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Jeff Malpasʼ concept of place as a bounded, open, and emergent structure is used in this article to understand the reasons for the differences in villagersʼ responses to 'artificial glaciers', or 'Ice stupas', built in two different places in the Himalayan village of Phyang, in Ladakh. Using archival material, geographic information system tools and ethnographic research, this study reveals how Phyang as a village is constituted by interacting ecological-technical, socio-symbolic, and bureaucratic-legal boundaries. It is observed that technologies such as land revenue records, and cadastral maps, introduced in previous processes of imperialist state formation, continue to inform water politics in this Himalayan region. It is further demonstrated how this politics is framed within the village of Phyang, but also shifts its boundaries to create the physical, discursive, and symbolic space necessary for projects like the Ice stupa to emerge. By examining the conflict through the lens of place, it is possible to identify the competing discursive frames employed by different stakeholders to legitimise their own projects for developing the arid area (or Thang) where the contested Ice stupa is located. Such an analysis allows critical water scholarship to understand both how places allow hydrosocial relationships to emerge, and how competing representations of place portray these relationships. Understanding the role of place in the constitution of hydrosocial relationships allows for a more nuanced appraisal of the challenges and opportunities inherent in negotiating development interventions aimed at mitigating the effects of climate change. It is also recommended that scholars studying primarily the institutional dimensions of community-managed resource regimes consider the impact on these institutions of technological artefacts such as the high density polyethylene (HDPE) pipes used to construct the Ice stupas.

IntroductionPercutaneous transforaminal endoscopic discectomy (PTED) is increasing in popularity as a minimally invasive procedure to treat sciatica caused by lumbar disc herniation. The objective of the current study is to evaluate safety of and satisfaction with the use of local anesthesia and conscious sedation during PTED.MethodsDuring a 12-month inclusion period, patients were prospectively included in this single center case series. Inclusion criteria consisted of sciatica lasting for at least 6 weeks, which was not responsive to conservative treatment. PTED was performed using dexmedetomidine as sedative and lidocaine as local anesthesia. Measurements included the numeric rating scale (NRS, from 0 to 10) for leg pain, back pain, COMI-back, and NRS for anxiety of anesthesia and perioperative continuously monitored hemodynamics. Furthermore, satisfaction with the sedation was scored by patients, surgeons, and anesthesiologists.ResultsNinety-two consecutive patients were enrolled. Of all patients, 18.5% had anxiety for undergoing surgery under local anesthesia. All but one patient underwent PTED successfully. There was one case of conversion due to severe, uncontrollable back pain during surgery. Throughout the procedure, hemodynamic parameters showed no clinically relevant change compared to baseline. Anesthesiologic complications were three cases (3.4%) of self-limiting hypoxia and five cases (8.6%) of nausea and/or vomiting. Surgeons and anesthesiologists had a high satisfaction rate (> 87%) with the conscious sedation during the procedure, while satisfaction with sedation was scored 8.4 ± 2.2 by patients.ConclusionsPTED performed under local anesthesia and conscious sedation is safe and effective to treat sciatica and yields high satisfaction rates from surgeons, anesthesiologists, and patients.

Autism spectrum condition (ASC) is primarily diagnosed by behavioural symptoms including social, sensory and motor aspects. Although stereotyped, repetitive motor movements are considered during diagnosis, quantitative measures that identify kinematic characteristics in the movement patterns of autistic individuals are poorly studied, preventing advances in understanding the aetiology of motor impairment, or whether a wider range of motor characteristics could be used for diagnosis. The aim of this study was to investigate whether data-driven machine learning based methods could be used to address some fundamental problems with regard to identifying discriminative test conditions and kinematic parameters to classify between ASC and neurotypical controls. Data was based on a previous task where 16 ASC participants and 14 age, IQ matched controls observed then imitated a series of hand movements. 40 kinematic parameters extracted from eight imitation conditions were analysed using machine learning based methods. Two optimal imitation conditions and nine most significant kinematic parameters were identified and compared with some standard attribute evaluators. To our knowledge, this is the first attempt to apply machine learning to kinematic movement parameters measured during imitation of hand movements to investigate the identification of ASC. Although based on a small sample, the work demonstrates the feasibility of applying machine learning methods to analyse high-dimensional data and suggest the potential of machine learning for identifying kinematic biomarkers that could contribute to the diagnostic classification of autism.

NOD1 and NOD2, founding members of the NOD-like receptor (NLR) family, play a crucial role in host defense against bacterial infections. Recognition of peptidoglycan-derived ligands triggers ATP-dependent oligomerization of the NACHT domain, exposing the CARD domains that recruit the adaptor protein RIP2 via CARD-CARD interactions to activate the NF-κB signaling cascade. Although NOD1/2-RIP2 interactions and RIP2CARD filament assembly are established, the precise interfaces that stabilize hetero-CARD filaments remain poorly defined. Here, we integrate in silico structural modeling with molecular dynamics (MD) simulations to elucidate structurally compatible arrangements of NOD1-RIP2 and NOD2-RIP2 hetero-CARD filaments. Our results reveal that NOD1CARD subunits form a structurally compatible homomeric scaffold via canonical (type-I-III) interfaces, accommodating multiple tiers of RIP2CARD rings at both filament termini. Meanwhile, the NOD2 tandem CARDs adopt multiple discrete conformations, reflecting a more intricate structural mechanism. In stable filament conformations, tandem CARDs converge at the type-II interface, with RIP2CARD rings stacking onto CARDa (top-down) and CARDb (bottom-up) interfaces, highlighting the structural role of NOD2CARDb in RIP2-mediated CARD-CARD interaction. In silico mutagenesis, involving charge-reversal and alanine scanning of key interfacial residues, disrupts NOD1-RIP2 and NOD2-RIP2 interactions at both top-down and bottom-up interfaces, leading to rapid interface destabilization within 0.1-0.4 μs of simulation. Together, these results reveal conserved and receptor-specific mechanisms governing NOD1/2-RIP2 CARD-CARD interactions and provide deeper structural and dynamic insights into the complex structural mechanisms for NLR-mediated inflammatory signaling.

Here, Sharma shares his personal experiences treating opioid addiction. Onto the table fall its contents: two brown vials, a pair of gloves, several packs of sterile swabs and a syringe that peaks quickly into a capped silver needle. The latter is primed with a dose of naloxone, which, when coursing through a body turned cold and blue, will free the brain's receptors from the suffocating grips of an opioid. It's a matter of seconds before he's pulled back to life, says a voice. The beginnings of those struggling with opioids are as varied as the people who call the Downtown Eastside home. On the service, his work has two parts. The first is to make sure that those who come to hospital receive (or are started on) the opioid-replacement therapies they take at their neighborhood clinic.

Polyphosphates are linear polymers and ubiquitous metabolites. Bacterial polyphosphates are long chains of hundreds of phosphate units. Here, we report that mouse survival of peritoneal Escherichia coli sepsis is compromised by long-chain polyphosphates, and improves with bacterial polyphosphatekinase deficiency or neutralization using recombinant exopolyphosphatase. Polyphosphate activities are chain-length dependent, impair pathogen clearance, antagonize phagocyte recruitment, diminish phagocytosis and decrease production of iNOS and cytokines. Macrophages bind and internalize polyphosphates, in which their effects are independent of P2Y1 and RAGE receptors. The M1 polarization driven by E. coli derived LPS is misdirected by polyphosphates in favor of an M2 resembling phenotype. Long-chain polyphosphates modulate the expression of more than 1800 LPS/TLR4-regulated genes in macrophages. This interference includes suppression of hundreds of type I interferon-regulated genes due to lower interferon production and responsiveness, blunted STAT1 phosphorylation and reduced MHCII expression. In conclusion, prokaryotic polyphosphates disturb multiple macrophage functions for evading host immunity. Production of polyphosphate polymers is a ubiquitous trait of bacteria. Here, the authors investigate the role of bacterial long polyphosphates in host immune suppression and show that long polyphosphates produced by E. coli inhibit LPS-mediated inflammation and bacterial clearance in mice.

We developed a rich dataset of Chest X-Ray (CXR) images to assist investigators in artificial intelligence. The data were collected using an eye-tracking system while a radiologist reviewed and reported on 1,083 CXR images. The dataset contains the following aligned data: CXR image, transcribed radiology report text, radiologist’s dictation audio and eye gaze coordinates data. We hope this dataset can contribute to various areas of research particularly towards explainable and multimodal deep learning/machine learning methods. Furthermore, investigators in disease classification and localization, automated radiology report generation, and human-machine interaction can benefit from these data. We report deep learning experiments that utilize the attention maps produced by the eye gaze dataset to show the potential utility of this dataset. Measurement(s) chest X-ray image • radiologist’s dictation audio data • radiologist’s eye gaze coordinates data Technology Type(s) eye tracking device • machine learning • Radiologist • Chest Radiography Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14035613

Guidelines recommend the treatment of emergent large vessel ischemic stroke (ELVIS) patients presenting beyond 6 hours of last known well time with endovascular thrombectomy (EVT) based on perfusion computed tomography (CT) neuroimaging. We compared the outcomes (long-term good clinical outcomes, symptomatic intracranial hemorrhage (sICH), and mortality) of ELVIS patients according to the type of CT neuroimaging they underwent. We searched the following databases: Medline, Embase, CENTRAL, and Scopus from January 1, 2015, to June 14, 2023. We included studies of late-presenting ELVIS patients undergoing EVT that had with data for non-perfusion and perfusion CT neuroimaging. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were pooled using a random effects model. We found 7 observational cohorts. Non-perfusion versus perfusion CT was not statistically significantly different for both long-term clinical (n = 3,224; RR: 0.96; 95% CI 0.86 to 1.06; I2 = 18%) and sICH (n = 3,724; RR: 1.08 95% CI 0.60 to 1.94; I2 = 76%). Perfusion CT had less mortality (n = 3874; RR: 1.22; 95% CI 1.07 to 1.40; I2 = 0%). The certainty of these findings is very low because of limitations in the risk of bias, indirectness, and imprecision domains of the Grading of Recommendations, Assessment, Development and Evaluations. The use of either non-perfusion or perfusion CT neuroimaging may have little to no effect on long-term clinical outcomes and sICH for late-presenting EVT patients. Perfusion CT neuroimaging may be associated with a reduced the risk of mortality. Evidence uncertainty warrants randomized trial data.

Background: Assessment of correlation between peri-implant parameters and C-reactive protein levels among patients with different obesity levels. Materials and Methods: Evaluation of 60 subjects was performed who were scheduled to undergo dental implant therapy for missing mandibular first molars. Three study cohorts were formed, namely, Group A: obese group (BMI between 30 Kg/m2 and 34.9 Kg/m2), Group B: high obese group (BMI over 34.9 Kg/m2), and Group C: non-obese group (BMI under 25 Kg/m2). Each cohort comprised 20 subjects. Dental implant therapy was carried out in all the patients. Peri-implant variables were evaluated in all the patients. Blood samples were obtained, and C-reactive protein levels in subjects having different obesity levels. Statistical analysis was performed using SPSS software. Results: Mean serum C-reactive protein levels among patients of groups A, B, and C occurred to be 3.28 mg/L, 3.65 g/L, and 3.61 g/L, respectively. On comparing numerically, noticeable outcomes were achieved. Mean probing depth among subjects of groups A, B, and C occurred to be 2.9 mm, 3.2 mm, and 1.3 mm, respectively. Mean marginal bone loss among subjects of groups A, B, and C occurred to be 2.1 mm, 2.7 mm, and 0.8 mm, respectively. On comparing numerically, noteworthy outcomes were gathered. Conclusion: There were significantly higher deranged peri-implant inflammatory variables among patients with higher levels of obesity.

De-Chen Lin and colleagues report whole-exome sequencing, targeted sequencing and SNP array analysis of 128 cases of nasopharyngeal carcinoma (NPC), a tumor type connected to Epstein-Barr virus infection. Their results identify a distinct mutational signature with nine significantly mutated genes and mutations enriched in cellular processes, including chromatin modification and autophagy. Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC.