bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostate cancer screening in African American men: a review of the evidence
Authors: Kensler Kevin H , Johnson Roman , Morley Faith , Albrair Mohamed , Dickerman Barbra A , Gulati Roman , Holt Sarah K , Iyer Hari S , Kibel Adam S , Lee Jenney R , Preston Mark A , Vassy Jason L , Wolff Erika M , Nyame Yaw A , Etzioni Ruth , Rebbeck Timothy R
Published: September 2023

Background

Prostate cancer is the most diagnosed cancer in African American men, yet prostate cancer screening regimens in this group are poorly guided by existing evidence, given underrepresentation of African American men in prostate cancer screening trials. It is critical to optimize prostate cancer screening and early detection in this high-risk group because underdiagnosis may lead to later-stage cancers at diagnosis and higher mortality while overdiagnosis may lead to unnecessary treatment.

Methods

We performed a review of the literature related to prostate cancer screening and early detection specific to African American men to summarize the existing evidence available to guide health-care practice.

Results

Limited evidence from observational and modeling studies suggests that African American men should be screened for prostate cancer. Consideration should be given to initiating screening of African American men at younger ages (eg, 45-50 years) and at more frequent intervals relative to other racial groups in the United States. Screening intervals can be optimized by using a baseline prostate-specific antigen measurement in midlife. Finally, no evidence has indicated that African American men would benefit from screening beyond 75 years of age; in fact, this group may experience higher rates of overdiagnosis at older ages.

Conclusions

The evidence base for prostate cancer screening in African American men is limited by the lack of large, randomized studies. Our literature search supported the need for African American men to be screened for prostate cancer, for initiating screening at younger ages (45-50 years), and perhaps screening at more frequent intervals relative to men of other racial groups in the United States.
The Philadelphia Lung Cancer Learning Community: a multi–health-system, citywide approach to lung cancer screening
Authors: Barta Julie A , Erkmen Cherie P , Shusted Christine S , Myers Ronald E , Saia Chelsea , Cohen Sarah , Wainwright Jocelyn , Zeigler-Johnson Charnita , Dako Farouk , Wender Richard , Kane Gregory C , Vachani Anil , Rendle Katharine A
Published: September 2023

Background

Lung cancer screening uptake for individuals at high risk is generally low across the United States, and reporting of lung cancer screening practices and outcomes is often limited to single hospitals or institutions. We describe a citywide, multicenter analysis of individuals receiving lung cancer screening integrated with geospatial analyses of neighborhood-level lung cancer risk factors.

Methods

The Philadelphia Lung Cancer Learning Community consists of lung cancer screening clinicians and researchers at the 3 largest health systems in the city. This multidisciplinary, multi-institutional team identified a Philadelphia Lung Cancer Learning Community study cohort that included 11 222 Philadelphia residents who underwent low-dose computed tomography for lung cancer screening from 2014 to 2021 at a Philadelphia Lung Cancer Learning Community health-care system. Individual-level demographic and clinical data were obtained, and lung cancer screening participants were geocoded to their Philadelphia census tract of residence. Neighborhood characteristics were integrated with lung cancer screening counts to generate bivariate choropleth maps.

Results

The combined sample included 37.8% Black adults, 52.4% women, and 56.3% adults who currently smoke. Of 376 residential census tracts in Philadelphia, 358 (95.2%) included 5 or more individuals undergoing lung cancer screening, and the highest counts were geographically clustered around each health system’s screening sites. A relatively low percentage of screened adults resided in census tracts with high tobacco retailer density or high smoking prevalence.

Conclusions

The sociodemographic characteristics of lung cancer screening participants in Philadelphia varied by health system and neighborhood. These results suggest that a multicenter approach to lung cancer screening can identify vulnerable areas for future tailored approaches to improving lung cancer screening uptake. Future directions should use these findings to develop and test collaborative strategies to increase lung cancer screening at the community and regional levels.
IAR4 mutation enhances cadmium toxicity by disturbing auxin homeostasis in Arabidopsis thaliana
Authors: Chen Jie , Huang Shao Bai , Wang Xue , Huang LiZhen , Gao Cheng , Huang Xin-Yuan , Zhao Fang-Jie
Published: September 2023

Cadmium (Cd) is highly toxic to plants, but the targets and modes of toxicity remain unclear. We isolated a Cd-hypersensitive mutant of Arabidopsis thaliana, Cd-induced short root 2 (cdsr2), in the background of the phytochelatin synthase-defective mutant cad1-3. Both cdsr2 and cdsr2 cad1-3 displayed shorter roots and were more sensitive to Cd than their respective wild type. Using genomic resequencing and complementation, IAR4 was identified as the causal gene, which encodes a putative mitochondrial pyruvate dehydrogenase E1α subunit. cdsr2 showed decreased pyruvate dehydrogenase activity and NADH content, but markedly increased concentrations of pyruvate and alanine in roots. Both Cd stress and IAR4 mutation decreased auxin level in the root tips, and the effect was additive. A higher growth temperature rescued the phenotypes in cdsr2. Exogenous alanine inhibited root growth and decreased auxin level in the wild type. Cadmium stress suppressed the expression of genes involved in auxin biosynthesis, hydrolysis of auxin-conjugates and auxin polar transport. Our results suggest that auxin homeostasis is a key target of Cd toxicity, which is aggravated by IAR4 mutation due to decreased pyruvate dehydrogenase activity. Decreased auxin level in cdsr2 is likely caused by increased auxin-alanine conjugation and decreased energy status in roots.
Katsue Misawa's sunspot observations in 1921–1934: a primary reference for the Wolfer–Brunner transition
Authors: Hayakawa Hisashi , Suyama Toru , Clette Frédéric , Bhattacharya Shreya , Lefèvre Laure , Ohnishi Kouji
Published: September 2023

Our knowledge of the centennial solar variability is largely based on the time series of international sunspot number ($S_{N}$), a composite index based on multiple visual sunspot observers’ records from the 18th century onward and maintained by the World Data Center (WDC) ‘Sunspot Index and Long-term Solar Observations’ (SILSO). However, over the period 1919–1944, our capacity to diagnose the homogeneity of this time series is currently limited, because most of the archived source data of the Zürich Observatory were never published over that interval and are presently still missing. Therefore, it is essential to recover any long-duration series from individual sunspot observers active during this period to bridge this Zürich data gap. In this context, Katsue Misawa has conducted regular sunspot observations from 1921 to 1934 (mean coverage of 25.4 days per month), which were not accessible for the Zürich Observatory and thus form a valuable addition to the data base maintained by the WDC–SILSO. In this study, we digitized his observational records, documented his observing technique, and reconstructed his total and hemispheric SNs. We compared his data with the international SN (current version V2) and evaluated their stability. Misawa's data series generally agrees well with SN V2. However, Misawa's data show a significant transitory drift in 1925–1928 against the SN V2, when the Zürich pilot observer changed from Alfred Wolfer to William Otto Brunner.
A search for magnetic δ Scuti stars in Kepler hybrid candidates
Authors: Thomson-Paressant K , Neiner C , Lampens P , Labadie-Bartz J , Monier R , Mathias P , Tkachenko A
Published: September 2023

Numerous candidate hybrid stars of type δ Scuti–γ Doradus have been identified with the Kepler satellite. However, many of them lie outside the theoretically expected instability strip for hybrid pulsation, where δ Sct and γ Dor pulsations can be simultaneously excited. We postulate that some of these pulsating stars may not be genuine hybrid pulsators but rather magnetic δ Sct stars, for which the rotational modulation from spots on the surface associated with the magnetic field produces frequencies in the same domain as γ Dor pulsations. We search for the presence of a magnetic field in a small sample of selected hybrid δ Sct–γ Dor stars using spectropolarimetry. At the time of observations, the only δ Sct star known to have a magnetic field was HD 188774 with a field strength of a few hundred Gauss. Our observations were thus tailored to detect fields of this typical strength. We find no magnetic field in the hybrid candidate stars we observed. However, two of the three other magnetic δ Sct stars discovered since these observations have much weaker fields than HD 188774, and are of dynamo origin rather than fossil fields. It is likely that our observations are not sensitive enough to detect such dynamo magnetic fields in the cooler stars of our sample if they are present. This work nevertheless provides reliable upper limits on possible fossil fields in the hotter stars, pointing towards typically weaker fields in δ Sct stars than in OBA stars in general.
Exploring the angular momentum – atomic gas content connection with eagle and IllustrisTNG
Authors: Hardwick Jennifer A , Cortese Luca , Obreschkow Danail , Lagos Claudia , Stevens Adam R H , Catinella Barbara , Garratt-Smithson Lilian
Published: September 2023

We use the Evolution and Assembly of GaLaxies and their Environments (eagle) and IllustrisTNG (The Next Generation) cosmological simulations to investigate the properties of the baryonic specific angular momentum (j), baryonic mass (M), and atomic gas fraction (fatm) plane for nearby galaxies. We find EAGLE and TNG to be in excellent agreement with each other. These simulations are also consistent with the results obtained with eXtended GALEX Arecibo SDSS Survey (xGASS) for gas fractions greater than 0.01. This implies that the disagreements previously identified between xGASS and predictions from simple analytical disc stability arguments also holds true for eagle and tng. For lower gas fraction (the regime currently unconstrained by observations), both simulations deviate from the plane but still maintain good agreement with each other. Despite the challenges posed by resolution limits at low gas fractions, our findings suggest a potential disconnect between angular momentum and gas fraction in the gas-poor regime, implying that not all gas-poor galaxies have low specific angular momentum.
On the non-dissipative tidal evolution of the misalignment between spin and orbital angular momenta
Authors: Ivanov P B , Papaloizou J C B
Published: September 2023

We extend our previous work on the evolution of close binary systems with misaligned orbital and spin angular momenta resulting from non-dissipative tidal interaction to include all physical effects contributing to apsidal motion. In addition to tidal distortion of the primary by the compact secondary, these include relativistic Einstein precession and the rotational distortion of the primary. The influence of the precession of the line of nodes is included. The dependence of the tidal torque on the apsidal angle $\hat{\varpi }$ couples the apsidal motion to the rate of evolution of the misalignment angle β which is found to oscillate. We provide analytical estimates for the oscillation amplitude Δβ over a wide range of parameter space confirmed by numerical integrations. This is found to be more significant near critical curves on which ${\mathrm{d}}{\hat{\varpi }} /{\mathrm{d}}t=0$ for a specified β. We find that to obtain 0.1 < Δβ < ∼1, the mass ratio q > ∼1, the initial eccentricity should be modest, $\cos \beta \lt 1/\sqrt{5},$ with cos β < 0 corresponding to retrograde rotation, initially, and the primary rotation rate should be sufficiently large. The extended discussion of apsidal motion and its coupled evolution to the misalignment angle given here has potential applications to close binaries with anomalous apsidal motion as well as transiting exoplanets such as warm Jupiters.
Sampling the Faraday rotation sky of TNG50: imprint of the magnetized circumgalactic medium around Milky Way-like galaxies
Authors: Jung S Lyla , McClure-Griffiths N M , Pakmor Rüdiger , Ma Yik Ki , Hill Alex S , Van Eck Cameron L , Anderson Craig S
Published: September 2023

Faraday rotation measure (RM) is arguably the most practical observational tracer of magnetic fields in the diffuse circumgalactic medium (CGM). We sample synthetic Faraday rotation skies of Milky Way-like galaxies in TNG50 of the IllustrisTNG project by placing an observer inside the galaxies at a solar circle-like position. Our synthetic RM grids emulate specifications of current and upcoming surveys; the NRAO VLA Sky Survey (NVSS), the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), and a future Square Kilometre Array (SKA1-mid) polarization survey. It has been suggested that magnetic fields regulate the survival of high-velocity clouds. However, there is only a small number of observational detections of magnetized clouds thus far. In the first part of the paper, we test conditions for the detection of magnetized circumgalactic clouds. Based on the synthetic RM samplings of clouds in the simulations, we predict upcoming polarimetric surveys will open opportunities for the detection of even low-mass and distant clouds. In the second part of the paper, we investigate the imprint of the CGM in the all-sky RM distribution. We test whether the RM variation produced by the CGM is correlated with global galaxy properties, such as distance to a satellite, specific star formation rate, neutral hydrogen covering fraction, and accretion rate to the supermassive black hole. We argue that the observed fluctuation in the RM measurements on scales less than 1○, which has been considered an indication of intergalactic magnetic fields, might in fact incorporate a significant contribution of the Milky Way CGM.
Super-Eddington accretion as a possible scenario to form GW190425
Authors: Zhang W T , Wang Z H T , Zhu J-P , Hu R-C , Shu X W , Tang Q W , Yi S X , Lyu F , Liang E W , Qin Y
Published: September 2023

On 2019 April 25, the LIGO/Virgo Scientific Collaboration detected a compact binary coalescence, GW190425. Under the assumption of the binary neutron star (BNS), the total mass of $3.4^{+0.3}_{-0.1}\, \mathrm{M}_\odot$ lies five standard deviations away from the known Galactic population mean. In the standard common envelope scenario, the immediate progenitor of GW190425 is a close binary system composed of an NS and a He-rich star. With the detailed binary evolutionary modelling, we find that in order to reproduce GW190425-like events, super-Eddington accretion (e.g. $1,000\, \dot{M}_{\rm Edd}$) from a He-rich star onto the first-born NS with a typical mass of 1.33 M⊙ via stable Case BB mass transfer (MT) is necessarily required. Furthermore, the immediate progenitors should potentially have an initial mass of MZamsHe in a range of 3.0–3.5 M⊙ and an initial orbital period of Pinit from 0.08 d to 0.12 d, respectively. The corresponding mass accreted onto NSs via stable Case BB MT phase varies from $0.70\, \mathrm{M}_\odot$ to $0.77\, \mathrm{M}_\odot$. After the formation of the second-born NS, the BNSs are expected to be merged due to gravitational wave emission from ∼11 Myr to ∼190 Myr.
OTUD5 limits replication fork instability by organizing chromatin remodelers
Authors: de Vivo Angelo , Song Hongseon , Lee Yujin , Tirado-Class Neysha , Sanchez Anthony , Westerheide Sandy , Dungrawala Huzefa , Kee Younghoon
Published: September 2023

Proper regulation of replication fork progression is important for genomic maintenance. Subverting the transcription-induced conflicts is crucial in preserving the integrity of replication forks. Various chromatin remodelers, such as histone chaperone and histone deacetylases are known to modulate replication stress, but how these factors are organized or collaborate are not well understood. Here we found a new role of the OTUD5 deubiquitinase in limiting replication stress. We found that OTUD5 is recruited to replication forks, and its depletion causes replication fork stress. Through its C-terminal disordered tail, OTUD5 assembles a complex containing FACT, HDAC1 and HDAC2 at replication forks. A cell line engineered to specifically uncouple FACT interaction with OTUD5 exhibits increases in FACT loading onto chromatin, R-loop formation, and replication fork stress. OTUD5 mediates these processes by recruiting and stabilizing HDAC1 and HDAC2, which decreases H4K16 acetylation and FACT recruitment. Finally, proteomic analysis revealed that the cells with deficient OTUD5-FACT interaction activates the Fanconi Anemia pathway for survival. Altogether, this study identified a new interaction network among OTUD5-FACT-HDAC1/2 that limits transcription-induced replication stress.
TERRA expression is regulated by the telomere-binding proteins POT-1 and POT-2 inCaenorhabditis elegans
Authors: Manzato Caterina , Larini Luca , Oss Pegorar Claudio , Dello Stritto Maria Rosaria , Jurikova Katarina , Jantsch Verena , Cusanelli Emilio
Published: September 2023

Several aspects of telomere biology are regulated by the telomeric repeat-containing RNA TERRA. While TERRA expression is conserved through evolution, species-specific mechanisms regulate its biogenesis and function. Here we report on the expression of TERRA in Caenorhabditis elegans. We show that C. elegans TERRA is regulated by the telomere-binding proteins POT-1 and POT-2 which repress TERRA in a telomere-specific manner. C. elegans TERRA transcripts are heterogeneous in length and form discrete nuclear foci, as detected by RNA FISH, in both postmitotic and germline cells; a fraction of TERRA foci localizes to telomeres. Interestingly, in germ cells, TERRA is expressed in all stages of meiotic prophase I, and it increases during pachytene, a stage in meiosis when homologous recombination is ongoing. We used the MS2-GFP system to study the spatiotemporal dynamics of single-telomere TERRA molecules. Single particle tracking revealed different types of motilities, suggesting complex dynamics of TERRA transcripts. Finally, we unveiled distinctive features of C. elegans TERRA, which is regulated by telomere shortening in a telomere-specific manner, and it is upregulated in the telomerase-deficient trt-1; pot-2 double mutant prior to activation of the alternative lengthening mechanism ALT. Interestingly, in these worms TERRA displays distinct dynamics with a higher fraction of fast-moving particles.
Transgene-free, virus-based gene silencing in plants by artificial microRNAs derived from minimal precursors
Authors: Cisneros Adriana E , Martín-García Tamara , Primc Anamarija , Kuziuta Wojtek , Sánchez-Vicente Javier , Aragonés Verónica , Daròs José-Antonio , Carbonell Alberto
Published: September 2023

Artificial microRNAs (amiRNAs) are highly specific, 21-nucleotide (nt) small RNAs designed to silence target transcripts. In plants, their application as biotechnological tools for functional genomics or crop improvement is limited by the need of transgenically expressing long primary miRNA (pri-miRNA) precursors to produce the amiRNAs in vivo. Here, we analyzed the minimal structural and sequence requirements for producing effective amiRNAs from the widely used, 521-nt long AtMIR390a pri-miRNA from Arabidopsis thaliana. We functionally screened in Nicotiana benthamiana a large collection of constructs transiently expressing amiRNAs against endogenous genes and from artificially shortened MIR390-based precursors and concluded that highly effective and accurately processed amiRNAs can be produced from a chimeric precursor of only 89 nt. This minimal precursor was further validated in A. thaliana transgenic plants expressing amiRNAs against endogenous genes. Remarkably, minimal but not full-length precursors produce authentic amiRNAs and induce widespread gene silencing in N. benthamiana when expressed from an RNA virus, which can be applied into leaves by spraying infectious crude extracts. Our results reveal that the length of amiRNA precursors can be shortened without affecting silencing efficacy, and that viral vectors including minimal amiRNA precursors can be applied in a transgene-free manner to induce whole-plant gene silencing.
Examining Tobacco-Related Social Media Research in Government Policy Documents: Systematic Review
Authors: Beard Trista A , Donaldson Scott I , Unger Jennifer B , Allem Jon-Patrick
Published: September 2023

Background

Social media data have been used to describe tobacco industry marketing practices, user experiences with tobacco, and youth-oriented protobacco content.

Objective

Examine the extent to which tobacco-related social media research is cited in government policy documents.

Search Methods

Peer-reviewed tobacco-related social media studies were searched for on Web of Science, PubMed, and other databases from 2004 to 2022. The DOI number for each identified article was then used to search the Overton database to find policy documents citing such research. A secondary, manual search of national and international governmental agency websites was also conducted.

Selection Criteria

Documents were included in this study if they were tobacco-related, written in English, cited social media research in the document text and reference section, and were published by a governmental office or agency.

Data Collection and Analysis

The analytic sample consisted of (n = 38) government policy documents, and were coded for content themes, agency type, document type, and subsequent citations.

Main Results

When this research was utilized, it was often in the context of highlighting tobacco industry marketing practices, bringing attention to an issue (eg, youth e-cigarette use), and/or describing how social media platforms can be used as a data source to understand tobacco-related attitudes and behaviors. Agencies that often cited this research were the WHO, FDA, and CDC. The document types included research reports, policy recommendations, industry guidance, legal complaints, and practice-based recommendations.

Conclusions

Tobacco-related social media research has been utilized by government agencies in the last decade to guide the policy process.

Implications

Tobacco-related social media research has been used in government policy documents to detail tobacco industry marketing and bring attention to youth exposure to protobacco content online. Continued surveillance of social media may be necessary to track the changing tobacco landscape.
Property rights, political connections, and corporate investment
Authors: Miao Meng , Tang Dragon Yongjun , Xu Lixin Colin , Yan Xiao
Published: September 2023

We study the impact of an urban land titling program on firm investment in Shenzhen, China. We find that this program increased the investment rate for titling firms, but this positive effect only holds for politically connected firms. Further analysis suggests that the titling effect is more pronounced for those titling firms associated with greater expropriation risk. During program implementation, the connected titling firms increased their investment perhaps because, as observed, they experienced fewer disputes than non-connected titling firms.
γ-H2AX and phospho-ATM enzyme-linked immunosorbent assays as biodosimetry methods for radiation exposure assessment: a pilot study
Authors: Ramadhani Dwi , Tetriana Devita , Purnami Sofiati , Suvifan Viria Agesti , Kurnia Hasan Basri Iin , Kisnanto Teja , Oktariyani Tiara Andalya , Syafira Dira , Yunus Muhamad Yasin , Miura Tomisato , Syaifudin Mukh , Widowati Retno
Published: September 2023

In the event of a radiological incident, a fast and accurate biological dosimetry (biodosimetry) method for evaluating people who have been potentially exposed to ionising radiation is crucial. Among the many biodosimetry methods available, the immunodetection of phosphorylated H2AX (γ-H2AX) stands as a promising method to be used in the triage of patients exposed to radiation. Currently, the most common way to measure γ-H2AX levels is through fluorescence microscopy. In this pilot study, we assessed the feasibility of using an enzyme-linked immunosorbent assay (ELISA) for quantifying γ-H2AX for biodosimetry purposes. Moreover, the usefulness of measuring phosphorylated ATM (pATM) levels through ELISA for biodosimetry was also evaluated. Blood samples were obtained from three male donors (38 y) and were irradiated with 60Co (0, 1, 2 and 6 Gy). Peripheral blood mononuclear cells (PBMCs) were isolated and lysed before measuring γ-H2AX, total H2AX protein and pATM using ELISA kits. The dicentric chromosome assay (DCA) using whole blood was also performed for comparison. Data from all donors at each dose were pooled before statistical analysis. The ratio of γ-H2AX/total H2AX and pATM levels increased in a radiation-dose-dependent manner. The average γ-H2AX/total H2AX ratios were 0.816 ± 0.219, 0.830 ± 0.685, 1.276 ± 1.151 and 1.606 ± 1.098, whereas the average levels of pATM were 59.359 ± 3.740, 63.366 ± 0.840, 66.273 ± 2.603 and 69.936 ± 4.439, in PBMCs exposed to 0, 1, 2 and 6 Gy, respectively. The linear-quadratic dose–response calibration curve for DCA was Y = 0.0017 (±0.0010) + 0.0251 (±0.0142) × D + 0.0342 (±0.0039) × D2  $\boldsymbol{Y}=\mathbf{0.0017}\left(\pm \mathbf{0.0010}\right)+\mathbf{0.0208}\left(\pm \mathbf{0.0218}\right)\times \boldsymbol{D}+\mathbf{0.0350}\left(\pm \mathbf{0.0050}\right)\times{\boldsymbol{D}}^{\mathbf{2}}$. Overall, despite a large variability in the ratio of γ-H2AX/total H2AX among donors, the present study revealed the suitability of using the ratio of γ-H2AX/total H2AX and pATM for biodosimetry. Still, more research with a larger group of subjects is necessary to construct a reliable calibration curve for the ratio of γ-H2AX/total H2AX and pATM levels for biodosimetry.
A large brush-footed trapdoor spider (Mygalomorphae: Barychelidae) from the Miocene of Australia
Authors: McCurry Matthew R , Frese Michael , Raven Robert
Published: September 2023

The aridification of the Australian continent led to the diversification of mygalomorph spiders in the Miocene, but a depauperate fossil record has made it difficult to investigate evolution across this epoch. Here, we describe the first fossil barychelid spider (Araneae: Barychelidae) in the world and the second fossil mygalomorph spider from Australia. It is placed as a new genus and species (Megamonodontium mccluskyi gen. et sp. nov.). Megamonodontium resembles Monodontium Kulczyński, 1908, a genus that persists in rainforests through Singapore, Indonesia and Papua New Guinea. The new specimen is the second largest spider fossil in the world and is approximately five times larger than extant Monodontium. The fossil shows that this lineage once occupied mesic rainforest habitats in Australia but has since been replaced by other spiders.
Psychological Treatment Targeting Acceptance and Compassion in Chronic Pain Patients
Authors: Buhrman Monica , Tillfors Maria , Holländare Fredrik , Lekström Emily , Håkansson Alexander , Boersma Katja
Published: September 2023

Objectives:

Chronic pain is often associated with lower function. Self-criticism is associated with depressive symptoms. The purpose of this study was to explore if fusing acceptance and commitment therapy (ACT) and compassion focused therapy (CFT), could improve psychological wellbeing and disability in chronic pain patients with high levels of self-criticism in comparison to a wait-list control group.

Methods:

Individuals with chronic pain (n=71) were randomly assigned to an 8-week internet-based intervention focused on acceptance and compassion or a wait-list condition. Primary treatment outcomes were Chronic Pain Acceptance Questionnaire, Self-Compassion Scale, and Pain Disability Index. Secondary outcomes were Montgomery Åsberg Depression Rating Scale, Anxiety Sensitivity Index, Quality of Life Inventory, Multidimensional Pain Inventory and Perseverative Thinking Questionnaire.

Results:

Missing data at post-intervention was 22.5%. Intention to treat (ITT) analyses were conducted using linear mixed-models. Results revealed greater levels of acceptance and self-compassion for the treatment group, which were primary outcomes, with effect sizes ranging from small to large and these results were maintained at six-month follow-up. Rates of clinically significant improvements were also greater for the treatment group in comparison to the wait-list control group on acceptance and compassion. The treatment group also improved in the third primary outcome, pain disability. Significant differences were found in several of the secondary outcomes, in favour for the treatment group.

Discussion:

Internet-based ACT with CFT components shows promise as a viable treatment option in the management of chronic pain.
An Exploration of Physical Therapy Outcomes and Psychometric Properties of the Patient-Specific Functional Scale Following an Interdisciplinary Pain Management Program
Authors: Gagnon Christine M. , Yuen Maya , Palmer Kelsey
Published: September 2023

Objectives:

The Patient-Specific Functional Scale (PSFS) has been used to assess physical functioning in various chronic pain populations. There is a lack evidence for its use with diverse pain populations who have high impact chronic pain (HICP). The primary aim of this study was to assess the psychometric properties of the PSFS with a heterogeneous sample of patients with HICP

Methods:

A retrospective observational study of prospective functional outcomes collected before and after participation an intensive pain management program (IPMP): (PSFS, Disabilities of the Arm, Shoulder, and Hand; Lower Extremity Functional Scale; Neck Disability Index; Oswestry Disability Index), Multidimensional Patient Impression of Change, pain intensity, pain limitation, and fear avoidance from the charts of 509 IPMP completers. The reliability, validity, and responsiveness of the PSFS were analyzed using Cronbach’s alpha, Pearson correlations, and receiver operating characteristic.

Results:

Significant improvements were found for all outcomes following program participation (all p’s <0.0001). Correlations of the PSFS with similar outcomes (convergent validity) were lower than expected (r’s 0.16 - 0.33). A low correlation (r=-0.12) with an unrelated measure, fear-avoidance, supported divergent validity. PSFS change score correlations with similar outcome measures ranged from 0.46 to 0.53. The area under the curve values for the PSFS ranged from 0.801 to 0.857 suggesting a moderate ability for the PSFS to detect improvement.

Discussion:

The psychometric properties of the PSFS showed mixed support for construct validity but good support for the responsiveness of the PSFS when used with a heterogeneous sample of patients with HICP.
The Effect of Genetic HLA Matching on Liver Transplantation Outcome: A Systematic Review and Meta-Analysis
Authors: Kok Gautam , Ilcken Eveline F. , Houwen Roderick H.J. , Lindemans Caroline A. , Nieuwenhuis Edward E.S. , Spierings Eric , Fuchs Sabine A.
Published: September 2023

Objective:

We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation

Background:

Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations. With emerging alternatives such as transplantation of bankable (stem) cells, HLA matching becomes feasible, which may decrease the need for immunosuppressive therapy and improve transplantation outcomes.

Methods:

We systematically searched the PubMed, Embase, and Cochrane databases and performed a meta-analysis investigating the effect of genetic HLA matching on liver transplantation outcomes (acute/chronic rejection, graft failure, and mortality).

Results:

We included 14 studies with 2682 patients. HLA-C mismatching significantly increased the risk of acute rejection (full mismatching: risk ratio = 1.90, 95% confidence interval = 1.08 to 3.33, P = 0.03; partial mismatching: risk ratio = 1.33, 95% confidence interval = 1.07 to 1.66, P = 0.01). We did not discern any significant effect of HLA mismatching per locus on acute rejection for HLA-A, -B, -DR, and -DQ, nor on chronic rejection, graft failure, or mortality for HLA-DR, and -DQ.

Conclusions:

We found evidence that genetic HLA-C matching reduces the risk of acute rejection after liver transplantation while matching for other loci does not reduce the risk of acute rejection, chronic rejection, graft failure, or mortality.
The Efficacy and Cost-Effectiveness of a Simulation-Based Primary Care Procedural Skills Training Program for Advanced Practice Providers
Authors: Clemens Lisa
Published: September 2023

Introduction:

The purpose of this program evaluation was to investigate the efficacy of simulation-based primary care procedural skills training to increase participant confidence, knowledge, and skill in performing the procedures included in the training and to evaluate the cost-effectiveness of the training.

Methods:

A retrospective, within-subjects analysis of the change in perceived confidence, skill, and knowledge in procedure performance after the simulation-based primary care procedural skills training program measured by pretraining and post-training Likert scale surveys and change in clinical procedure performance frequency for abscess incision and drainage and laceration repair up to 6 months before and 6 months after the training in the outpatient setting was performed.

Results:

Participants self-reported higher median confidence, perceived skill, and perceived knowledge of all procedures included in the training course, with statistically significant increases for all procedures. A mean increase in laceration repairs in the clinical setting of 10% after training was found. Higher median performance of abscess incision and drainage after training (median = 20.00%, n = 25) compared with before training (median = 0.00%, n = 25) and a mean increase in performance of abscess incision and drainage in the clinical setting of 6% after training was found, but increases were not statistically significant.

Discussion:

Participation in a 2-day simulation-based primary care procedural skills training program was an effective method to increase confidence, perceived skill, and knowledge of outpatient procedures among practicing providers. Further evaluation to establish return on investment is needed, because statistically significant increases in clinical procedure performance were unable to be demonstrated.
Accelerating HIV vaccine development through meaningful engagement of local scientists and communities
Authors: Chinyenze Kundai , Nduati Eunice , Muturi-Kioi Vincent
Published: September 2023

Purpose of review

There is a need to conduct multiple experimental medicine trials in regions with significant burden of disease to ensure the global relevance of vaccines under development including the African context.

Recent findings

African scientists can support accelerated HIV vaccine development by leading EMVTs in the region in a complementary fashion to global efforts and augment evidence generated to optimize and advance relevant vaccines towards licensure. The ADVANCE program enables EMVTs, where local scientists lead trial implementation and immunogenicity endpoint analysis of promising vaccine approaches. Concerted efforts towards scientific collaboration, enhancing specific clinical and lab capacity, and improving ethical and regulatory systems to review EMVTs in Africa will be catalytic. Appropriate engagement of local communities and stakeholders will be equally important, and the field needs to refine existing research literacy approaches to effectively partner with communities around current complex scientific approaches. Review of inclusion of relevant populations in early research is also needed.

African scientists and communities can help accelerate HIV vaccine development through stronger global collaboration. Now is the time for bold investments to enable the conduct of innovative EMVTs in Africa where the eventual vaccines will have the greatest impact.
Assessing Guidelines on the Need for Colonoscopy after Initial Flexible Sigmoidoscopy in Young Patients with Outlet-Type Rectal Bleeding
Authors: Bagshaw Philip F. , Tuck Anita , Aramowicz Jaana , Cox Brian , Frizelle Francis Antony , Church James M.
Published: September 2023

BACKGROUND:

While young age of onset colorectal cancer is increasing in incidence lack of screening leads to symptomatic presentation, often with rectal bleeding. Because most cancers in patients under 50 are left-sided, flexible sigmoidoscopy is a reasonable way of investigating bleeding in these patients.

OBJECTIVE:

To predict which patients undergoing flexible sigmoidoscopy for outlet rectal bleeding need a full colonoscopy.

DESIGN:

Findings at colonoscopy were compared with published indications for colonoscopy after flexible sigmoidoscopy. These were: (1) Any number of advanced adenomas defined as a tubular adenoma >9 mm, a tubulovillous or villous adenoma of any size, or any adenoma with high grade dysplasia. (2) Three or more tubular adenomas of any size or histology. (3) Any sessile serrated lesion. (4) Twenty or more hyperplastic polyps.

SETTING:

Charity Hospital with volunteer specialists.

PATIENTS:

Under age 57, outlet type rectal bleeding, undergoing flexible sigmoidoscopy at least to the descending colon, followed by colonoscopy with biopsy of all resected lesions.

INTERVENTIONS:

Flexible sigmoidoscopy and colonoscopy with excision of all removable lesions.

MAIN OUTCOME MEASURES:

Findings at colonoscopy.

RESULTS:

66 cases who had a colonoscopy between 5 and 811 days after sigmoidoscopy, who also had complete data. Forty-three male and 23 female with mean age of 39.5 years. Analysis of flexible sigmoidoscopy criteria for finding proximal high-risk lesions on colonoscopy showed a sensitivity of 76.9%, a specificity of 67.9%, a positive predictive value of 37%, a negative predictive value of 92.3%, and an accuracy of 69.7%.

LIMITATIONS:

Large number of exclusions for inadequate colonoscopy or inadequate data causing reduced patient number in the study.

CONCLUSION:

Our criteria for follow-up colonoscopy based on the findings at initial flexible sigmoidoscopy in young patients with outlet rectal bleeding are reliable enough to be used in routine clinical practice, provided this is audited.
Tranexamic Acid Prevention of Hemorrhagic Complications Following Interpolated Flap Repair: A Single-Center, Retrospective, Cohort Study
Authors: Freeman S. Caleb , Heath Michael S. , Neill Brett , Morris Caroline , Lucero Olivia M. , Yu Wesley , Bar Anna , Leitenberger Justin J.
Published: September 2023

BACKGROUND

Tranexamic acid (TXA) is increasingly being used to prevent hemorrhagic complications after dermatologic surgery. Interpolated flap repairs following Mohs micrographic surgery are at risk for increased bleeding events and unplanned health care utilization, particularly among patients on antithrombotic medication.

OBJECTIVE

To assess bleeding events after interpolated flap repair in patients receiving TXA compared with those who did not.

MATERIALS AND METHODS

A retrospective review identified interpolated flap repairs in a 5-year period. Hemorrhagic complications were analyzed, defined as major bleeding events, which included all unplanned medical visits, and minor bleeding events, which included any unplanned patient phone calls or messages through electronic medical record.

RESULTS

One hundred fifteen patients had interpolated flap repair during the 5-year period, of which 21 (18.3%) received TXA postprocedure. Twenty-seven bleeding events were identified in the non-TXA group compared with 1 event in the TXA-treated group. Patients who received TXA were less likely to have had a bleeding event (28.7% vs 4.8%, p < .01).

CONCLUSION

Patients undergoing interpolation flap repair were less likely to experience a bleeding event after subcutaneous injection of TXA.
Clinical standardization for the detection of hemispheric dominance for steady-state auditory evoked fields in normal hearing
Authors: Wang Mao-Che , Chi Tai-Shih , Shiao An-Suey , Li Lieber Po-Hung , Hsieh Jen-Chuen
Published: September 2023

Background:

Steady-state auditory evoked responses (SSAERs) are promising indicators of major auditory function. The improvement in accessibility in the clinical setting depends on the standardization and definition of the characteristics of SSAERs. There have been some insights into the changes in the interhemispheric dominance of SSAERs in some clinical entities. However, the hemispheric asymmetry of SSAERs in healthy controls remains inconclusive.

Methods:

Twelve right-handed healthy volunteers with normal hearing were recruited. Steady-state auditory evoked fields (SSAEFs) were measured binaurally using magnetoencephalography (MEG) under pure-tone auditory stimuli at 1000 Hz with an amplitude modulation frequency of 43 Hz. The laterality index, based on the ratio of SSAEF strength over the right hemisphere to that over the left hemisphere, was also analyzed.

Results:

The SSAEFs source was localized bilaterally on the superior temporal plane, with an orientation centripetal to the auditory cortex. The laterality index ranged from 1.1 to 2.3, and there were no sex differences. In all subjects, the strength of the SSAEFs was significantly weaker in the left hemisphere than in the right hemisphere (p = 0.014).

Conclusion:

Right-sided dominance of the SSAEFs was verified in subjects with normal hearing. Acoustic sources clinically available in audiometric tests were used as stimuli. Such a simplification of parameters would be helpful for the standardization of precise production and the definition of the characteristics of SSAERs. Because MEG is still not easily accessible clinically, further studies using electroencephalography with larger sample sizes are necessary to address these issues.
Surgical stabilization of rib fractures is associated with better return on investment for a health care institution than nonoperative management
Authors: Bauman Zachary M. , Khan Hason , Cavlovic Lindsey , Raposo-Hadley Ashley , Todd Sydney J. , King Tylor , Cahoy Kevin , Kamien Andrew , Cemaj Samuel , Sheppard Olabisi , Matos Miguel , Berning Bennett , Evans Charity H. , Cantrell Emily
Published: September 2023

BACKGROUND

Surgical stabilization of rib fractures (SSRFs) continues to gain popularity due to patient benefits. However, little has been produced regarding the economic benefits of SSRF and its impact on hospital metrics such as Vizient. The aim of this study was to explore these benefits hypothesizing SSRF will demonstrate positive return on investment (ROI) for a health care institution.

METHODS

This is a retrospective review of all rib fracture patients over 5 years at our Level I trauma center. Patients were grouped into SSRF versus nonoperative management. Basic demographics were obtained including case mix index (CMI). Outcomes included narcotic requirements in morphine milliequivalents prior to discharge, mortality, and discharge disposition. Furthermore, actual hospital length of stay (ALOS) versus Vizient expected length of stay were compared between cohorts. Contribution margin (CM) was also calculated. Independent t-test, paired t-test, and linear regression analysis were performed, and significance set at p < 0.05.

RESULTS

A total of 1,639 patients were included; 230 (14%) underwent SSRF. Age, gender, and Injury Severity Score were similar. Surgical stabilization of rib fracture patients had more ribs fractured (7 vs. 4; p < 0.001) and more patients with flail chest (43.5% vs. 6.7%; p < 0.001). Surgical stabilization of rib fracture patients also had a significantly higher CMI (4.33 vs. 2.78; p = 0.001). Narcotic requirements and mortality were less in the SSRF cohort; 155 versus 246 morphine milliequivalents (p < 0.001) and 1.7% versus 7.1% (p = 0.003), respectively. Surgical stabilization of rib fracture patients were more likely to be discharged home (70.4% vs. 63.7%; p = 0.006). Surgical stabilization of rib fracture patients demonstrated shorter ALOS where nonoperative management patients demonstrated longer ALOS compared with Vizient expected length of stay. Contribution margins for SSRF patients were significantly higher and linear regression analysis showed a CM $1,128.14 higher per patient undergoing SSRF (p < 0.001).

CONCLUSION

Patients undergoing SSRF demonstrate a significant ROI for a health care organization. Despite SSRF patients having a higher CMI, they were able to be discharged sooner than expected by Vizient calculations resulting in better a CM.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Large-scale computational modelling of the M1 and M2 synovial macrophages in Rheumatoid Arthritis
Authors: Zerrouk Naouel , Alcraft Rachel , Hall Benjamin A. , Augé Franck , Niarakis Anna
Published: September 2023

Macrophages play an essential role in rheumatoid arthritis (RA). Depending on their phenotype (M1 or M2), they can play a role in the initiation or resolution of inflammation. The M1/M2 ratio in RA is higher than in healthy controls. Despite this, no treatment targeting specifically macrophages is currently used in clinics. Thus, devising strategies to selectively deplete proinflammatory macrophages and promote anti-inflammatory macrophages could be a promising therapeutic approach in RA.

State-of-the-art molecular interaction maps of M1 and M2 macrophages in rheumatoid arthritis are available and represent a dense source of knowledge; however, these maps remain limited by their static nature. Discrete dynamic modelling can be employed to study the emergent behaviours of these systems. Nevertheless, handling such large-scale models is challenging. Due to their massive size, it is computationally demanding to identify biologically relevant states in a cell- and disease-specific context.

In this work, we developed an efficient computational framework that converts molecular interaction maps into Boolean models using the CaSQ tool. Next, we use a newly developed BMA tool version deployed to a high-performance computing cluster to identify the models’ steady states. The identified attractors are then validated using gene expression datasets and prior knowledge. We successfully applied our framework to generate and calibrate the first RA M1 and M2 macrophage Boolean models. Using single and double knockout simulations, we identified NFkB, JAK1/JAK2, and ERK1/Notch1 as potential targets that could selectively suppress proinflammatory macrophages, and GSK3B as a promising target that could promote anti-inflammatory macrophages in RA.