bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting myeloid-derived suppressor cells by inhibiting hypoxia-inducible factor 1α could improve tumor progression
Authors: Xu Qiying , Liu Huifang , Song Xiaoyan , Wuren Tana , Ge Ri-li
Published: May 2024

Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells that inhibit anti-tumor immunity and contribute to poor cancer outcomes. In this study, the authors used multi-color flow cytometry to detect changes in MDSCs in patients with cancer and tumor-bearing mice. Then the authors studied changes in MDSCs ratio and mouse tumors after administration of hypoxia-inducible factor 1α (HIF-1α) inhibitor. The results showed that the ratio of MDSCs, specifically polymorphonuclear MDSCs (PMN-MDSCs), was higher in patients with cancer, and both PMN-MDSCs and monocytic MDSCs (M-MDSCs) ratio were higher in tumor-bearing mice. When provided with the HIF-1α inhibitor LW-6, the ratio of MDSCs decreased in tumor-bearing mice, particularly PMN-MDSCs, and the volume of liver metastases also decreased. The authors’ findings suggest that reducing MDSCs by inhibiting hypoxia-inducible factor 1α may slow tumor progression.
An agricultural livelihood intervention is associated with reduced HIV stigma among people with HIV
Authors: Weiser Sheri D. , Sheira Lila A. , Weke Elly , Zakaras Jennifer M. , Wekesa Pauline , Frongillo Edward A. , Burger Rachel L. , Mocello Adrienne Rain , Thirumurthy Harsha , Dworkin Shari L. , Tsai Alexander C. , Kahn James G. , Butler Lisa M. , Bukusi Elizabeth A. , Cohen Craig R.
Published: May 2024

Objective:

HIV stigma undermines antiretroviral treatment (ART) adherence and viral suppression. Livelihood interventions may target drivers of negative attitudes towards people with HIV (PWH) by improving their health and strengthening their economic contributions. We examined the effects of a multisectoral agricultural livelihood intervention on HIV stigma among PWH in western Kenya.

Design:

Sixteen health facilities were randomly allocated (1 : 1) to intervention or control arms in Shamba Maisha, a cluster randomized controlled trial that aimed to improve HIV-related health through behavioral, mental health, and nutritional pathways.

Methods:

The intervention included a farming loan and agricultural and financial training. Participants had access to farmland and surface water and were at least 18 years old, on ART for more than 6 months, and moderately-to-severely food insecure. We measured internalized, anticipated, and enacted HIV stigma semiannually over 2 years using validated scales. In blinded intent-to-treat analyses, we compared changes in scores over 24 months by study arm, using longitudinal multilevel difference-in-differences linear regression models that accounted for clustering.

Results:

Of 720 enrolled participants (354 intervention), 55% were women, and the median age was 40 years [interquartile range 34–47 years]. Two-year retention was 94%. Compared with the control arm, the intervention resulted in significant decreases (P < 0.001) of 0.42 points [95% confidence interval (CI) −0.52 to −0.31) in internalized stigma, 0.43 points (95% CI −0.51 to −0.34) in anticipated stigma, and 0.13 points (95% CI −0.16 to −0.09) in enacted stigma over 24 months.

Conclusion:

The agricultural livelihood intervention reduced HIV stigma among PWH. Poverty-reduction approaches may be a novel strategy for reducing HIV stigma.
A Novel Method for Patients With Ear Keloid
Authors: Işık Halil , Yaşar Emrah Kağan , Alagöz Murat Şahin
Published: May 2024

Background

Keloid is a dermal fibroproliferative disease unique to humans. Due to the ambiguity in its pathophysiology and the frequent recurrence of keloid, there is no clear consensus on the treatment of keloid and there are many treatment methods defined. In order to benefit from the positive effects of fat grafting on pathological scars, we applied fat grafting to patients who underwent keloid enucleation.

Methods

Fifteen ear keloid patients included in the study. All patients underwent the same surgical procedure by the same surgeon. Routine follow-ups and examinations were performed to evaluate the results and in addition, the Patient and Observer Scar Assessment Scale (POSAS) survey was used.

Results

In the study, 15 patients were followed for a median (IQR) period of 21 (13–28) months. No recurrence was observed in any patient during follow-up, which occurred for a median of 21 (13–28) months. In the questionnaire filled out by the patients, the preoperative median value was found to be 48 (IQR: 12), whereas the postoperative median value was found to be 14 (IQR: 8). According to the patients, there was a statistically significant (P < 0.05) positive improvement after surgery.

Conclusions

Historically, surgical procedures were avoided because the surgical recurrence rate was very high, but today, recurrence rates are decreasing with combined treatments. These treatment combinations may require more than one intervention and require frequent clinical follow-ups. With our technique of fat grafting after enucleation, the treatment was completed with a single operation and no additional intervention was required.
Sociodemographic Disparities and Postoperative Outcomes Following Cranial Vault Remodeling for Craniosynostosis: Analysis of the 2012 to 2021 NSQIP-Pediatric Database
Authors: Hengartner Astrid C. , Serrato Paul , Sayeed Sumaiya , Sadeghzadeh Sina , Prassinos Alexandre J. , Alperovich Michael , DiLuna Michael , Elsamadicy Aladine A.
Published: May 2024

Objective:

The objective of this study was to assess whether race and ethnicity are independent predictors of inferior postoperative clinical outcomes, including increased complication rates, extended length of stay (LOS), and unplanned 30-day readmission following cranial vault repair for craniosynostosis.

Methods:

A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database. Pediatric patients under 2 years of age undergoing cranial vault repair for craniosynostosis between 2012 and 2021 were identified using the International Classification of Diseases-9/10 and Current Procedural Terminology codes. Patients were dichotomized into 4 cohorts: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and other. Only patients with available race and ethnicity data were included in this study. Patient demographics, comorbidities, surgical variables, postoperative adverse events, and hospital resource utilization were assessed. Multivariate logistic regression analysis was used to assess the impact of race on complications, extended LOS, and unplanned readmissions.

Results:

In our cohort of 7764 patients, 72.80% were NHW, 8.44% were NHB, 15.10% were Hispanic, and 3.67% were categorized as “other.” Age was significantly different between the 4 cohorts (P<0.001); NHB patients were the oldest, with an average age of 327.69±174.57 days old. Non-Hispanic White experienced the least adverse events while NHB experienced the most (P=0.01). Total operative time and hospital LOS were shorter for NHW patients (P<0.001 and P<0.001, respectively). Rates of unplanned 30-day readmission, unplanned reoperation, and 30-day mortality did not differ significantly between the 4 cohorts. On multivariate analysis, race was found to be an independent predictor of extended LOS [NHB: adjusted odds ratio: 1.30 (1.04–1.62), P=0.021; other: 2.28 (1.69–3.04), P=0.005], but not of complications or readmission.

Conclusions:

Our study demonstrates that racial and ethnic disparities exist among patients undergoing cranial vault reconstruction for craniosynostosis. These disparities, in part, may be due to delayed age of presentation among non-Hispanic, non-White patients. Further investigations to elucidate the underlying causes of these disparities are necessary to address gaps in access to care and provide equitable health care to at-risk populations.
Physiologic validation of the Compensatory Reserve Metric obtained from pulse oximetry: A step toward advanced medical monitoring on the battlefield
Authors: Roden Richard T. , Webb Kevin L. , Pruter Wyatt W. , Gorman Ellen K. , Holmes David R. , Haider Clifton R. , Joyner Michael J. , Curry Timothy B. , Wiggins Chad C. , Convertino Victor A.
Published: May 2024

BACKGROUND

The Compensatory Reserve Metric (CRM) provides a time sensitive indicator of hemodynamic decompensation. However, its in-field utility is limited because of the size and cost-intensive nature of standard vital sign monitors or photoplethysmographic volume-clamp (PPGVC) devices used to measure arterial waveforms. In this regard, photoplethysmographic measurements obtained from pulse oximetry may serve as a useful, portable alternative. This study aimed to validate CRM values obtained using pulse oximeter (PPGPO).

METHODS

Forty-nine healthy adults (25 females) underwent a graded lower body negative pressure (LBNP) protocol to simulate hemorrhage. Arterial waveforms were sampled using PPGPO and PPGVC. The CRM was calculated using a one-dimensional convolutional neural network. Cardiac output and stroke volume were measured using PPGVC. A brachial artery catheter was used to measure intra-arterial pressure. A three-lead electrocardiogram was used to measure heart rate. Fixed-effect linear mixed models with repeated measures were used to examine the association between CRM values and physiologic variables. Log-rank analyses were used to examine differences in shock determination during LBNP between monitored hemodynamic parameters.

RESULTS

The median LBNP stage reached was 70 mm Hg (range, 45–100 mm Hg). Relative to baseline, at tolerance, there was a 47% ± 12% reduction in stroke volume, 64% ± 27% increase in heart rate, and 21% ± 7% reduction in systolic blood pressure (p < 0.001 for all). Compensatory Reserve Metric values obtained with both PPGPO and PPGVC were associated with changes in heart rate (p < 0.001), stroke volume (p < 0.001), and pulse pressure (p < 0.001). Furthermore, they provided an earlier detection of hemodynamic shock relative to the traditional metrics of shock index (p < 0.001 for both), systolic blood pressure (p < 0.001 for both), and heart rate (p = 0.001 for both).

CONCLUSION

The CRM obtained from PPGPO provides a valid, time-sensitized prediction of hemodynamic decompensation, opening the door to provide military medical personnel noninvasive in-field advanced capability for early detection of hemorrhage and imminent onset of shock.

LEVEL OF EVIDENCE

Diagnostic Tests or Criteria; Level III.
Surgical Complications Following Renal Transplantation in a Large Institutional Cohort
Authors: Dagnæs-Hansen Julia , Kristensen Gitte H. , Stroomberg Hein V. , Rohrsted Malene , Sørensen Søren S. , Røder Andreas
Published: May 2024

Background.

Successful renal transplantation (RTx) relies on immunosuppression and an optimal surgical course with few surgical complications. Studies reporting the postoperative complications after RTx are heterogeneous and often lack systematic reporting of complications. This study aims to describe and identify postoperative short-term and long-term complications after RTx in a large institutional cohort and identify risk factors for a complicated surgical course.

Methods.

The study is a retrospective single-center cohort of 571 recipients who underwent living or deceased donor open RTx between 2014 and 2021. Data were collected on background information and perioperative and postoperative data. Complications were defined as short-term (<30 d) or long-term (>30 d) after transplantation and graded according to the Clavien-Dindo classification. Multivariable logistic regression was performed to evaluate risk factors for serious short-term complications and multivariable time-dependent Cox regression to evaluate risk factors for long-term complications.

Results.

A total of 351 patients received a graft from a deceased donor, and 144 of these grafts were on perfusion machine before transplantation. One or more short-term complications occurred in 345 (60%) patients. Previous RTx was associated with short-term Clavien-Dindo >2 complications in recipients (odds ratio = 2.08; 95% confidence interval [CI], 1.18-3.69; P = 0.01). Being underweight (body mass index <18.5) in combination with increasing age increased the odds of short-term Clavien-Dindo >2 and vascular complications. Increasing blood loss per 100 mL was associated with increased odds of short-term Clavien-Dindo >2 (odds ratio = 1.11; 95% CI, 1.01-1.21; P = 0.032). No associations were found for long-term complications after RTx. The 5-y cumulative incidence of graft loss was 12.6% (95% CI, 8.9-16.3).

Conclusions.

Short-term complications are common after RTx, and risk factors for severe short-term complications include previous RTx, increasing age, and low body mass index. No risk factors were identified for severe long-term complications. Further studies should explore whether new surgical techniques can reduce surgical complications in RTx.
Pancreas Transplantation Outcome Predictions—PTOP: A Risk Prediction Tool for Pancreas and Pancreas-Kidney Transplants Based on a European Cohort
Authors: Miller Gregor , Ankerst Donna P. , Kattan Michael W. , Hüser Norbert , Stocker Felix , Vogelaar Serge , van Bruchem Milou , Assfalg Volker
Published: May 2024

Background.

For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined pancreas and kidney transplantation (PKT) is the therapy of choice. However, the shortage of available grafts and complex impact of risk factors call for individualized, impartial predictions of PKT and pancreas transplantation (PT) outcomes to support physicians in graft acceptance decisions.

Methods.

Based on a large European cohort with 3060 PKT and PT performed between 2006 and 2021, the 3 primary patient outcomes time to patient mortality, pancreas graft loss, and kidney graft loss were visualized using Kaplan-Meier survival curves. Multivariable Cox proportional hazards models were developed for 5- and 10-y prediction of outcomes based on 26 risk factors.

Results.

Risk factors associated with increased mortality included previous kidney transplants, rescue allocations, longer waiting times, and simultaneous transplants of other organs. Increased pancreas graft loss was positively associated with higher recipient body mass index and donor age and negatively associated with simultaneous transplants of kidneys and other organs. Donor age was also associated with increased kidney graft losses. The multivariable Cox models reported median C-index values were 63% for patient mortality, 62% for pancreas loss, and 55% for kidney loss.

Conclusions.

This study provides an online risk tool at https://riskcalc.org/ptop for individual 5- and 10-y post-PKT and PT patient outcomes based on parameters available at the time of graft offer to support critical organ acceptance decisions and encourage external validation in independent populations.
Is competitive ability the key adaptation to benign environments? Revisiting experiments on closely related species of tidal plants
Authors: Martin Paul R. , Ghalambor Cameron K.
Published: May 2024

A central goal in biology is to understand which traits underlie adaptation to different environments. Yet, few studies have examined the relative contribution of competitive ability towards adaptive divergence among species occupying distinct environments. Here, we test the relative importance of competitive ability as an adaptation to relatively benign versus challenging environments, using previously published studies of closely related species pairs of primarily tidal plants subjected to reciprocal removal with transplant experiments in nature. Subordinate species typically occupy more challenging environments and showed consistent evidence for adaptation to challenging conditions, with no significant competitive effect on non-local, dominant species. In contrast, dominant species typically occupy relatively benign environments and performed significantly better than non-local, subordinate species that faced competition from the dominant species. Surprisingly, when the two species were not allowed to compete, the subordinate species performed as well as the dominant species in the benign environments where the subordinate species do not occur. These results suggest that competitive ability is the most important adaptation distinguishing the species that occupy relatively benign environments. The limited scope and number of suitable experimental studies encourage future work to test if these results are generalizable across taxa and environments.
Evolution of neural circuitry and cognition
Authors: Farnworth Max S. , Montgomery Stephen H.
Published: May 2024

Neural circuits govern the interface between the external environment, internal cues and outwardly directed behaviours. To process multiple environmental stimuli and integrate these with internal state requires considerable neural computation. Expansion in neural network size, most readily represented by whole brain size, has historically been linked to behavioural complexity, or the predominance of cognitive behaviours. Yet, it is largely unclear which aspects of circuit variation impact variation in performance. A key question in the field of evolutionary neurobiology is therefore how neural circuits evolve to allow improved behavioural performance or innovation. We discuss this question by first exploring how volumetric changes in brain areas reflect actual neural circuit change. We explore three major axes of neural circuit evolution—replication, restructuring and reconditioning of cells and circuits—and discuss how these could relate to broader phenotypes and behavioural variation. This discussion touches on the relevant uses and limitations of volumetrics, while advocating a more circuit-based view of cognition. We then use this framework to showcase an example from the insect brain, the multi-sensory integration and internal processing that is shared between the mushroom bodies and central complex. We end by identifying future trends in this research area, which promise to advance the field of evolutionary neurobiology.
Electrodeposition of iron from 1-ethyl-3-methylimidazolium trifluoromethanesulfonate and reverse microemulsions of Triton X-100
Authors: Tabassum Nazifa , Saha Shimul , Islam Md. Mominul , Susan Md. Abu Bin Hasan
Published: May 2024

Electrodeposition of iron (Fe) was investigated in three different media, namely a hydrophilic ionic liquid (IL), 1-ethyl-3-methylimidazolium trifluoromethanesulfonate, conventional reverse microemulsion (RME)/reverse micellar solution, and IL-based RME of a non-ionic surfactant, Triton X-100, with a view to electrodepositing iron with desired morphology. Electrochemical behaviour of Fe
2+
was studied using cyclic voltammetric technique with a copper electrode as the working electrode. Electrochemical reduction of Fe
2+
in all the studied media was found to be an electrochemically irreversible, diffusion-controlled process. Successful potentiostatic electrodeposition of metallic iron was performed in all the studied media on copper substrate using bulk electrolysis method. The obtained iron electrodeposits were characterized using a scanning electron microscope and an X-ray diffractometer. The controlled diffusion of Fe
2+
towards electrode surface in all the media resulted in the formation of nanoparticles of iron, but compact layers of granular nanoparticles could be achieved from both the conventional and IL-based RME systems. The IL-based microemulsions synergistically combined the advantageous features of both the IL and RME and showed promise for tuning the size, shape, and morphology of the electrodeposited iron.
Collective order and group structure of shoaling fish subject to differing risk-level treatments with a sympatric predator
Authors: Schaerf Timothy M. , Wilson Alexander D. M. , Welch Mitchell , Ward Ashley J. W.
Published: May 2024

It is imperative for individuals to exhibit flexible behaviour according to ecological context, such as available resources or predation threat. Manipulative studies on responses to threat often focus on behaviour in the presence of a single indicator for the potential of predation, whereas in the wild perception of threat will probably be more nuanced. Here, we examine the collective behaviour of eastern mosquitofish (
Gambusia holbrooki
) subject to five differing threat scenarios relating to the presence and hunger state of a jade perch (
Scortum barcoo
). Across threat scenarios, groups exhibit unique behavioural profiles that differ in the durations that particular collective states are maintained, the probability of transitions between states, the size and duration of persistence of spatially defined subgroups, and the patterns of collective order of these subgroups. Under the greatest level of threat, subgroups of consistent membership persist for longer durations. Group-level behaviours, and their differences, are interconnected with differences in estimates of the underlying rules of interaction thought to govern collective motion. The responses of the group are shown to be specific to the details of a potential threat, rather than a binary response to the presence or absence of some form of threat.
Expanding the data Ark: an attempt to make the data from highly cited social science papers publicly available
Authors: Dulitzki Coby , Crane Steven Michael , Hardwicke Tom E. , Ioannidis John P. A.
Published: May 2024

Access to scientific data can enable independent reuse and verification; however, most data are not available and become increasingly irrecoverable over time. This study aimed to retrieve and preserve important datasets from 160 of the most highly-cited social science articles published between 2008–2013 and 2015–2018. We asked authors if they would share data in a public repository—the Data Ark—or provide reasons if data could not be shared. Of the 160 articles, data for 117 (73%, 95% CI [67%–80%]) were not available and data for 7 (4%, 95% CI [0%–12%]) were available with restrictions. Data for 36 (22%, 95% CI [16%–30%]) articles were available in unrestricted form: 29 of these datasets were already available and 7 datasets were made available in the Data Ark. Most authors did not respond to our data requests and a minority shared reasons for not sharing, such as legal or ethical constraints. These findings highlight an unresolved need to preserve important scientific datasets and increase their accessibility to the scientific community.
Newtonian gravitational waves from a continuum
Authors: Vadasz Peter
Published: May 2024

Gravitational waves are being shown to derive directly from Newtonian dynamics for a continuous mass distribution, e.g. compressible fluids or equivalent. It is shown that the equations governing a continuous mass distribution, i.e. the inviscid Navier–Stokes equations for a general variable gravitational field

g

(

t
,

x

)

, are equivalent to a form identical to the Maxwell equations from electromagnetism, subject to a specified condition. The consequence of this equivalence is the creation of gravity waves that propagate at a finite speed. The latter implies that Newtonian gravitation as presented in this paper is not ‘spooky action at a distance’ but rather is similar to electromagnetic waves propagating at finite speed, despite the apparent form appearing in the integrated field formula. In addition, this proves that, in analogy to the Maxwell equations, the Newtonian gravitation equations are Lorentz invariant for waves propagating at the speed of light. Since gravitational waves were so far derived only from Einstein’s general relativity theory, it becomes appealing to check if there is a connection between the Newtonian waves presented in this paper and the general relativity type of waves at least in a certain limit of overlapping validity, i.e. as a flat-space approximation. The latter is left for follow-up research.
Fossil evidence for the ancient link between clonal fragmentation, six-fold symmetry and an epizoic lifestyle in asterozoan echinoderms
Authors: Thuy Ben , Numberger-Thuy Lea D. , Härer Jürgen , Kroh Andreas , Winkler Viola , Schweigert Günter
Published: May 2024

Asexual reproduction by means of splitting, also called fissiparity, is a common feature in some asterozoan groups, especially in ophiactid brittle stars. Most fissiparous brittle stars show six instead of the usual five rays, live as epibionts on host organisms, and use clonal fragmentation to rapidly colonize secluded habitats and effectively expand the margins of their distribution area. While the biology and ecology of clonal fragmentation are comparatively well understood, virtually nothing is known about the evolution and geological history of that phenomenon. Here, we describe an exceptional fossil of an articulated six-armed brittle star from the Late Jurassic of Germany, showing one body half in the process of regeneration, and assign it to the new species
Ophiactis hex
sp. nov. Phylogenetic inference shows that the fossil represents the oldest member of the extant family Ophiactidae. Because the
Ophiactis hex
specimen shows an original six-fold symmetry combined with a morphology typically found in epizoic ophiuroids, in line with recent fissiparous ophiactid relatives, we assume that the regenerating body half is an indication for fissiparity.
Ophiactis hex
thus shows that fissiparity was established as a means of asexual reproduction in asterozoan echinoderms by the Late Jurassic.
The last ceratosaur of Asia: a new noasaurid from the Early Cretaceous Great Siberian Refugium
Authors: Averianov Alexander O. , Skutschas Pavel P. , Atuchin Andrey A. , Slobodin Dmitry A. , Feofanova Olga A. , Vladimirova Olga N.
Published: May 2024

The noasaurid ceratosaur
Kiyacursor longipes
gen. et sp. nov. is described based on a fragmentary skeleton including cervical vertebra, pectoral girdle, humerus and hind limbs from the Lower Cretaceous (Aptian) Ilek Formation at Shestakovo 1 locality in Western Siberia, Russia. This is the first ceratosaur from the Early Cretaceous of Asia, extending the stratigraphic range of Ceratosauria by 40 Myr on that continent.
Kiyacursor
shares unique hind limb proportions with
Elaphrosaurus
and
Limusaurus
, suggesting improved cursorial ability. These taxa show an ostrich-like specialization of the pes, with a large third metatarsal and greatly reduced second metatarsal. By contrast, all other fast running non-avian theropod dinosaurs have an arctometatarsalian pes, with the third metatarsal strongly reduced proximally. The new taxon lived in the Early Cretaceous ecosystem containing a number of other Jurassic relics, such as stem salamanders, protosuchian and shartegosuchid crocodyliforms, tritylodontid synapsids and docodontan mammaliaforms.
Embryonic diversification of adult neural stem cells and ependymal cells
Authors: Yamaguchi Shima , Kuniya Takaaki , Omiya Hanae , Suzuki Yutaka , Seki Masahide , Ukai Hideki , Fang Lingyan , Harada Yujin , Kawaguchi Daichi , Gotoh Yukiko
Published: May 2024

Both adult neural stem (type B) cells and ependymal (type E) cells in the mouse ventricular-subventricular zone (V-SVZ) are derived from slowly dividing (or quiescent) embryonic neural stem-progenitor cells (NPCs) that are set aside during development. However, it has remained unclear whether fate diversification between adult type B and type E cells actually occurs during embryogenesis. Here we performed single-cell transcriptomic analysis of slowly dividing embryonic NPCs and identified cell subpopulations transcriptionally similar to adult type B or type E cells. The type B- like embryonic cells appeared to emerge before embryonic day (E) 13.5, whereas the type E-like cells became evident between E13.5 and E16.5. Genes differentially expressed in B-like embryonic cells (versus E-like cells) includedTmem100,Cadm2, and bone morphogenetic protein (BMP)-induced genes. Forced expression of an active form of BMP receptor (ALK2QD), TMEM100, or CADM2 in embryonic NPCs resulted in preferential generation of adult type B cells relative to type E cells in the postnatal brain. Moreover, knockdown of TMEM100 resulted in relative enrichment of type E cells over type B cells. Our results indicate that the embryonic origin of adult type B cells and that of type E cells have already diverged molecularly during embryogenesis, and they have identified key molecular players in this fate bifurcation.
The role of noise in the tumour-immune interactions reveals memoryless shifting response
Authors: Alharbi Yamen
Published: May 2024

In the present study, the effects of randomness on the model of the immune and cancer cells is discussed. First, we uncover the existence of a bistable response in this interaction where portion of population are cancerous cells. We then discuss how the individual variation within these cells can affect this bistable response. The dominance duration of the tumour and immune cells are highlighted. We calculated the mean of the elimination time of the tumour cells and how can be affected by some key parameters. The analysis reveals that the switching from a stable state to another has a memoryless property.
Neuroinflammation at the Grey-White Matter Interface in Active-Duty United States Special Operations Forces
Authors: Edlow Brian L. , Tseng Chieh-En J. , Gilmore Natalie , McKinney Isabella R. , Tromly Samantha L. , Deary Katryna B. , Hu Collin G. , Healy Brian C. , Mac Donald Christine L. , Dams-O’Connor Kristen , Greve Douglas N. , Bodien Yelena G. , Perl Daniel P. , Hooker Jacob M. , Zürcher Nicole R.
Published: May 2024

Emerging evidence from autopsy studies indicates that interface astroglial scarring (IAS) at the grey-white matter junction is a pathological signature of repeated blast brain injury in military personnel. However, there is currently no neuroimaging test that detects IAS, which is a major barrier to diagnosis, prevention, and treatment. In 27 active-duty United States Special Operations Forces personnel with high levels of cumulative blast exposure, we performed translocator protein (TSPO) positron emission tomography (PET) using [11C]PBR28 to detect neuroinflammation at the cortical grey-white matter interface, a neuroanatomic location where IAS has been reported in autopsy studies. TSPO signal in individual Operators was compared to the mean TSPO signal in a control group of 9 healthy civilian volunteers. We identified five Operators with TSPO signal at the cortical grey-white matter interface that was more than two standard deviations above the control mean. Cumulative blast exposure, as measured by the Generalized Blast Exposure Value, did not differ between the five Operators with elevated TSPO signal and the 22 Operators without elevated TSPO signal. While the pathophysiologic link between neuroinflammation and IAS remains uncertain, these observations provide the basis for further investigation into TSPO PET as a potential biomarker of repeated blast brain injury.

Disclaimer

The views expressed in this manuscript are entirely those of the authors and do not necessarily reflect the views, policy, or position of the United States Government, Department of Defense, or United States Special Operations Command, or the Uniformed Services University of the Health Sciences.
Benchmarking Machine Learning Missing Data Imputation Methods in Large-Scale Mental Health Survey Databases
Authors: Prakash Preethi , Street Kelly , Narayanan Shrikanth , Fernandez Bridget A. , Shen Yufeng , Shu Chang
Published: May 2024

Databases with mental and behavioral health surveys suffer from missingness when participants skip the entire survey, affecting the data quality and sample size. We investigated the missing data patterns and evaluate the imputation performance in Simons Powering Autism Research (SPARK), a large-scale autism cohort consists of over 117,000 participants. Four common methods were assessed – Multiple Imputation by Chained Equations (MICE), K-Nearest Neighbors (KNN), MissForest, and Multiple Imputation with Denoising Autoencoders (MIDAS). In a complete subset of 15,196 autism participants, we simulated three types of missingness patterns. We observed that MIDAS and KNN performed the best as the rate of random missingness increased and when blockwise missingness was simulated. The average computational times for MIDAS and KNN were 10 minutes, 35 minutes for MissForest, and 290 minutes for MICE. MIDAS and KNN both provide promising imputation performance in mental and behavioral health survey data that exhibit blockwise missingness patterns.
Auranofin and reactive oxygen species inhibit protein synthesis and regulate the level of the PLK1 protein in Ewing sarcoma cells
Authors: Haight Joseph A. , Koppenhafer Stacia L. , Geary Elizabeth L. , Gordon David J.
Published: May 2024

Novel therapeutic approaches are needed for the treatment of Ewing sarcoma tumors. We previously identified that Ewing sarcoma cell lines are sensitive to drugs that inhibit protein translation. However, translational and therapeutic approaches to inhibit protein synthesis in tumors are limited. In this work, we identified that reactive oxygen species, which are generated by a wide range of chemotherapy and other drugs, inhibit protein synthesis and reduce the level of critical proteins that support tumorigenesis in Ewing sarcoma cells. In particular, we identified that both hydrogen peroxide and auranofin, an inhibitor of thioredoxin reductase and regulator of oxidative stress and reactive oxygen species, activate the repressor of protein translation 4E-BP1 and reduce the levels of the oncogenic proteins RRM2 and PLK1 in Ewing and other sarcoma cell lines. These results provide novel insight into the mechanism of how ROS-inducing drugs target cancer cells via inhibition of protein translation and identify a mechanistic link between ROS and the DNA replication (RRM2) and cell cycle regulatory (PLK1) pathways.
Stop and go: exploring alternative mechanisms for task allocation in social insects - response and satisfaction thresholds trade off cost, accuracy, and speed differently
Authors: Lynch CM , Wilson RC , Dornhaus A
Published: May 2024

Division of labor, a key feature of many complex systems, requires a mechanism that allows individuals to choose tasks. The popular ‘response threshold hypothesis’ posits that some workers start engaging in particular tasks at a lower level of need than others. However, individuals may only have access to information about need after they actually engage in a task. We therefore introduce two novel interpretations of this task-allocation mechanism. While the ‘response threshold mechanism’ determines when individualsstartworking, the ‘satisfaction threshold mechanism’ drives when individualsstopworking. We also model a ‘composite threshold mechanism’ where workers consider task need both to start and end working. Second, we model the possibility that the stimulus perceived by workers is a ‘completion’ cue instead of a ‘demand’ cue. While these may seem like subtle variations, we show here that they can yield dramatically different collective dynamics. In simulations with biologically relevant parameter ranges, response thresholds produced the quickest reaction to increases in task demand, satisfaction thresholds yielded the lowest task-switching rate, and composite thresholds most closely matched the number of workers allocated to the number needed. Different threshold types thus differentially trade off speed, cost, and accuracy. We did not model benefits of specialization; purely in terms of allocating workers to tasks, we also found that response thresholds usually perform worse than a null random choice model in terms of cost and efficiency, and variation among workers does not improve task allocation. Colonies utilizing task demand cues also tend to perform better than those using task completion cues. Our results ultimately suggest that different threshold mechanisms may be suited for different situations or types of tasks.

Author Summary

Division of labor is a phenomenon where workers in a community consistently differ in the tasks they work on. Many scientists believe division of labor arises in social insects (i.e. ants and bees) as a result of difference in workers’ responsiveness to cues that correspond to the demand for work in a task. For example, some ants in a colony start feeding brood much sooner than others, possibly because of a higher sensitivity, or lower ‘response threshold’, to brood pheromone. We show that instead of using such a cue to decide when to start on a task, theoretically workers may instead use it only to decide when to stop working; similarly, workers may use a cue that tells them how much work is needed in a task, or they may use one that corresponds to how much work has already been done. These seemingly subtle differences affect how much a colony invests in work and how quickly stability is reached when the balance of work needed in different tasks changes. Therefore, these different mechanisms may evolve to solve different problems.
Differential effects of prolonged post-fixation on immunohistochemical and histochemical staining for postmortem human brains
Authors: Ma Weiya , Frigon Eve-Marie , Maranzano Josefina , Zeighami Yashar , Dadar Mahsa
Published: May 2024

Immunohistochemical (IHC) and histochemical (HC) staining is widely used for human brains post-fixed in formalin and stored in brain banks worldwide for months, years and decades. Understanding the effect of prolonged post-fixation, postmortem interval (PMI) and age on these staining procedures is important for interpreting their outcomes, thus improving diagnosis and research of brain disorders afflicting millions of world populations. In this study, we performed both IHC and HC staining for prefrontal cortex (PFC) of postmortem human brains post-fixed for 1, 5, 10, 15 and 20 years. A negative correlation was detected between the intensity of neuron marker neuron nuclear specific marker (NeuN), microglia marker ionized calcium-binding adaptor molecule 1 (Iba1), cresyl violet (CV) and Luxol fast blue (LFB) staining versus post-fixation durations. By contrast, a positive correlation was seen between the intensity of astrocyte marker glial fibrillary acidic protein (GFAP) and hemaetoxylin and eosin Y (H&E) staining versus post-fixation durations. No correlation was found between the staining intensity of NeuN, GFAP, Iba1, H&E, CV and LFB versus PMI. Moreover, no correlation was seen between NeuN, Iba1, H&E, CV and LFB, except GFAP, versus age. These data suggest that prolonged post-fixation exerts both positive and negative effects, but age and PMI have limited effects, on these IHC and HC parameters. Hence these differential changes need to be considered in interpretation of the results when using tissues with prolonged post-fixation. Furthermore, if feasible, it is recommended to perform IHC and HC staining for human brains with the same post-fixation time windows and to use the most optimal antibodies to offset its impact on downstream analyses.
Single-shot water-fat imaging with multi-echo blip-rewound EPI
Authors: Wu Wenchuan
Published: May 2024

Purpose

To develop a method for single-shot water-fat imaging.

Methods

Single-shot blip-rewound EPI (rEPI) is a fast imaging technique that can acquire multiple echo MRI images with a snapshot. Dixon’s method separates water and fat signals using signals acquired with different echo times. Combining multi-echo rEPI with properly chosen echo times and Dixon-based post-processing generates water and fat images with a single-shot scan.

Results

Phantom and in vivo experiments were performed to evaluate the proposed method. In phantom scans, water and fat signals are robustly separated using the proposed method, and the obtained water signal is much cleaner than that obtained by conventional EPI acquisition with fat suppression. In vivo experiments show that fat suppression can be obtained using the proposed method without fat saturation pulses, reducing SAR and shortening scan time. In addition, fat signal can also be reconstructed based on the proposed method.

Conclusion

A single-shot water-fat imaging technique has been successfully developed, a significant advancement that offers speed and robustness in separating water and fat signals for human MRI scans.
Impact of the use of cannabis as a medicine in pregnancy, on the unborn child: a systematic scoping review protocol
Authors: Dinant Alexa Ulana Annette , Bonomo Yvonne Ann , Canaway Rachel , Hallinan Christine Mary
Published: May 2024

Introduction

The use of cannabis for medicinal purposes is on the rise. As more people place their trust in the safety of prescribed alternative plant-based medicine and find it easily accessible, there is a growing concern that pregnant women may be increasingly using cannabis for medicinal purposes to manage their pregnancy symptoms and other health conditions. The objectives of this scoping review are to: conduct a systematic search of the literature to investigate the use of cannabis as a medicine in the context of the recent legislative changes and the resulting increase in use and acceptance, specifically in pregnancy; describe the characteristics of the demographic population using cannabis for medicinal purposes during pregnancy; and to map evidence of its impact on the unborn child and on the child up to twelve months postpartum.

Methods and analyses

Research on pregnant women who use cannabis for medicinal purposes only, and infants up to one year after birth who experienced in utero exposure to cannabis for medicinal purposes, will be included in this review. Reviews, randomised controlled trials, case-control, cross-sectional and cohort studies, that have been peer reviewed and published between 1996 and April 2024 as a research paper that investigates prenatal use of cannabis for medicinal purposes and foetal, perinatal, and neonatal outcomes, will be selected for review. Excluding cover editorials, letters, commentaries, protocols, conference papers and book chapters. Effects of illicit drugs use, alcohol misuse and nicotine exposure on neonate outcome will be controlled by excluding studies reporting on the concomitant use of such substances when cannabis data cannot be isolated.

All titles and abstracts will be reviewed by one researcher. Records will be excluded based on title and abstract screening as well as publication type. The full text articles will then be reviewed independently by at least two researchers. Where initial disagreement exists between reviewers regarding the inclusion of a study, team members will review disputed articles’ status until consensus is gained. Selected studies will then be assessed by at least two independent researchers for risk bias assessment using validated tools. Two researchers will pilot-test the data extraction form and independently screen the literature and extract the data. Data will be extracted and synthesised following a systematic review methodology and reported in accordance with the PRISMA guidelines to facilitate transparent reporting [1].
Incidence of Creutzfeldt-Jakob Disease in the United States from 2000 to 2019
Authors: Seitz Alison , Zhang Cenai , Navi Babak B. , Kamel Hooman , Merkler Alexander E.
Published: May 2024

Background and purpose

To test the hypothesis that the incidence of Creutzfeldt-Jakob disease (CJD) has remained constant, we calculated the rate of hospitalizations for CJD in the United States using the National Inpatient Sample (NIS) from 2000 to 2019.

Methods

We used ICD-9 and ICD-10 codes to identify people hospitalized with presumed CJD in the National Inpatient Sample (NIS) from 2000 to 2019. Survey weights were used to calculate nationally representative estimates. We used 2000 census data to calculate age-adjusted standardized rates of CJD hospitalizations by sex and race-ethnicity and then used Joinpoint regression to evaluate changes in those rates.

Results

From 2000 to 2019, there were 11,064 admissions for CJD across the U.S. Across this period, the age-adjusted rate of CJD-related hospitalizations increased significantly from 1.25 (95% CI, 1.25-1.26) to 1.98 (95% CI, 1.98-1.99) per million U.S. adults per year, with a significant annual percentage change between 2004 and 2013 of 7.6% (95% CI, 4.4%-10.9%).

Conclusions

The incidence of CJD increased in the United States from 2000 to 2019, with a significant increase specifically between 2004 and 2013, though the overall case rate remains low.
Exploring the feasibility, acceptability and impact of genomic newborn screening for rare diseases in England: A study protocol for the Generation Study - Process and Impact Evaluation
Authors: Lewis Celine , Boardman Felicity , Buchanan James , Clark Sigrún , Gilchrist Katie , Hardelid Pia , Hunter Amy , Jones Jennifer , Leeson-Beevers Kerry , Stafford-Smith Bethany , Vindrola-Padros Cecilia , Vu Martin , Wu Wing Han , Zylbersztejn Ania , Hill Melissa
Published: May 2024

The role of genomics in healthcare is expanding rapidly and many countries are set to explore the possibility of using genomic sequencing to expand current newborn screening programmes. Offering routine genomic newborn screening (gNBS) would allow newborn screening to include a much broader range of rare conditions, but there are many technical, practical, psychosocial, ethical and economic challenges to be addressed. Genomics England and NHS England have established the Generation Study to deliver gNBS for 100,000 births in 2024/5 to explore the benefits, challenges, and practicalities of offering gNBS to parents in England. Here we describe the study protocol for the Generation Study - Process and Impact Evaluation, an independent mixed-methods evaluation of the Generation Study. The evaluation will have oversight from a Study Advisory Group that includes academic, clinical and patient representatives and a Patient and Public Involvement and Engagement (PPIE) Advisory Group that includes members from parent and patient organisations and parents with relevant experiences. The Process and Impact Evaluation will examine whether offering gNBS in routine care is feasible and acceptable and inform our understanding of the clinical utility and cost effectiveness of gNBS in England. Through surveys and interviews we will explore the attitudes and experiences of parents, professionals and patient organisations. We will also consider the clinical, psychosocial and health economic impacts, both positive and negative. The results will be presented at national and international conferences and submitted for peer review and publication.