bluuebunny/crossref_metadata_2025 huggingface dataset:
LMIC-13. ENCOURAGING EXPERIENCE OF CONCURRENT CARBOPLATIN DURING CRANIOSPINAL IRRADIATION USING IMAGE GUIDED INTENSITY MODULATED PROTON BEAM (IMPT) IN HIGH-RISK EMBRYONAL TUMORS: FIRST REPORT FROM A LOW MIDDLE-INCOME COUNTRY
Authors: K Vasudeva Bhat , Uppuluri Ramya , Krishna Uday , Das Anindita , KC Ganapathy , S Preethi , VS Venkateswaran , R Adithyan , Patil Sushma , Jalali Rakesh
Published: June 2024

BACKGROUND

Concurrent carboplatin during craniospinal irradiation (CSI) using photon radiotherapy in High risk (HR) embryonal tumors has been shown to improve the event free survival in select subgroup of patients. Experience of using concurrent carboplatin during CSI using proton therapy is limited.

METHOD

A retrospective audit was done in Children <18 years from January 2018 to December 2023 diagnosed with HR embryonal tumors who received image guided pencil beam intensity modulated proton beam therapy-based CSI (35Gy/21#) along with concurrent carboplatin 35mg/m2 at least for 15 fractions. The patient demographics, pathological diagnosis, treatment related toxicities and date of follow-up were recorded in predesigned proforma using electronic medical record.

RESULTS

Twenty children with HR embryonal tumors with median age at diagnosis 5 years (Range: 1-15 years) with M: F ratio of 3:1 were included in the study. Fifteen (75%) of the patients had HR medulloblastoma defined by spinal metastases or HR molecular subtype of which 5 patients had group 3 medulloblastoma (3- leptomeningeal disease at baseline, 2- MYC amplification) while rest had embryonal tumors (3-NOS, 1-Pinealoblastoma and 1-ETMR). Carboplatin was well tolerated, however 12 (60%) patients developed neutropenia requiring daily G-CSF for an average of 5 days. Average time to complete radiotherapy was 45 days with median interruption of 4 days (Range 1-7). Radiotherapy induced toxicities included Grade 3 skin toxicity in 6 (30%) and grade 2 weight loss in 3 (15%). At a median follow up of 14 months (Range: 4-58), the PFS was 80% in the whole cohort while in the Group 3 Medulloblastoma the PFS was only 20% which was statistically significant(p=0.004).

CONCLUSIONS

Carboplatin along with proton CSI is well tolerated in children with HR embryonal tumors without significant adversities. Experience is encouraging especially in non-group 3 medulloblastoma patients in our cohort of children with HR embryonal tumors.
MODL-15. CHARACTERIZATION OF SPONTANEOUS CANINE HIGH-GRADE GLIOMA MODELS AS CLINICALLY-RELEVANT SURROGATES OF PEDIATRIC HIGH-GRADE GLIOMA
Authors: Link Gabrielle , Garey Simon , DeSisto John , Antonakakis Markos , McGrath Stephanie , Chow Lyndah , Slade Mathew , Dow Steven , Green Adam L
Published: June 2024

BACKGROUND

High-grade glioma (HGG) occurring spontaneously in canines shows histological and genetic resemblance to pediatric high-grade glioma (PHGG). Both canine HGG and PHGG are treated with combinations of surgical resection, radiation therapy, and/or chemotherapy, but outcomes for both groups are poor. Studying canine HGG both serves companion dogs and provides an orthogonal preclinical model of PHGG.

METHODS

Canine HGG lines J3T, SDT3G, and G06A were characterized and compared with H3K27M-mutant PHGG lines DIPG7, DIPG13, and BT245 using neurosphere dilution assay and drug screening with all FDA-approved anti-cancer agents. J3T and SDT3G were orthotopically implanted into mice and monitored using MRI and bioluminescence.

RESULTS

Like PHGG, the canine lines J3T and SDT3G were highly sensitive to proteasome and XPO1 inhibition; compared to PHGG, the canine lines were most sensitive to protein translation inhibitors and DNA intercalators. Canine HGG lines were not as sensitive to other targeted inhibitors effective in PHGG. Compared to PHGG cell lines, canine cell lines had greater variance in self-renewal capability. J3T and SDT3G were also injected into the cortex of immunodeficient mice. Bioluminescent signal confirmed J3T engraftment one week post-surgery with rapid tumor growth, while SDT3G presented initial engraftment by MRI two weeks post-surgery but did not exhibit sustained growth.

DISCUSSION

Canine HGG and PHGG showed similar sensitivity to proteasome and XPO1 inhibition; they differed in self-renewal capability and susceptibility to other anti-cancer agents. This could be because canine target proteins often differ from their human counterparts and thus may respond differently to targeted medications designed for humans. Overall, canine HGG provides a novel, primary, immunocompetent surrogate that resembles PHGG and may provide a step for clinical investigation between xenograft models and PHGG trials and/or opportunities for co-clinical trials.
RADT-09. IMMUNE RESPONSE IN DIFFUSE MIDLINE GLIOMA (DMG) FOLLOWING FLASH OR CONVENTIONAL RADIATION
Authors: Minns Hanna E , Padilla Oscar , Wei Hong-Jian , Webster-Carrion Andrea , Gallitto Matthew , Szalontay Luca , Pavisic Jovana , Tan Yuewen , Deoli Naresh , Garty Guy , Garvin James H , Canoll Peter , Vanpouille-Box Claire I , Rabadan Raul , Wu Cheng-Chia , Gartrell Robyn D
Published: June 2024

BACKGROUND

Diffuse Midline Glioma (DMG) is a fatal, unresectable, pediatric brain tumor with limited treatment options and a median survival of 9-15mths. As radiation therapy (RT) can only extend life by 3mths, novel RT techniques are needed, including ultra-high dose rate RT (FLASH). RT can stimulate immune responses in many cancers especially via type 1 interferon (IFN1) but the effect of RT on DMG is understudied as post treatment tissue is not readily available.

METHODS

We evaluated the effect of RT on immune response in an orthotopic syngeneic model of DMG, comparing FLASH, given at 90Gy/second, to conventional dose rate RT (CONV), given at 2Gy/min. We evaluated single-cell RNA sequencing (scRNA-seq) on CD45+ immune cells isolated from tumors 4 days post 15Gy FLASH or CONV RT and compared to unirradiated tumor (SHAM). We also performed flow cytometry on tumors at both day 4 and day 10 post-RT.

RESULTS

We find microglia (MG) are the most abundant immune cell type followed by non-resident myeloid cells including macrophages (MAC) and dendritic cells (DC). While there’s no significant difference in tumor growth or proportion of immune subtypes comparing FLASH, CONV and SHAM, we see similar IFN1 enrichment in MG comparing FLASH and CONV at day 4. Interestingly, at day 10 post-RT we observe higher IFN1 receptor (IFNAR1) by flow in MGs after CONV (p=0.016) and SHAM (p=0.040) compared to FLASH. At day 4 CONV shows higher IFN1 gene set enrichment in MACs and DCs compared to FLASH (both p<0.0001) as well as higher IFNAR1 in DCs comparing CONV to FLASH (p=0.0079), while day 10 post-RT shows equivalent IFNAR1 in MACs and DCs between dose rates.

CONCLUSION

Changes in DMG tumor immune microenvironment post-RT differ over time. Though both RT modalities increase IFN1, the timing of this response is dependent on both cell phenotype and dose.
RADT-12. CLINICAL RELEVANCE OF RADIATION-INDUCED CAVERNOUS MALFORMATIONS
Authors: Burnett Lauren A , Cavannaugh Corey , Sato Mariko
Published: June 2024

BACKGROUND

Radiation-induced cavernous malformations (RICMs) are delayed complications of brain irradiation during childhood. The prevalence of cavernomas in the general population was found to be 0.5% in a large prospective study. However, the exact incidence of RICM in children and the mechanisms of the development of RICM remain largely unknown since the cumulative incidence of RICM is underreported. Recent systemic review revealed 113 children with RICM after treatment of brain tumors and leukemias. 67% were asymptomatic and 21% showed signs of hemorrhage. In this review, the average dose of radiation was 50Gy and the mean time to detection was 9.2 years.

METHODS

We conducted a retrospective review of RICM in children who underwent total body irradiation (TBI) for bone marrow transplant. Our study goals were to better understand the incidence and patterns of RICMs and to develop a risk stratification for monitoring. Between 9/2000-1/2023, 161 patients underwent TBI. Of 47 patients who had post-transplant brain MR imaging done, 15 patients had MRIs available for review.

RESULTS

Of 15 reviewed MRIs, 11 (73.3%) had RICMs identified. 6 cases had >5 small (<3mm) RICMs. Most RICMs were in the frontal lobes. MRIs were obtained an average of 64 months from TBI. Radiation doses ranged from 200-2760cGy with an average of 1144cGy. There was 1 case of microhemorrhage due to RICM. None of our patients deceased as a result of their RICM.

CONCLUSIONS

Our cohort showed a high incidence (73.3%) of RICM despite low doses of radiation. Due to their typically small size and lack of clinical symptoms, RICM is often underreported. Although the outcome of cavernous malformation is favorable, it is important to understand the incidence and risk of adverse neurologic outcomes posed by RICMs. By performing regular surveillance, complications related to RICMs may be intervened with preventative procedures such as microsurgery.
Public Support for Tobacco Endgame Policies: A Systematic Review and Meta-Analysis
Authors: Kim Hana , Gartner Coral , Edwards Richard , Puljević Cheneal , Morphett Kylie , Kim Dong Ha , Chun Hae-ryoung , Ekdahl Martin , Kang Heewon
Published: June 2024

Introductions

An increasing number of countries are adopting the tobacco endgame goal. High levels of public support can accelerate momentum towards implementing tobacco endgame policies. We aimed to conduct a systematic review of public support for tobacco endgame policies and to examine the geographical distribution of studies, support among key populations (adolescents and young adults, people who smoke), and the association between survey design and support.

Aims and Methods

We searched Embase, PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2013 onwards. Google was used to search the gray literature. The reference lists of included articles were hand-searched. Studies were included if they reported the proportions of people supporting one or more endgame policies. Risk of bias was assessed using the JBI checklist for prevalence studies.

Results

Forty-seven articles were included. Aotearoa/New Zealand and the United States were the countries with the most studies (n = 11, respectively). Three-level meta-analyses showed the highest support for mandating a very low nicotine content in tobacco products (76%, 95% CI: 61% to 87%). Meta-regressions were performed to assess the associations of population subgroup and survey design with support levels. The level of support was lower among people who smoke compared to the general population (β range: −1.59 to −0.51). Support for some policies was lower when neutral or don’t know response options were included.

Conclusions

Public support for most tobacco endgame policies was high.

Implications

Assessing public support can assist with progressing tobacco endgame policies. Policies that are widely supported by the public may be more politically feasible to implement. Qualitative studies and trial studies can further inform communication and implementation strategies for tobacco endgame policies.
Thinking about the Future
Authors: Brady Henry E.
Published: June 2024

The five projective inference methods of statistical forecasting and modeling, technological forecasting, constructing future scenarios, configurative analysis, and robust decision-making (RDM) evaluate the possibility, attainability, and sustainability of plans or projections about the future such as a new constitution for a fledgling democratic republic in 1787–89, a transcontinental railroad in the 1860s, and a California Global Warming Solutions Act (AB 32) in 2006. This chapter considers these five approaches to the projective inference problem of portraying causal relationships leading to future outcomes. The first two (statistical and technological forecasting) ask what is likely and focus on determining the probabilities of relationships and outcomes. The second two (scenario and configurative analysis) ask what is possible and best and focus on the values embedded in outcomes. The last one (RDM) asks what must be avoided or can be adventitiously exploited and focuses on robust actions and decision-rules to produce acceptable and sustainable outcomes. These different questions and emphases lead to different methods and procedures—all of which constitute legitimate forms of projective inference based upon modern understandings of scientific method reviewed in the last part of the paper. Because projective inference is important and because it poses special problems, political methodologists should pay more attention to it and develop better methods and standards for doing it.
E3 ligase DECREASED GRAIN SIZE 1 promotes degradation of a G-protein subunit and positively regulates grain size in rice
Authors: Hao Qixian , Zhu Xingjie , Huang Yunshuai , Song Jiawei , Mou Changling , Zhang Fulin , Miao Rong , Ma Tengfei , Wang Ping , Zhu Ziyan , Chen Cheng , Tong Qikai , Hu Chen , Chen Yingying , Dong Hui , Liu Xi , Jiang Ling , Wan Jianmin
Published: June 2024

Grain size is one of the most important traits determining crop yield. However, the mechanism controlling grain size remains unclear. Here, we confirmed the E3 ligase activity of DECREASED GRAIN SIZE 1 (DGS1) in positive regulation of grain size in rice (Oryza sativa) suggested in a previous study. Rice G-protein subunit gamma 2 (RGG2), which negatively regulates grain size, was identified as an interacting protein of DGS1. Biochemical analysis suggested that DGS1 specifically interacts with canonical Gγ subunits (rice G-protein subunit gamma 1 [RGG1] and rice G-protein subunit gamma 2 [RGG2]) rather than non-canonical Gγ subunits (DENSE AND ERECT PANICLE 1 [DEP1], rice G-protein gamma subunit type C 2 [GCC2], GRAIN SIZE 3 [GS3]). We also identified the necessary domains for interaction between DGS1 and RGG2. As an E3 ligase, DGS1 ubiquitinated and degraded RGG2 via a proteasome pathway in several experiments. DGS1 also ubiquitinated RGG2 by its K140, K145, and S147 residues. Thus, this work identified a substrate of the E3 ligase DGS1 and elucidated the post-transcriptional regulatory mechanism of the G-protein signaling pathway in the control of grain size.
CBP60b clade proteins are prototypical transcription factors mediating immunity
Authors: Li Lu-Shen , Yang Yan-Yan , Chen Yun-Xia , Yu Fei , Hao Guang-Jiu , Yin Gui-Min , Dou Yan , Zhi Jing-Yu , Ma Lin , Wang Jing-Fan , Feng Qiang-Nang , Zhang Yan , Li Sha
Published: June 2024

Transcriptional reprogramming is critical for plant immunity. Several calmodulin (CaM)-binding protein 60 (CBP60) family transcription factors (TFs) in Arabidopsis (Arabidopsis thaliana), including CBP60g, systemic acquired resistance deficient 1 (SARD1), CBP60a, and CBP60b, are critical for and show distinct roles in immunity. However, there are additional CBP60 members whose function is unclear. We report here that Arabidopsis CBP60c–f, 4 uncharacterized CBP60 members, play redundant roles with CBP60b in the transcriptional regulation of immunity responses, whose pCBP60b-driven expression compensates the loss of CBP60b. By contrast, neither CBP60g nor SARD1 is interchangeable with CBP60b, suggesting clade-specific functionalization. We further show that the function of CBP60b clade TFs relies on DNA-binding domains (DBDs) and CaM-binding domains, suggesting that they are downstream components of calcium signaling. Importantly, we demonstrate that CBP60s encoded in earliest land plant lineage Physcomitrium patens and Selaginella moellendorffii are functionally homologous to Arabidopsis CBP60b, suggesting that the CBP60b clade contains the prototype TFs of the CBP60 family. Furthermore, tomato and cucumber CBP60b–like genes rescue the defects of Arabidopsis cbp60b and activate the expression of tomato and cucumber SALICYLIC ACID INDUCTION DEFICIIENT2 (SID2) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) genes, suggesting that immune response pathways centered on CBP60b are also evolutionarily conserved. Together, these findings suggest that CBP60b clade TFs are functionally conserved in evolution and positively mediate immunity.
Soundness arguments for consistency and their epistemic value: A critical note
Authors: Zicchetti Matteo
Published: June 2024

Soundness Arguments for the consistency of a (mathematical) theory S aim to show that S is consistent by first showing or employing the fact that S is sound, i.e., that all theorems of S are true. Although soundness arguments are virtually unanimously accepted as valid and sound for most of our accepted theories, philosophers disagree about their epistemic value, i.e., about whether such arguments can be employed to improve our epistemic situation concerning questions of consistency. This article provides a (partial) negative answer to this question and argues that soundness arguments cannot be employed to justify their conclusion. Additionally, soundness arguments are unconvincing; they cannot be employed to overcome reasonable open-mindedness about their conclusion.
United States: Tax classification and treatment of non-U.S. private foundations
Authors: Georgiev Lyubomir , Noked Noam , Desrosiers Christiana
Published: June 2024

This article discusses a U.S. Court of Appeals decision from August 2022 regarding the proper classification of a Liechtenstein Stiftung foundation for U.S. federal tax purposes. It also discusses at a high level the implications of different classifications. Founders (including non-U.S. persons) and their advisers should consider these implications when establishing foundations, particularly when the foundations’ beneficiaries are U.S. persons or if the foundations hold U.S. situs assets.
Patient Preferences for Immediate Compared With Delayed Postpartum Intrauterine Device Placement
Authors: Christensen Theresa , Ostrowski Susanna , McAllister Arden , Bynum Blythe , Schapira Marilyn M. , Sonalkar Sarita
Published: June 2024

OBJECTIVE:

To use choice-based conjoint survey methodology to evaluate patient values and decision making regarding immediate compared with delayed placement of postpartum intrauterine devices (IUDs).

METHODS:

We conducted a cross-sectional study in which we surveyed 200 nonpregnant, parous patients. Participants chose between hypothetical postpartum IUDs varying in multiple attributes (hormonal or nonhormonal IUD type, placement timing, 1-year efficacy, expulsion risk, risk of lost strings, and malposition risk). The primary outcome was preference for immediate compared with delayed postpartum IUD placement and importance of placement timing relative to other attributes. Secondarily, we evaluated whether demographic and neighborhood characteristics were associated with timing preference and attribute importance.

RESULTS:

We included 190 participants for analysis. Most participants (62.6%) preferred delayed placement. There was no significant difference in timing preference by race (P=.28) or block-level Area Deprivation Index score (P=.27). Patients who preferred immediate placement were more likely to have public insurance than private insurance (70.4% vs 29.6%, P=.04); however, the majority of patients (55.1%) with public insurance still preferred delayed placement. Attributes of IUD type, malposition risk, 1-year efficacy, and expulsion risk all had greater effects on patient decision making than placement timing. There was no difference in attribute importance by race (P=.30), Area Deprivation Index score (P=.88), or insurance type (P=.22).

CONCLUSION:

Patients preferred the higher efficacy and lower complication rates of delayed postpartum IUD placement over the convenience of immediate placement. Insurance considerations may affect these timing preferences. There was no difference in attribute importance between demographic groups or based on neighborhood-level factors, indicating that, although both immediate and delayed postpartum IUD placement should be offered, counseling should not vary according to individual demographic characteristics.
Efficacy of 785-nm Picosecond Titanium Sapphire Laser for Treatment of Brown Nevus of Ota Lesions in FST II-V: A Retrospective Analysis
Authors: Swali Ritu N. , Estupiñan Blanca , Guo Emily L. , Richmond Heather , Friedman Paul M.
Published: June 2024

BACKGROUND

Nevus of Ota (NOTA) is a dermal melanocytosis acquired in early childhood or pregnancy. Given their color variability, NOTA often require a combination of wavelengths for successful treatment. Quality-switched lasers have consistently shown efficacy in targeting dermal pigment, while picosecond lasers (PSLs) are an emerging technology for pigmentary disorders.

OBJECTIVE

To further elucidate its efficacy, the authors conducted a retrospective review of 17 patients with NOTA treated with a 785-nm PSL for brown NOTA lesions between 2021 and 2023.

MATERIALS AND METHODS

The primary end point analyzed clinical improvement based on before and after photography reviewed by 3 board-certified dermatologists using a five-point visual analog scale.

RESULTS

Seventeen patients of Fitzpatrick skin types (FSTs) II to V, ranging from ages 14 to 38 years, were included in this study. Patients were treated for an average of 3.2 sessions in 2 to 3-month intervals. Visual analog scale scores demonstrated a mean clearance of 51% to 75%. No pigmentary alterations were noted.

CONCLUSION

Because NOTA is common in higher FSTs, the authors believe that the 785-nm PSL is an excellent treatment option for brown NOTA in these skin types. This study highlights the need for further investigation to determine optimal treatment parameters for the color-based laser treatment approach for NOTA.
Case Series of Orbital Lymphoma: Cardinal Presentations
Authors: Urrutia Yordan A. , Fezza Tyler , Kosek Kalie , Fezza John P.
Published: June 2024

Periorbital lymphomas may present with nonspecific symptoms and may disguise as other ocular conditions, which may result in a missed diagnosis. The purpose of his case series is to add to the existing literature and raise awareness of this rare and lethal cancer so early detection and treatment can be instituted. A retrospective review of four diverse cases of periorbital lymphoma is described, highlighting the important role of plastic surgeons in early recognition and prompt diagnosis through extensive examination, imaging studies, and biopsies. The histological subtype and site of lesion play a critical role in the prognosis of patients with periorbital lymphoma. This article also underscores the significance of early detection and a multidisciplinary team approach.
Optimizing the Use of Pedicled versus Random Pattern Local Flaps in the Foot and Ankle
Authors: Li Karen R. , Lava Christian X. , Lee Seo Yeon , Suh Julie , Berger Lauren E. , Attinger Christopher E.
Published: June 2024

Background:

The aim of this study was to compare the use of pedicled local (PFs) versus random pattern flaps (RpFs) in foot and ankle reconstruction in patients with chronic, nonhealing wounds.

Methods:

A single-center, retrospective review of 204 patients with 118 PFs and 86 RpFs was performed. The primary outcome included rates of limb salvage.

Results:

PFs were used more often in the hindfoot (44.1% versus 30.2%, P = 0.045), lateral and medial surface (39.8% versus 18.6%, P = 0.001), and wounds containing exposed bone and hardware (78.8% versus 62.8%, P = 0.018). RpFs were used more for forefoot (19.8% versus 10.2%, P = 0.053) and plantar defects (58.1% versus 30.3%, P = 0.000). RpFs had a higher rate of immediate success (100% versus 95.8%, P = 0.053), with no significant differences in rate of long-term limb salvage (77.1% versus 69.8%, P = 0.237). PFs had higher rates of ischemia requiring intervention (11.0% versus 3.5%, P = 0.048). RpFs had a higher rate of minor amputations (15.12% versus 6.8%, P = 0.053) but similar rates of major amputation (15.1% versus 16.1%, P = 0.848). There were no significant differences in rates of mortality or ambulatory status.

Conclusions:

Both RpFs and PFs remain reliable options to reconstruct defects of the foot and ankle. Optimizing the use of each flap type should consider wound characteristics. RpFs are preferred for dorsal and plantar defects, whereas PFs are protective for minor infections and preferred for deeper wounds despite a higher rate of partial necrosis.
The Importance of Social Support in the Management of Hypertension in Brazil
Authors: de Sales Paloma Cesar , McCarthy Margaret M. , Dickson Victoria Vaughan , Sullivan-Bolyai Susan , Melkus Gail D'Eramo , Chyun Deborah
Published: June 2024

Background

The prevalence of hypertension (HTN) is high in Brazil, and control rates are low. Little is known about the factors that contribute to HTN control from a family-based perspective.

Objectives

Guided by the Family Management Style Framework, specific aims were to (1) describe the prevalence of adequate blood pressure (BP) control in individuals cared for the Family Health Strategy, (2) identify facilitators and barriers to HTN management, and (3) identify individual contextual sociocultural influences (sociocultural context and social and Family Health Strategy support), definition of the situation, and management behaviors that help or interfere with individual functioning (BP control in the individual with HTN).

Methods

This descriptive, cross-sectional study included 213 individuals with HTN randomly selected from 3 Family Health Strategy units from July 2016 until July 2017.

Results

Most of the individuals were female (n = 139, 65.3%), retired (n = 129, 60.5%), and White (n = 129, 60.2%) and had less than a high school education (n = 123, 57.6%). Family income (n = 166, 77.8%) was less than 5500 reals (US $1117/month). Mean (SD) systolic BP was 137.1 (±24.1) mm Hg, and mean (SD) diastolic BP was 83.8 (±18.6) mm Hg, with 47.9% (n = 102) having uncontrolled BP. In the multivariate logistic model, only high levels of perceived social support were significantly associated (odds ratio, 3.29; 95% confidence interval, 1.44–7.5; P = .005) with controlled BP.

Conclusions

Social support is strongly associated with BP control. Optimizing support may play an important role in BP control and preventing HTN-related complications.
Factors Influencing the Personal Recovery of Inpatients in a Forensic Psychiatric Hospital in South Korea
Authors: Gang Moonhee , Gwak Donghyeon
Published: June 2024

Purpose

This study aimed to identify the factors influencing the personal recovery of inpatients of a forensic psychiatric hospital.

Methods

A descriptive study design was assigned. The participants were 136 inpatients in a forensic psychiatric hospital in South Korea. The data were analyzed using SPSS Statistics Version 26.0 with descriptive statistics, independent t test, analysis of variance, Pearson correlation coefficient, and multiple regression.

Results

Perceived physical health status (β = 0.16, p = 0.034), perceived mental health status (β = 0.20, p = 0.023), perceived family support (β = 0.17, p = 0.013), duration of hospitalization (β = 0.25, p < 0.001), and recovery attitudes (β = 0.36, p < 0.001) were the significant factors explaining 42.6% of the variance in the personal recovery of participants.

Conclusion

The findings of this study indicate that recovery attitudes, health status, and personal support affect forensic mental health personal recovery. Personal recovery can be strengthened through nursing intervention and support to strengthen recovery attitudes and health status. It is necessary to get used to personal recovery through long-term and systematic education, and organizations and nurses need to make efforts to provide services centered on personal recovery.
Paraoxonase 1: evolution of the enzyme and of its role in protecting against atherosclerosis
Authors: Durrington Paul , Soran Handrean
Published: June 2024

Purpose of review

To review the discoveries which led to the concept that serum paraoxonase 1 (PON1) is inversely related to atherosclerotic cardiovascular disease (ASCVD) incidence, how this association came to be regarded as causal and how such a role might have evolved.

Recent findings

Animal models suggest a causal link between PON1 present on HDL and atherosclerosis. Serum PON1 activity predicts ASCVD with a similar reliability to HDL cholesterol, but at the extremes of high and low HDL cholesterol, there is discordance with PON1 being potentially more accurate. The paraoxonase gene family has its origins in the earliest life forms. Its greatest hydrolytic activity is towards lactones and organophosphates, both of which can be generated in the natural environment. It is active towards a wide range of substrates and thus its conservation may have resulted from improved survival of species facing a variety of evolutionary challenges.

Protection against ASCVD is likely to be the consequence of some promiscuous activity of PON1, but nonetheless has the potential for exploitation to improve risk prediction and prevention of ASCVD.
Clinical Observation of Infarct Volume ≥150 mL in Endovascular Thrombectomy Treatment
Authors: Zeng Hai , Zhou Jia , Xue Qing , Zhao Fengli , Liu Tingyu , Zhu Qingfeng
Published: June 2024

Objectives:

Whether patients with infarct volume ≥150 mL could benefit from endovascular thrombectomy (EVT) remains unclear.

Methods:

Patients (n=104) with anterior circulation Alberta Stroke Program Early Computed Tomography Score <6 were screened for infarct volume ≥150 mL using the Pullicino formula × (1–22%). The following were compared with the baseline at 90 days: the modified Rankin scale score (mRS) ≤3, mortality rate, symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours, and modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b between the EVT and drug therapy (DT) groups.

Results:

In patients with infarct volumes ≥150 mL, mRS≤3 at 90 days was higher in the EVT group than in the DT group [adjusted odds risk (aOR), 5.52; 95% CI: 1.10-28.24, P=0.04), and mTICI ≥2b at 82.8%. Intracranial hemorrhage within 48 hours occurred in 7 (24.1%) patients in the EVT group and 5 (14.7%) in the DT group (aOR, 0.75; 95% CI: 0.16-3.46; P=0.71). Older age (aOR, 0.94; 95% CI: 0.90-0.99, P=0.01), EVT treatment (aOR, 4.51; 95% CI: 1.60-12.78, P=0.01), and infarct volume ≥150 mL (aOR, 0.11; 95% CI: 0.04-0.31, P<0.01) were significantly associated with patient prognosis.

Conclusions:

Patients with infarct volume ≥150 mL who received EVT had a higher proportion of mRS≤3 compared with those who received DT. However, there was no statistically significant difference in intracranial hemorrhage and death between the groups. EVT, smaller infarct volume, and younger age were associated with a good prognosis. The findings require large sample data verification.
Use of Neuromuscular Electrical Stimulation to Elicit Muscle Contractions Does Not Impair the Hyperemic Response Compared to Volitional Contractions
Authors: Tomko Patrick M. , Davis B. Ryan , Pelka Edward Z. , Gallagher Sydney F. , McDaniel John
Published: June 2024

Purpose

Electrical stimulation-induced muscle contractions in individuals with paralyzed muscles are often associated with early-onset fatigue. We examined whether electrical stimulation of the quadriceps muscle results in vasoconstriction and a reduction in blood flow, which may contribute to this early-onset fatigue.

Methods

Seventeen young individuals completed 40 electrical stimulation isometric contractions (stimulation frequency of 75 Hz, pulse duration of 400 μs, on-off ratio 6.0–20 secs) and force matched voluntary isometric contractions. Isometric force, heart rate, blood pressure, superficial femoral diameter, and blood velocity were measured at baseline and during exercise (contractions 1, 5, 10, 15, 20, 25, 30, 35, and 40). Net, antegrade, and retrograde blood flow, and conductance were quantified. Two-way, within-subjects analyses of variance were used to evaluate diameter, blood flow, and conductance.

Results

Diameter was not different between electrical stimulation and voluntary (P = 0.57). Net blood flow increased during both conditions with the greatest blood flow occurring during electrical stimulation compared to voluntary (P ≤ 0.01). Electrical stimulation showed a greater increase antegrade and reduced retrograde flow compared to voluntary. After the twentieth contraction, electrical stimulation also elicited greater conductance than voluntary (P ≤ 0.049).

Conclusions

The use of neuromuscular electrical stimulation to elicit muscle contractions does not result in vasoconstriction or a reduced hyperemic response compared to volitional contractions.
A Nomogram Based on Conventional Ultrasound Radiomics for Differentiating Between Radial Scar and Invasive Ductal Carcinoma of the Breast
Authors: Su Huan-Zhong , Hong Long-Cheng , Su Yi-Ming , Chen Xiao-Shuang , Zhang Zuo-Bing , Zhang Xiao-Dong
Published: June 2024

We aimed to develop and validate a nomogram based on conventional ultrasound (CUS) radiomics model to differentiate radial scar (RS) from invasive ductal carcinoma (IDC) of the breast. In total, 208 patients with histopathologically diagnosed RS or IDC of the breast were enrolled. They were randomly divided in a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Overall, 1316 radiomics features were extracted from CUS images. Then a radiomics score was constructed by filtering unstable features and using the maximum relevance minimum redundancy algorithm and the least absolute shrinkage and selection operator logistic regression algorithm. Two models were developed using data from the training cohort: one using clinical and CUS characteristics (Clin + CUS model) and one using clinical information, CUS characteristics, and the radiomics score (radiomics model). The usefulness of nomogram was assessed based on their differentiating ability and clinical utility. Nine features from CUS images were used to build the radiomics score. The radiomics nomogram showed a favorable predictive value for differentiating RS from IDC, with areas under the curve of 0.953 and 0.922 for the training and validation cohorts, respectively. Decision curve analysis indicated that this model outperformed the Clin + CUS model and the radiomics score in terms of clinical usefulness. The results of this study may provide a novel method for noninvasively distinguish RS from IDC.
SEPTIC SHOCK: LPS TOLERANCE PROTECTS MITOCHONDRIAL BIOGENESIS AND RESPIRATION
Authors: Silva Andre Augusto Botêga , Barbeiro Denise Frediani , Ariga Suely Kunimi Kubo , Barbeiro Hermes Vieira , Coelho Ana Maria Mendonça , Chaib Eleazar , Passarelli Marisa , Soriano Francisco Garcia
Published: June 2024

Mitochondrial dysfunction is a recognized feature of sepsis, characterized by ultrastructural damage, diminished oxidative phosphorylation, and depletion of mitochondrial antioxidant capacity observed in deceased septic patients. LPS tolerance induces a controlled response to sepsis. This study aimed to evaluate the function of tolerant mitochondria after cecal ligation and puncture (CLP)–induced sepsis. Mytochondrial oxygen consumption was determined using polarography. Extraction and quantification of RNA for the expression of Tfam, Nrf-1, and Ppargc-1α, and respiratory complex activity were measured. CLP-tolerant animals presented preserved respiratory rates of S3 and S4 and a ratio of respiratory control (RCR) compared to CLP-nontolerant animals with reduced oxidative phosphorylation and increased uncoupled respiration. Complex I Vmax was reduced in septic animals; however, CLP animals sustained normal Vmax. Mitochondrial biogenesis was preserved in CLP-tolerant animals compared to the CLP-nontolerant group, likely due to increased TFAM expression. LPS tolerance protected septic animals from mitochondrial dysfunction, favoring mitochondrial biogenesis and preserving mitochondrial respiration and respiratory complex I activity.
EXAMINING THE IMPACT OF PERMISSIBILITY HYPERCAPNIA ON POSTOPERATIVE DELIRIUM AMONG ELDERLY PATIENTS UNDERGOING THORACOSCOPIC-LAPAROSCOPIC ESOPHAGECTOMY: A SINGLE-CENTER INVESTIGATIVE STUDY
Authors: Song Jie , Shao Yan-Mei , Zhang Guang-Hui , Fan Bing-Qian , Tao Wen-Hui , Liu Xiao-Fen , Huang Xiao-Ci , Hu Xian-Wen
Published: June 2024

Objective: This study explores how permissive hypercapnia, a key aspect of lung-protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. Methods: A single-center trial at The Second Hospital of Anhui Medical University involved 136 elderly patients undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO2 35–45 mm Hg (group N) or 46–55 mm Hg (group H). Primary outcome: postoperative delirium (POD) incidence 1–3 days post-surgery. Secondary endpoints included monitoring rSO2, cardiovascular parameters (MAP, HR), pH, OI, and respiratory parameters (VT, RR, Cdyn, PIP) at specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) and systemic inflammatory index (SII). VAS scores were documented for 3 postoperative days. Results: Postoperatively, group H showed significantly lower POD incidence than group N (7.4% vs. 19.1%, P = 0.043). Group H exhibited higher PaCO2 and rSO2 during surgery (P < 0.05). Patients in group H maintained better cardiovascular stability with higher blood pressure and lower heart rate on T2–4 (P < 0.05). Respiratory parameters were more stable in group H with lower TV, RR, and PIP, and higher Cdyn during OLV (P < 0.05). Group H had lower pH and higher OI at T2–4 (P < 0.05). CRP and CAR levels rose less in group H on the first day and 1 week later (P < 0.05). Conclusions: Maintaining PaCO2 at 46–55 mm Hg reduces POD incidence, possibly by enhancing rSO2 levels and stabilizing intraoperative respiration/circulation.
Research progress in natural N-glycosides and synthetic methodologies for the formation of N-glycosidic bonds
Authors: Xia Yingting , Xu Qingxia , Herron Alastair N. , Wang Wenjun , Shao Lidong , Li Guodong , Liu An , Cheng Jintang
Published: June 2024

N-glycosides comprise a broad range of compounds, some of which have demonstrated a variety of bioactivities, such as antiviral, antitumor, and antibacterial activities. Serving as essential building blocks for DNA and RNA, nucleosides are a particularly important subclass of N-glycosides. Accordingly, natural N-glycosides and their analogs have garnered great interests of both organic and pharmaceutical chemists, who have developed numerous synthetic methods for the preparation of N-glycosides. By reviewing the natural N-glycosides published between 1980 and 2023, this article summarizes current strategies for synthesizing N-glycosides, aiming to provide support for the development and research of N-glycosides.
Altered socio-affective communication and amygdala development in mice with protocadherin10-deficient interneurons
Authors: Aerts Tania , Boonen Anneleen , Geenen Lieve , Stulens Anne , Masin Luca , Pancho Anna , Francis Annick , Pepermans Elise , Baggerman Geert , Van Roy Frans , Wöhr Markus , Seuntjens Eve
Published: June 2024

Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with deficits in social interaction and communication, together with repetitive behaviours. The cell adhesion molecule protocadherin10 (
PCDH10
) is linked to ASD in humans.
Pcdh10
is expressed in the nervous system during embryonic and early postnatal development and is important for neural circuit formation. In mice, strong expression of
Pcdh10
in the ganglionic eminences and in the basolateral complex (BLC) of the amygdala was observed at mid and late embryonic stages, respectively. Both inhibitory and excitatory neurons expressed
Pcdh10
in the BLC at perinatal stages and vocalization-related genes were enriched in
Pcdh10
-expressing neurons in adult mice. An epitope-tagged
Pcdh10
-HAV5 mouse line revealed endogenous interactions of PCDH10 with synaptic proteins in the young postnatal telencephalon. Nuanced socio-affective communication changes in call emission rates, acoustic features and call subtype clustering were primarily observed in heterozygous pups of a conditional knockout (cKO) with selective deletion of
Pcdh10
in
Gsh2
-lineage interneurons. These changes were less prominent in heterozygous ubiquitous
Pcdh10
KO pups, suggesting that altered anxiety levels associated with
Gsh2
-lineage interneuron functioning might drive the behavioural effects. Together, loss of
Pcdh10
specifically in interneurons contributes to behavioural alterations in socio-affective communication with relevance to ASD.
The three YTHDF paralogs and VIRMA are the major tumor drivers among the m6A core genes in a pan-cancer analysis
Authors: Destefanis Eliana , Sighel Denise , Dalfovo Davide , Gilmozzi Riccardo , Broso Francesca , Cappannini Andrea , Bujnicki Janusz M. , Romanel Alessandro , Dassi Erik , Quattrone Alessandro
Published: June 2024

N6-methyladenosine (m6A) is the most abundant internal modification in mRNAs. Despite accumulating evidence for the profound impact of m6A on cancer biology, there are conflicting reports that alterations in genes encoding the m6A machinery proteins can either promote or suppress cancer, even in the same tumor type. Using data from The Cancer Genome Atlas, we performed a pan-cancer investigation of 15 m6A core factors in nearly 10,000 samples from 31 tumor types to reveal underlying cross-tumor patterns. Altered expression, largely driven by copy number variations at the chromosome arm level, results in the most common mode of dysregulation of these factors. YTHDF1, YTHDF2, YTHDF3, and VIRMA are the most frequently altered factors and the only ones to be uniquely altered when tumors are grouped according to the expression pattern of the m6A factors. These genes are also the only ones with coherent, pan-cancer predictive power for progression-free survival. On the contrary, METTL3, the most intensively studied m6A factor as a cancer target, shows much lower levels of alteration and no predictive power for patient survival. Therefore, we propose the non-enzymatic YTHDF and VIRMA genes as preferred subjects to dissect the role of m6A in cancer and as priority cancer targets.

Graphical abstract
Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections
Authors: Nooruzzaman Mohammed , Johnson Katherine E.E. , Rani Ruchi , Finkelsztein Eli J. , Caserta Leonardo C. , Kodiyanplakkal Rosy P. , Wang Wei , Hsu Jingmei , Salpietro Maria T. , Banakis Stephanie , Albert Joshua , Westblade Lars , Zanettini Claudio , Marchionni Luigi , Soave Rosemary , Ghedin Elodie , Diel Diego G. , Salvatore Mirella
Published: June 2024

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n=15). All patients received remdesivir and some also received nirmatrelvir-ritonavir or monoclonal antibodies. Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient treated with remdesivir and nirmatrelvir-ritonavir.In vitrocharacterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibilityin vivo.
Differences in early life cognitive function explain the association between low education and early dementia risk
Authors: Bratsberg Bernt , Fjell Anders Martin Martin , Rogeberg Ole J , Skirbekk Vegard Fykse , WALHOVD KRISTINE B
Published: June 2024

Major initiatives are currently attempting to prevent dementia by targeting modifiable risk factors. Low education is frequently pointed to as a potential key factor, due to its robust relationship with dementia risk. Impact of education is notoriously difficult to assess, however, because of associations with multiple other risk and protective factors, and large population-representative samples are required to tease the relationships apart. Here, we studied 207,814 Norwegian men born between 1950 and 1959 who underwent compulsory cognitive testing during military conscription as young adults, to systematically test associations of education, cognition, and other potentially important factors. While low education was associated with increased risk for dementia diagnosis (Hazard ratio [HR] = 1.37, CI: 1.17-1.60), this association was fully explained by earlier cognitive test scores (HR = 1.08, CI: .91-1.28). In contrast, low cognitive score was associated with double risk of later dementia diagnosis, even when taking education into account (HR = 2.00, CI: 1.65-2.42). This relationship survived controlling for early-life socioeconomic status and was replicated within pairs of brothers. The latter finding suggests that genetic and environmental factors shared within families, such as common genetics, parental education, childhood socioeconomic status, or other shared experiences, cannot account for the association. Rather, independent, non-familial factors are more important. In contrast, within-family factors accounted for the relationship between low education and diagnosis risk. In conclusion, implementing measures to increase cognitive function in childhood and adolescence appears to be a more promising strategy for reducing dementia burden.