bluuebunny/crossref_metadata_2025 huggingface dataset:
A qualitative systematic review of the significance of adjuvant therapy in patients with low-risk endometrial cancer presenting positive peritoneal cytology: a relevant study to the guideline update for endometrial cancer by the Japan society of gynecologic oncology guideline committee
Authors: Shigeta Shogo , Konno Yosuke , Terai Yoshito , Morisada Tohru , Tokunaga Hideki , Baba Tsukasa , Kobayashi Yoichi , Nagase Satoru
Published: October 2023

In association with an update of the Japan Society of Gynecologic Oncology clinical practice guidelines for endometrial cancer in 2023, a systematic review was conducted about the therapeutic benefit of adjuvant therapy on patients with early-stage endometrial carcinoma, who presented positive peritoneal cytology (PPC) without the risk factors for recurrence. The systematic review only included two eligible retrospective studies. Both studies included patients with risk factors for recurrence. A nationwide study in the United States reported that adjuvant chemotherapy was associated with the reduced risk of death among patients with stages I–II endometrial cancer with PPC by multivariate, propensity score-adjusted analysis. Another single-center study in Japan reported no association between adjuvant chemotherapy and relapse-free survival among patients with stage IA endometrial cancer by univariate analysis. This systematic review identified that evidence was limited with conflicting results. Continuous evaluation is warranted to address this clinical question.
Education for Refugees: Building Durable Futures?
Authors: Dryden-Peterson Sarah , Horst Cindy
Published: October 2023

Education is one of the key tools of nation-building, as it aims to create future citizens. Yet what happens in seemingly ‘futureless’ contexts where refugees cannot access even social membership, let alone legal citizenship? In this introduction to our special issue on education for refugees, we explore the aspirations and conceptions of possible futures that students, teachers, governments, international non-governmental organizations (INGOs), and funders have when they promote and pursue education as the solution to the liminal position that refugees in protracted refugee situations find themselves in. Based on insights from the articles, we analyse disconnects between aspirations for education and realities of access to quality education and to opportunities after completing education. We argue that to address these disconnects requires us to move beyond temporal and spatial binaries—present vs. future, here vs. there—that are so common in refugee education discourse and policy. Our suggestion is to draw on and support stakeholders’ work, powerfully exemplified in this special issue, to contribute to improved conditions through pedagogies, practices, and policies that address these binaries.
Detectability of gas-rich E/IMRI’s in LISA band: observable signature of transonic accretion flow
Authors: Chatterjee Sangita , Mondal Soumen , Basu Prasad
Published: October 2023

Real extreme/intermediate-mass ratio inspiral (E/IMRI) systems are likely to contain large accretion discs which could be as massive as the central supermassive black hole. Therefore, contrary to its ideal model, a real E/IMRI system contains a third important component: the accretion disc. We study the influence of these discs on the emitted gravitational wave (GW) profile and its detectability through proposed LISA observation. We use a semirelativistic formalism in the Kerr background for the case of transonic accretion flow which is a potential candidate to describe the accretion flows around active galactic nuclei. The hydrodynamic drag of the discs modified the motion of the companion as a result of the emitted wave changes in amplitude and phase. We found that these changes are detectable through the last few years of observation by LISA (in some cases as small as 6 months) for EMRIs residing within redshift z = 1 from the detector and for the accretion rate of the primary black hole of the order of $\dot{M}=1 \dot{M}_{\mathrm{ Edd}}$. These choices of parameter values are consistent with real systems. The drag effect and hence the detectability of the emitted GW is sensitive to the hydrodynamical model of the disc. Therefore, we vary the disc parameters, accretion rate, and duration of observation of E/IMRIs, and find that in comparison with other disc models, transonic solution offers relatively better observable signatures in detecting the gas-rich E/IMRI’s within the LISA band. Such observations will help one to probe the nature of the accretion flow and verify various paradigms of accretion physics.
BRCA1–BARD1 combines multiple chromatin recognition modules to bridge nascent nucleosomes
Authors: Burdett Hayden , Foglizzo Martina , Musgrove Laura J , Kumar Dhananjay , Clifford Gillian , Campbell Lisa J , Heath George R , Zeqiraj Elton , Wilson Marcus D
Published: October 2023

Chromatin association of the BRCA1–BARD1 heterodimer is critical to promote homologous recombination repair of DNA double-strand breaks (DSBs) in S/G2. How the BRCA1–BARD1 complex interacts with chromatin that contains both damage induced histone H2A ubiquitin and inhibitory H4K20 methylation is not fully understood. We characterised BRCA1–BARD1 binding and enzymatic activity to an array of mono- and di-nucleosome substrates using biochemical, structural and single molecule imaging approaches. We found that the BRCA1–BARD1 complex preferentially interacts and modifies di-nucleosomes over mono-nucleosomes, allowing integration of H2A Lys-15 ubiquitylation signals with other chromatin modifications and features. Using high speed- atomic force microscopy (HS-AFM) to monitor how the BRCA1–BARD1 complex recognises chromatin in real time, we saw a highly dynamic complex that bridges two nucleosomes and associates with the DNA linker region. Bridging is aided by multivalent cross-nucleosome interactions that enhance BRCA1–BARD1 E3 ubiquitin ligase catalytic activity. Multivalent interactions across nucleosomes explain how BRCA1–BARD1 can recognise chromatin that retains partial di-methylation at H4 Lys-20 (H4K20me2), a parental histone mark that blocks BRCA1–BARD1 interaction with nucleosomes, to promote its enzymatic and DNA repair activities.
Neuronal differentiation drives the antitumor activity of mitogen-activated protein kinase kinase (MEK) inhibition in glioblastoma
Authors: Khan Sabbir , Martinez-Ledesma Emmanuel , Dong Jianwen , Mahalingam Rajasekaran , Park Soon Young , Piao Yuji , Koul Dimpy , Balasubramaniyan Veerakumar , de Groot John F , Yung W K Alfred
Published: October 2023

Background

Epidermal growth factor receptor (EGFR) amplification is found in nearly 40%–50% of glioblastoma cases. Several EGFR inhibitors have been tested in glioblastoma but have failed to demonstrate long-term therapeutic benefit, presumably because of acquired resistance. Targeting EGFR downstream signaling with mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) inhibitors would be a more effective approach to glioblastoma treatment. We tested the therapeutic potential of MEK1/2 inhibitors in glioblastoma using 3D cultures of glioma stem-like cells (GSCs) and mouse models of glioblastoma.

Methods

Several MEK inhibitors were screened in an unbiased high-throughput platform using GSCs. Cell death was evaluated using flow cytometry and Western blotting (WB) analysis. RNA-seq, real-time quantitative polymerase chain reaction, immunofluorescence, and WB analysis were used to identify and validate neuronal differentiation.

Results

Unbiased screening of multiple MEK inhibitors in GSCs showed antiproliferative and apoptotic cell death in sensitive cell lines. An RNA-seq analysis of cells treated with trametinib, a potent MEK inhibitor, revealed upregulation of neurogenesis and neuronal differentiation genes, such as achaete-scute homolog 1 (ASCL1), delta-like 3 (DLL3), and neurogenic differentiation 4 (NeuroD4). We validated the neuronal differentiation phenotypes in vitro and in vivo using selected differentiation markers (β-III-tubulin, ASCL1, DLL3, and NeuroD4). Oral treatment with trametinib in an orthotopic GSC xenograft model significantly improved animal survival, with 25%–30% of mice being long-term survivors.

Conclusions

Our findings demonstrated that MEK1/2 inhibition promotes neuronal differentiation in glioblastoma, a potential additional mechanism of action of MEK1/2 inhibitors. Thus, MEK inhibitors could be efficacious in glioblastoma patients with activated EGFR/MAPK signaling.
Discovery of microRNAs in Pyrus stigma exudates opens new research avenues in Horticulture
Authors: Ambastha Vivek , Nevo Yuval , Matityhu Ifat , Honys David , Leshem Yehoram
Published: October 2023

In many plant species, flower stigma secretions are important in early stages of sexual reproduction. Previous chemical analysis and proteomic characterization of these exudates provided insights into their biological function. Nevertheless, the presence of nucleic acids in the stigma exudates has not been previously reported. Here, we studied the stigma exudates of Pyrus communis, Pyrus pyrifolia, and Pyrus syriaca and showed them to harbor extracellular RNAs of various sizes. RNA sequencing revealed, for the first time, the presence of known Rosaceae mature microRNAs (miRs), also abundant in the stigma source tissue. Predicted targets of the exudate miRs in the Arabidopsis thaliana genome include genes involved in various biological processes. Several of these genes are pollen transcribed, suggesting possible involvement of exudate miRs in transcriptional regulation of the pollen. Moreover, extracellular miRs can potentially act across kingdoms and target genes of stigma interacting organisms/microorganisms, thus opening novel applicative avenues in Horticulture.
Mutagenesis-Derived Resistance to Black Point in Wheat
Authors: Qu Kefei , Yin Zhao , Gao Chuang , Song Gaili , Guo Zhenfeng , Yin Guihong , Tang Jianwei , Yuan Yuhao , Dong Chunhao , Jiang Yumei , Niu Jishan , Li Qiaoyun
Published: October 2023

Black point, a severe global wheat disease, necessitates deploying resistant cultivars for effective control. However, susceptibility remains prevalent among most wheat cultivars. Identifying new sources of resistance and understanding their mechanisms are crucial for breeding resistant cultivars. This study pinpointed black point resistance in an ethyl methane sulfonate (EMS)-mutagenized wheat population of Wanyuanbai 1 (WYB) and analyzed resistant mutants using RNA-Seq. The findings revealed the following: (i) wyb-18, among 10,008 EMS-mutagenized lines, exhibited robust resistance with significantly lower black point incidence under artificial Bipolaris sorokiniana inoculation in 2020 and 2021 (average incidence of 5.2% over 2 years), markedly reduced compared with WYB (50.9%). (ii) wyb-18 kernels displayed black point symptoms at 12 days after inoculation (dai), 3 days later than WYB. At 15 dai, wyb-18 kernels had isolated black spots, unlike WYB kernels, where the entire embryo turned black. (iii) wyb-18 showed heightened antioxidant enzyme activity, including peroxidase, catalase, and superoxide dismutase. (iv) Analysis of 543 differentially expressed genes between wyb-18 and WYB at 9 dai identified enrichment in the MAPK signaling pathway through KEGG analysis. Ten genes in this pathway exhibited upregulated expression, while one was downregulated in wyb-18. Among these genes, PR1, WRKY11, SAPK5, and TraesCS1A02G326800 (chitin recognition protein) consistently showed upregulation in wyb-18, making them potential candidates for black point resistance. These results offer valuable germplasm resources for breeding and novel insights into the mechanisms of black point resistance.
Visual Assessment of Phony Peach Disease: Evaluating Rater Accuracy and Reliability
Authors: Johnson Kendall A. , Brannen Phillip M. , Chen Chunxian , Bock Clive H.
Published: October 2023

Phony peach disease (PPD), found predominantly in central and southern Georgia, is a re-emerging disease caused by Xylella fastidiosa (Xf) subsp. multiplex. Accurate detection and rapid removal of symptomatic trees are crucial to effective disease management. Currently, peach producers rely solely on visual identification of symptoms to confirm PPD, which can be ambiguous if early in development. We compared visual assessment to quantitative PCR (qPCR) for detecting Xf in ‘Julyprince’ in 2019 and 2020 (JP2019 and JP2020) and in ‘Scarletprince’ in 2020 (SP2020). With no prior knowledge of qPCR results, all trees in each orchard were assessed by a cohort of five experienced and five inexperienced raters in the morning and afternoon. Visual identification accuracy of PPD was variable, but experienced raters were more accurate when identifying PPD trees. In JP2019, the mean rater accuracy for experienced and inexperienced raters was 0.882 and 0.805, respectively. For JP2020, the mean rater accuracy for experienced and inexperienced raters was 0.914 and 0.816, respectively. For SP2020, the mean rater accuracy for experienced and inexperienced raters was 0.898 and 0.807, respectively. All raters had false positive (FP) and false negative (FN) observations, but experienced raters had significantly lower FN rates compared with the inexperienced group. Almost all raters overestimated the incidence of PPD in the orchards. Reliability of visual assessments was demonstrated as moderate to good, regardless of experience. Further research is needed to develop accurate and reliable methods of detection to aid management of PPD as both FPs and FNs are costly to peach production.
In vivo transfection of cytokine genes into tumor cells using a synthetic vehicle promotes antitumor immune responses in a visceral tumor model
Authors: Watanabe Shunichi , Takagi Ayaka , Yuba Eiji , Kojima Chie , Dei Nanako , Matsumoto Akikazu , Tanikawa Jun , Kawamura Tetsuya , De Silva Nadeeka H. , Izawa Takeshi , Akazawa Takashi , Kanegi Ryoji , Hatoya Shingo , Inaba Toshio , Sugiura Kikuya
Published: October 2023

The tumor microenvironment (TME) strongly affects the clinical outcomes of immunotherapy. This study aimed to activate the antitumor immune response by manipulating the TME by transfecting genes encoding relevant cytokines into tumor cells using a synthetic vehicle, which is designed to target tumor cells and promote the expression of transfected genes. Lung tumors were formed by injecting CT26.WT intravenously into BALB/c mice. Upon intravenous injection of the green fluorescent protein‐coding plasmid encapsulated in the vehicle, 14.2% tumor‐specific expression was observed. Transfection of the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and CD40 ligand (L)‐plasmid combination and interferon gamma (IFNγ) and CD40L‐plasmid combination showed 45.5% and 54.5% complete remission (CR), respectively, on day 60; alternate treatments with both the plasmid combinations elicited 66.7% CR, while the control animals died within 48 days. Immune status analysis revealed that the density of dendritic cells significantly increased in tumors, particularly after GM‐CSF‐ and CD40L‐gene transfection, while that of regulatory T cells significantly decreased. The proportion of activated killer cells and antitumoral macrophages significantly increased, specifically after IFNγ and CD40L transfection. Furthermore, the level of the immune escape molecule programmed death ligand‐1 decreased in tumors after transfecting these cytokine genes. As a result, tumor cell‐specific transfection of these cytokine genes by the synthetic vehicle significantly promotes antitumor immune responses in the TME, a key aim for visceral tumor therapy.
Color Does Matter
Authors: Carter Brigit M. , Newberry Desi , Leonard Christina
Published: October 2023

Background:

The observation of color is an integral part of the nursing assessment. However, the current understanding of individual skin qualities and pigmentation has not yet been integrated thoroughly into foundational assessment courses, clinical education, simulation, and textbooks.

Evidence Acquisition:

Literature is scarce regarding racial groups, skin color, and physical assessment for patients across the lifespan, but even more so for the neonatal population. Historically, many nursing textbooks did not provide visual pictures or observational assessment strategies for the assessment of the Black, Indigenous, and people of color (BIPOC) population. This is improving in some nursing textbooks; however, the descriptors of and visual differences and anticipated assessment findings for the BIPOC population are not comprehensive.

Results:

Evidence-based assessment findings, which may occur in newborns with varying skin tones/pigmentations, are presented.

Implications for Practice and Research:

The most essential step to having an accurate assessment is acknowledging the importance of color awareness. Color blindness, while thought to support inclusivity, only contributes to exclusion of one of the most important components of a person's being—their color.
Variables Associated With Resolution and Persistence of Ovarian Cysts
Authors: Lasher Anne , Harris Lauren E. , Solomon Angelica L. , Harbin Laura M. , Raby Lauren , Dietrich Charles S. , Kryscio Richard J. , van Nagell John R. , Pavlik Edward J.
Published: October 2023

OBJECTIVE:

To estimate surveillance intervals of incident ovarian cysts, and describe variables associated with cyst resolution times.

METHODS:

The UK-OCST (University of Kentucky Ovarian Cancer Screening Trial) was a prospective cohort that enrolled 47,762 individuals over 30 years, including 2,638 individuals with incident cysts. Cyst diameter and structure and patient age, body mass index, use of hormone therapy (HT), family history of ovarian cancer, and menopausal status were examined as variables associated with cyst resolution using t tests, χ2 test, Kaplan Meier, and Cox multiple regression.

RESULTS:

Of 2,638 individuals with incident cysts, 1,667 experienced resolution (63.2%) within 1.2 years, and 971 experienced persistence (36.8%). Within 1 year, unilocular and septated cysts had similar resolution rates (35.4% and 36.7%, respectively, P>.05), but time to resolution was shorter for unilocular cysts compared with septated cysts (mean 1.89 years vs 2.58 years, respectively, P<.001). Both unilocular and septated cysts smaller than 3 cm resolved faster than cysts larger than 6 cm (P<.001). Variables associated with percent resolution included being of younger age, premenopausal status (but not for synchronous bilateral cysts), and those reporting a family history of ovarian cancer (P<.05). Variables associated with a faster cyst resolution rate included being older than age 70 years and not using hormone therapy. Body mass index and family history were not associated with cyst resolution time.

CONCLUSION:

Different surveillance times may be appropriate depending on cyst structure and size and patient age and HT use.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04473833.
Correlation between Microperimetry and Imaging in Extensive Macular Atrophy with Pseudodrusen-like appearance (EMAP).
Authors: Romano Francesco , Boon Camiel J F , Invernizzi Alessandro , Bosello Francesca , Casati Stefano , Zaffalon Chiara , Riva Ester , Bertoni Alice Ingrid , Agarwal Aniruddha , Kalra Gagan , Cozzi Mariano , Staurenghi Giovanni , Salvetti Anna Paola
Published: October 2023

PURPOSE:

To determine the correlation between microperimetry and imaging findings in extensive macular atrophy with pseudodrusen-like appearance (EMAP).

MTHODS:

This cross-sectional, observational study included 44 consecutive EMAP patients (88 eyes) and 30 healthy subjects (60 eyes). Both groups underwent visual acuity assessment, mesopic and scotopic microperimetry, fundus photography, autofluorescence, optical coherence tomography (OCT) and OCT angiography. Retinal sensitivity (RS) was also subdivided in macular (0-4°) and para-macular areas (8-10°). Scotopic sensitivity loss was defined as the difference between scotopic and mesopic sensitivities for each tested point. Eyes with EMAP were further classified into the 3 stages described by Romano et al: 19 eyes in stage 1, 31 in stage 2, 38 in stage 3.

RESULTS:

Mesopic and scotopic RS were significantly reduced in EMAP patients compared with controls, particularly in the macular area (all p<0.001). Mesopic RS progressively declined in more advanced EMAP stages (all p<0.01), but no scotopic differences were observed between stages 2 and 3 (p=0.08). Remarkably, scotopic sensitivity loss was significantly higher in stage 1 (p<0.05).

On multivariate analysis, mesopic dysfunction was associated with larger atrophic areas (p<0.01), foveal involvement (p=0.03) and fibrosis (p=0.02). Conversely, no independent variable was associated with a reduced scotopic RS (all p>0.05).

CONCLUSIONS:

Our findings highlight that EMAP patients suffer from a severe cone- and rod-mediated dysfunction on microperimetry. The predominant rod impairment in the early cases (stage 1) emphasizes the importance of dark-adapted scotopic microperimetry as clinical endpoint and suggests a defective transportation across the RPE-Bruch’s membrane complex in its pathogenesis.
Genetic testing in the evaluation of recipient candidates and living kidney donors
Authors: Lee Brian K. , Thomas Christie P.
Published: October 2023

Purpose of review

The aim of this study is to provide an overview of the role of genetic testing in the evaluation of kidney transplant candidates and living donors who may be at risk for heritable kidney disease. We focus our discussion on monogenic diseases, excluding renal diseases that have complex polygenic influences. Adoption of new technologies such as next-generation sequencing (NGS) with comprehensive gene panels has greatly enabled access to genetic testing recently; yet transplant professionals rarely receive adequate training in clinical genetics. In addition to a broad discussion of genetic testing, we hope to illustrate the thought processes and resources used in clinical genetic evaluation of recipient candidates and donors.

Recent findings

Targeted renal genetic panels, whole exome and genome sequencing have greatly expanded our ability to test for pathogenic variants. Testing methods, analytic tools and the subsequent interpretation by the testing laboratory and treating physician impacts patient management and clinicians may lack the resources to practice in this new era of genomic medicine.

The expansion of genomics into transplant medicine can provide improved diagnosis in transplant candidates and potentially disease prediction in living donors. Transplant professionals need to be familiar with emerging trends, promises and limitations of NGS-based testing.
Correlation of the apparent diffusion coefficient with the standardized uptake value in meningioma of the skull plane using [68]Ga-DOTATOC PET/MRI
Authors: Milosevic Aleksandar , Styczen Hanna , Haubold Johannes , Kessler Lukas , Grueneisen Johannes , Li Yan , Weber Manuel , Fendler Wolfgang P. , Morawitz Janna , Damman Philipp , Wrede Karsten , Kebir Sied , Glas Martin , Guberina Maja , Blau Tobias , Schaarschmidt Benedikt M , Deuschl Cornelius
Published: October 2023

Purpose

To evaluate a correlation between an MRI-specific marker for cellular density [apparent diffusion coefficient (ADC)] and the expression of Somatostatin Receptors (SSTR) in patients with meningioma of the skull plane and orbital space.

Methods

68Ga-DOTATOC PET/MR imaging was performed in 60 Patients with suspected or diagnosed meningiomas of the skull base and eye socket. Analysis of ADC values succeeded in 32 patients. ADC values (ADCmean and ADCmin) were analyzed using a polygonal region of interest. Tracer-uptake of target lesions was assessed according to corresponding maximal (SUVmax) and mean (SUVmean) values. Correlations between assessed parameters were evaluated using the Pearson correlation coefficient.

Results

One out of 32 patients (3%) was diagnosed with lymphoma by histopathological examination and therefore excluded from further analysis. Median ADCmean amounted to 822 × 10-5 mm²/s-1 (95% CI: 570–1497) and median ADCmin was 493 × 10-5 mm2/s-1 (95% CI: 162–783). There were no significant correlations between SUVmax and ADCmin (r = 0.60; P = 0.76) or ADCmean (r = -0.52; P = 0.79), respectively. However, Pearson’s test showed a weak, inverse but insignificant correlation between ADCmean and SUVmean (r = −0.33; P = 0.07).

Conclusion

The presented data displays no relevant correlations between increased SSTR expression and cellularity in patients with meningioma of the skull base. SSTR-PET and DWI thus may offer complementary information on tumor characteristics of meningioma.
Closing the Fluid Gap: Improving Isotonic Maintenance Intravenous Fluid Use in a Community Hospital Network
Authors: Mittal Shraddha , Knerr Sheila , Prasto Julianne , Hunt Jessica , Mattern Carolyn , Chang Tsae , Marchese Ronald , Jessee Morgan , Marlowe Lauren , Haupt Josh
Published: October 2023

Introduction:

The American Academy of Pediatrics recommends using isotonic intravenous fluids (IVF) for maintenance needs to decrease the risk of hyponatremia. We conducted a quality improvement project to increase the use of isotonic maintenance IVF in pediatric patients admitted to three sites in a community hospital network to >85% within 12 months.

Methods:

We used improvement methodology to identify causes of continued hypotonic fluid use, which involved provider behavior and systems factors. We implemented interventions to address these factors including: (1) education; (2) clinical decision support; and (3) stocking automated medication dispensing systems with isotonic IVF. We compared isotonic IVF use before and after interventions in all admitted patients aged 28 days to 18 years who received maintenance IVFs at the rate of at least 10 mL/hour. We excluded admissions of patients with active chronic medical conditions like diabetic ketoacidosis. Balancing measures were the occurrence of adverse events from hypo- or hypernatremia. Data were analyzed using Laney P′ statistical process control charts.

Results:

Isotonic IVF use among patients requiring maintenance fluids at all three sites surpassed the goal of >85% within 12 months. There were no reports of hypo- or hypernatremia or other adverse outcomes related to the use of isotonic IVF.

Conclusion:

A combination of interventions aimed at provider behavior and systems factors was critical to successfully adopting the American Academy of Pediatrics guideline regarding the use of maintenance isotonic IVF in hospitalized children.
Stratification of Stage II Colon Cancer Using Recurrence Prediction Value
Authors: Mizuno Shodai , Shigeta Kohei , Kato Yujin , Okui Jun , Morita Satoru , Sonal Swati , Goldstone Robert , Berger David , Al-Masri Rama , Al-Masri Mahmoud , Tajima Yuki , Kikuchi Hiroto , Hirata Akira , Nakadai Jumpei , Baba Hideo , Sugiura Kiyoaki , Hoshino Go , Seo Yuki , Makino Akitsugu , Suzumura Hirofumi , Suzuki Yoshiyuki , Adachi Yoko , Shimada Takehiro , Kondo Takayuki , Matsui Shimpei , Seishima Ryo , Okabayashi Koji , Kitagawa Yuko , Kunitake Hiroko
Published: October 2023

Objective:

To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence.

Background:

There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence.

Methods:

We performed a multi-institutional international retrospective analysis of patients with stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from 2 countries were used as the Validation data. The primary endpoint was recurrence-free survival.

Results:

A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n=564) and RPV high (n=175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low [hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887–3.660; P<0.001). Validation data patients were divided into 2 groups (RPV low, n=420) and RPV high (n=47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962–4.750; P<0.001).

Conclusions:

RPV can identify stage II colon cancer patients with high risk of cancer recurrence worldwide.
Emergency vascular repairs in trauma: Predictors of poor prognosis and a novel scoring system
Authors: Boyev Artem , Sutton Gabrielle , Rosenblad Harris , Eisenberg Michael , Mills Alexander , Miller Charles C. , McNutt Michelle K.
Published: October 2023

BACKGROUND

Vascular injuries comprise 1% to 4% of all trauma patients, and there are no widely used risk-stratification tools. We sought to establish predictors of revascularization failures and compare outcomes of trauma and vascular surgeons.

METHODS

We performed a single-institution, case-control study of consecutive patients with traumatic arterial injuries who underwent open repair between 2016 and 2021. Multivariable logistic regression was used to investigate covariates impacting the primary composite outcome of repair failure/revision, amputation, or in-hospital mortality.

RESULTS

Among 165 patients, the median age was 34 years, 149 (90%) were male, and 99 (60%) suffered penetrating injury. Popliteal (46%) and superficial femoral (44%) arterial injuries were most common. Interposition graft/bypass was the most frequent repair (n = 107 [65%]). Revascularization failure was observed in 24 patients (15%). Compared with trauma surgeons, vascular surgeons more frequently repaired blunt injuries (66% vs. 20%, p < 0.001), anterior tibial (18% vs. 5%, p = 0.012), or tibioperoneal injuries (28% vs. 4%, p < 0.001), with a below-knee bypass (38% vs. 20%, p = 0.019). Revascularization failure occurred in 10% (9 of 93) of repairs by trauma surgeons and 21% (13 of 61) of repairs by vascular surgeons. Mangled Extremity Severity Score >8 (odds ratio, 15.6; 95% confidence interval, 4.4–55.9; p < 0.001) and concomitant laparotomy or orthopedic procedure (odds ratio, 6.7; 95% confidence interval, 1.6–28.6; p = 0.010) were independently associated with revascularization failure. A novel composite scoring system (UT Houston Score) was developed by combining Mangled Extremity Severity Score, concomitant procedure, mechanism of injury, and injury location. This score demonstrated a sensitivity of 100% with a score of 0 and a specificity of 95% with a score of >3.

CONCLUSION

After traumatic arterial injury, trauma surgeons repaired less-complex injuries but with fewer revascularization failures than vascular surgeons. The UT Houston Score may be used to risk stratify patients to determine who may benefit from vascular surgery consultation.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Lactobacillus isalae sp. nov., isolated from the female reproductive tract
Authors: Eilers Tom , Dillen Jelle , Ahannach Sarah , Vander Donck Leonore , Van de Vliet Nele , Wittouck Stijn , Lebeer Sarah
Published: October 2023

A novel strain of the genus

Lactobacillus

, named AMBV1719T, was isolated from the vagina of a healthy participant in our large-scale citizen science project on the female microbiome, named Isala. Phylogenetic analysis showed that the 16S rRNA gene of AMBV1719T is most similar to that of

Lactobacillus taiwanensis

with a sequence similarity of 99.873 %. However, a genome-wide comparison using average nucleotide identity (ANI) revealed that isolate AMBV1719T showed the highest ANI with

Lactobacillus paragasseri

JCM 5343T, with a value of only 88.17 %. This low ANI value with the most closely related strains known to date indicated that AMBV1719T represents a distinct species. This strain has a limited ability to degrade carbon sources compared to

Lactobacillus gasseri

, indicating its adaptation to the host. Its genome has a length of 2.12 Mb with a G+C content of 34.8 mol%. We thus propose the name Lactobacillus isalae sp. nov. for this novel species, with AMBV1719T (=LMG 32886T=CECT 30756T) as the type strain.
Leucobacter tenebrionis sp. nov., isolated from the gut of Tenebrio molitor
Authors: Ying Yu , Yuan Bo , Liu Tingting , Bai Xiaoshuan , Zhao Haifeng
Published: October 2023

A novel Gram-stain-positive bacterium, designated NB10T, was isolated from the gut of Tenebrio molitor. The isolate was rod-shaped, aerobic, non-motile and non-spore-forming. Colonies of strain NB10T were light yellow, circular and smooth. Phylogenetic analysis based on 16S rRNA gene sequence comparisons indicated that the isolate was related to the genus Leucobacter. Its closest relatives were

Leucobacter holotrichiae

T14T (97.8 % 16S rRNA gene sequence similarity),

Leucobacter zeae

CC-MF41T (97.0%) and

Leucobacter salsicius

M1-8T (96.4%). The DNA G+C content of strain NB10T was 68.8 mol%. The average nucleotide identity (ANI) and digital DNA–DNA hybridization values among strain NB10T and the selected

Leucobacter

species were ≤83.8 % (ANI-blast), 87.6 % (ANI-MUMmer) and 29.6%, which were below the recommended cutoff values for species delineation. The predominant cellular fatty acids were anteiso-C15 : 0 (39.0%), anteiso-C17 : 0 (35.5%) and iso-C16 : 0 (17.0%). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipids. The predominant respiratory quinones were MK-11 and MK-10. The cell wall amino acids were Gly, Glu, Tr, Ala, and DAB. Based on these phylogenetic and phenotypic results, strain NB10T can be clearly distinguished from all of the recognized species of the genus

Leucobacter

and is considered to represent a novel species of that genus. The name Leucobacter tenebrionis sp. nov. is proposed, with the type strain NB10T (=MCCC 1K07072T=KCTC 49728T).
Independent Inheritance of Cognition and Bipolar Disorder in a Family Sample
Authors: D’Amico Alexander , Sung Heejong , Arbona-Lampaya Alejandro , Freifeld Ally , Hosey Katie , Garcia Joshua , Lacbawan Ley , Besançon Emily , Kassem Layla , Akula Nirmala , Knowles Emma E. M. , Dickinson Dwight , McMahon Francis J.
Published: October 2023

Background

The basis of cognitive deficits in people with bipolar disorder (BD) has not been elucidated. These deficits may be the result of the illness or its treatment, but could also reflect genetic risk factors that are shared between BD and cognition. We investigated this question using empirical genetic relationships within a sample of patients with BD and their unaffected relatives.

Methods

Participants with bipolar I, II, or schizoaffective disorder (“narrow” BD, n=69), related mood disorders (“broad” BD, n=135), and their clinically unaffected relatives (n=227) completed tests of matrix reasoning, trail making, digit-symbol coding, semantic short-term recall, and affect recognition (DANVA2). General cognitive function (g) was quantified via principal components analysis (PCA). Heritability and genetic correlations were estimated with SOLAR-Eclipse.

Results

Participants with a “narrow” or “broad” BD diagnosis showed deficits in g, though affect recognition was not impaired. Cognitive performance was significantly heritable (h2= 0.322 for g, p<0.005). Coheritability between BD and cognition was small (coheritability for g & Narrow = 0.0184, for g & Broad = 0.0327) and healthy relatives of those with BD were cognitively unimpaired.

Conclusions

In this family sample, cognitive deficits were present in participants with BD, but social cognition, measured by affect recognition, was not impaired. Deficits were largely not explained by overlapping genetic determinants of mood and cognition. These findings support the view that cognition comprises separable social and non-social domains and that cognitive deficits in BD are largely the result of the illness or its treatment.
Gentle label-free nonlinear optical imaging relaxes linear-absorption-mediated triplet
Authors: Wang Geng , Li Lianhuang , Sorrells Janet E. , Chen Jianxin , Tu Haohua
Published: October 2023

Sample health is critical for live-cell fluorescence microscopy and has promoted light-sheet microscopy that restricts its ultraviolet-visible excitation to one plane inside a three-dimensional sample. It is thus intriguing that laser-scanning nonlinear optical microscopy, which similarly restricts its near-infrared excitation, has not broadly enabled gentle label-free molecular imaging. We hypothesize that intense near-infrared excitation induces phototoxicity via linear absorption of intrinsic biomolecules with subsequent triplet buildup, rather than the commonly assumed mechanism of nonlinear absorption. Using a reproducible phototoxicity assay based on the time-lapse elevation of auto-fluorescence (hyper-fluorescence) from a homogeneous tissue model (chicken breast), we provide strong evidence supporting this hypothesis. Our study justifies a simple imaging technique, e.g., rapidly scanned sub-80-fs excitation with full triplet-relaxation, to mitigate this ubiquitous linear-absorption-mediated phototoxicity independent of sample types. The corresponding label-free imaging can track freely movingC. elegansin real-time at an irradiance up to one-half of water optical breakdown.
In vitroreconstitution reveals membrane clustering and RNA recruitment by the enteroviral AAA+ ATPase 2C
Authors: Shankar Kasturika , Sorin Marie N. , Sharma Himanshu , Skoglund Oskar , Dahmane Selma , Ter Beek Josy , Tesfalidet Solomon , Nenzén Louise , Carlson Lars-Anders
Published: October 2023

Enteroviruses are a vast genus of positive-sense RNA viruses that cause diseases ranging from common cold to poliomyelitis and viral myocarditis. They encode a membrane-bound AAA+ ATPase, 2C, that has been suggested to serve several roles in virus replication, e.g. as an RNA helicase and capsid assembly factor. Here, we report the reconstitution of full-length, poliovirus 2C’s association with membranes. We show that the N-terminal membrane-binding domain of 2C contains a conserved glycine, which is suggested by structure predictions to divides the domain into two amphipathic helix regions, which we name AH1 and AH2. AH2 is the main mediator of 2C oligomerization, and is necessary and sufficient for its membrane binding. AH1 is the main mediator of a novel function of 2C: clustering of membranes. Cryo-electron tomography reveal that several 2C copies mediate this function by localizing to vesicle-vesicle interfaces. 2C-mediated clustering is partially outcompeted by RNA, suggesting a way by which 2C can switch from an early role in coalescing replication organelles and lipid droplets, to a later role where 2C assists RNA replication and particle assembly. 2C is sufficient to recruit RNA to membranes, with a preference for double-stranded RNA (the replicating form of the viral genome). Finally, thein vitroreconstitution revealed that full-length, membrane-bound 2C has ATPase activity and ATP-independent, single-strand ribonuclease activity, but no detectable helicase activity. Together, this study suggests novel roles for 2C in membrane clustering, RNA membrane recruitment and cleavage, and calls into question a role of 2C as an RNA helicase. The reconstitution of functional, 2C-decorated vesicles provides a platform for further biochemical studies into this protein and its roles in enterovirus replication.
Ultrahigh throughput evolution of tryptophan synthase in droplets via an aptamer-biosensor
Authors: Scheele Remkes A. , Weber Yanik , Nintzel Friederike E. H. , Herger Michael , Kaminski Tomasz S. , Hollfelder Florian
Published: October 2023

Tryptophan synthase catalyzes the synthesis of a wide array of non-canonical amino acids and is an attractive target for directed evolution. Droplet microfluidics offers an ultrahigh throughput approach to directed evolution (>107experiments per day), enabling the search for biocatalysts in wider regions of sequence space with reagent consumption minimized to the picoliter volume (per library member). While the majority of screening campaigns in this format on record relied on an optically active reaction product, a new assay is needed for tryptophan synthase. Tryptophan is not fluorogenic in the visible light spectrum and thus falls outside the scope of conventional droplet microfluidic read-outs which are incompatible with UV light detection at high throughput. Here, we engineer a tryptophan DNA aptamer into a biosensor to quantitatively report on tryptophan production in droplets. The utility of the biosensor was validated by identifying 5-fold improved tryptophan synthases from ∼100,000 protein variants. More generally this work establishes the use of DNA-aptamer sensors with a fluorogenic read-out in widening the scope of droplet microfluidic evolution.
A human prenatal skin cell atlas reveals immune cell regulation of skin morphogenesis
Authors: Gopee Nusayhah Hudaa , Huang Ni , Olabi Bayanne , Admane Chloe , Botting Rachel A. , Foster April Rose , Torabi Fereshteh , Winheim Elena , Sumanaweera Dinithi , Goh Issac , Miah Mohi , Stephenson Emily , Tun Win Min , Moghimi Pejvak , Rumney Ben , He Peng , Lawrence Sid , Roberts Kenny , Sidhpura Keval , Englebert Justin , Jardine Laura , Reynolds Gary , Rose Antony , Ganier Clarisse , Rowe Vicky , Pritchard Sophie , Mulas Ilaria , Fletcher James , Popescu Dorin-Mirel , Poyner Elizabeth , Dubois Anna , Filby Andrew , Lisgo Steven , Barker Roger A. , Park Jong-Eun , Vento-Tormo Roser , Le Phuong Ahn , Serdy Sara , Kim Jin , Deakin CiCi , Lee Jiyoon , Nikolova Marina , Rajan Neil , Ballereau Stephane , Li Tong , Moore Josh , Horsfall David , Lozada Daniela Basurto , O’Toole Edel A. , Treutlein Barbara , Bayraktar Omer , Kasper Maria , Mazin Pavel , Gambardella Laure , Koehler Karl , Teichmann Sarah A. , Haniffa Muzlifah
Published: October 2023

Human prenatal skin is populated by innate immune cells including macrophages, and whether they act solely in immunity or have additional functions in morphogenesis is unclear. We assembled the first comprehensive multi-omic reference atlas of prenatal human skin (7-16 post-conception weeks), combining single cell and spatial transcriptomic data, to characterise the skin’s microenvironmental cellular organisation. This revealed that crosstalk between non-immune and immune cells underpins formation of hair follicles, has implications for scarless wound healing, and is critical for skin angiogenesis. We benchmarked a skin organoid model, derived from human embryonic stem (ES) and induced pluripotent stem (iPS) cells, against prenatal and adult skin, demonstrating close recapitulation of the epidermal and dermal skin components during hair follicle development. Notably, the skin organoid lacked immune cells and had markedly diminished endothelial cell heterogeneity and quantity. From ourin vivoskin cell atlas data, we found that macrophages and macrophage-derived growth factors play a key role in driving endothelial development prenatally. Indeed, vascular network formation was enhanced following transfer of autologous iPS-derived macrophages into both endothelial cell angiogenesis assays and skin organoid cultures. In summary, innate immune cells moonlight as key players in skin morphogenesis beyond their conventional immune roles, a function they achieve via extensive crosstalk with non-immune cells. Finally, we leveraged our human prenatal skin cell atlas to further our understanding of the pathogenesis of genetic hair and skin disorders.
Synthesis and characterization of a glutathione-responsive drug delivery system based on aptamer-coated mesoporous silica
Authors: Zhou Lu , Zhang Yajie , Ma Yong
Published: October 2023

Chemotherapy drugs, though effective against cancer, often pose challenges due to their high toxicity and adverse effects. To address these issues and prevent premature drug release, a straightforward yet smart glutathione (GSH)-responsive drug delivery system (DDS) based on aptamer-coated mesoporous silica has been developed. Mesoporous silica serves as the drug carrier, with the anticancer drug model doxorubicin (Dox) efficiently loaded in, sealed by coating with aptamer AS1411. The characteristics of the resulting microspheres were investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis and zeta potential measurements. These analyses confirmed the successful bonding of AS1411 to the surface of the mesoporous silica. Drug-release tests were conducted under two distinct pH conditions (pH 5.0 and 7.4), both in the presence and in the absence of GSH. The results demonstrate the remarkable ability of this DDS to respond to GSH, facilitating controlled drug release. The single coated layer on the particle serves a dual purpose by blocking pore openings and triggering an endogenous stimulus response, ensuring the precise release of pharmaceuticals during drug delivery. This GSH-responsive DDS holds the potential to mitigate drug-induced harm to healthy tissues, offering a new approach for cancer treatment.
Automatic simulated dental implants method with implant parameter estimation based on CBCT images
Authors: Wang Kai , Liu Jiaying , Yang Shuai , Guo Jing , Ke Yongzhen
Published: October 2023

Purpose

This paper aims to automatically obtain the implant parameter from the CBCT images to improve the outcome of implant planning.

Design/methodology/approach

This paper proposes automatic simulated dental implant positioning on CBCT images, which can significantly improve the efficiency of implant planning. The authors introduce the fusion point calculation method for the missing tooth's long axis and root axis based on the dental arch line used to obtain the optimal fusion position. In addition, the authors proposed a semi-interactive visualization method of implant parameters that be automatically simulated by the authors' method. If the plan does not meet the doctor's requirements, the final implant plan can be fine-tuned to achieve the optimal effect.

Findings

A series of experimental results show that the method proposed in this paper greatly improves the feasibility and accuracy of the implant planning scheme, and the visualization method of planting parameters improves the planning efficiency and the friendliness of system use.

Originality/value

The proposed method can be applied to dental implant planning software to improve the communication efficiency between doctors, patients and technicians.
Board gender diversity and corporate litigation: evidence from China
Authors: Zheng Xiaojing , Wang Xiaoxian
Published: October 2023

Purpose

This study aims to examine the effect of board gender diversity on corporate litigation in China’s listed firms. The key questions this study addresses are: what are the effect of board gender diversity on corporate litigation in terms of both the frequency and severity of consequence, is there any heterogeneous effects of the relationships across firm performance?

Design/methodology/approach

A sample consists of 25,668 firm-year observations from over 3,340 firms is examined using logistic regression analysis and negative binomial regression analysis. The authors also use event study method and ordinary least square (OLS) regression to explore female directors’ effects on reducing the negative consequences of litigation. The logistic regression and OLS regression are reestimated with interaction terms when examining the firm performance heterogeneity.

Findings

The authors document that firms with greater female representation on their boards experience fewer and less severe corporate litigations. Moreover, in high-performing firms, board gender diversity plays a more potent role in reducing the frequency and consequences of corporate litigation than low-performing firms.

Originality/value

This study is among the first to examine the relationship between board gender diversity and the comprehensive corporate litigations under Chinese context. It sheds new light on China’s boardroom dynamics, offering valuable empirical implication to Chinese corporate policymakers on the role of female directors.