein, we propose a novel approach for anchoring water soluble phosphotungstic acid (HPW) by polydopamine (PDA) coated graphene oxide and halloysite nanotubes (DGO and DHNTs) in order to construct hybrid three-dimensional proton transport networks in a sulfonated poly(ether ether ketone) (SPEEK) membrane. The introduction of PDA on the surfaces of the hybrid fillers could provide hydroxyl groups and secondary amine groups to anchor HPW, resulting in the uniform dispersion of HPW in the SPEEK matrix. The SPEEK/DGO/DHNTs/HPW (90/5/5/60) composite membrane exhibited higher water uptake and much better conductivity than the SPEEK membrane at low relative humidity. The best conductivity reached wass 0.062 S cm-1 for the composite membrane, which is quite stable during the water immersion test.

Salicylic acid-primed defence response in octoploid strawberry 'Benihoppe' leaves induces resistance against Podosphaera aphanis through enhanced accumulation of proanthocyanidins and upregulation of pathogenesis-related genes.

BACKGROUND: Podosphaera aphanis, a predominately biotrophic fungal pathogen, causes significant yield losses of strawberry. China is the largest strawberry producer in the world, and selecting for powdery mildew-resistant cultivars is desirable. However, the resistance mechanism against P. aphanis in the octoploid strawberry remains unclear. RESULTS: To understand possible mechanisms of disease resistance, we inoculated strawberry leaves with P. aphanis, and examined the expression profiles of candidate genes and the biochemical phenotypes in strawberry leaves of two groups. The unigenes obtained from ddH2O- and SA-pretreated leaves resulted in a total of 48,020 and 45,896 genes, respectively. KEGG enrichment showed that phenylpropanoid biosynthesis and plant hormone signal transduction pathways were enriched to a noticeable extent. DEG analysis showed that key TFs genes associated with the SA signaling pathway could play important role in the strawberry-P. aphanis interaction. In particular, FaWRKY70, FaJAZ1 and FaMYC2-like, involved in regulating the antagonistic effect of SA and JA signaling pathway, leading to increased expression of SA-responsive genes (in particular PR1, PR2, PR3, and PR5) compared to a decline in expression of JA-responsive genes (FaJAR1, FaAOS, and FaLOX2). Furthermore, SA pretreatment induced accumulation of PAs by activating the MBW complex and inhibit powdery mildew growth. CONCLUSIONS: This study describes the role of the proanthocyanidins (PAs), pathogenesis-related (PR) genes, SA, and transcription factors in regulatory model against P. aphanis, which coincided with an early activation of defense, leading to the accumulation of PAs and the PR proteins.

CD44 Promotes PD-L1 Expression and Its Tumor-Intrinsic Function in Breast and Lung Cancers.

The PD-L1 (CD274) immune-checkpoint ligand is often upregulated in cancers to inhibit T cells and elicit immunosuppression. Independent of this activity, PD-L1 has recently been shown to also exert a cancer cell-intrinsic function promoting tumorigenesis. Here, we establish this tumor-intrinsic role of PD-L1 in triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). Using FACS-assisted shRNA screens, we identified the cell-surface adhesion receptor CD44 as a key positive regulator of PD-L1 expression in these cancers. Mechanistically, CD44 activated PD-L1 transcription in part through its cleaved intracytoplasmic domain (ICD), which bound to a regulatory region of the PD-L1 locus containing a consensus CD44-ICD binding site. Supporting this genetic interaction, CD44 positively correlated with PD-L1 expression at the mRNA and protein levels in primary tumor samples of TNBC and NSCLC patients. These data provide a novel basis for CD44 as a critical therapeutic target to suppress PD-L1 tumor-intrinsic function. SIGNIFICANCE: CD44 is a potential target to suppress PD-L1 function in TNBC. This finding has the potential to open a new area of therapy for TNBC.

Multimodal Affective Analysis Using Hierarchical Attention Strategy with Word-Level Alignment.

Multimodal affective computing, learning to recognize and interpret human affect and subjective information from multiple data sources, is still challenging because:(i) it is hard to extract informative features to represent human affects from heterogeneous inputs; (ii) current fusion strategies only fuse different modalities at abstract levels, ignoring time-dependent interactions between modalities. Addressing such issues, we introduce a hierarchical multimodal architecture with attention and word-level fusion to classify utterance-level sentiment and emotion from text and audio data. Our introduced model outperforms state-of-the-art approaches on published datasets, and we demonstrate that our model's synchronized attention over modalities offers visual interpretability.

Hybrid Attention based Multimodal Network for Spoken Language Classification.

We examine the utility of linguistic content and vocal characteristics for multimodal deep learning in human spoken language understanding. We present a deep multimodal network with both feature attention and modality attention to classify utterance-level speech data. The proposed hybrid attention architecture helps the system focus on learning informative representations for both modality-specific feature extraction and model fusion. The experimental results show that our system achieves state-of-the-art or competitive results on three published multimodal datasets. We also demonstrated the effectiveness and generalization of our system on a medical speech dataset from an actual trauma scenario. Furthermore, we provided a detailed comparison and analysis of traditional approaches and deep learning methods on both feature extraction and fusion.

Human Conversation Analysis Using Attentive Multimodal Networks with Hierarchical Encoder-Decoder.

Human conversation analysis is challenging because the meaning can be expressed through words, intonation, or even body language and facial expression. We introduce a hierarchical encoder-decoder structure with attention mechanism for conversation analysis. The hierarchical encoder learns word-level features from video, audio, and text data that are then formulated into conversation-level features. The corresponding hierarchical decoder is able to predict different attributes at given time instances. To integrate multiple sensory inputs, we introduce a novel fusion strategy with modality attention. We evaluated our system on published emotion recognition, sentiment analysis, and speaker trait analysis datasets. Our system outperformed previous state-of-the-art approaches in both classification and regressions tasks on three datasets. We also outperformed previous approaches in generalization tests on two commonly used datasets. We achieved comparable performance in predicting co-existing labels using the proposed model instead of multiple individual models. In addition, the easily-visualized modality and temporal attention demonstrated that the proposed attention mechanism helps feature selection and improves model interpretability.

Metallofullerene nanoparticles promote osteogenic differentiation of bone marrow stromal cells through BMP signaling pathway.

Although endohedral metallofullerenol [Gd@C(82)(OH)(22)](n) nanoparticles have anti-tumor efficiency and mostly deposit in the bones of mice, how these nanoparticles act in bone marrow stromal cells (MSCs) remains largely unknown. Herein, we observed that [Gd@C(82)(OH)(22)](n) nanoparticles facilitated the differentiation of MSCs toward osteoblasts, as evidenced by the enhancement of alkaline phosphatase (ALP) activity and mineralized nodule formation upon [Gd@C(82)(OH)(22)](n) nanoparticle treatment. Mechanistically, the effect of [Gd@C(82)(OH)(22)](n) nanoparticles on ALP activity was inhibited by the addition of noggin as an inhibitor of the BMP signaling pathway. Moreover, the in vivo results of the ovariectomized rats further indicated that [Gd@C(82)(OH)(22)](n) nanoparticles effectively improved bone density and prevented osteoporosis.