bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S8 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

UMAP Cluster Analysis for Patients 7 and 8
Supplementary Figure S4 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Subasumstat induces IFN response genes in CIVO micro-injected tumors
Supplementary Figure S2 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Expression of IFNB1 and ISG15 as a function of subasumstat exposure.
Supplementary Figure S15 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Percentage of each of three macrophage populations in individual FOVS from Patient 8
Data from T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
Authors: Kilian Michael , Friedrich Mirco , Sanghvi Khwab , Green Edward , Pusch Stefan , Kawauchi Daisuke , Löwer Martin , Sonner Jana K. , Krämer Christopher , Zaman Julia , Jung Stefanie , Breckwoldt Michael O. , Willimsky Gerald , Eichmüller Stefan B. , von Deimling Andreas , Wick Wolfgang , Sahm Felix , Platten Michael , Bunse Lukas
Published: July 2023

AbstractPurpose:
Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy.
Experimental Design:
Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intraventricular TCR-transgenic T-cell therapy was assessed in a newly developed glioma model in MHC-humanized mice induced by CRISPR-based delivery of tumor suppressor–targeting guide RNAs.
Results:
We identify recurrent capicua transcriptional repressor (CIC) inactivating hotspot mutations at position 215 CICR215W/Q as immunogenic MHC class II (MHCII)-restricted neoepitopes. Vaccination of MHC-humanized mice resulted in the generation of robust MHCII-restricted mutation-specific T-cell responses against CICR215W/Q. Adoptive intraventricular transfer of CICR215W-specific TCR-transgenic T cells exert antitumor responses against CICR215W-expressing syngeneic gliomas.
Conclusions:
The integration of immunocompetent MHC-humanized orthotopic glioma models in the discovery of shared immunogenic glioma neoepitopes facilitates the identification and preclinical testing of human leukocyte antigen (HLA)-restricted neoepitope-specific TCRs for locoregional TCR-transgenic T-cell adoptive therapy.
Data from HLA-I Evolutionary Divergence Confers Response to PD-1 Blockade plus Chemotherapy in Untreated Advanced Non–Small Cell Lung Cancer
Authors: Jiang Tao , Jin Qiqi , Wang Jiahao , Wu Fengying , Chen Jian , Chen Gongyan , Huang Yunchao , Chen Jianhua , Cheng Ying , Wang QiMing , Pan Yueyin , Zhou Jianying , Shi Jianhua , Xu Xingxiang , Lin LiZhu , Zhang Wei , Zhang Yiping , Liu Yunpeng , Fang Yong , Feng Jifeng , Wang Zhehai , Hu Sheng , Fang Jian , Shu Yongqian , Cui Jiuwei , Hu Yi , Yao Wenxiu , Li Xingya , Lin Xiaoyan , Wang Rui , Wang Yongsheng , Shi Wei , Feng Gaohua , Ni Jun , Mao Beibei , Ren Dandan , Sun Huaibo , Zhang Henghui , Chen Luonan , Zhou Caicun , Ren Shengxiang
Published: July 2023

AbstractPurpose:
PD-1 blockade plus chemotherapy has become the new standard of care in patients with untreated advanced non–small cell lung cancer (NSCLC), whereas predictive biomarkers remain undetermined.
Patients and Methods:
We integrated clinical, genomic, and survival data of 427 NSCLC patients treated with first-line PD-1 blockade plus chemotherapy or chemotherapy from two phase III trials (CameL and CameL-sq) and investigated the predictive and prognostic value of HLA class I evolutionary divergence (HED).
Results:
High HED could predict significantly improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in those who received PD-1 blockade plus chemotherapy [in the CameL trial, ORR: 81.8% vs. 53.2%; P = 0.032; PFS: hazard ratio (HR), 0.47; P = 0.012; OS: HR, 0.40; P = 0.014; in the CameL-sq trial, ORR: 89.2% vs. 62.3%; P = 0.007; PFS: HR, 0.49; P = 0.005; OS: HR, 0.38; P = 0.002], but not chemotherapy. In multivariate analysis adjusted for PD-L1 expression and tumor mutation burden, high HED was independently associated with markedly better ORR, PFS, and OS in both trials. Moreover, the joint utility of HED and PD-L1 expression showed better performance than either alone in predicting treatment benefit from PD-1 blockade plus chemotherapy. Single-cell RNA sequencing of 58,977 cells collected from 11 patients revealed that tumors with high HED had improved antigen presentation and T cell–mediated antitumor immunity, indicating an inflamed tumor microenvironment phenotype.
Conclusions:
These findings suggest that high HED could portend survival benefit in advanced NSCLC treated with first-line PD-1 blockade plus chemotherapy.
A Pilot Study Omitting Radiation in the Treatment of Children with Newly Diagnosed Wnt-Activated Medulloblastoma
Authors: Cohen Kenneth J. , Munjapara Vasu , Aguilera Dolly , Castellino Robert C. , Stapleton Stacie L. , Landi Daniel , Ashley David M. , Rodriguez Fausto J. , Hawkins Cynthia , Yang Edward , London Wendy , Chi Susan , Bandopadhayay Pratiti
Published: July 2023

Purpose:

Treatment of wingless (WNT)-activated medulloblastoma (WNT+MB) with surgery, irradiation (XRT), and chemotherapy results in excellent outcomes. We studied the efficacy of therapy de-intensification by omitting XRT entirely in children with WNT+MB.

Patients and Methods:

Tumors were molecularly screened to confirm the diagnosis of WNT+MB. Eligible children were treated within 31 days following surgery with nine cycles of adjuvant chemotherapy per ACNS0331. No XRT was planned. The primary endpoint was the occurrence of relapse, progression, or death in the absence of XRT within the first two years after study enrollment. Four events in the first 10 evaluable patients would result in early study closure.

Results:

Fourteen children were prescreened, and nine met the protocol definition of WNT+MB. Six of the nine eligible patients consented to protocol therapy, and five completed planned protocol therapy. The first two children enrolled relapsed shortly after therapy completion with local and leptomeningeal recurrences. The study was closed early due to safety concerns. Both children are surviving after XRT and additional chemotherapy. A third child relapsed at completion of therapy but died of progressive disease 35 months from diagnosis. Two children finished treatment but immediately received post-treatment XRT to guard against early relapse. The final child's treatment was aborted in favor of a high-dose therapy/stem cell rescue approach. Although OS at 5 years is 83%, no child received only planned protocol therapy, with all receiving eventual XRT and/or alternative therapy.

Conclusions:

Radiotherapy is required to effectively treat children with WNT-altered medulloblastoma.

See related commentary by Gottardo and Gajjar, p. 4996
Supplementary Table 3 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Authors: Yaeger Rona , Mezzadra Riccardo , Sinopoli Jenna , Bian Yu , Marasco Michelangelo , Kaplun Esther , Gao Yijun , Zhao HuiYong , Paula Arnaud Da Cruz , Zhu Yingjie , Perez Almudena Chaves , Chadalavada Kalyani , Tse Edison , Chowdhry Sudhir , Bowker Sydney , Chang Qing , Qeriqi Besnik , Weigelt Britta , Nanjangud Gouri J. , Berger Michael F. , Der-Torossian Hirak , Anderes Kenna , Socci Nicholas D. , Shia Jinru , Riely Gregory J. , Murciano-Goroff Yonina R. , Li Bob T. , Christensen James G. , Reis-Filho Jorge S. , Solit David B. , de Stanchina Elisa , Lowe Scott W. , Rosen Neal , Misale Sandra
Published: July 2023

Patients Longitudinal Cell Free DNA data
Supplementary Methods from Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches
Authors: Nair Pramod C. , Piehler Jacob , Tvorogov Denis , Ross David M. , Lopez Angel F. , Gotlib Jason , Thomas Daniel
Published: July 2023

Supplementary Information: Figure S1 X-ray crystal structure of JNJ-77006621(ball and stick, C-atoms in green) bound to JAK2-PK domain (cartoon, yellow). Key residues are displayed in sticks [C-atoms in green near the optimisation domain (Peuleo et al. 2017, Liosi et al 2020) and C-atoms in yellow at the dimerization domain]. Supplementary Methods.
Table S2 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: July 2023

Mouse cluster 2 genes whose H3K27me3 in TSS’s was decreased.
Table S1 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: July 2023

Human cluster 2 genes whose H3K27me3 in TSS’s was decreased.
Data from Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches
Authors: Nair Pramod C. , Piehler Jacob , Tvorogov Denis , Ross David M. , Lopez Angel F. , Gotlib Jason , Thomas Daniel
Published: July 2023

Abstract
Selective inhibitors of Janus kinase (JAK) 2 have been in demand since the discovery of the JAK2 V617F mutation present in patients with myeloproliferative neoplasms (MPN); however, the structural basis of V617F oncogenicity has only recently been elucidated. New structural studies reveal a role for other JAK2 domains, beyond the kinase domain, that contribute to pathogenic signaling. Here we evaluate the structure-based approaches that led to recently-approved type I JAK2 inhibitors (fedratinib and pacritinib), as well as type II (BBT594 and CHZ868) and pseudokinase inhibitors under development (JNJ7706621). With full-length JAK homodimeric structures now available, superior selective and mutation-specific JAK2 inhibitors are foreseeable.
Significance:
The JAK inhibitors currently used for the treatment of MPNs are effective for symptom management but not for disease eradication, primarily because they are not strongly selective for the mutant clone. The rise of computational and structure-based drug discovery approaches together with the knowledge of full-length JAK dimer complexes provides a unique opportunity to develop better targeted therapies for a range of conditions driven by pathologic JAK2 signaling.
Supplementary Table S3 from A pilot study of neoadjuvant nivolumab, ipilimumab and intralesional oncolytic virotherapy for HER2-negative breast cancer
Authors: Nguyen Vina P , Campbell Katie M. , Nowicki Theodore S , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L , Chang Helena R. , Oseguera Denise K , Ribas Antoni , Glaspy John A.
Published: July 2023

Individual details of baseline patient characteristics
Supplementary Table S2 from A pilot study of neoadjuvant nivolumab, ipilimumab and intralesional oncolytic virotherapy for HER2-negative breast cancer
Authors: Nguyen Vina P , Campbell Katie M. , Nowicki Theodore S , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L , Chang Helena R. , Oseguera Denise K , Ribas Antoni , Glaspy John A.
Published: July 2023

Summary of antibodies, antigen retrieval conditions, incubation conditions, and opal dye labeling for multiplex immunofluorescence experiments
Supplementary Table S1 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

Potency of inhibition of colony formation by different imidazopyridines in breast and prostate cancer cells.
Figure S6 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695 does not induce apoptosis in LNCaP and LAPC-4 cells.
Adaptações de Os Lusíadas: engenho e arte?
Authors: Ramalho Christina , Barreto Marta Ginólia Lima
Published: July 2023

Pretende-se aqui investigar os recursos linguísticos e estéticos de que fizeram uso três adaptações para o público infanto-juvenil de Os Lusíadas ao introduzirem, por meio do trabalho com a proposição épica do poema, o conteúdo da epopeia camoniana, de modo a averiguar, de um lado, a intencionalidade desses recursos e, de outro, a relação entre engenho, arte e fidelidade à obra original e dessacralização da literatura.
A new species of Oxalis sect. Thamnoxys (Oxalidaceae) from the state of Bahia, Brazil
Authors: FIASCHI PEDRO , CABRAL FERNANDO SANTOS , LIMA DUANE FERNANDES
Published: July 2023

Oxalis jacobinensis, a new species of Oxalis sect. Thamnoxys, is described from the State of Bahia, in the northern sector of the Chapada Diamantina mountains. It can be distinguished from other species of the section by the leaves usually grouped at the stem apex, terminal leaflet blades rhombic-ovate to lanceolate, usually appearing grayish when fresh on the abaxial side, pedicels articulated at ca. 1/3 of their length, usually leaving a conspicuous foot, and capsules with two-seeded carpels narrowing distally, and abaxially covered with short stalked glandular hairs. We provide a description, illustrations, a geographic distribution map, a preliminary evaluation of its conservation status, and taxonomic notes.
Columnea karstenianum R.Kr.Singh, a new name of C. picta H.Karst. (Gesneriaceae)
Authors: SINGH RAJEEV KUMAR
Published: July 2023

N/A
Three new species of the subfamily Nossidiinae (Coleoptera: Ptiliidae) from South Korea
Authors: JANG TAEYOUNG , SÖRENSSON MIKAEL , PARK JONG-SEOK
Published: July 2023

The subfamily Nossidiinae was established in 2019 and is comprised of five genera including one fossil genus. Among them, Nossidium Erichson and Sindosium Johnson share many morphological similarities. To this point, two extant Nossidium-species, N. flachi Ganglbauer and N. pilosellum (Marsham) have been recorded in the Palaearctic realm. In this paper, we describe three new species, Nossidium koreanum sp. nov., Sindosium longifilum sp. nov. and S. chungbukicum sp. nov. from South Korea. These are the first Nossidiinae species described from Korea, as well as the first Palaearctic record of the genus Sindosium.
Triple-Dip La Niña Contributes to Pakistan Flooding and Southern China Drought in Summer 2022
Authors: Jeong Hyein , Park Hyo-Seok , Chowdary Jasti S. , Xie Shang-Ping
Published: July 2023

In the summer of 2022, a long-lasting La Niña entered its third year. In Asia, southern China was in the grip of a historic drought while heavy rainfall ravaged Pakistan. Using a climate model forced by observed sea surface temperatures (SST) over the equatorial Pacific, we show that the back-to-back La Niña events from 2020 to 2022 are a key contributor to the global SST pattern in 2022, including the negative-phase Pacific decadal oscillation and exceptionally strong negative Indian Ocean dipole. The model reproduces the observed precipitation pattern over South and East Asia, including enhanced rainfall over Pakistan–northwest India and reduced rainfall over southern China. Additional model simulations indicate that the negative Indian Ocean dipole combined with La Niña reduces southern China rainfall by causing anomalous subsidence and anticyclonic flows. These results highlight the dominant role of long-lasting La Niña in modulating rainfall over heavily populated monsoon Asia.
Estimation of Transmitted Differential Phase on Dual-Polarization Radars
Authors: Zrnić D. S. , Melnikov V. M.
Published: July 2023

A measurement procedure to determine transmitted differential phase between horizontally and vertically polarized radiation of a dual-polarization radar is presented. It is applicable to radars that transmit and receive simultaneously horizontally and vertically (SHV) polarized waves. The method relies solely on weather data with no instrument intrusions whatsoever. It takes data at vertical incidence while the antenna rotates in azimuth. That way, a large number of samples is collected to reduce statistical errors in estimates. The theory indicates that the transmitted differential phase appears prominently in the backscatter signals off the melting layer. That and relations between various elements of the backscattering matrix are used to derive a set of nonlinear equations whereby the differential phase on transmission is one of the unknowns. Steps for solving these equations are presented as well as a demonstration of the results on radar data. A simplified algorithm that bypasses the coupled nonlinear equations is exposed. Conditions under which the simplification can be applied are presented. These restrict the range of the transmitted differential phase for which the simplified procedure may be applied.
Pre-Writing and Post-Writing Explicit Instruction: Differential Effects on L2 Learners’ Writing Accuracy
Authors: Trang Nguyen Huynh , Barrot Jessie S.
Published: July 2023

This quasi-experimental study investigates the effects of pre-writing (Pre-EI) and post-writing explicit instruction (Post-EI) on L2 learners’ overall writing accuracy and errors at different severity levels. Situated within process-genre-oriented writing classrooms, a total of three intact groups ( N = 101) were designated as two experimental conditions (Pre-EI and Post-EI) and a control group (no explicit instruction). Overall, the improvement by the two treatment groups compared to the control group suggested that both Pre-EI and Post-EI were effective in improving learners’ overall writing accuracy and reducing level 2 and level 3 errors. However, the results of between-group comparisons revealed the superiority of Post-EI. These findings indicated that writing accuracy was conditional to both timing and availability and provided a more nuanced understanding of the differential effects of Pre-EI and Post-EI on writing accuracy. Implications for L2 writing pedagogy and future studies are discussed.
Effect of intra-aortic balloon pump with veno-arterial extracorporeal membrane oxygenation in acute myocardial infarction with cardiogenic shock: A meta-analysis
Authors: Liu Yidan , Zeng Min , Zhou Yifang , Qiu Wenjie , Zeng Ruixiang , Zhou Yuanshen
Published: July 2023

Background

The effectiveness of a concomitant intra-aortic balloon pump (IABP) with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) intervention in acute myocardial infarction with cardiogenic shock (AMICS) patients is contested in the literature. This study sought to compare short-term mortality weaning rate from VA-ECMOin AMICS cases.

Methods

We conducted a literature review and compared the primary and secondary endpoints in the following treatment groups of AMICS patients: (1) VA-ECMO plus IABP vs. IABP alone and (2) VA-ECMO plus IABP vs. VA-ECMO alone. The primary endpoint was in-hospital all-cause mortality; while 30-days mortality, weaning from VA-ECMO, and vascular complications comprised secondary endpoints.

Results

VA-ECMO concomitant with IABP was administered to 3,580 (76.4%) patients, while IABP alone and VA-ECMO alone treatments accounted for 1.7% and 21.9% of the patients, respectively. We found that in-hospital mortality was significantly lower in patients treated with VA-ECMO plus IABP vs. VA-ECMO alone (odds ratio (OR) = 0.52; 95% Confidence Interval (CI) = 0.21–1.31; I-squared statistic ( I2 = 30%) or IABP alone (OR = 0.20; 95% CI = 0.08–0.55; I2 = 0%). Additionally, 30-days mortality was significantly lower in patients treated with VA-ECMO plus IABP vs. VA-ECMO alone (OR = 0.31; 95% CI = 0.25–0.40; I2 = 0%) or IABP alone (OR = 0.24; 95% CI = 0.11–0.50; I2 = 0%). A significant difference was observed in weaning from VA-ECMO in patients treated with VA-ECMO plus IABP vs. VA-ECMO alone (OR = 1.91; 95% CI = 1.09–3.33; I2 = 0%).

Conclusion

In-hospital and 30-days mortality were significantly lower in AMICS patients treated with VA-ECMO plus IABP vs. VA-ECMO alone or IABP alone. VA-ECMO with concomitant IABP could increase the proportion of patients weaned from VA-ECMO, significantly reducing in-hospital mortality, without increasing complications.
A novel SCN8A variant of unknown significance in pediatric epilepsy: a case report
Authors: Bouzroud Wafaa , Tazzite Amal , Boussakri Ikhlass , Gazzaz Bouchaïb , Dehbi Hind
Published: July 2023

Variants in SCN8A are associated with several diseases, including developmental and epileptic encephalopathy, intermediate epilepsy or mild-to-moderate developmental and epileptic encephalopathy, self-limited familial infantile epilepsy, neurodevelopmental delays with generalized epilepsy, neurodevelopmental disorder without epilepsy, hypotonia, and movement disorders. Herein, we report an 8-year-old Moroccan boy with intermediate epilepsy of unknown origin, intellectual disability, autism spectrum disorder, and hyperactivity. The patient presented a normal 46, XY karyotype and a normal comparative genomic hybridization profile. Whole-exome sequencing was performed, and heterozygous variants were identified in KCNK4 and SCN8A. The SCN8A variant [c.4499C > T (p.Pro1500Leu)] was also detected in the healthy mother and was classified as a variant of uncertain clinical significance. This variant occurs in a highly conserved domain, which may affect the function of the encoded protein. More studies are needed to confirm the pathogenicity of this novel variant to establish the effective care, management, and genetic counselling of affected individuals.
Exploration of Gross Motor Function in Aicardi-Goutières Syndrome
Authors: Gavazzi Francesco , Glanzman Allan M. , Woidill Sarah , Formanowski Brielle , Dixit Agrani , Isaacs David , Kornafel Tracy , Ballance Elizabeth , Pierce Samuel R. , Modesti Nicholson , Barcelos Isabella , Cusack Stacy V. , Jan Amanda K. , Flores Zaida , Sherbini Omar , Vincent Ariel , D’Aiello Russell , Lorch Scott A. , DeMauro Sara B. , Jawad Abbas , Vanderver Adeline , Adang Laura
Published: July 2023

Background: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by a spectrum of motor abilities. While the Aicardi-Goutières syndrome severity score favors severely impacted individuals, there is an unmet need to define tools measuring function across the Aicardi-Goutières syndrome spectrum as potential outcome assessments for future clinical trials. Methods: Gross Motor Function Measure–88 (GMFM-88) and AGS Severity Scale were administered in individuals affected by Aicardi-Goutières syndrome (n = 71). We characterized the performance variability by genotype. Derived versions of the GMFM-88, including the GMFM-66, GMFM-66 item set (GMFM-66IS), and GMFM-66 Basal&Ceiling (GMFM-66BC) were calculated. The Aicardi-Goutières syndrome cohort was divided into severe (AGS Severity Scale score <4) or attenuated (≥4). Performance on the AGS Severity Scale highly correlated with total GMFM-88 scores (Spearman Correlation: R = 0.91). To assess variability of the GMFM-88 within genotypic subcohorts, interquartile ranges (IQRs) were compared. Results: GMFM-88 performance in the TREX1 cohort had least variability while the SAMHD1 cohort had the largest IQR (4.23 vs 81.8). Floor effect was prominent, with most evaluations scoring below 20% (n = 46, 64.79%), particularly in TREX1- and RNASEH2-cohorts. Performance by the GMFM-66, GMFM-66IS, and GMFM-66BC highly correlated with the full GMFM-88. The Aicardi-Goutières syndrome population represents a broad range of gross motor skills. Conclusions: This work identified the GMFM-88 as a potential clinical outcome assessment in subsets of the Aicardi-Goutières syndrome population but underscores the need for additional validation of outcome measures reflective of the diverse gross motor function observed in this population, including low motor function. When time is limited by resources or patient endurance, shorter versions of the GMFM-88 may be a reasonable alternative.
Boundary Work and Transactive Memory Systems in Teams: Moderating Effects of the Visibility Affordance
Authors: Yoon Kay , Piercy Cameron W. , Kim Young Ji , Zhu Yaguang
Published: July 2023

Individuals in work teams frequently cross boundaries across teams, often by using information and communication technologies (ICTs). The current study investigates the effects of members’ boundary work and the visibility affordance of teams’ ICTs on Transactive Memory Systems (TMS) in teams. Survey data from 212 full-time employees whose work hours were divided between multiple teams reveals that boundary spanning enhances the focal team’s TMS specialization and credibility and negatively influences TMS coordination. Additionally, boundary reinforcement positively affects TMS credibility and coordination. The visibility affordance has a direct positive effect on all three dimensions of TMS and a moderating effect for boundary reinforcement such that higher visibility overrides the positive direct effect of boundary reinforcement on TMS. These findings suggest that different types of boundary work contribute to different dimensions of TMS and that teams might consider prioritizing the use of ICTs with high visibility to enhance their TMS.
The Anatomy of the Stomatognathic System in Different Skull Types in Dogs
Authors: de Albuquerque Cristina E. , da Silva Mônica D. , Magalhães Henrique I. Riceti , de Carvalho Hianka J. C. , Miglino Maria A. , Gioso Marco A.
Published: July 2023

The anatomy of the stomatognathic system is important for both clinical evaluations and surgical approaches in all animal species. The aim of this study was to describe the innervation and vascularization of the stomatognathic system of the dog. Twelve dogs without a history of disease or cranial malformation were used: 4 brachycephalic, 4 mesocephalic, and 4 dolichocephalic. The dogs were dissected, and arteries, veins, and nerves related to the masticatory and swallowing components were identified. The distribution pattern of these structures in the 3 different skull types were observed. The entire blood supply of the stomatognathic system is derived from the external carotid artery, which originates from the common carotid artery, and terminates as it branches into the superficial temporal and maxillary arteries. The other main branches of the common carotid artery are the occipital, cranial laryngeal, ascending pharyngeal, lingual, facial, caudal auricular, and parotid arteries. Blood drainage was achieved via the external jugular vein, which originates from the union of the linguofacial and maxillary veins. Brachycephalic dogs had blood vessels with greater sinuosity (more deviations) when compared to dolichocephalic and mesocephalic dogs. The stomatognathic system innervation of brachycephalic skull dogs showed differences in the distribution of the facial nerve in the labial commissure and maxillary and mandibular regions. The cranial conformation of dogs demonstrated anatomical variations of the vascular and neural structures of the stomatognathic system. This data may be useful to improve clinical practice, surgical planning, and interpretation of clinical dysfunctions.
Polytopal approximation for thrust magnitude constraints in rocket trajectory optimization
Authors: Wang Jiawei , Zhang Ran , Li Huifeng
Published: July 2023

This paper proposes a linear programming approach for onboard optimization of rocket trajectories, motivated by the need for reliable and computationally efficient trajectory optimization methods in real-time applications. To reformulate rocket trajectory optimization problems within a linear programming framework, a polytopal approximation method is developed. The polytopal approximation method approximates the thrust magnitude constraint using a set of artificial variables and linear constraints. Compared with a state-of-the-art approximation method, the polytopal approximation method demonstrates a higher accuracy-to-size ratio, enabling rocket trajectory optimization problems to be cast into linear subproblems without significantly increasing problem sizes. As linear subproblems can be readily solved by linear programming solvers, the proposed trajectory optimization approach inherits the solver’s reliability and computational efficiency, making it potentially useful for critical onboard applications. An ascent trajectory optimization problem is provided as an illustrative example to demonstrate the effectiveness of the proposed linear programming approach.
Bi-fractional-order reference model parameters-based control system design
Authors: Keçeci Ertuğrul , Yumuk Erhan , Güzelkaya Müjde , Eksin İbrahim
Published: July 2023

It is known that analytical manipulation of the time-domain representation of fractional order transfer function is, hitherto, a challenging task. In this study, a controller design methodology based on the direct synthesis design method is proposed using bi-fractional order transfer function as a reference model and certain time-domain criteria. First, an analysis examines the effects of bi-fractional order transfer function parameters, that is, commensurate fractional order, damping ratio and natural frequency, on the system time-domain criteria. This examination has allowed us to set up a relation between damping ratio and commensurate fractional order. Next, a polynomial function fitting is established in order to express the damping ratio in terms of this commensurate order. Bi-fractional-order reference model is regenerated using the above-mentioned relationship. Furthermore, a control design algorithm that utilizes the newly derived bi-fractional order reference model is developed by considering control signal limitations. The proposed fractional order control design method is then compared with globally optimized fractional order proportional-integral-derivative (PID) controllers under the same circumstances and performance index. Finally, the implementation of the proposed controller design algorithm is done on a real-time active suspension system. The results are very satisfactory and incoherent with the simulations.
Diversion: A Systems Theory Perspective
Authors: Gittner Lisaann S. , Dennis Jeff A. , Forbis Robert E.
Published: July 2023

There is a distinct lack of a normative theory for diversion of justice-involved individuals with mental illness at the intersection of the criminal justice and health care systems. The nexus where the criminal justice and health care systems are supposed to connect during diversion is not conceptually framed in a measurable way. The paper proposes a potential systems theory of diversion that explicates the overlapping boundaries within and between the criminal justice and health care systems. From a systems perspective, diversion is operationalized differently depending on the entry of an individual with justice involvement and mental illness into one of the systems. The criminal justice and health care systems have multiple levels (micro-, meso-, and macro-), but individuals enter both systems at the respective systems intersection of the micro- and meso-levels. The theoretical disconnect may fail to consider the impact of criminal justice diversion on the health care system. We propose a unified systems theory of diversion to improve evaluation, comparability, sustainability, resource allocation, and outcomes of diversion programs.
A critical analysis of classical severity-based knock control strategies
Authors: Peyton Jones James C , Patel Vatsal
Published: July 2023

A common variant of classical knock control strategies replaces fixed magnitude control moves with control actions that depend on the knock severity of the prior cycle. Though appealing to notions of proportional control, it is unclear whether such strategies offer benefit given the random nature of knock events. In this paper a new generalized event-based framework is developed and used to extend both time domain simulation and stochastic analysis methods for analyzing the closed loop behavior of such systems. These tools are then used to perform a rigorous analysis and comparison between standard advance-retard and severity-based control strategies. The analysis is also repeated using a lower knock threshold definition. The results show that the performance of severity-based knock control differs minimally from a similarly tuned standard advance-retard controller, and there is little benefit to recompense the additional complexity of severity-based control.
Intracranial stenting for large vessel intracranial atherosclerotic disease: Retrospective study
Authors: Naftali Jonathan , Findler Michael , Perlow Alain , Barnea Rani , Brauner Ran , Auriel Eitan , Raphaeli Guy
Published: July 2023

Background

Intracranial atherosclerotic disease (ICAD) is a common cause for stroke and can be defined as symptomatic (stroke) or asymptomatic. Current guidelines recommend against intracranial stenting (ICS) for patients with ICAD; treatment of patients who failed the best medical therapy is still debatable.

Methods

We introduce a preliminary retrospective analysis of our tertiary stroke center during 2018–2022 of patients that were treated with ICS either in acute phase or elective (eICS). Study endpoints were stroke, functional outcome (modified Rankin Score [mRS] at 3 months), and serious adverse events.

Results

Thirty-three stents were implanted, 21 in acute group and 12 in the eICS group. Most patients (75%) were treated with a new generation self-expandible stent. One patient had peri-procedural stroke and four patients had transient ischemic event or stroke during follow-up. There were eight cases of death (all acute group patients, seven of which occurred in the posterior circulation). Fifteen patients (62%) had favorable clinical outcomes (mRS 0-2 for pre-stroke), of which 10/10 (100%) in the eICS, the other two eICS patients had pre-morbid mRS 3 with no clinical change.

Conclusions

The evolution of new devices for ICS and the accumulating interventional experience might open a new era. As no other effective alternative treatment options exist for preventing recurrent stroke, stenting is still common practice in many tertiary centers either urgently or as elective procedure for refractory cases.
Estimating the impact of balloon guide catheter with mechanical thrombectomy for acute ischemic stroke: A U.S. cost analysis
Authors: Brinjikji Waleed , Kottenmeier Emilie , Kabiri Mina , Khaled Alia , Pederson John M , Al-Bayati Alhamza R
Published: July 2023

Background

Balloon guide catheters (BGCs) can be used adjunctively during mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Evaluating the potential economic impact associated with adjunctive BGC use is an important consideration for resource allocation.

Methods

Decision tree models were used to estimate the economic value of BGC use in MT through its impact on functional outcomes. Healthcare utilization cost estimates in the short- and long-term for patients with different 90-day mRS scores were analyzed for MT-only and MT + BGC scenarios. Deterministic (one-way) and probabilistic sensitivity analyses were performed to evaluate the robustness and uncertainty of model parameters.

Results

Per-patient index hospitalization cost was estimated at $65,260 for MT-only and $62,883 for MT + BGC scenarios. Per-patient one-year post-index hospitalization cost was estimated at $27,569 for MT-only and $24,830 for MT + BGC. MT + BGC had a total cost savings of $5117 compared with MT-only. Deterministic (one-way) sensitivity analysis demonstrated that cost saving per patient was most sensitive to the proportion of patients in the mRS 0–2 category in both MT + BGC and MT-only. In a probabilistic sensitivity analysis, mean per-patient costs for the index hospitalization were estimated at $63,737 for MT-only and $61,425 for MT + BGC. Mean per-patient cost estimates one-year post-index hospitalization was $27,445 for MT-only and $24,715 for MT + BGC. MT + BGC had a total cost savings of $5043 compared with MT-only.

Conclusion

Mechanical thrombectomy with adjunctive BGC use may reduce short-term and long-term patient costs due to improved functional outcomes when compared to MT treatment alone for AIS.
Jordanian mothers’ perspectives on having their intellectually disabled daughters undergo hysterectomies: A qualitative study
Authors: Al-Zyoud Nawaf S , Hyassat Mizyed A , Bataineh Osamah M
Published: July 2023

The current study aims to identify Jordanian mothers’ perspectives on their intellectually disabled daughters receiving hysterectomies. A qualitative methodology was employed; for the study sample, twelve mothers were chosen using a snowballing technique. Semi-structured interviews were carried out, and thematic analysis was utilized. Two main themes arose from the data analysis process: the reasons why mothers made the decision for their daughters to have hysterectomies – which included fears about unwanted pregnancy and keeping family honor – despite this conflicting with their religious and cultural values, and their concerns about their daughters having hysterectomies. Based on these findings, some implications and suggestions for future research were provided.
‘Bridging the gap’: Differences in training and match physical load in 1st team and U23 players from the English Premier League
Authors: Kavanagh Ronan , Carling Christoper , Malone Shane , Di Michele Rocco , Morgans Ryland , Rhodes David
Published: July 2023

Objectives

To explore the differences in training and match load in English Premier League (EPL) 1st team and U23 players. Identifying differences in relative and absolute physical outputs in relation to Maximal Aerobic Speed (MAS) and Maximal Sprint Speed (MSS) and how this informs monitoring and training prescription.

Methods

Two groups of full-time professional football players (1st team, n = 24 and U23 squad, n = 27) participated in this study. Training and match data were categorised into weekly blocks from Monday to Sunday. Each player's weekly total was then averaged to provide a squad average for each metric examined.

Results

Match analysis identified significantly higher distance covered above 120% MAS and distance between 120% MAS and 85% MSS ( p = .04, effect size [ES] = 0.64; p < .01, ES = 1.13) for the 1st team. Distance above 85% MSS was significantly higher for the U23's ( p < .01, ES = 2.92). Training and match data during one-match weeks displayed significantly higher differences in all high-speed variables for 1st team players compared to U23 players ( p ≤ .05, ES = 0.82–1.78). Analysis of training and match data during a two-match week displayed no significant differences for all physical variables ( p > .05).

Conclusions

Practitioners should consider the utilisation of individual relative thresholds to identify differences between physical performance variables during training and matches for 1st team and U23 players. Utilising these comparisons to inform training design, could maximise players physical development and potential for successful transition. Importantly, these findings relate to only one EPL club and therefore practitioners should assess their own players’ relative training and game outputs.
A systematic review of digital health technologies for the care of older adults during COVID-19 pandemic
Authors: Zou Chenyu , Harvard Abbey , Qian Jingjing , Fox Brent I
Published: July 2023

Objective

During the Coronavirus Disease 2019 (COVID-19) pandemic, digital health technologies (DHTs) became increasingly important, especially for older adults. The objective of this systematic review was to synthesize evidence on the rapid implementation and use of DHTs among older adults during the COVID-19 pandemic.

Methods

A structured, electronic search was conducted on 9 November 2021, and updated on 5 January 2023, among five databases to select DHT interventional studies conducted among older adults during the pandemic. The bias of studies was assessed using Version 2 of the Cochrane Risk-of-Bias Tool for randomized trials (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I).

Results

Among 20 articles included in the review, 14 (70%) focused on older adults with chronic diseases or symptoms, such as dementia or cognitive impairment, type 2 diabetes, and obesity. DHTs included traditional telehealth interventions via telephone, video, and social media, as well as emerging technologies such as Humanoid Robot and Laser acupuncture teletherapy. Using RoB 2 and ROBINS-I, four studies (20%) were evaluated as high or serious overall risk of bias. DHTs have shown to be effective, feasible, acceptable, and satisfactory for older adults during the COVID-19 pandemic compared to usual care. In addition, some studies also highlighted challenges with technology, hearing difficulties, and communication barriers within the vulnerable population.

Conclusions

During the COVID-19 pandemic, DHTs had the potential to improve various health outcomes and showed benefits for older adults’ access to health care services.
Analysis on epidemiological characters and HIV care continuum of HIV-infected students: a retrospective cohort study in Shandong province, China
Authors: Yang Xingguang , Li Ling , Zhang Na , Hao Lianzheng , Zhu Xiaoyan , Yu Haiying , Wang Guoyong , Kang Dianmin
Published: July 2023

Backgroud

The proportion of HIV-infected students in China showed an increasing trend. This study aimed to identify the epidemiological characteristics and the HIV care continuum for HIV-infected students in Shandong Province, China.

Methods

Case report and follow-up data of HIV-infected students were obtained from the National HIV/AIDS comprehensive response information management system. Logistic regression analyses were used to analyze the associating factors of HIV-infected students accepting CD4 + T cells (CD4) test and antiviral therapy (ART) in 30 days, and ArcGIS software was used for the spatial anlysis.

Results

From 2017 to 2019, 403 HIV-infected students were reported in Shandong Province. The majority of them were male (99.5%) and transmitted through homosexual sexual activity(92.1%). Most of them lived in Jinan city and Qingdao city. 68.5% (276 cases) accepted CD4 test in 30 days, and 48.6% (196 cases) started ART in 30 days. The heterosexual transmitted cases (AOR = 0.458, 95%CI: 0.210–0.998), patients accepting HIV care in western area (AOR = 0.266,95%CI: 0.147–0.481) were less likely to test CD4 within 30 days; patients aged 23–25 (AOR = 2.316, 95%CI: 1.009–5.316) and patients who had tested CD4 within 30 days (AOR = 4.377; 95%CI: 2.572–7.447) prefered to receive ART within 30 days; patients accepted HIV care in central area (AOR = 0.407; 95%CI: 0.251–0.657) and western area (AOR = 0.508; 95%CI: 0.261–0.989) and patients diagnosed by voluntary blood donation (AOR = 0.352; 95%CI: 0.144–0.864) were less willing to receive ART in 30 days.

Conclusions

The HIV care continuum of HIV-infected students in Shandong Province still needed strenghthing. More health education and case management should be done for cases transmitted through heterosexual behavior, accepted HIV care in central and western area, and diagnosed by voluntary blood donation.
Efficacy of repetitive transcranial magnetic stimulation (rTMS) adjunctive therapy for major depressive disorder (MDD) after two antidepressant treatment failures: meta-analysis of randomized sham-controlled trials
Authors: Vida Róbert György , Sághy Eszter , Bella Richárd , Kovács Sándor , Erdősi Dalma , Józwiak-Hagymásy Judit , Zemplényi Antal , Tényi Tamás , Osváth Péter , Voros Viktor
Published: July 2023

Background

Several meta-analyses demonstrated the efficacy of unilateral High-Frequency Left-sided (HFL) repetitive Transcranial Magnetic Stimulation (rTMS) for individuals with Major Depressive Disorder (MDD); however, results are contradictory due to heterogeneity of the included studies.

Methods

A systematic literature review (SLR) of English language articles published since 2000 was performed in March 2022 on PubMed and Scopus databases. Empirical evidence on the relative efficacy of rTMS treatment compared with standard pharmacotherapy in Treatment-Resistant Depression (TRD) were extracted. Random effects models were used to assess the effects of rTMS on response and remission rates.

Results

19 randomized double-blinded sham-controlled studies were included for quantitative analysis for response (n = 854 patients) and 9 studies for remission (n = 551 patients). The risk ratio (RR) for response and remission are 2.25 and 2.78, respectively for patients after two treatment failures using rTMS as add-on treatment compared to standard pharmacotherapy. Cochrane’s Q test showed no significant heterogeneity. No publication bias was detected.

Conclusions

rTMS is significantly more effective than sham rTMS in TRD in response and remission outcomes and may be beneficial as an adjunctive treatment in patients with MDD after two treatment failures. This finding is consistent with previous meta-analyses; however, the effect size was smaller than in the formerly published literature.