bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Next-generation Multi-target Stool DNA Panel Accurately Detects Colorectal Cancer and Advanced Precancerous Lesions
Authors: Gagrat Zubin D. , Krockenberger Martin , Bhattacharya Abhik , Gagrat Bridget Z. , Leduc Christine M. , Matter Michael B. , Fourrier Keith D. , Mahoney Douglas W. , Edwards V David K. , Lidgard Graham P. , Limburg Paul J. , Johnson Scott C. , Domanico Michael J. , Kisiel John B.
Published: March 2024

Abstract
The multi-target stool DNA (mt-sDNA) test screens for colorectal cancer by analyzing DNA methylation/mutation and hemoglobin markers to algorithmically derive a qualitative result. A new panel of highly discriminant candidate methylated DNA markers (MDM) was recently developed. Performance of the novel MDM panel, with hemoglobin, was evaluated in a simulated screening population using archived stool samples weighted to early-stage colorectal cancer and prospectively collected advanced precancerous lesions (APL). Marker selection study (MSS) and separate preliminary independent verification studies (VS) were conducted utilizing samples from multi-center, case–control studies. Sample processing included targeted MDM capture, bisulfite conversion, and MDM quantitation. Fecal hemoglobin was quantified using ELISA. Samples were stratified into 75%/25% training-testing sets; model outcomes were cross-validated 1,000 times. All laboratory operators were blinded. The MSS included 232 cases (120 colorectal cancer/112 APLs) and 490 controls. The VS featured 210 cases (112 colorectal cancer/98 APLs) and 567 controls; APLs were 86.7% adenomas and 13.3% sessile serrated lesions (SSL). Average age was 65.5 (cases) and 63.2 (controls) years. Mean sensitivity in the VS from cross-validation was 95.2% for colorectal cancer and 57.2% for APLs, with specificities of 89.8% (no CRC/APLs) and 92.4% (no neoplasia). Subgroup analyses showed colorectal cancer sensitivities of 93.4% (stage I) and 94.2% (stage II). APL sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSLs. These data support high sensitivity and specificity for a next-generation mt-sDNA test panel. Further evaluation of assay performance will be characterized in a prospective, multi-center clinical validation study (NCT04144738).
Prevention Relevance:
This study highlights performance of the next-generation mt-sDNA test, which exhibits high sensitivity and specificity for detecting colorectal cancer and APLs. This noninvasive option has potential to increase screening participation and clinical outcomes. A multi-center, clinical validation trial is underway.

See related commentary by Bresalier, p. 93
Figure S14 from Neutralizing Antibodies Impair the Oncolytic Efficacy of Reovirus but Permit Effective Combination with T cell–Based Immunotherapies
Authors: Groeneveldt Christianne , Kinderman Priscilla , Griffioen Lisa , Rensing Olivia , Labrie Camilla , van den Wollenberg Diana J.M. , Hoeben Rob C. , Coffey Matt , Loghmani Houra , Verdegaal Els M.E. , Welters Marij J.P. , van der Burg Sjoerd H. , van Hall Thorbald , van Montfoort Nadine
Published: March 2024

Figure S14. Frequency of circulating phagocytic myeloid cells during Reo preexposure.
Figure S11 from Neutralizing Antibodies Impair the Oncolytic Efficacy of Reovirus but Permit Effective Combination with T cell–Based Immunotherapies
Authors: Groeneveldt Christianne , Kinderman Priscilla , Griffioen Lisa , Rensing Olivia , Labrie Camilla , van den Wollenberg Diana J.M. , Hoeben Rob C. , Coffey Matt , Loghmani Houra , Verdegaal Els M.E. , Welters Marij J.P. , van der Burg Sjoerd H. , van Hall Thorbald , van Montfoort Nadine
Published: March 2024

Figure S11. Induction of circulating VSV-specific NAbs and CD8+ T cells by VSV preexposure.
Figure S10 from Neutralizing Antibodies Impair the Oncolytic Efficacy of Reovirus but Permit Effective Combination with T cell–Based Immunotherapies
Authors: Groeneveldt Christianne , Kinderman Priscilla , Griffioen Lisa , Rensing Olivia , Labrie Camilla , van den Wollenberg Diana J.M. , Hoeben Rob C. , Coffey Matt , Loghmani Houra , Verdegaal Els M.E. , Welters Marij J.P. , van der Burg Sjoerd H. , van Hall Thorbald , van Montfoort Nadine
Published: March 2024

Figure S10. Preexposure affects the specificity of Reo-specific CD8+ T cells.
Supplementary table 4 from An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype
Authors: Zhang Yaochuan , Song Yifu , Wang Xiaoliang , Shi Mengwu , Lin Yibin , Tao Dongxia , Han Sheng
Published: March 2024

Primary and secondary antibodies used in assays
Supplementary table 2 from An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype
Authors: Zhang Yaochuan , Song Yifu , Wang Xiaoliang , Shi Mengwu , Lin Yibin , Tao Dongxia , Han Sheng
Published: March 2024

PCR setting of Nfat1-/- mice detection
Supplementary Figure 3 from An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype
Authors: Zhang Yaochuan , Song Yifu , Wang Xiaoliang , Shi Mengwu , Lin Yibin , Tao Dongxia , Han Sheng
Published: March 2024

Expression of C3 in tumor-associated macrophages and its correlation with glioma clinical characteristics.
Supplementary Figure 2 from An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype
Authors: Zhang Yaochuan , Song Yifu , Wang Xiaoliang , Shi Mengwu , Lin Yibin , Tao Dongxia , Han Sheng
Published: March 2024

NFAT1 was significantly associated with M2-like tumor-associated macrophages.
Figure S8 from Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer
Authors: Zhang Han , Lee Sanghoon , Muthakana Renee R. , Lu Binfeng , Boone David N. , Lee Daniel , Wang Xiao-Song
Published: March 2024

Figure S8. IGR burden was not predictive of ICB benefit in a dataset for advanced melanoma treated with nivolumab (Riaz et al. Cell 2017). Treatment-naïve tumor samples showed no significant difference between responders and non-responders in terms of their IGR burden levels.
Figure S6 from Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer
Authors: Zhang Han , Lee Sanghoon , Muthakana Renee R. , Lu Binfeng , Boone David N. , Lee Daniel , Wang Xiao-Song
Published: March 2024

Figure S6. Violin plots showing the expressions of genes relevant to anti-tumor immune response and immune checkpoints in esophageal adenocarcinomas from the ICGC ESAD UK project.
Figure S4 from T-cell States, Repertoire, and Function in Classical Hodgkin Lymphoma Revealed through Single-Cell Analyses
Authors: Chen Xiufen , Yu Jovian , Venkataraman Girish , Smith Sonali M. , Chen Mengjie , Cooper Alan , Tumuluru Sravya , Brody Joshua D. , Godfrey James , Kline Justin
Published: March 2024

Supplemental Figure S4. Distribution of samples across each T-cell cluster
Abstract P07: Identification of the unique preleukemic bone marrow niche in acute myeloid leukemia
Authors: Goda Chinmayee , Kulkarni Rohan , Rudich Alexander , Karunasiri Malith , Bustos Yaphet , Chidester Sadie , Balcioglu Ozlen , Garfinkle Elizabeth AR , Mundy-Bosse Bethany , Mardis Elaine R , Marcucci Guido , Garzon Ramiro , Miller Katherine , Dorrance Adrienne M
Published: March 2024

Preleukemic stem cells (LSCs) can remain dormant within the bone marrow (BM) for decades before disease onset, suggesting acquisition of mutations within hematopoietic stem/progenitor cells (HSPCs) alone is insufficient for acute myeloid leukemia (AML). It is likely that alterations within BM microenvironment (BMM) also occur due to dysregulated crosstalk with mutant HSCs thus favoring LSC growth over normal HSCs. Uncovering novel mechanisms by which preleukemic LSCs remodel the BMM is critical in understanding therapy resistance and to develop novel therapies targeting aberrant pathways in both the LSCs and cells within the BMM. To address this, we compared cells of the BMM of wildtype (WT) mice to our Mll-PTD;Flt3-ITD mouse model of AML, which has a distinct preleukemic phase. Using single cell RNA-sequencing we identified 17 stromal cell clusters and observed substantial changes in both cell numbers and transcriptional profiles of several key stromal cell subpopulations. Specifically, we found decreases in normal HSC regulatory populations such as LepR+ MSCs and Cdh5+ ECs (2 and 2.7-fold decreases, respectively) and increases in pericytes and fibroblasts in preleukemic BM compared to WT (2.7 and 3.5-fold increase, respectively). Unlike what is observed in full-blown AML, we found an increase in CD55+ fibroblasts resulting from increased proliferation (13% vs 6% cell cycling, P=0.0016). Importantly, co-culture assays found that CD55+ BM fibroblasts expanded LSCs at increased levels over normal HSCs (83+/-7.5 vs 57+/-10.1, P=0.0006). Downregulation of several collagen genes (Col1a1, Col1a2, Col3a1, Col4a1, and Col6a1, P< 0.05) was found in these preleukemic CD55+ fibroblasts, suggesting that remodeling of the extracellular matrix might be an important mechanism by which these CD55+ fibroblast remodel the normal BMM and promote leukemogenesis. Furthermore, sequencing of full-blown leukemic BM niche cells have identified several key differences in the BM architecture, suggesting that the preleukemic BM is indeed distinct from full-blown leukemic BM and is important for disease initiation and progression, and not disease maintenance.

Citation Format: Chinmayee Goda, Rohan Kulkarni, Alexander Rudich, Malith Karunasiri, Yaphet Bustos, Sadie Chidester, Ozlen Balcioglu, Elizabeth AR Garfinkle, Bethany Mundy-Bosse, Elaine R Mardis, Guido Marcucci, Ramiro Garzon, Katherine Miller, Adrienne M Dorrance. Identification of the unique preleukemic bone marrow niche in acute myeloid leukemia [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P07.
Abstract P23: RHOA inactivation subverts IFN-γ response and promotes antigen escape in CAR-T resistant diffuse large B-cell lymphoma
Authors: Newsam Austin D , Coughlin Caroline A , Goretsky Yitzhar E , Alaoui Abdessumad Y , Tsai Daniel E , Coffey David G , Sondhi Anya K , Roberts Evan R , Gallego Natalia Campos , Manara Paola , Bilbao Daniel , Ziccheddu Bachisio , Spiegel Jay Y , Jain Michael D , Locke Frederick L , Alderuccio Juan P , Maura Francesco , Schatz Jonathan H
Published: March 2024

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies have shown breakthrough responses for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), however, over half of patients still progress. Whole genome sequencing of CAR-T treated patients revealed RHOA (3p21.31) deletions highly enriched in patients with poor responses (p = 0.0013). RHOA is altered in approximately 25% of newly diagnosed DLBCL, yet no work has comprehensively defined its role in lymphoma biology or immune resistance. We created RHOA loss-of-function (LoF) cell lines and performed RNA-sequencing followed by drug viability assays to interrogate pathways of dependence in RHOA deficient DLBCL. We also created immunocompetent models of RHOA deficient lymphoma in vivo and conducted single-cell RNA sequencing to assess the resulting lymphoma microenvironments. CAR-T cells were engineered and used to challenge RHOA LoF tumors in vitro. Upon discovering highly upregulated gene sets involving PI3K/AKT/mTOR signaling, we employed drug viability assays and established a critical reliance on AKT signaling in RHOA LoF cell lines. Upregulated AKT was found to suppress JAK2-STAT1 mediated (IFN-γ) signaling and this effect was reversed with PI3K inhibition. Single-cell transcriptomics of RHOA deficient mouse lymphomas revealed decreased Cd8a expression and increased Cd4 expression of T-cells (p = 0.09 and p = 0.028, respectively), suggesting an immunosuppressive microenvironment as a result of abolished IFN-γ mediated immunorecognition. RHOA deficient cell lines were also found to downregulate surface CD19 expression (p < 0.0001) and demonstrated significantly decreased CAR-T cell killing in vitro (p = 0.0005). Future experiments will challenge RHOA deficient immunocompetent tumors in vivo with and without PI3K inhibitors to assess efficacy of combinatorial therapy.

Citation Format: Austin D Newsam, Caroline A Coughlin, Yitzhar E Goretsky, Abdessumad Y Alaoui, Daniel E Tsai, David G Coffey, Anya K Sondhi, Evan R Roberts, Natalia Campos Gallego, Paola Manara, Daniel Bilbao, Bachisio Ziccheddu, Jay Y Spiegel, Michael D Jain, Frederick L Locke, Juan P Alderuccio, Francesco Maura, Jonathan H Schatz. RHOA inactivation subverts IFN-γ response and promotes antigen escape in CAR-T resistant diffuse large B-cell lymphoma [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P23.
TABLE 1 from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma
Authors: Chai Annie Wai Yeeng , Yee Shi Mun , Lee Hui Mei , Abdul Aziz Norazlin , Yee Pei San , Marzuki Marini , Wong Ka Wo , Chiang Alan K.S. , Chow Larry Ka-Yue , Dai Wei , Liu Teng Fei , Tan Lu Ping , Khoo Alan Soo Beng , Lo Kwok Wai , Lim Paul V.H. , Rajadurai Pathmanathan , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: March 2024

Summary of the NPC268 EBV classification and status of high-risk variants
Supplementary Table 9 from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma
Authors: Chai Annie Wai Yeeng , Yee Shi Mun , Lee Hui Mei , Abdul Aziz Norazlin , Yee Pei San , Marzuki Marini , Wong Ka Wo , Chiang Alan K.S. , Chow Larry Ka-Yue , Dai Wei , Liu Teng Fei , Tan Lu Ping , Khoo Alan Soo Beng , Lo Kwok Wai , Lim Paul V.H. , Rajadurai Pathmanathan , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: March 2024

Summary table comparing NPC268 with other three EBV-positive lines
Supplementary Table 6 from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma
Authors: Chai Annie Wai Yeeng , Yee Shi Mun , Lee Hui Mei , Abdul Aziz Norazlin , Yee Pei San , Marzuki Marini , Wong Ka Wo , Chiang Alan K.S. , Chow Larry Ka-Yue , Dai Wei , Liu Teng Fei , Tan Lu Ping , Khoo Alan Soo Beng , Lo Kwok Wai , Lim Paul V.H. , Rajadurai Pathmanathan , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: March 2024

Comparison of variants identified between NPC268 and C666-1
Supplementary Table 5 from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma
Authors: Chai Annie Wai Yeeng , Yee Shi Mun , Lee Hui Mei , Abdul Aziz Norazlin , Yee Pei San , Marzuki Marini , Wong Ka Wo , Chiang Alan K.S. , Chow Larry Ka-Yue , Dai Wei , Liu Teng Fei , Tan Lu Ping , Khoo Alan Soo Beng , Lo Kwok Wai , Lim Paul V.H. , Rajadurai Pathmanathan , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: March 2024

Antibodies used for western blotting
Supplementary Methods from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma
Authors: Chai Annie Wai Yeeng , Yee Shi Mun , Lee Hui Mei , Abdul Aziz Norazlin , Yee Pei San , Marzuki Marini , Wong Ka Wo , Chiang Alan K.S. , Chow Larry Ka-Yue , Dai Wei , Liu Teng Fei , Tan Lu Ping , Khoo Alan Soo Beng , Lo Kwok Wai , Lim Paul V.H. , Rajadurai Pathmanathan , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: March 2024

Supplementary Methods
Supplementary Figure 4 from Establishment and Characterization of an Epstein-Barr Virus–positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma
Authors: Chai Annie Wai Yeeng , Yee Shi Mun , Lee Hui Mei , Abdul Aziz Norazlin , Yee Pei San , Marzuki Marini , Wong Ka Wo , Chiang Alan K.S. , Chow Larry Ka-Yue , Dai Wei , Liu Teng Fei , Tan Lu Ping , Khoo Alan Soo Beng , Lo Kwok Wai , Lim Paul V.H. , Rajadurai Pathmanathan , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: March 2024

The genomically unstable NPC268 showed high levels of gamma H2A.X and LINE1 RNA
Data from Identification and Characterization of a Small Molecule Bcl-2 Functional Converter
Authors: Kopparapu Prasad R. , Pearce Martin C. , Löhr Christiane V. , Duong Cathy , Jang Hyo Sang , Tyavanagimatt Shanthakumar , O'Donnell Edmond F. , Nakshatri Harikrishna , Kolluri Siva K.
Published: March 2024

Abstract
Cancer cells exploit the expression of anti-apoptotic protein Bcl-2 to evade apoptosis and develop resistance to therapeutics. High levels of Bcl-2 leads to sequestration of pro-apoptotic proteins causing the apoptotic machinery to halt. In this study, we report discovery of a small molecule, BFC1108 (5-chloro-N-(2-ethoxyphenyl)-2-[(4-methoxybenzyol)amino]benzamide), which targets Bcl-2 and converts it into a pro-apoptotic protein. The apoptotic effect of BFC1108 is not inhibited, but rather potentiated, by Bcl-2 overexpression. BFC1108 induces a conformational change in Bcl-2, resulting in the exposure of its BH3 domain both in vitro and in vivo. BFC1108 suppresses the growth of triple-negative breast cancer xenografts with high Bcl-2 expression and inhibits breast cancer lung metastasis. This study demonstrates a novel approach to targeting Bcl-2 using BFC1108, a small molecule Bcl-2 functional converter that effectively induces apoptosis in Bcl-2–expressing cancers.
Significance:
We report the identification of a small molecule that exposes the Bcl-2 killer conformation and induces death in Bcl-2–expressing cancer cells. Selective targeting of Bcl-2 and elimination of cancer cells expressing Bcl-2 opens up new therapeutic avenues.
Supra-Threshold LS CE-Chirp Auditory Brainstem Response in the Elderly
Authors: Maass Juan C. , Leiva Alexis , Torrente Mariela , Vergara Rodrigo , Belkhiria Chama , Delgado Carolina , Delano Paul H.
Published: March 2024

Introduction: Aging deteriorates peripheral and central auditory structures and functions. In elders, for an accurate audiological evaluation, it is important to explore beyond the cochlear receptor. Audiograms provide an estimation of hearing thresholds, while the amplitudes and latencies of supra-threshold auditory brainstem response (ABR) can offer noninvasive measures of the auditory pathways functioning. Regarding ABR, in young populations, level-specific chirp (LS CE-chirp) stimulus has been proposed as an alternative synchronizing method to obtain larger ABR responses than those evoked by clicks. However, the supra-threshold characteristics of chirp evoked ABR, and their association to hearing thresholds is relatively unknown in the elderly. The aim of this study was to evaluate supra-threshold LS CE-chirp ABRs in an aged population by comparing their features with click ABRs, and evaluating their relationship with audiometric hearing thresholds. Methods: We carried out a cross-sectional study to characterize the hearing of 125 adults aged over 65 years. We determined the audiometric hearing thresholds and supra-threshold ABRs elicited by LS CE-chirp and click stimuli at 80 dB nHL. We evaluated associations by means of partial correlations and covariate adjustment. We performed specific frequencies’ analysis and subgroup analysis per hearing level. Results: Wave V responses had significantly shorter latencies and larger amplitudes when elicited by LS CE-chirp as compared to click-evoked responses. Audiometric hearing thresholds correlated with age, but ABR characteristics did not. We found mild correlations between hearing thresholds and ABR characteristics, predominantly at higher frequencies and with chirp. We found scarce evidence of correlation between ABR characteristics and the average of behavioral hearing thresholds between 0.5 to 4 kHz (0.5–4 kHz PTA). After subgroup analysis according to the hearing level, no stronger or more significant correlations were found between ABR characteristics and 0.5–4 kHz PTA. Discussion: In this study, we found that supra-threshold LS CE-chirp ABR presented some of the previously described similitudes and differences with supra-threshold click ABR in younger populations. Although, the average amplitude and latency of wave V evoked by LS CE-chirp were larger and faster than those evoked by clicks, these results should be taken with caution at the individual level, and further studies are required to state that LS CE-chirp ABRs are better than click ABRs in elders for clinical evaluations. We did not find consistent associations between hearing thresholds and supra-threshold wave V features, suggesting that these measures should be considered independently in the elderly.
Modeling the Therapeutic Process of Patients with Cocaine Use Disorders: A Guide for Predicting Readmission
Authors: Dacosta-Sánchez Daniel , Fernández-Calderón Fermín , Díaz-Batanero Carmen , Mancheño-Velasco Cinta , Lozano Óscar M.
Published: March 2024

Introduction: Patients with cocaine use disorders have very high readmission rates. Our aim was to model the relationships between attributes of patients with cocaine use disorder at the beginning of treatment, therapeutic process indicators of time in treatment or proportion of appointments attended, and treatment outcomes, including outcomes at discharge and non-readmissions posttreatment as indicators of therapeutic success. Method: A retrospective observational design was used with 10,298 cocaine use disorder patients. Electronic health records were used for statistical analysis of the data. Randomized subsample 1 (n = 5,150) was used for exploratory analysis and subsample 2 (n = 5,148) for modeling relationships between the variables. Results: Patients attributes at intake (e.g., legal services as the source of referral) were of limited significance in explaining time in treatment, proportion of appointments attended, and treatment outcomes. Time in treatment and proportion of appointments attended emerged as significant factors in explaining outcomes at discharge. However, readmissions were primarily explained by time in treatment and outcomes at discharge, although referrals to addiction centers by health services also appeared to be relevant for explaining readmission. Discussion/Conclusion: Our study has shown that maintaining a sufficient appointment attendance rate and remaining in treatment for a longer duration are critical therapeutic process indicators for explaining outcomes at the point of discharge and therapeutic success, as indicated by a reduced likelihood of readmissions. Patients who remained in treatment for an extended period were found to have a reduced risk of future readmissions. In addition, our study highlights the importance of maintaining a satisfactory appointment attendance rate to attain successful short- and medium-term therapeutic discharge outcomes. These guidelines could help to increase the efficiency of patient treatment and alleviate the suffering of both patients and their families.
Leigh Syndrome due to MT-ATP6 Variants: A Case Presentation and the Review of the Literature
Authors: Akar Halil Tuna , Sayar Esra , Sarıtaş Nakip Özlem , Sönmez Esra , Özkan Mehmet Burak , Olgaç Asburçe
Published: March 2024

Introduction: Leigh syndrome is a rare mitochondrial disorder characterized by subacute necrotizing encephalomyelopathy, resulting from defects in mitochondrial respiratory enzymes or pyruvate dehydrogenase complex. Symptoms can manifest in infancy, childhood, or adulthood. We present a case of a 7-month-old girl initially misdiagnosed with septic shock but was later found to have Leigh encephalomyelopathy due to MT-ATP6 deficiency. Case Presentation: A 7-month-old girl was admitted with fever, drowsiness, and wheezing, initially diagnosed with septic shock. She had a history of parental consanguinity and hypotonia. Physical examination revealed unconsciousness, miotic pupils, and respiratory distress. Initial laboratory tests showed significant metabolic acidosis and elevated lactate, creatine kinase, and ammonia levels. The patient was treated for sepsis and shock, but her condition worsened with elevated lactate and liver transaminases, eventually leading to hypertrophic cardiomyopathy and multiorgan failure. Her basic metabolic scans showed extremely low citrulline levels, whole-exome sequencing analysis did not show any pathologic change in nuclear genome, and mitochondrial genome analysis revealed an MT-ATP homoplasmic variant. She passed away on the 22nd day of hospitalization. Discussion/Conclusion: While mitochondrial disorders are broadly acknowledged for their phenotypic diversity, it is essential to note that specific disorders, such as Leigh syndrome, display distinctive presentations with varying degrees of severity. Factors such as the percentage of homoplasmy contribute to the variability in manifestations. Notably, MT-ATP6-associated Leigh syndrome is predominantly characterized by an early onset, typically occurring before the age of 2 years. Low citrulline levels have been observed in approximately 90% of patients with MT-ATP6-related disorders, distinguishing them from other mitochondrial disorders. The exact mechanisms underlying this specific metabolic alteration are not fully understood, but it could be linked to disruptions in the mitochondrial energy production process. The mitochondria are essential for various metabolic pathways, including the urea cycle, where citrulline is involved. The association between low citrulline levels and MT-ATP6-related disorders raises the possibility of using citrulline as a potential biomarker for disease identification. MT-ATP6 defects should be kept in mind in cases with mitochondrial disease and low plasma citrulline levels.
Comparison of Transcatheter Edge-to-Edge Mitral Valve Repair for Primary Mitral Regurgitation Outcomes to Hospital Volumes of Surgical Mitral Valve Repair
Authors: Grayburn Paul A. , Mack Michael J. , Manandhar Pratik , Kosinski Andrzej S. , Sannino Anna , Smith Robert L. , Szerlip Molly , Vemulapalli Sreekanth
Published: March 2024

BACKGROUND:

Transcatheter edge-to-edge mitral valve (MV) repair (TEER) is an effective treatment for patients with primary mitral regurgitation at prohibitive risk for surgical MV repair (MVr). High-volume MVr centers and high-volume TEER centers have better outcomes than low-volume centers, respectively. However, whether MVr volume predicts TEER outcomes remains unknown. We hypothesized that high-volume MV surgical centers would have superior risk-adjusted outcomes for TEER than low-volume centers.

METHODS:

We combined data from the American College of Cardiology/Society of Thoracic Surgeons Transcatheter Valve Therapy registry and the Society of Thoracic Surgeons adult cardiac surgery database. MVr was defined as leaflet resection or artificial chords with or without annuloplasty and was evaluated as a continuous variable and as predefined categories (<25, 25–49, and ≥50 MV repairs/year). A generalized linear mixed model was used to evaluate risk-adjusted in-hospital/30-day mortality, 30-day heart failure readmission, and TEER success (mitral regurgitation ≤2+ and gradient <5 mm Hg).

RESULTS:

The study comprised 41 834 patients from 500 sites of which 332 (66.4%) were low, 102 (20.4%) intermediate, and 66 (13.2%) high-volume surgical centers (
P
<0.001). TEER success was 54.6% and was not statistically significantly different across MV surgical site volumes (
P
=0.4271). TEER mortality at 30 days was 3.5% with no significant difference across MVr volume on unadjusted (
P
=0.141) or adjusted (
P
=0.071) analysis of volume as a continuous variable. One-year mortality was 15.0% and was lower for higher MVr volume centers when adjusted for clinical and demographic variables (
P
=0.027). Heart failure readmission at 1 year was 9.4% and was statistically significantly lower in high-volume centers on both unadjusted (
P
=0.017) or adjusted (
P
=0.015) analysis.

CONCLUSIONS:

TEER can be safely performed in centers with low volumes of MV repair. However, 1-year mortality and heart failure readmission are superior at centers with higher MVr volume.
Design of a Stem Cell–Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages
Authors: Rodriguez-Perez Luis M. , Ojeda-Pérez Betsaida , López-de-San-Sebastián Javier , García-Bonilla María , González-García Marcos , Fernández-Muñoz Beatriz , Sánchez-Pernaute Rosario , García-Martín María L. , Domínguez-Pinos Dolores , Cárdenas-García Casimiro , Jiménez Antonio J. , Paez-Gonzalez Patricia
Published: March 2024

BACKGROUND:

In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells.

METHODS:

GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student
t
or Wilcoxon-Mann-Whitney
U
test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively.

RESULTS:

PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema).

CONCLUSIONS:

In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.
A Novel Alignment-based Approach for PARSEVAL Measuress
Authors: Jo Eunkyul Leah , Park Angela Yoonseo , Park Jungyeul
Published: March 2024

We propose a novel method for calculating PARSEVAL measures to evaluate constituent parsing results. Previous constituent parsing evaluation techniques were constrained by the requirement for consistent sentence boundaries and tokenization results, proving to be stringent and inconvenient. Our new approach handles constituent parsing results obtained from raw text, even when sentence boundaries and tokenization differ from the preprocessed gold sentence. Implementing this measure is our evaluation by alignment approach. The algorithm enables the alignment of tokens and sentences in the gold and system parse trees. Our proposed algorithm draws on the analogy of sentence and word alignment commonly used in machine translation (MT). To demonstrate the intricacy of calculations and clarify any integration of configurations, we explain the implementations in detailed pseudo-code and provide empirical proof for how sentence and word alignment can improve evaluation reliability.
Lesion-symptom Mapping of Acceptability Judgments in Chronic Poststroke Aphasia Reveals the Neurobiological Underpinnings of Receptive Syntax
Authors: Fahey Danielle , Fridriksson Julius , Hickok Gregory , Matchin William
Published: March 2024

Disagreements persist regarding the neural basis of syntactic processing, which has been linked both to inferior frontal and posterior temporal regions of the brain. One focal point of the debate concerns the role of inferior frontal areas in receptive syntactic ability, which is mostly assessed using sentence comprehension involving complex syntactic structures, a task that is potentially confounded with working memory. Syntactic acceptability judgments may provide a better measure of receptive syntax by reducing the need to use high working memory load and complex sentences and by enabling assessment of various types of syntactic violations. We therefore tested the perception of grammatical violations by people with poststroke aphasia (n = 25), along with matched controls (n = 16), using English sentences involving errors in word order, agreement, or subcategorization. Lesion data were also collected. Control participants performed near ceiling in accuracy with higher discriminability of agreement and subcategorization violations than word order; aphasia participants were less able to discriminate violations, but, on average, paralleled control participants discriminability of types of violations. Lesion-symptom mapping showed a correlation between discriminability and posterior temporal regions, but not inferior frontal regions. We argue that these results diverge from models holding that frontal areas are amodal core regions in syntactic structure building and favor models that posit a core hierarchical system in posterior temporal regions.
Molecular data and morphological characters clarify the taxonomic status of Pintara heringi pieridoides (Liu & Gu, 1994) (Hesperiidae, Pyrginae)
Authors: LI MENG , LU KE , CUI YING , LIU HAIWEI , YANG JINCHU , XUE GUOXI , WANG QIULING
Published: March 2024

We found Albiphasma heringi (Mell, 1922) and A. pieridoides (Liu & Gu, 1994) to be conspecific by the 658 bp COI gene sequences and male genitalia characters. Considering the distinguishable wing patterns and allopatric distribution of the two taxa, we treat pieridoides as a subspecies of heringi. Therefore, the genus Albiphasma Huang, Chiba, Wang and Fan, 2016, which was established for heringi and pieridoides, becomes monotypic, and in light of morphological similarities and close genetic distance between heringi and Pintara bowringi (Joicey & Talbot, 1921), we propose its synonymy with Pintara Evans, 1932. The adults and male genitalia of both P. heringi heringi (Mell, 1922) and P. heringi pieridoides (Liu & Gu, 1994) are illustrated.
Numerical simulation and experimental investigation of lattice-apron compact spinning with an air guide
Authors: Song Kaili , Guo Mingrui , Gao Weidong
Published: March 2024

The four-roller compact spinning system is widely used today and is considered an improvement over traditional ring spinning because of its excellent yarn properties. Reducing energy consumption in compact spinning has always been a key issue for the textile industry. This paper proposed a method for installing an air guide on compact spinning to reduce energy consumption. Four types of air guides were designed with different side shapes (Type-N, Type-L, Type-R, and Type-LR), and the airflow characteristics in the converging zone were analyzed using numerical simulation. In addition, high-speed photography technology and image-processing technology were used to study the dynamic state of the fiber bundle in the flow field of the converging zone. The effectiveness of the preferred solution of the air guide was also verified by spinning experiments. The results revealed that the best air guide was Type-LR, achieving a 3.7% reduction in yarn hairiness even after a decrease in negative pressure by 800 Pa and a 58.4% reduction in power of the fan motor, surpassing the yarn quality observed without any air guide.
The politics of drains: Everyday negotiations of infrastructure imaginaries in Accra
Authors: Foli Afra , Uitermark Justus
Published: March 2024

In this article we unpack the infrastructural imaginary of urban residents in a neighbourhood in the northern periphery of Accra in Ghana, focussing on drainage. Based on interviews and observations, we describe how residents characterise their neighbourhood’s development as a linear progression in stages, each marked by the completion of different infrastructures. Our analysis brings out the visceral and affective underpinnings of infrastructure imaginaries, showing how residents sense their environment and attempt to change it. On the one hand, the aspiration towards linear neighbourhood development results in the stigmatisation of residents – referred to as ‘squatters’ even if they rent – some of whose practices are deemed unhygienic and who are therefore considered out of place. On the other hand, everyday interactions and mutual interdependence provide the foundation for collaboration and compromises across social divides. Studying how aspirations translate into neighbourhood development, we argue, requires that we engage with infrastructure as both political and pragmatic.
Understanding the Interplay of Religion, Social Relationships, and Depressive Symptoms in Later Life: An Analysis of Dynamics in Individual and Dyadic Contexts
Authors: Park Hayoung , Joo Susanna , Kim Hyoun K.
Published: March 2024

This study examined how religious participation at the individual level and the dyadic religious similarity at the couple level influenced depressive symptoms via social relationships among older Korean couples aged 65 and above. The sample included 1,191 couples from the seventh assessment of the Korean Longitudinal Study of Ageing. The findings indicated that older adults who participated in religious activities more frequently showed lower levels of depressive symptoms through increased social interactions and marital satisfaction. Additionally, older couples with similar religious backgrounds showed higher levels of marital satisfaction than those without similar religious backgrounds, subsequently leading to lower levels of depressive symptoms. Overall, the associations between religion and depressive symptoms were similar for both genders. The findings provided insights into potential mechanisms leading to later-life depressive symptoms at both the individual and couple levels in terms of religion and social relationships and informed practical implications for older couples’ marital relationships.
A ‘field transformation and social integration’: Settlement information practices of relocated ethnic minorities with small populations in poverty-alleviation areas of Yunnan, China
Authors: Zhu Ming , Su Han , Niu Longxiao
Published: March 2024

This study investigates the settlement information practices of ethnic minorities with small populations (EMSPs) who were relocated to poverty-alleviation areas in Yunnan, China. Data were gathered using interviews and surveys. A face-to-face survey was administered to 126 and 147 EMSPs before and after relocation, respectively, focusing on their information needs, acquisition, and sharing. In addition, in-depth interviews were conducted with 16 relocated EMSP participants to identify the factors influencing their settlement information practices. This study’s findings showed that ethnic characteristics, spatial reconstruction and social inclusion were the primary factors affecting the context of changing living spaces and social communication relationships. Furthermore, the results contribute to a conceptual framework for the settlement information practices of EMSPs and provide valuable insights for research on settlement information practices of newcomer populations across cultures and ethnicities.
Surgical treatment for a child with traumatic ventricular septal rupture and ventricular aneurysm
Authors: Tomotsuka Sanae , Ikeda Tadashi , Ide Yujiro , Baba Shiro , Hirata Takuya , Minatoya Kenji
Published: March 2024

A five-year-old boy was diagnosed with the ventricular septal rupture and ventricular aneurysm after blunt chest trauma in child abuse. Because of the intractable heart failure, he underwent operation in subacute period. Postoperative course was uneventful. The blunt cardiac injury in children can be caused by mild trauma and can be lethal. Surgical intervention should be considered when the clinical condition is unstable.
Simultaneous bilateral bullectomy and coronary artery bypass grafting through median sternotomy approach
Authors: Goyal Vikas Deep , Misra Gaurav , Pahade Akhilesh , Prajapati Neeraj
Published: March 2024

Lung bullae can severely compromise lung function. Smoking is an important cause of chronic obstructive pulmonary disease, as well as coronary artery disease and peripheral arterial disease. Significant diseases in the cardiovascular and thoracic systems may require multiple interventions apart from medical management. We discuss a patient in which simultaneous bilateral bullectomy and coronary artery bypass grafting were performed through the median sternotomy approach.
Examining the effects of reciprocal emoji use on interpersonal and communication outcomes
Authors: Cavalheiro Bernardo P. , Prada Marília , Rodrigues David L.
Published: March 2024

Research has shown that emoji can determine how interlocutors who use emoji are perceived (e.g., warmer) and can help complement written communication (e.g., clarify the meaning of a message). We argue that reciprocal emoji use may be particularly beneficial for user perceptions and communication outcomes. In two experiments ( N = 568), we examined if using emoji, and reciprocating emoji use, in a work context (i.e., message between colleagues) influenced inferences about interlocutors and communication outcomes (Study 1), and if such effects differed according to the level of conflict between interlocutors (Study 2). Study 1 showed that using [Formula: see text] (vs. [Formula: see text]) resulted in higher perceptions of warmth, playfulness, and message’s positivity, whereas no benefits of using [Formula: see text] (vs. [Formula: see text]) were observed. Likewise, reciprocating emoji use ([Formula: see text] vs. no emoji) resulted in higher perceptions of warmth, playfulness, and communication positivity. Study 2 showed only an effect of conflict in the scenario, such that, regardless of reciprocal emoji use, in the lower (vs. higher) conflict situation, perceptions of the interlocutor (e.g., warmer, more competent, more playful), and the conversation (e.g., messages more positive, less confrontational) were more favorable. Overall, our results reinforce the importance of emoji valence for person perception and communication outcomes, while also suggesting some emoji may not impact communication under specific circumstances (e.g., during situations of conflict).
Reported and Enacted Emergent Literacy Instruction: Understanding Young Students With Extensive Support and Complex Communication Needs, Opportunity to Learn
Authors: Benson-Goldberg Sofia , Erickson Karen
Published: March 2024

Literacy instruction has an important role in augmentative and alternative communication (AAC) because spelling and writing support precise communication. Unfortunately, few students with extensive support needs and complex communication needs (ESN/CCN) develop literacy skills at or above the first grade reading-level. Given that learning to read and write begins with extensive emergent literacy learning opportunities, limited skills may result from insufficient opportunity to learn (OTL) emergent literacy skills. This study examined the instruction provided in early U.S. childhood classrooms to students with ESN/CCN to understand OTL during this critical period. This study used a concurrent embedded mixed methods design integrating a survey of teachers of students with ESN/CCN ( n = 26) with a qualitative multiple case study ( n = 2). Results suggest the time teachers are devoting to instruction is not translating into increased OTL for individual students. Solutions that may increase learning opportunities and implications for future research are discussed.
Comparison of cerebral oxygen extraction fraction using ASE and TRUST methods in patients with sickle cell disease and healthy controls
Authors: Fellah Slim , Ying Chunwei , Wang Yan , Guilliams Kristin P , Fields Melanie E , Chen Yasheng , Lewis Josiah , Mirro Amy , Cohen Rachel , Igwe Nkemdilim , Eldeniz Cihat , Jiang Dengrong , Lu Hanzhang , Powers William J , Lee Jin-Moo , Ford Andria L , An Hongyu
Published: March 2024

Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a T2-relaxation-under-spin-tagging (TRUST) MRI method with different calibration models. In this study, we aimed to compare the average ASE-OEF in the SSS drainage territory and TRUST-OEF in the SSS from the same SCD patients and healthy controls. 74 participants (SCD: N = 49; controls: N = 25) underwent brain MRI. TRUST-OEF was quantified using the Lu-bovine, Bush-HbA and Li-Bush-HbS models. ASE-OEF and TRUST-OEF were significantly associated in healthy controls after controlling for hematocrit using the Lu-bovine or the Bush-HbA model. However, no association was found between ASE-OEF and TRUST-OEF in patients with SCD using either the Bush-HbA or the Li-Bush-HbS model. Plausible explanations include a discordance between spatially volume-averaged oxygenation brain tissue and flow-weighted volume-averaged oxygenation in SSS or sub-optimal calibration in SCD. Further work is needed to refine and validate non-invasive MR OEF measurements in SCD.