bluuebunny/crossref_metadata_2025_split huggingface dataset:
RESPIRATORY VARIABILITY OF VALVULAR PEAK SYSTOLIC VELOCITY AS A NEW INDICATOR OF FLUID RESPONSIVENESS IN PATIENTS WITH SEPTIC SHOCK
Authors: Ma Qiang , Ding Caiyun , Jiang Feng , Hu Guobin , Wu Jingyi , Zhang Xia 
Published: May 2023

ABSTRACT

Objective: The aim of this study was to evaluate the reliability and feasibility of pulse Doppler measurements of peak velocity respiratory variability of mitral and tricuspid valve rings during systole as new dynamic indicators of fluid responsiveness in patients with septic shock. Methods: Transthoracic echocardiography (TTE) was performed to measure the respiratory variability of aortic velocity-time integral (∆VTI), respiratory variability of tricuspid annulus systolic peak velocity (∆RVS), respiratory variability of mitral annulus systolic peak velocity (∆LVS), and other related indicators. Fluid responsiveness was defined as a 10% increase in cardiac output after fluid expansion, assessed by TTE. Results: A total of 33 patients with septic shock were enrolled in this study. First, there was no significant difference in the population characteristics between the fluid responsiveness positive group (n = 17) and the fluid responsiveness negative group (n = 16) (P > 0.05). Second, Pearson correlation test showed that ∆RVS, ∆LVS, and TAPSE with the relative increase in cardiac output after fluid expansion (R = 0.55, P = 0.001; R = 0.40, P = 0.02; R = 0.36, P = 0.041). Third, multiple logistic regression analysis demonstrated that ∆RVS, ∆LVS, and TAPSE were significantly correlated with fluid responsiveness in patients with septic shock. Fourth, receiver operating characteristic (ROC) curve analysis revealed that ∆VTI, ∆LVS, ∆RVS, and TAPSE had good predictive ability for fluid responsiveness in patients with septic shock. The area under the curve (AUC) of ∆VTI, ∆LVS, ∆RVS, and TAPSE for predicting fluid responsiveness was 0.952, 0.802, 0.822, and 0.713, respectively. The sensitivity (Se) values were 1.00, 0.73, 0.81, and 0.83, whereas the specificity (Sp) values were 0.84, 0.91, 0.76, and 0.67, respectively. The optimal thresholds were 0.128, 0.129, 0.130, and 13.9 mm, respectively. Conclusion: Tissue Doppler ultrasound evaluation of respiratory variability of mitral and tricuspid annular peak systolic velocity could be a feasible and reliable method for the simple assessment of fluid responsiveness in patients with septic shock.
Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status
Authors: Convertino Victor A. , Thompson Patrick , Koons Natalie J. , Le Tuan D. , Lanier J. Brian , Cardin Sylvain 
Published: May 2023

BACKGROUND
Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock.

METHODS
We measured HR, SBP, and CRM in 172 human subjects (19–55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI.

RESULTS
The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater (p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94–0.97) compared with 0.91 (0.89–0.94) for SI (p = 0.0002).

CONCLUSION
Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia.

LEVEL OF EVIDENCE
Diagnostic Test or Criteria; Level III.
A Mixed-Methods Comparison of Gender Differences in Alcohol Consumption and Drinking Characteristics among Patients in Moshi, Tanzania
Authors: Pauley Alena , Buono Mia , West Kirstin , Metcalf Madeline , Rent Sharla , Kilasara Joseph , Sawe Yvonne , Mikindo Mariana , Mmbaga Blandina T. , Boshe Judith , Vissoci João Ricardo Nickenig , Staton Catherine A. 
Published: May 2023

ABSTRACTBackgroundExcessive alcohol use stands as a serious threat to individual and community well-being, having been linked to a wide array of physical, social, mental, and economic harms.Alcohol consumption differs by gender, a trend seen both globally and in Moshi, Tanzania, a region with especially high rates of intake and few resources for alcohol-related care. To develop effective gender-appropriate treatment interventions, differences in drinking behaviors between men and women must be better understood. Our study aims to identify and explore gender-based discrepancies in alcohol consumption among Kilimanjaro Christian Medical Center (KCMC) patients.MethodsA systematic random sampling of adult patients presenting to KCMC’s Emergency Department (ED) or Reproductive Health Center (RHC) was conducted from October 2020 until May 2021. Patients answered demographic and alcohol use-related questions and completed brief surveys including the Alcohol Use Disorder Identification Test (AUDIT). Through purposeful sampling, 19 subjects also participated in in-depth interviews (IDIs) focused on identifying gender differences in alcohol use.ResultsDuring the 8-month data collection timeline, 655 patients were enrolled. Men and women patients at KCMC’s ED and RHC were found to have significant differences in their alcohol use behaviors including lower rates of consumption among women, (average [SD] AUDIT scores were 6.76 [8.16] among ED men, 3.07 [4.76] among ED women, and 1.86 [3.46] among RHC women), greater social restrictions around women’s drinking, and more secretive alcohol use behaviors for where and when women would drink. For men, excess drinking was normalized within Moshi, tied to men’s social interactions with other men, and generally motivated by stress, social pressure, and despair over lack of opportunity.ConclusionSignificant gender differences in drinking behaviors were found, primarily influenced by sociocultural norms. These dissimilarities in alcohol use suggest that future alcohol-related programs should incorporate gender in their conceptualization and implementation.
For Better or Worse? Subjective Expectations and Cost-Benefit Trade-Offs in Health Behavior
Authors: Conti Gabriella , Giustinelli Pamela 
Published: May 2023

AbstractWe provide a framework to disentangle the role of preferences and beliefs in health behavior, and we apply it to compliance behavior during the acute phase of the COVID-19 pandemic. Using rich data on subjective expectations collected during the spring 2020 lockdown in the UK, we estimate a simple model of compliance behavior with uncertain costs and benefits, which we employ to quantify the utility trade-offs underlying compliance, to decompose group differences in compliance plans, and to compute the monetary compensation required for people to comply. We find that, on average, individuals assign the largest disutility to passing away from COVID-19 and being caught transgressing, and the largest utility to preserving their mental health. But we also document substantial heterogeneity in preferences and/or expectations by vulnerability status, gender, and other individual characteristics. In our data, both preferences and expectations matter for explaining gender differences in compliance, whereas compliance differences by vulnerability status are mainly driven by heterogeneity in preferences. We also investigate the relationship between own and others’ compliance. When others fail to comply and trust breaks down, individuals respond heterogeneously depending on their own circumstances and characteristics. When others around them comply less, those with higher risk tolerance and those without prior COVID-19 experience plan to comply less themselves, while the vulnerables plan to comply more. When a high-level public figure breaches the rules, supporters of the opposing political party plan to comply less. These findings emphasize the need for public health policies to account for heterogenous beliefs, preferences, and responses to others in citizens’ health behaviors.JEL Codes: C25, C83, D84, I12, I18.
Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification
Authors: Peretz Cheryl A. C. , Kennedy Vanessa E. , Walia Anushka , Delley Cyrille L. , Koh Andrew , Tran Elaine , Clark Iain C. , Hayford Corey E. , D’Amato Chris , Xue Yi , Fontanez Kristina M. , Roy Ritu , Logan Aaron C. , Perl Alexander E. , Abate Adam , Olshen Adam , Smith Catherine C. 
Published: May 2023

AbstractMixed phenotype acute leukemia (MPAL) is a leukemia whose biologic drivers are poorly understood, therapeutic strategy remains unclear, and prognosis is poor. We performed multiomic single cell (SC) profiling of 14 newly diagnosed adult MPAL patients to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. However, progressive acquisition of mutations is associated with increased expression of immunophenotypic markers of immaturity. Using SC transcriptional profiling, we find that MPAL blasts express a stem cell-like transcriptional profile distinct from other acute leukemias and indicative of high differentiation potential. Further, patients with the highest differentiation potential demonstrated inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in this cohort, is applicable to bulk RNA sequencing data and was predictive of survival in an independent patient cohort, suggesting utility for clinical risk stratification.
Comparing mental imagery experiences across visual, auditory, and other sensory modalities
Authors: Sulfaro Alexander A , Robinson Amanda K , Carlson Thomas A 
Published: May 2023

AbstractAlthough mental imagery is often studied as a visual phenomenon, it can occur in any sensory modality. Given that mental images may recruit similar modality-specific neural systems to those which support veridical perception, the properties of mental images may be constrained by the modality in which they are experienced. Yet, little is known about how mental images are experienced at all, let alone how such experiences may vary depending on the modality in which they occur. Here we explored how mental images are experienced in different modalities using an extensive questionnaire. Mainly focusing on visual and auditory mental imagery, we surveyed participants on if and how they experienced their thought content in a sensory way when thinking about the appearance or sound of the letter “O”. Specifically, we investigated temporal properties of imagined content (e.g. onset latency, duration), as well as spatial properties (e.g. apparent location), effort (e.g. ease, spontaneity, control), dependence on body movements (e.g. eye movements), interactions between real and imagined content (e.g. inner speech during reading), the perceived normality of imagery experiences, and how participants labeled their own experiences. Participants also ranked their mental imagery experiences in the five traditional sensory modalities and reported on the involvement of each modality during their thoughts, imagination, and dreams. Confidence ratings were taken for every answer recorded. Overall, visual and auditory experiences tended to dominate mental events relative to other sensory modalities. However, most people reported that auditory mental imagery was superior to visual mental imagery on almost every metric tested, except with respect to spatial properties. Our findings suggest that mental images are restrained in a similar matter to other modality-specific sensory processes in the brain. Broadly, our work also provides a wealth of insights and observations into how mental images are experienced by individuals, acting as a useful resource for future investigations.
Evidence that ultrafast non-quantal transmission underlies short-latency vestibular evoked potentials
Authors: Pastras Christopher J. , Curthoys Ian S. , Asadnia Mohsen , McAlpine David , Rabbitt Richard D. , Brown Daniel J. 
Published: May 2023

AbstractAmniotes evolved a unique calyceal postsynaptic terminal in the vestibular organs of the inner ear that underpins quantal and non-quantal transmission at the synapse of sensory hair cells and vestibular afferent neurons. The non-quantal component is of particular interest as it includes an ultrafast synaptic current thought to underlie the exquisite synchronization of action potentials in vestibular afferent fibres to dynamic stimuli such as sound and vibration. Here we demonstrate evidence that non-quantal transmission is responsible for short latency vestibular evoked potentials (vCAPs) in the guinea pig utricle. We first show that, unlike auditory nerve responses which are completely abolished, vCAPs are insensitive to local administration of the AMPA receptor agonist CNQX. Moreover, latency comparisons between presynaptic hair cell and postsynaptic neural responses reveal that the vCAP occurs without measurable synaptic delay. Finally, using a paired-pulse stimulus designed to deplete the readily releasable pool of synaptic vesicles in hair cells, we reveal that forward masking is lacking in vestibular responses, compared to the equivalent cochlear responses. Our data support the hypothesis that the fast component of non-quantal transmission at calyceal synapses is indefatigable and responsible for ultrafast responses of vestibular organs evoked by transient stimulation.SignificanceThe mammalian vestibular system drives some of the fastest reflex pathways in the nervous system, ensuring stable gaze and postural control for locomotion on land. To achieve this, terrestrial amniotes evolved a large, unique calyx afferent terminal which completely envelopes one or more pre-synaptic vestibular hair cells, which transmits mechanosensory signals mediated by quantal and nonquantal (NQ) synaptic transmission. We present several lines of data in the guinea pig that reveal the pre-synaptic transmission of the most sensitive vestibular afferents are faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from Type I hair cells to their calyx partners.
Enteric pharmacokinetics of monomeric and multimeric camelid nanobody single-domain antibodies
Authors: Debatis Michelle , Danz Hillary , Tremblay Jacqueline M. , Gaspie Kimberly , Kudej Raymond K. , Vigdorovich Vladimir , Sather Noah , Jaskiewicz Justyna J. , Tzipori Saul , Shoemaker Charles B. 
Published: May 2023

AbstractSingle-domain antibodies (sdAbs) derived fromCamelidaeheavy-chain-only antibodies (also called nanobodies or VHHs) have advantages over conventional antibodies in terms of their small size and stability to pH and temperature extremes, their ability to express well in microbial hosts, and to be functionally multimerized for enhanced properties. For these reasons, VHHs are showing promise as enteric disease therapeutics, yet little is known as to their pharmacokinetics (PK) within the digestive tract. To improve understanding of enteric VHH PK, we investigated the functional and structural stability of monomeric and multimeric camelid VHH-agents followingin vitroincubation with intestinal extracts (chyme) from rabbits and pigs or fecal extracts from human sources, andin vivoin rabbits. The results showed that unstructured domains such as epitopic tags and flexible spacers composed of different amino acid sequences were rapidly degraded by enteric proteases while the functional core VHHs were much more stable to these treatments. Individual VHHs were widely variable in their functional stability to GI tract proteases. Some VHH-based agents which neutralize enteric Shiga toxin Stx2 displayed a functional stability to chyme incubations comparable to that of Stx2-neutralizing IgG and IgA mAbs, thus indicating that selected nanobodies can approach the functional stability of conventional immunoglobulins. Enteric PK data obtained fromin vitroincubation studies were consistent with similar incubations performedin vivoin rabbit surgical gut loops. These findings have broad implications for enteric use of VHH-based agents, particularly VHH fusion proteins.
Characterisation of an Omnitrap-Orbitrap platform equipped with IRMPD, UVPD and ExD for the analysis of peptides and proteins
Authors: Smyrnakis Athanasios , Levin Nikita , Kosmopoulou Mariangela , Jha Ajay , Fort Kyle , Makarov Alexander , Papanastasiou Dimitris , Mohammed Shabaz 
Published: May 2023

AbstractWe describe an instrument configuration based on the Orbitrap Exploris 480 mass spectrometer that has been coupled to an Omnitrap platform. The Omnitrap possesses three distinct ion-activation regions, that can be used to perform resonant based collision induced dissociation, several forms of electron associated fragmentation, and ultraviolet photodissociation. Each section can also be combined with infrared multiphoton dissociation. In this work, we demonstrate all these modes of operation on a range of peptides and proteins. The results show that this instrument configuration produces similar data to previous implementations of each activation technique and at similar efficiency levels. We demonstrate that this unique instrument configuration is extremely versatile for the interrogation of polypeptides.
Memory at your fingertips: how viscoelasticity affects tactile neuron signaling
Authors: Saal Hannes P. , Birznieks Ingvars , Johansson Roland S. 
Published: May 2023

AbstractHuman skin and its underlying tissues constitute a viscoelastic medium, implying that any deformation depends not only on the currently applied force, but also the recent loading history. The extent to which this physical memory influences the signaling of first-order tactile neurons during natural hand use is not well understood. Here, we examined the effect of past loading on the responses of fast-adapting (FA-1) and slowly-adapting (SA-1 and SA-2) first-order tactile neurons innervating the human fingertip to loadings applied in different directions representative of object manipulation tasks. We found that variation in the preceding loading affected neurons’ overall signaling of force direction. Some neurons kept signaling the current direction, while others signaled both the current and preceding direction, or even primarily the preceding direction. In addition, ongoing impulse activity in SA-2 neurons between loadings signaled information related to the fingertip’s viscoelastic deformation state. We conclude that tactile neurons at the population level signal continuous information about the fingertip’s viscoelastic deformation state, which is shaped by both its recent history and current loading. Such information might be sufficient for the brain to correctly interpret current force loading and help in computing accurate motor commands for interactions with objects in manipulation and haptic tasks.
Divergent host innate immune response to the smooth-to-roughM. abscessusadaptation to chronic infection
Authors: Wheeler Emily A , Lenhart-Pendergrass Patricia M. , Rysavy Noel M. , Poch Katie , Caceres Silvia , Calhoun Kara M. , Serban Karina , Nick Jerry A. , Malcolm Kenneth C. 
Published: May 2023

AbstractMycobacterium abscessusis a nontuberculous mycobacterium emerging as a significant pathogen for individuals with chronic lung disease, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. New strategies of bacterial control based on host defenses are appealing, but anti-mycobacterial immune mechanisms are poorly understood and are complicated by the appearance of smooth and rough morphotypes with distinct host responses. We explored the role of the complement system in the clearance ofM. abscessusmorphotypes by neutrophils, an abundant cell in these infections.M. abscessusopsonized with plasma from healthy individuals promoted greater killing by neutrophils compared to opsonization in heat-inactivated plasma. Rough clinical isolates were more resistant to complement but were still efficiently killed. Complement C3 associated strongly with the smooth morphotype while mannose-binding lectin 2 was associated with the rough morphotype. M. abscessus killing was dependent on C3, but not on C1q or Factor B; furthermore, competition of mannose-binding lectin 2 binding with mannan or N-acetyl-glucosamine during opsonization did not inhibit killing. These data suggest thatM. abscessusdoes not canonically activate complement through the classical, alternative, or lectin pathways. Complement-mediated killing was dependent on IgG and IgM for smooth and on IgG for roughM. abscessus. Both morphotypes were recognized by Complement Receptor 3 (CD11b), but not CR1 (CD35), and in a carbohydrate- and calcium-dependent manner. These data suggest the smooth-to-rough adaptation changes complement recognition ofM. abscessusand that complement is an important factor forM. abscessusinfection.
Optimization of 3-Cyano-7-cyclopropylamino-pyrazolo[1,5-a]pyrimidines Toward the Development of an In Vivo Chemical Probe for CSNK2A
Authors: Yang Xuan , Ong Han Wee , Dickmander Rebekah J. , Smith Jeffery L. , Brown Jason W. , Tao William , Chang Edcon , Moorman Nathaniel J. , Axtman Alison D. , Willson Timothy M. 
Published: May 2023

Abstract3-cyano-7-cyclopropylamino-pyrazolo[1,5-a]pyrimidines, including the chemical probe SGC-CK2-1, are potent and selective inhibitors of CSNK2A in cells but have limited utility in animal models due to their poor pharmacokinetic properties. While developing analogs with reduced intrinsic clearance and the potential for sustained exposure in mice, we discovered that Phase II conjugation by GST enzymes was a major metabolic transformation in hepatocytes. A protocol for co-dosing with ethacrynic acid, a covalent reversible GST inhibitor, was developed to improve the exposure of analog2hin mice. A double co-dosing protocol, using a combination of ethacrynic acid and irreversible P450 inhibitor 1-aminobenzotriazole increased the blood level of2hby 40-fold at a 5 h time point.Graphical Abstract