bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EUROPEAN SHOCK SOCIETY MEETS THE IMMUNOSEP CONSORTIUM FOR PERSONALIZED SEPSIS TREATMENT
Authors: Giamarellos-Bourboulis Evangelos J. , Dimopoulos George , Flohé Stefanie , Kotsaki Antigoni , van der Poll Tom , Skirecki Tomasz , Torres Antoni , Netea Mihai G. 
Published: March 2023

ABSTRACT
The unacceptable high mortality of severe infections and sepsis led over the years to understand the need for adjunctive immunotherapy to modulate the dysregulated host response of the host. However, not all patients should receive the same type of treatment. The immune function may largely differ from one patient to the other. The principles of precision medicine require that some biomarker is used to capture the immune function of the host and guide the best candidate therapy. This is the approach of the ImmunoSep randomized clinical trial (NCT04990232) where patients are allocated to treatment with anakinra or recombinant interferon gamma tailored to immune signs of macrophage activation-like syndrome and immunoparalysis respectively. ImmunoSep is a first-in-class paradigm of precision medicine for sepsis. Other approaches need to consider classification by sepsis endotypes, targeting T cell and application of stem cells. Basic principle for any trial to be successful is the delivery of appropriate antimicrobial therapy as standard-of-care taking into consideration not just the likelihood for resistant pathogens but also the pharmacokinetic/pharmacodynamic mode of action of the administered antimicrobial.
Opioid use disorder in cancer patients
Authors: Lewis Cara E.S. , Schutzer-Weissmann John , Farquhar-Smith Paul 
Published: March 2023

Purpose of review
The misuse of opioids has increased significantly in recent decades. Historically, cancer patients have not been considered at risk of opioid misuse. However, cancer pain is common, and opioids are often prescribed. Guidelines addressing opioid misuse often exclude cancer patients. Given that misuse is associated with significant harm and a reduction in quality of life, it is important to understand the risk of opioid misuse in cancer patients and how we can recognise and treat it.

Recent findings
Early cancer diagnoses and treatments have improved cancer survival rates, leading to a larger population of cancer patients and survivors. Opioid use disorder (OUD) may precede a cancer diagnosis or may develop during or after treatment. The effect of OUD extends from an individual patient to a societal level. This review examines the increasing incidence of OUD in cancer patients, ways to identify patients with OUD such as behaviour change and screening scales, prevention of OUD such as limited and targeted opioid prescriptions, and evidence-based treatment suggestions for OUD.

Summary
OUD in cancer patients has only relatively recently been recognised as a growing problem. Early identification, involvement of the multidisciplinary team, and treatment can reduce the negative impact of OUD.
The Effect of Prophylactic Silicone Dressings on the Incidence of Pressure Injuries on Patients in the Acute Care Setting
Authors: Sugrue Claire , Avsar Pinar , Moore Zena , Patton Declan , O'Connor Tom , Nugent Linda , Budri Aglecia 
Published: March 2023

PURPOSE:
To explore the effect of silicone dressings on the prevention of pressure injuries in patients cared for in the acute care setting. Three main comparisons were explored: silicone dressing versus no dressing, all anatomical areas; silicone dressing versus no dressing on the sacrum; and silicone dressing versus no dressing on the heels.

METHODS:
Using a systematic review methodology, published randomized controlled trials and cluster randomized controlled trials were included. The search was conducted from December 2020 to January 2021 using CINAHL, full text on EBSCOhost, MEDLINE on EBSCOhost, and Cochrane databases. The search returned 130 studies; 10 met inclusion criteria. Data were extracted using a predesigned extraction tool. The Cochrane Collaboration tool was used to assess the risk of bias and the certainty of the evidence was appraised using a software program specifically designed for this purpose.

RESULTS:
Silicone dressings probably reduce the incidence of pressure injuries compared to no dressings (relative risk [RR]: 0.40, 95% confidence interval [CI]: 0.31-0.53; moderate certainty evidence). Furthermore, silicone dressings probably reduce the incidence of pressure injuries on the sacrum compared to no dressings (RR: 0.44, 95% CI: 0.31-0.62; moderate certainty evidence). Finally, silicone dressings probably reduce the incidence of pressure injuries on the heels compared to no dressings (RR: 0.44, 95% CI: 0.31-0.62; moderate certainty evidence).

CONCLUSION:
There is moderate certainty evidence of the effect of silicone dressings as a component of a pressure injury prevention strategy. The main limiting factor in the study designs was a high risk of performance and detection bias. Although this is a challenge to achieve in trials such as these, consideration should be given to how the effect of this could be minimized. A further issue is the lack of head-to-head trials that limits clinicians' abilities to determine whether any of the products in this category are more effective than others.
Incidence and Characteristics of Suspected Deep Tissue Pressure Injuries on the Foot and Ankle
Authors: Canfor James , Michailidis Lucia , Williams Cylie 
Published: March 2023

PURPOSE:
The purpose of this study was to measure the incidence of suspected deep tissue pressure injuries (DTPIs) in patients admitted to the hospital, describe their location, identify the related hospital length of stay, and explore any associations between intrinsic or extrinsic factors relevant to DTPI development.

DESIGN:
Retrospective review/audit of clinical data.

SUBJECTS AND SETTING:
We reviewed pertinent medical data from patients reported as developing a suspected deep tissue injury during hospital admission from January 2018 to March 2020. The study setting was a large tertiary public health service in Victoria, Australia.

METHODS:
Patients who developed a suspected deep tissue injury during hospital admission between January 2018 and March 2020 were identified through the hospital online risk recording system. Data were extracted from the relevant health records, including demographics, admission data, and pressure injury data. The incidence rate was expressed per 1000 patient admissions. Multiple regression analyses were used to determine associations between the time (days) to develop a suspected deep tissue injury and intrinsic (patient level) or extrinsic (hospital level) factors.

RESULTS:
Six hundred fifty-one pressure injuries were recorded during the audit period. A minority (9.5%; n = 62) of patients developed a suspected deep tissue injury; all were located on the foot and ankle. The incidence of suspected deep tissue injuries was 0.18 per 1000 patient admissions. The mean length of stay among patients who developed a DTPI was 59.0 (SD = 51.9) days as compared to a mean of 4.2 (SD = 11.8) days for all patients admitted to the hospital during this period. Multivariate regression analysis determined that the longer time (in days) to develop a pressure injury was associated with having a higher body weight (Coef = 0.02; 95% CI = 0.00 to 0.04; P = .043), not having off-loading (Coef =−3.63; 95% CI =−6.99 to −0.27; P = .034), and an increasing number of ward transfers (Coef = 0.46; 95% CI = 0.20 to 0.72; P = .001).

CONCLUSIONS:
Findings identified factors that may play a role in the development of suspected deep tissue injuries. A review of risk stratification in health services may be beneficial, with consideration to adjustments of procedural assessments of patients at risk.
Hematological malignancies as disorders negatively impacting specificities of the direct agglutination and rapid rK39 strip tests as reference diagnostics for visceral leishmanisis
Authors: Nail Abd Elsalam , Ahmed Ikram , Ali Osman Hussam , el Harith Abdallah 
Published: March 2023

AbstractIntroduction: During several years of work in Sudan, we occasionally had been confronted with patients who presented clinical features highly suggestive of visceral leishmaniasis (VL) however direct agglutination test (DAT) readings that were either at the high negative or low positive titre range. Inquiries on the fate of those particular patients revealed mortality, undetermined diagnosis or that in some of them leukemia was finally diagnosed.Gap statement: Investigate as to what extent hematological malignancies (HMs) interfere with VL diagnosis.Aim: Evaluate specificity of DAT version newly developed in this study wherein sodium dodecyle sulphate (SDS) was incorporated as a test sample denaturant in comparison with a standard reference wherein β-mercaptoethanol (β-ME) was used in test execution.Methodology: Seventy plasma samples from patients with HMs were collected and tested in a primary DAT version (P-DAT). The results obtained were compared with those of the rK39 strip test as VL reference diagnostic. HM samples revealing titres higher than the start dilution (1:100) in P-DAT were further tested in a β-ME- and urea- modified DAT versions. The specificity of the newly developed SDS-DAT was assessed against that of β-ME-DAT and rK39 strip tests as current reference diagnostics for VL.Results: Seven out of 70 patients with HMs scored positive outcomes (titre >1:3200) in P-DAT and 4 in the reference rK39 strip test. Of the 7 that tested positive in P-DAT or 4 in the reference rK39, none reacted at titre > 1:100 in the SDS-DAT. Significant reduction in non-specific agglutination reactions was achieved as a result in respect to the HM plasma samples (P. value < 0.05).Conclusion: To establish desired specificity for VL diagnosis in respect to HMs and subsequently minimize or avoid serious side effects due to unjustified anti-leishmanials prescription the combined application of the SDS-DAT here described and an improved version of the rK39 for confirmation is recommended. Key words: Visceral leishmaniasis; diagnosis; hematological malignancies; DAT; rK39; anti-leishmanials; SDS.
Video-rate Mid-infrared Photothermal Imaging by Single Pulse Photothermal Detection per Pixel
Authors: Yin Jiaze , Zhang Meng , Tan Yuying , Guo Zhongyue , He Hongjian , Lan Lu , Cheng Ji-Xin 
Published: March 2023

AbstractBy optically sensing the mid-infrared absorption induced photothermal effect, midinfrared photothermal (MIP) microscope enables super-resolution IR imaging and scrutinizing of biological systems in an aqueous environment. However, the speed of current lock-in based sample-scanning MIP system is limited to 1.0 millisecond or longer per pixel, which is insufficient for capturing dynamics inside living systems. Here, we report a single pulse laserscanning MIP microscope that dramatically increases the imaging speed by three orders of magnitude. We harness a lock-in free demodulation scheme which uses high-speed digitization to resolve single IR pulse induced contrast at nanosecond time scale. To realize single pulse photothermal detection at each pixel, we employ two sets of galvo mirrors for synchronized scanning of mid-infrared and probe beams to achieve an imaging line rate over 2 kHz. With video-rate imaging capability, we observed two types of distinct dynamics of lipids in living cells. Furthermore, by hyperspectral imaging, we chemically dissected a single cell wall at nanometer scale. Finally, with a uniform field of view over 200 by 200 μm2and 2 Hz frame rate, we mapped fat storage in free-movingC. elegansand live embryos.
Estimating the vertical ionization potential of single-stranded DNA molecules
Authors: Rooman Marianne , Pucci Fabrizio 
Published: March 2023

AbstractThe electronic properties of DNA molecules, defined by the sequence-dependent ionization potentials of nucleobases, enable long-range charge transport along the DNA stacks. This has been linked to a range of key physiological processes in the cells and to the triggering of nucleobase substitutions, some of which may cause diseases. To gain molecular-level understanding of the sequence dependence of these phenomena, we estimated the vertical ionization potential (vIP) of all possible nucleobase stacks in B-conformation, containing one to four Gua, Ade, Thy, Cyt or methylated Cyt. To do this, we used quantum chemistry calculations and more precisely the second-order Møller-Plesset perturbation theory (MP2) and three double-hybrid density functional theory (DFT) methods, combined with several basis sets for describing atomic orbitals. The calculated vIP of single nucleobases were compared to experimental data and those of nucleobase pairs, triplets and quadruplets, to observed mutability frequencies in the human genome, reported to be correlated with vIP values. This comparison selected MP2 with the 6-31G* basis set as the best of the tested calculation levels. These results were exploited to set up a recursive model, called vIPer, which estimates the vIP of all possible single-stranded DNA sequences of any length based on the calculated vIPs of overlapping quadruplets. vIPer’s vIP values correlate well with oxidation potentials measured by cyclic voltammetry and activities obtained through photoinduced DNA cleavage experiments, further validating our approach. vIPer is freely available on thegithub.com/3BioCompBio/vIPerrepository.
Mechanosensitive channel MscS is critical for termination of the bacterial hypoosmotic permeability response
Authors: Moller Elissa , Britt Madolyn , Schams Anthony , Cetuk Hannah , Anishkin Andriy , Sukharev Sergei 
Published: March 2023

AbstractFree-living microorganisms are subjected to drastic changes in osmolarity. To avoid lysis under sudden osmotic down-shock, bacteria quickly expel small metabolites through the tension-activated channels MscL, MscS, and MscK. We examined five chromosomal knockout strains, ΔmscL, ΔmscS, a double knockout ΔmscSΔmscK, and a triple knockout ΔmscLΔmscSΔmscKin comparison to the wild-type parental strain. Stopped-flow experiments confirmed that both MscS and MscL mediate fast osmolyte release and curb cell swelling, but osmotic viability assays indicated that they are not equivalent. MscS alone was capable of rescuing the cell population, but in some strains MscL did not rescue and additionally became toxic in the absence of both MscS and MscK. Furthermore, MscS was upregulated in the ΔmscLstrain, suggesting either a cross-talk between the two genes/proteins or the influence of cell mechanics onmscSexpression. The data shows that for the proper termination of the permeability response, the high-threshold (MscL) and the low-threshold (MscS/MscK) channels must act sequentially. In the absence of low-threshold channels, at the end of the release phase, MscL should stabilize membrane tension at around 10 mN/m. Patch-clamp protocols emulating the tension changes during the release phase indicated that the non-inactivating MscL, residing at its own tension threshold, flickers and produces a protracted leakage. The MscS/MscK population, when present, stays open at this stage to reduce tension below the MscL threshold and silence the large channel. When MscS reaches its own threshold, it inactivates and thus ensures proper termination of the hypoosmotic permeability response. This functional interplay between the high- and low-threshold channels is further supported by the compromised osmotic survival of bacteria expressing non-inactivating MscS mutants.Summary (for the table of contents)The kinetics of hypotonic osmolyte release fromE. coliis analyzed in conjunction with bacterial survival. It is shown that MscL, the high-threshold ‘emergency release valve’, rescues bacteria from down-shocks only in the presence of MscS, MscK or other low-threshold channels that are necessary to pacify MscL at the end of the release phase.
A conserved local structural motif controls the kinetics of PTP1B catalysis
Authors: Yeh Christine Y. , Izaguirre Jesus A. , Greisman Jack B. , Willmore Lindsay , Maragakis Paul , Shaw David E. 
Published: March 2023

AbstractProtein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin signaling pathways, making it a highly attractive target for the treatment of type II diabetes. For PTP1B to perform its enzymatic function, a loop referred to as the “WPD loop” must transition between open (catalytically incompetent) and closed (catalytically competent) conformations, which have both been resolved by X-ray crystallography. Although prior studies have established this transition as the rate-limiting step for catalysis, the transition mechanism for PTP1B and other PTPs has been unclear. Here we present an atomically detailed model of WPD-loop transitions in PTP1B based on unbiased, long-timescale molecular dynamics simulations and weighted ensemble simulations. We found that a specific WPD-loop region— the PDFG motif—acted as the key conformational switch, with structural changes to the motif being necessary and sufficient for transitions between long-lived open and closed states of the loop. Simulations starting from the closed state repeatedly visited open states of the loop that quickly closed again unless the infrequent conformational switching of the motif stabilized the open state. The functional role of the PDFG motif is supported by the fact that it (or the similar PDHG motif) is conserved across all PTPs. Bioinformatic analysis shows that the PDFG motif is also conserved, and adopts two distinct conformations, in deiminases, and the related DFG motif is known to function as a conformational switch in many kinases, suggesting that PDFG-like motifs may control transitions between structurally distinct, long-lived conformational states in multiple protein families.
Efficient and scalable prediction of spatio-temporal stochastic gene expression in cells and tissues using graph neural networks
Authors: Cao Zhixing , Chen Rui , Xu Libin , Zhou Xinyi , Fu Xiaoming , Zhong Weimin , Grima Ramon 
Published: March 2023

AbstractThe simulation of spatial stochastic models is highly computationally expensive, an issue that has severely limited our understanding of the spatial nature of gene expression. Here we devise a graph neural network based method to learn, from stochastic trajectories in a small region of space, an effective master equation for the time-dependent marginal probability distributions of mRNA and protein numbers at sub-cellular resolution for every cell in a tissue. Numerical solution of this equation leads to accurate results in a small fraction of the computation time of standard simulation methods. Moreover its predictions can be extrapolated to a spatial organisation (a cell network topology) and regions of parameter space unseen in its neural network training. The scalability and accuracy of the method suggest it is a promising approach for whole cell modelling and for detailed comparisons of stochastic models with spatial genomics data.
Farewell to single-well: An automated single-molecule FRET platform for high-content, multiwell plate screening of biomolecular conformations and dynamics
Authors: Hartmann Andreas , Sreenivasa Koushik , Schenkel Mathias , Chamachi Neharika , Schake Philipp , Krainer Georg , Schlierf Michael 
Published: March 2023

AbstractSingle-molecule FRET (smFRET) has become a widely used tool for probing the structure, dynamics, and functional mechanisms of biomolecular systems, and is extensively used to address questions ranging from biomolecular folding to drug discovery. Investigations by smFRET often require sampling of a large parameter space, for example, by varying one or more constituent molecular components in ten or more steps to reliably extract distances, kinetic rates, and other quantitative parameters. Confocal smFRET measurements, for example, which are amongst the widely used smFRET assays, are typically performed in a single-well format and measurements are conducted in a manual manner, making sampling of many experimental parameters laborious and time consuming. To address this challenge, we extend here the capabilities of confocal smFRET beyond single-well measurements by integrating a multiwell plate functionality into a confocal microscope to allow for continuous and automated smFRET measurements. We show that the multiwell plate assay is on par with conventional single-well smFRET measurements in terms of accuracy and precision yet enables probing tens to hundreds of conditions in a fully automized manner. We demonstrate the broad applicability of the multiwell plate assay towards DNA hairpin dynamics, protein folding, and competitive and cooperative protein–DNA interactions, revealing new insights that would be hard if not impossible to achieve with conventional single-well format measurements. The higher sampling density afforded by the multiwell plate format increases the accuracy of data analysis by at least 10-fold. We further showcase that the assay provides access to smFRET-based screening of drug–protein interactions. For the adaptation into existing instrumentations, we provide a detailed guide and open-source acquisition and analysis software. Taken together, the automated multiwell plate assay developed here opens up new possibilities to acquire high-content smFRET datasets for in-depth single-molecule analysis of biomolecular conformations, interactions, and dynamics.
Cerebellar Activity in Hemi-Parkinsonian Rats during Volitional Gait and Freezing
Authors: DeAngelo Valerie , Gehan Arianna , Paliwal Siya , Ho Katherine , Hilliard Justin D , Chiang Chia-Han , Viventi Jonathan , McConnell George C 
Published: March 2023

AbstractParkinson’s disease is a neurodegenerative disease characterized by gait dysfunction in the advanced stages of the disease. The unilateral 6-OHDA toxin-induced model is the most studied animal model of Parkinson’s disease, which reproduces gait dysfunction after greater than 68% dopamine (DA) loss in the substantia nigra pars compacta (SNc). The extent to which the neural activity in hemi-parkinsonian rats correlates to gait dysfunction and DAergic cell loss is not clear. In this paper we report the effects of unilateral DA depletion on cerebellar vermis activity using micro-electrocorticography (μECoG) during walking and freezing on a runway. Gait and neural activity were measured in 6-OHDA lesioned and sham lesioned rats at 14d, 21d, and 28d after infusion of 6-OHDA or control vehicle into the medial forebrain bundle (MFB) (n=20). Gait deficits in 6-OHDA rats were different from sham rats at 14d (p<0.05). Gait deficits in 6-OHDA rats improved at 21d and 28d except for run speed, which decreased at 28d (p=0.018). No differences in gait deficits were observed in sham lesioned rats at any time points. Hemiparkinsonian rats showed hyperactivity in the cerebellar vermis at 21d (p<0.05), but not at 14d and 28d, and the activity was reduced during freezing epochs in lobules VIa, VIb, and VIc (p<0.05). These results suggest that DAergic cell loss causes pathological cerebellar activity at 21d postlesion and suggests that compensatory mechanisms from the intact hemisphere contribute to normalized cerebellar activity at 28d. The decrease in cerebellar oscillatory activity during freezing may be indicative of neurological changes during freezing of gait in Parkinson’s disease patients making this region a potential location for biomarker detection. Although the unilateral 6-OHDA model presents gait deficits that parallel clinical presentations of Parkinson’s disease, further studies in animal models of bilateral DA loss are needed to understand the role of the cerebellar vermis in Parkinson’s disease.