bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between Diverticular Rebleeding and Early-Morning Blood Pressure and Surge: A Prospective Observational Trial
Authors: Arai Junya , Niikura Ryota , Yamada Atsuo , Aoki Tomonori , Suzuki Nobumi , Tsuji Yosuke , Hayakawa Yoku , Kawai Takashi , Fujishiro Mitsuhiro
Published: July 2023

Introduction: Colonic diverticular bleeding is the major cause of lower gastrointestinal bleeding. Hypertension is a major risk factor for diverticular rebleeding. Direct evidence of an association between actual 24-h blood pressure (BP) and rebleeding is lacking. Therefore, we analyzed the association between 24-h BP and diverticular rebleeding. Methods: We performed a prospective observational cohort trial involving hospitalized patients with colonic diverticular bleeding. We performed 24-h BP measurements (ambulatory BP monitoring [ABPM]) in the patients. The primary outcome was diverticular rebleeding. We evaluated the 24-h BP difference and the morning and pre-awaking BP surge between rebleeding and non-rebleeding patients. Morning BP surge was defined as early-morning systolic BP minus the lowest night systolic BP >45 mm Hg (highest quartile of morning BP surge). The pre-awaking BP surge was defined as the difference between morning BP and pre-awaking BP. Results: Of 47 patients, 17 were excluded, leaving 30 who underwent ABPM. Of the 30 patients, 4 (13.33%) had rebleeding. The mean 24-h systolic and diastolic BP were 125.05 and 76.19 mm Hg in rebleeding patients and 129.98 and 81.77 mm Hg in non-rebleeding patients, respectively. Systolic BP at 5:00 (difference −23.53 mm Hg, p = 0.031) and 11:30 (difference −31.48 mm Hg, p = 0.006) was significantly lower in rebleeding patients than in non-rebleeding patients. Diastolic BP at 2:30 (difference −17.75 mm Hg, p = 0.023) and 5:00 (difference −16.12 mm Hg, p = 0.043) was significantly lower in rebleeding patients than in non-rebleeding patients. A morning surge was observed in one rebleeding patient and no non-rebleeding patients. The pre-awaking surge was significantly higher in rebleeding patients (28.44 mm Hg) than in non-rebleeding patients (9.30 mm Hg) (p = 0.015). Conclusion: Lower BP in the early-morning and a higher pre-awaking surge were risk factors for diverticular rebleeding. A 24-h ABPM can identify these BP findings and reduce the risk of rebleeding by enabling interventions in patients with diverticular bleeding.
Attitudes of Teachers toward Multilingualism, Heritage Language Maintenance, and Second Language Learning at School
Authors: Daelman Julie , Van Lierde Kristiane , Bettens Kim , Nys Jana , D’haeseleer Evelien
Published: July 2023

Introduction: Providing an adapted language input in a multicultural classroom is often challenging to educators. Teachers are frequently the parents’ first contacts for language counseling and educational support, and therefore, they may influence the language exposure not only in the classroom but at home as well. This study aimed to investigate the cognitive, emotional, and behavioral attitudes of teachers toward multilingualism in Flanders. The effects of contextual teacher- and school-related properties on the attitudes of teachers were also considered. Methods: An online survey questioning the cognitive, emotional, and behavioral attitudes of teachers was developed and distributed to all schools in Flanders. 710 preschool, primary, and secondary teachers completed the questionnaire. Results: The results showed rather positive attitudes toward heritage language maintenance and multilingualism. However, there are still some misconceptions about multilingual language learning strategies. Teachers are interested in extra training, as they find it hard to use the languages of their pupils as a resource in their teaching practice. Discussion: Teachers mostly consider multilingualism an added value. Supplementary training and extra advice given by speech-language therapists could be helpful to inform teachers about the importance of their students’ proficiency in the heritage language and could give teachers insight into the principles of second language acquisition.
A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin
Authors: Vize Colin J. , Kim Stella K. , Matthews Tim , Macsai Marian , Merrell Ryan , Hsu Sigmund , Kundu Madan Gopal , Yoon Jennifer , Kennedy Emma , Pai Madhavi , Bain Earle , Lassman Andrew B. , Moazami Golnaz
Published: July 2023

Introduction: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries. Methods: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0–5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade ≥3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases. Results: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing ≥+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade ≥3 CEAE. There were no definitive differences among prophylactic treatments. Conclusions: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs.
Novel Phenylethanoid Glycosides Improve Hippocampal Synaptic Plasticity via the Cyclic Adenosine Monophosphate-CREB-Brain-Derived Neurotrophic Growth Factor Pathway in APP/PS1 Transgenic Mice
Authors: Ji Shiliang , Wu Yijie , Zhu Ruifang , Guo Dongkai , Jiang Yiguo , Huang Lifeng , Ma Xinwei , Yu Liqiang
Published: July 2023

Introduction: Alzheimer’s disease (AD) is a major public health concern worldwide, but there are still no drugs available that treat it effectively. Previous studies have shown that phenylethanoid glycosides have pharmacological effects, which include anti-AD properties, but the underlying mechanisms by which they ameliorate AD symptoms remain unknown. Methods: In this study, we used an APP/PS1 AD mouse model to explore the function and mechanisms underlying savatiside A (SA) and torenoside B (TB) in the treatment of AD. SA or TB (100 mg·kg-1·d-1) was orally administered to 7-month-old APP/PS1 mice for 4 weeks. Cognitive and memory functions were measured using behavioral experiments (including the Morris water maze test and the Y-maze spontaneous alternation test). Molecular biology experiments (including Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays) were used to detect any corresponding changes in signaling pathways. Results: The results showed that SA or TB treatment could significantly reduce cognitive impairment in APP/PS1 mice. We also showed that chronic treatment with SA/TB could prevent spine loss, synaptophysin immunoreactivity, and neuronal loss in mice, thereby improving synaptic plasticity and moderating learning and memory deficits. SA/TB administration also promoted the expression of synaptic proteins in APP/PS1 mouse brains and upregulated phosphorylation of proteins in the cyclic adenosine monophosphate (cAMP)/CREB/brain-derived neurotrophic growth factor (BDNF) pathway that are responsible for synaptic plasticity. Additionally, chronic SA/TB treatment increased the levels of BDNF and nerve growth factor (NGF) in the brains of APP/PS1 mice. Both astrocyte and microglia volumes, as well as the generation of amyloid β, were also decreased in SA/TB-treated APP/PS1 mice compared to control APP/PS1 mice. Conclusion: In summary, SA/TB treatment was associated with activation of the cAMP/CREB/BDNF pathway and increased BDNF and NGF expression, indicating that SA/TB improves cognitive functioning via nerve regeneration. SA/TB is a promising candidate drug for the treatment of AD.
Predicting Successful Hematopoietic Stem Cell Collection in Healthy Allogeneic Donors
Authors: Kayser Sabine , Schlenk Richard F. , Steiner Marcus , Klüter Harald , Wuchter Patrick
Published: July 2023

Introduction: Collection of peripheral blood stem cells (PBSCs) from healthy donors is a well-established process. We aimed to identify factors predictive of successful CD34+ PBSC collection and established a formula capable of predicting CD34+ cell yield. Methods: We retrospectively evaluated 588 healthy adult donors (median age 29 years, range 18–69 years) at our institution from 2017 to 2022. The predicted minimal number of CD34+ cells was calculated as follows: (peripheral CD34+ cells/µL × adjusted collection efficiency of 30%) × total liters processed. This formula was further modified according to donor and recipient body weight (BW). Results: Median total collection was 8.0 × 106 CD34+ cells/kg BW (range 1.0–47.1 × 106 cells/kg BW) with 522 donors (89%) collecting ≥5.0 × 106 cells/kg of recipient BW. A second leukapheresis (LP) was performed in 49 donors. Need for two LPs was more common in female donors (OR 6.68, 95% CI, 2.62–17.05; p < 0.001), donors with higher age (OR for 10 years difference 1.53, 95% CI, 1.15–2.03, p = 0.003), donors with WBC count <30 × 109/L after 5 days of granulocyte-colony stimulating factor (G-CSF) stimulation (OR, 4.33; 95% CI, 1.59–11.83; p = 0.004), and a donor/recipient weight ratio <1 (OR 6.21, 95% CI, 2.69–14.34; p < 0.001). Predictive factors for optimal LP (i.e., ≥5.0 × 106 CD34+ cells/kg of recipient BW) were peripheral blood (PB) CD34+ cell count >50/µL (OR 12.82, range 6.34–25.92, p < 0.001), male donor (OR 2.77, range 1.06–7.23, p = 0.04), and a donor/recipient weight ratio >1 (OR 3.12, range 1.57–6.24, p = 0.001). WBC, platelets, hemoglobin, and age had no significant predictive value. Predicted versus observed number of CD34+ cells/kg BW collected demonstrated a very strong linear correlation (r = 0.925, 95% CI, 0.912–0.936, p < 0.0001). Conclusions: Of the routinely monitored indicators in PBSC donors, CD34+ cell count in PB is the most important factor in predicting G-CSF-induced PBSC yields. Higher age, female sex, WBC <30 × 109/L, and a donor/recipient weight ratio <1 are useful indicators for identifying suboptimal mobilizers. The modified formula has shown successful and consistent performance in the prediction of key outcome measures including the minimum CD34+ cell collection, determination of the required length of apheresis, and whether a second day of PBSC collection was necessary to achieve the respective collection goal.
Cerebellar Abscess Induced by Cochlear Fistula due to Chronic Suppurative Otitis Media
Authors: Shibamiya Natsuko , Yamauchi Moriyasu , Kuratomi Yuichiro , Komune Shizuo
Published: July 2023

Cochlear fistulas with cholesteatoma as the primary disease have been reported frequently in the relevant literature. However, there are no reports of cochlear fistula without cholesteatoma due to chronic suppurative otitis media with intracranial complications. We report a case of cochlear fistula due to chronic otitis media that was diagnosed after the onset of a cerebellar abscess. The patient was a 25-year-old man with severe autism. He was admitted to our hospital with otorrhea from his left ear, emesis, and impaired consciousness. Computed tomography (CT) of the head showed left suppurative otitis media, left cerebellar abscess, and brainstem compression due to hydrocephalus. Right extra-ventricular drainage and brain abscess drainage were urgently performed. The next day, foramen magnum decompression and abscess drainage with partial resection of the swollen cerebellum were performed for decompression purposes. He was subsequently treated with antimicrobial therapy, but magnetic resonance imaging of the head showed an increase in the size of the cerebellar abscess. Re-examination of the temporal bone CT scans revealed a bony defect in the left cochlear promontory angle. We assumed that the cochlear fistula was responsible for the otogenic brain abscess. Thus, the patient underwent surgical closure of the cochlear fistula. After the operation, the cerebellar abscess lesion gradually shrank, and his general condition stabilized. Cochlear fistula should be considered in the management of patients with inflammatory middle ear disease associated with otogenic intracranial complications in the middle ear.
Current Open Trials and Molecular Update for Pediatric Embryonal Tumors
Authors: Rosenberg Tom , Cooney Tabitha
Published: July 2023

Background: Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive multimodal treatment, the prognosis of many types is guarded, and treatment-related toxicity is significant. Recent advances in molecular diagnostics allowed the discovery of novel entities and inter-tumor subgroups, with opportunities for improved risk-stratification and treatment approaches. Summary: Medulloblastomas separate into four distinct subgroups with distinct clinicopathologic characteristics, and data from recent clinical trials for newly diagnosed medulloblastoma support subgroup-specific treatment approaches. Atypical teratoid rhabdoid tumor (ATRT), embryonal tumor with multilayered rosettes (ETMR), and pineoblastoma, as well as other rare embryonal tumors, can be distinguished from histologically similar tumors by virtue of characteristic molecular findings, with DNA methylation analysis providing a strong adjunct in indeterminate cases. Methylation analysis can also allow further subgrouping of ATRT and pineoblastoma. Despite the dire need to improve outcomes for patients with these tumors, their rarity and lack of actionable targets lead to a paucity of clinical trials and novel therapeutics. Key Messages: (1) Embryonal tumors can be accurately diagnosed with pediatric-specific sequencing techniques. (2) Medulloblastoma risk stratification and treatment decisions should take into account molecular subgroups. (3) There is a dire need for a novel collaborative clinical trial design to improve outcomes is rare pediatric embryonal tumors.
Low-Level Germline 48,XYY,+21 Mosaicism Associated with Transient Abnormal Myelopoiesis in a Phenotypically Normal Neonate
Authors: Kobayashi Kenichiro , Iwai Atsushi , Tanaka Kuniaki , Mizuta Shumpei , Yoshida Saya , Maihara Toshiro , Nishida Yoshinobu , Wada Takahito , Usami Ikuya , Heike Toshio
Published: July 2023

Transient abnormal myelopoiesis (TAM) is a unique neonatal leukemoid reaction caused by a pathognomonic GATA1 mutation in conjunction with the gene dosage effect of trisomy 21, which is either of germline or somatic origin. We encountered a 48,XYY,+21 phenotypically normal neonate with Down syndrome who developed TAM due to cryptic germline mosaicism. Quantification of the mosaic ratio was complicated by an overestimation bias of hyperproliferating TAM within the germline component. To establish a workflow for such a clinical scenario, we analyzed the cytogenetic findings of neonates with TAM associated with somatic or low-level germline mosaicism. We showed that multistep diagnostic procedures (i.e., paired cytogenetic analyses of peripheral blood specimens in culture with or without phytohemagglutinin; serial cytogenetic studies of more than one tissue, such as the buccal membrane; and complementary DNA-based GATA1 mutation screening) can verify the specificity of cytogenetic testing for phenotypically normal neonates with TAM suspected of mosaicism.
Warfarin-Associated Fetal Subdural Hematoma Causing Severe Neurodevelopmental Delay: A Case Report
Authors: Safra Ibrahim , Gad Ashraf , Alnaimi Shaikha Jabor
Published: July 2023

Fetal subdural hematoma is an antenatal finding associated with significant morbidity and mortality. It can occur due to maternal or fetal risk factors, and its management varies based on the underlying cause and the anticipated long-term outcomes. We present a case of warfarin-associated fetal subdural hematoma resulting in a live birth and severe neurodevelopmental delay by 10 years of age. In conclusion, counseling regarding the risk of fetal intracranial hemorrhage and the potential neurodevelopmental delay is essential in women who require anticoagulation with warfarin. In addition, close antenatal follow-up with fetal sonography and strict INR monitoring are essential preventative measures.
Neonatal Participation in Neonatal Imitation: Narrative in Newborn Dialogues
Authors: McGowan Timothy , Delafield-Butt Jonathan
Published: July 2023

Since the publication of Meltzoff and Moore’s seminal paper, neonatal imitation has been discussed, debated, and scrutinised at considerable length. Despite this, the temporal structure within which the interaction sits, has received limited attention. We hypothesise that underlying successful examples of neonatal imitation exists a narrative temporal structure, expressed and perceived not only through vocalisations but also (if not primarily) through movement. We contextualise neonatal imitation through a communicative lens, viewing the phenomenon as an early dialogue between adult and infant, underpinned by the same narrative structure as other “proto-conversations” in infancy. From this perspective, several of the leading and traditional theories that have been proposed to explain neonatal imitation are considered. Ultimately, we argue neonatal imitation is an innately dialogical phenomenon that forms one of the first examples of primary intersubjectivity, exemplifying the importance of the neonatal period in human psychological and social development. On this basis we propose further study is required into the temporal structure underlying neonatal imitation.
Glioblastoma Multiforme: The Latest Diagnostics and Treatment Techniques
Authors: Czarnywojtek Agata , Borowska Magdalena , Dyrka Kamil , Van Gool Stefaan , Sawicka-Gutaj Nadia , Moskal Jakub , Kościński Jeremi , Graczyk Patryk , Hałas Tomasz , Lewandowska Agnieszka Marta , Czepczyński Rafał , Ruchała Marek
Published: July 2023

Background: Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy. An unusual and modern treatment has been created, especially for stage 4 GBM, using the latest therapeutic techniques, including immunotherapy and virotherapy. Modern oncological medicine is producing extraordinary and progressive therapeutic methods. Oncological therapy includes individual analysis of the properties of a tumour and targeted therapy using small-molecule inhibitors. Individualised medicine covers the entire patient (tumour and host) in the context of immunotherapy. An example is individualised multimodal immunotherapy (IMI), which relies on individual immunological tumour-host interactions. In addition, IMI is based on the concept of oncolytic virus-induced immunogenic tumour cell death. Summary: In this review, we outline current knowledge of the various available treatment options used in the therapy of GBM including both traditional therapeutic strategy and modern therapies, such as tomotherapy, electro-hyperthermia, and oncolytic virotherapy, which are promising treatment strategies with the potential to improve prognosis in patients with GBM. Key Messages: This newest therapy, immunotherapy combined with virotherapy (oncolytic viruses and cancer vaccines), is displaying encouraging signs for combating GBM. Additionally, the latest 3D imaging is compared to conventional two-dimensional imaging.
Roles of Krüppel-Like Transcription Factors KLF6 and KLF15 in Proximal Tubular Metabolism
Authors: Piret Sian E.
Published: July 2023

Members of the Krüppel-like family of transcription factors are widely expressed, including in the kidney. Expression of some KLFs changes in acute kidney injury, and this may be adaptive or maladaptive, and result in effects on various cellular pathways. This mini-review will highlight the roles of KLF6 and KLF15 in control of proximal tubular cell metabolism.
A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma: TACTICS-L Trial
Authors: Kudo Masatoshi , Ueshima Kazuomi , Saeki Issei , Ishikawa Toru , Inaba Yoshitaka , Morimoto Naoki , Aikata Hiroshi , Tanabe Nobukazu , Wada Yoshiyuki , Kondo Yasuteru , Tsuda Masahiro , Nakao Kazuhiko , Ito Takanori , Hosaka Tetsuya , Kawamura Yusuke , Kuzuya Teiji , Nojiri Shunsuke , Ogawa Chikara , Koga Hironori , Hino Keisuke , Ikeda Masafumi , Moriguchi Michihisa , Hisai Takashi , Yoshimura Kenichi , Furuse Junji , Arai Yasuaki
Published: July 2023

Introduction: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14–21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0–2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0–1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1–31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months–NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.
Impact of Pulmonary Hypertension Hemodynamic Phenotype on Incident Atrial Fibrillation
Authors: Morales-Lara Andrea Carolina , Elkhatib Wiaam , Oluleye Oludamilola , Alhusain Rashid , Saad Amjad , Salwa Najiyah , Siddiqui Habeeba , Wieczorek Mikolaj A. , Ray Jordan , Parikh Pragnesh , Burger Charles , Shapiro Brian , Kusumoto Fred , Pillai Dilip , Adedinsewo Demilade
Published: July 2023

Introduction: Atrial fibrillation/flutter (AF) is common among patients with pulmonary hypertension (PH) and is associated with poor clinical outcomes. AF has been shown to occur more commonly among patients with postcapillary PH, although AF also occurs among patients with precapillary PH. The goal of this study was to evaluate the independent impact of PH hemodynamic phenotype on incident AF among patients with PH. Methods: We retrospectively identified 262 consecutive patients, without a prior diagnosis of atrial arrhythmias, seen at the PH clinic at Mayo Clinic, Florida, between 1997 and 2017, who had right heart catheterization and echocardiography performed, with follow-up for outcomes through 2021. Kaplan-Meier analysis and Cox-proportional hazards regression modeling were used to evaluate the independent effect of PH hemodynamic phenotype on incident AF. Results: Our study population was classified into two broad PH hemodynamic groups: precapillary (64.9%) and postcapillary (35.1%). The median age was 59.5 years (Q1: 48.4, Q3: 68.4), and 72% were female. In crude models, postcapillary PH was significantly associated with incident AF (HR 2.17, 95% CI: 1.26–3.74, p = 0.005). This association was lost following multivariable adjustment, whereas left atrial volume index remained independently associated with incident AF (aHR 1.30, 95% CI: 1.09–1.54, p = 0.003). Conclusion: We found PH hemodynamic phenotype was not significantly associated with incident AF in our patient sample; however, echocardiographic evidence of left atrial remodeling appeared to have a greater impact on AF development. Larger studies are needed to validate these findings and identify potential modifiable risk factors for AF in this population.
Early Gray Matter Structural Covariance Predicts Longitudinal Gain in Arithmetic Ability in Children
Authors: Ren Tian , Li Zheng , Wang Chunjie , Li Bao-ming
Published: July 2023

Previous neuroimaging studies on arithmetic development have mainly focused on functional activation or functional connectivity between brain regions. It remains largely unknown how brain structures support arithmetic development. The present study investigated whether early gray matter structural covariance contributes to later gain in arithmetic ability in children. We used a public longitudinal sample comprising 63 typically developing children. The participants received structural magnetic resonance imaging scanning when they were 11 years old and were tested with a multiplication task at 11 years old (time 1) and 13 years old (time 2), respectively. Mean gray matter volumes were extracted from eight brain regions of interest to anchor salience network (SN), frontal-parietal network (FPN), motor network (MN), and default mode network (DMN) at time 1. We found that longitudinal gain in arithmetic ability was associated with stronger structural covariance of the SN seed with frontal and parietal regions and stronger structural covariance of the FPN seed with insula, but weaker structural covariance of the FPN seed with motor and temporal regions, weaker structural covariance of the MN seed with frontal and motor regions, and weaker structural covariance of the DMN seed with temporal region. However, we did not detect correlation between longitudinal gain in arithmetic ability and behavioral measure or regional gray matter volume at time 1. Our study provides novel evidence for a specific contribution of gray matter structural covariance to longitudinal gain in arithmetic ability in childhood.
Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial
Authors: Ding Yuqin , Mo Wenju , Xie Xiaohong , Wang Ouchen , He Xiangming , Zhao Shuai , Gu Xidong , Liang Chenlu , Qin Chengdong , Ding Kaijing , Yang Hongjian , Ding Xiaowen
Published: July 2023

Introduction: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). Methods: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL·min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. Results: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31–69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. Conclusion: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups.
COPD: Konsequente Schulung älterer Patienten im Umgang mit ihrem Applikator etablieren
Authors: Frohnhofen Helmut
Published: July 2023

Background: Maintaining correct inhaler technique is crucial in the management of chronic obstructive pulmonary disease (COPD). We aimed to investigate the inhaler technique in patients with COPD, to compare it immediately after and at 1 month after training, and to identify the predictors of incorrect inhaler use at 1 month after training. Methods: This prospective study was conducted at the COPD clinic of Siriraj Hospital (Bangkok, Thailand). Patients demonstrating improper inhaler use were trained face-to-face by pharmacists. Inhaler technique was re-assessed immediately after and at 1 month after training. The Montreal Cognitive Assessment (MoCA) score, pulmonary function tests, 6-min walk distance (6 MWD), modified Medical Research Council scale score, and COPD Assessment Test (CAT) score were evaluated. Results: Sixty-six patients with COPD who demonstrated at least one critical error during the use of any controller inhaler were enrolled. The mean age was 73.0 ± 9.0 years, and 75.8% patients had moderate/severe COPD. Immediately after training, all patients used dry powder inhalers correctly and 88.1% used pressurized metered-dose inhalers correctly. At 1 month, the number of patients demonstrating the correct technique decreased across all devices. Multivariable analysis revealed that MoCA score ≤ 16 was independently associated with a critical error at 1 month after training (adjusted odds ratio: 12.7, 95% confidence interval: 1.8-88.2, p = 0.010). At 1 month, CAT score (11.4 ± 8.9 vs. 8.4 ± 5.5, p = 0.018) and 6 MWD (351 ± 93 m vs. 372 ± 92 m, p = 0.009) had significantly improved in patients demonstrating the correct technique, and CAT score met the minimal clinically important difference.
Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression
Authors: Souza da Silva Ricella , Queiroga Eduardo M. , de Toledo Osório Cynthia , Cunha Karin S. , Neves Fabiana P. , Andrade Julieth P. , Dias Eliane P.
Published: July 2023

Introduction: The characterization of tumor microenvironment (TME) related factors and their impact on tumor progression have attracted much interest. We investigated cancer cells and cancer-associated fibroblasts (CAFs) to evaluate biomarkers that are associated with neoplastic progression, observing them in different interface zones of colorectal cancer. Methods: On 357 CRC tissue microarrays, using immunohistochemistry, we examined the associations of podoplanin and α-SMA expressed in cancer cells and CAFs and evaluated them in different areas: tumor core, invasive front, tumor budding, tumor-stroma ratio (TSR) scoring, and desmoplastic stroma. Results: CAFs expressing α-SMA were found in more than 90% of the cases. Podoplanin+ was detected in cancer cells and CAFs, with positivities of 38.6% and 70%, respectively. Higher α-SMA+ CAFs and podoplanin+ cancer cells were observed predominantly at the TSR score area: 94.3% and 64.3% of cases, respectively. The status of podoplanin in CAFs+ was higher in the desmoplastic area (71.6%). Stroma-high tumors showed increased expression of α-SMA and podoplanin in comparison with stroma-low tumors. The status of podoplanin in cancer cells was observed in association with lymphatic invasion and distant metastasis. Conclusion: The substance of the CRC was composed predominantly of the surrounding stroma-α-SMA+ CAFs. Podoplanin expressed in the prognosticator zones was associated with unfavorable pathological features. The combination of histologic and protein-related biomarkers can result in a tool for the stratification of patients with CRC.
White and Gray Matter Perfusion in Children with Moyamoya Angiopathy after Revascularization Surgery
Authors: Filimonova Elena , Martirosyan Azniv , Ovsiannikov Konstantin , Pashkov Anton , Rzaev Jamil
Published: July 2023

Introduction: Surgical revascularization is very effective in patients with moyamoya angiopathy (MMA) and leads to improvements in cortical perfusion parameters. However, changes in white matter hemodynamics are still underestimated. To date, only a few studies have examined brain perfusion changes within deep white matter after bypass surgery in patients with MMA. Methods: Ten children with MMA were evaluated using the CT perfusion technique before and after revascularization surgery. Brain perfusion parameters within gray and white matter were compared before and after surgery. The correlations between the perfusion parameters before surgery and the Suzuki stage, as well as between the perfusion parameters and the cognitive scores, were also evaluated. Results: Brain perfusion parameters improved significantly in both gray matter (predominantly due to cerebral blood flow within the anterior circulation, p < 0.01) and white matter (predominantly due to cerebral blood volume within the semiovale centrum, p < 0.001). We revealed that the pattern of improvement in perfusion in white matter differed from the pattern of improvement in perfusion in gray matter. Significant correlations were revealed between the Suzuki stage before surgery and the perfusion parameters within the posterior cerebral artery circulation (adjusted p < 0.05). There were also significant correlations between cognitive scores and brain perfusion parameters in gray matter and white matter (adjusted p < 0.05). Conclusions: The perfusion parameters of gray matter and white matter in the brain improve differently after bypass surgery in patients with MMA. Different hemodynamics within these compartments could explain this.
DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA
Authors: Gong Yujiao , Liang Yan , Liu Jie , Wei Jiaxing , Zhang Shushan , Chen Fangbin , Zhang Qianqian , Wang Lijie , Lan Huimin , Wu Lily , Ge Wei , Li Shuai , Wang Li , Shan Hong , He Huanhuan
Published: July 2023

BACKGROUND:

The DEAD-box family is essential for tumorigenesis and embryogenesis. Previously, we linked the malfunction of DDX (DEAD-box RNA helicase)-24 to a special type of vascular malformation. Here, we aim to investigate the function of DDX24 in vascular smooth muscle cells (VSMCs) and embryonic vascular development.

METHODS:

Cardiomyocyte (CMC) and VSMC-specific
Ddx24
knockout mice were generated by crossing
Tagln
-Cre mice with
Ddx24

flox/flox

transgenic mice. The development of blood vessels was explored by stereomicroscope photography and immunofluorescence staining. Flow cytometry and cell proliferation assays were used to verify the regulation of DDX24 on the function of VSMCs. RNA sequencing and RNA immunoprecipitation coupled with quantitative real-time polymerase chain reaction were combined to investigate DDX24 downstream regulatory molecules. RNA pull-down and RNA stability experiments were performed to explore the regulation mechanism of DDX24.

RESULTS:

CMC/VSMC-specific
Ddx24
knockout mice died before embryonic day 13.5 with defects in vessel formation and abnormal vascular remodeling in extraembryonic tissues.
Ddx24
knockdown suppressed VSMC proliferation via cell cycle arrest, likely due to increased DNA damage. DDX24 protein bound to and stabilized the mRNA of
FANCA
(FA complementation group A) that responded to DNA damage. Consistent with the function of DDX24, depletion of FANCA also impacted cell cycle and DNA repair of VSMCs. Overexpression of FANCA was able to rescue the alterations caused by DDX24 deficiency.

CONCLUSIONS:

Our study unveiled a critical role of DDX24 in VSMC-mediated vascular development, highlighting a potential therapeutic target for VSMC-related pathological conditions.
How can we make Shakespeare more accessible in Japan?
Authors: Endo Rena
Published: July 2023

Although there used to be many opportunities to see Shakespeare's plays regularly in Japan, many of the theatre companies that performed Shakespeare have been dissolved in recent years. This article focuses on the Shakespeare for Children Company, a group that was founded in 1995 and is still performing Shakespeare under the company's new name, Yellow Helmets. Their success comes from the fact that they work to make Shakespeare enjoyable, understandable, and accessible. These features are analysed in this article with a close look at their scripts and questionnaire for a production of The Winter's Tale in 2018.
The brightest star: The Meisei Shakespeare Collection
Authors: Nagase Mariko , Jowett John
Published: July 2023

The Kodama Memorial Library at Meisei University contains one of the world's most important Shakespeare collections. This article introduces the Meisei collection to Shakespearians internationally, describing the history and scope of the collection, and the website reproducing copies of some of its Shakespeare and Jonson folios. The article examines examples of Meisei copies of early editions from the perspective of bibliography and book history. These case studies highlight the importance of individual copies in the collection in preserving information about publishing and ownership from the early modern period to our own and the significance of the Meisei collection itself.
Pedagogical strategy for scholarly communication literacy and avoiding deceptive publishing practices
Authors: Buitrago Ciro Jairo , Hernández Pérez Jonathan
Published: July 2023

Informing and supporting researchers’ understanding of the challenges of scholarly communication, particularly how to avoid deceptive publishing practices, remains a challenge for the academic community and its stakeholders. Over the past decade, this community has developed various strategies to assist its members in addressing this issue. However, these measures do not seem to be sufficient, and many researchers, particularly younger and less experienced ones, continue to fall prey to predatory publications. This article presents a series of workshops on scholarly communication literacy as a pedagogical strategy to raise awareness and to prevent novice researchers from falling victim to the challenges of scholarly communication and unethical publishing practices. Most participants perceived these training workshops as an effective educational approach. The results of these educational seminars demonstrate that this type of pedagogical strategy that consists of training, awareness-raising, and prevention approaches is a key factor to informing and warning novice researchers about scholarly communication pitfalls and deceptive publishing practices.
Exhibiting toxicity: sprayed strawberries and geographies of hope
Authors: Sabin Lucy , Komposch Nora , Mestrot Adrien
Published: July 2023

Exposición was a 2022 art exhibition that explored seasonal farm labourers’ exposure to strawberry herbicides in Huelva, Andalusia. Drawing upon a multidisciplinary collaboration of art, social geography and soil science, the following discussion contextualises Exposición and offers reflection on the exhibition as an immersive site for figuratively re-sensing lived experiences of heavily polluted places. The exhibition provided space in which configurations of matter, affect and atmospherics might allow contemplation of environmental toxicity, while also being a means of voicing the care, solidarity and hope enacted by affected communities.
SUDEP: A Local Low Pressure [pO2] System Makes It Hard to Breathe
Authors: Simeone Kristina A.
Published: July 2023

[Box: see text]
Revisiting Anticoagulation in Spine Surgery: Balancing Venous Thromboembolic Events and Epidural Hematoma
Authors: Massaro Allie M. , Frier Sven , Strot Sarah M. , Scherman Ashley , Oskouian Rod J. , Chapman Jens R.
Published: July 2023

Study Design

Retrospective Cohort Study.

Objective

Venous thromboembolic events (VTE) and post-operative epidural hematoma (EDH) are significant complications after spine surgery. Guidelines for chemoprophylaxis are controversial and variability amongst surgeons remains. The objective of this study was to establish the incidence of clinical VTE and EDH at our institution and evaluate the association of chemoprophylaxis with clinical VTE and EDH.

Methods

We conducted a retrospective cohort study of patients undergoing spine surgery at a high-volume tertiary care center in Seattle, WA between January 2016 and December 2019. The Premier Health Care Database and Agency for Healthcare Research and Quality (AHRQ) patient indicators PSI-9 (Perioperative hemorrhage and hematoma) and PSI-12(Perioperative PE or DVT) were used to identify patients experiencing VTE and/or post-operative EDH. The primary outcome was the incidence of clinical VTE and EDH in post-operative spine patients. Secondary outcomes included the association of chemoprophylaxis with clinical VTE and EDH.

Results

From 2016 to 2019, 4587 patients underwent spine surgery, totaling 4764 hospital stays. The incidence of clinical VTE was .21% (10/4764) and the incidence of EDH was .10% (5/4764). Most hemorrhages occurred prior to the initiation of chemoprophylaxis. One patient with EDH received chemoprophylaxis prior to hemorrhage.

Conclusions

The rate of post-operative clinical VTE and EDH in spine surgery is low. Despite early initiation of chemoprophylaxis after major spine surgery we did not appreciate a high rate of EDH. We attribute our low rate of clinical VTE to multimodal prophylaxis with SCDs, early mobilization and chemoprophylaxis on post-operative day 1.
Salvage surgery for advanced non-small cell lung cancer following previous immunotherapy: a retrospective study
Authors: Higuchi Mitsunori , Inomata Sho , Yamaguchi Hikaru , Saito Takuro , Suzuki Hiroyuki
Published: July 2023

Background

The development of systemic chemotherapy including immune checkpoint inhibitors (ICIs) has provided patients with unresectable advanced non-small cell lung cancer (NSCLC) an opportunity to undergo surgical intervention after initial treatment. However, no consensus regarding the indication for salvage surgery in these patients has been reached.

Methods

We conducted a retrospective study of patients who underwent salvage surgery for advanced NSCLC (cStage IIIA–IVB) after treatment with ICIs from January 2018 to December 2022 at Aizu Medical Center and Fukushima Medical University Hospital. We evaluated the patients’ clinical data, calculated disease-free survival (DFS) and overall survival (OS), and assessed the survival benefit using the Kaplan–Meier method.

Results

Thirteen patients underwent salvage surgery after immunotherapy. All patients achieved downstaging after initial chemotherapy. Eleven patients underwent lobectomy, and one patient underwent extirpation of intra-abdominal lymph nodes. The mean surgery time and intraoperative blood loss were 242.2 min and 415.1 g, respectively. The mean drainage period was 4.2 days (range, 2–9 days). Grade ≥ 3 postoperative complications were confirmed in three patients. The 2-year DFS rate was 71.2%, and the 2-year OS rate was 76.2%. A pathological complete response compatible with ypStage 0 was achieved in four (30.8%) patients. Patients with ypStage 0 and I achieved significantly better OS than those with ypStage ≥ II (p = 0.044), and patients without severe complications achieved significantly better DFS and OS than those with severe complications (p = 0.001 and p < 0.001, respectively).

Conclusions

Salvage surgery after chemotherapy including ICIs is a feasible and effective treatment option for patients with advanced NSCLC, especially those who acquire downstaging to pathological stage 0 or I. However, severe perioperative complications might affect patient survival. A prospective study is urgently needed to evaluate the efficacy of salvage surgery.