bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine Signaling Promotes Tissue-Resident Memory Differentiation of CD8+ T Cells and Antitumor Immunity
Authors: Chen Yingshi , Yan Shu-Mei , Pu Zeyu , Feng Jinzhu , Tan Likai , Li Yuzhuang , Hu Hongrong , Huang Wenjing , Lin Yingtong , Peng Zhilin , He Xin , Huang Feng , Zhang Hui , Zhang Yiwen
Published: July 2022

Tissue-resident memory CD8+ T (TRM) cells have been associated with robust protective antitumor immune responses and improved prognosis of patients with cancer. Therefore, therapeutic strategies that modulate either the production or activity of TRM cells could be effective for treating cancer. Using a high-throughput drug screen, we showed that the neurotransmitter dopamine drives differentiation of CD8+ T cells into CD103+ TRM cells. In murine syngeneic tumor xenograft models and clinical human colon cancer samples, DRD5 served as the major functional dopamine receptor on CD8+ T cells and positively correlated with TRM cell density. DRD5 deficiency led to a failure of CD8+ T cells to accumulate in tissues, resulting in impaired TRM cell formation, reduced effector function, and uncontrolled disease progression. Moreover, dopamine treatment promoted the antitumor activity of CD8+ T cells and suppressed colorectal cancer growth in immunocompentent mouse models, and ex vivo preconditioning with dopamine enhanced the in vivo efficacy of chimeric antigen receptor (CAR)-T cells. Finally, in a patient with colorectal cancer cohort, dopamine expression was positively associated with patient survival and CD8+ T-cell infiltration. These findings suggest that dopaminergic immunoregulation plays an important role in the differentiation of CD8+ cells into CD103+ TRM cells and thereby modulates TRM-elicited antitumor immunity in colorectal cancer.

Significance:

Identification of an immunostimulatory function of dopamine signaling by promoting tissue-resident memory T-cell differentiation and sustaining T-cell effector functions reveals potential therapeutic strategies and prognostic biomarkers for colorectal cancer.
FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma
Authors: Baines Andrea C. , Ershler Rachel , Kanapuru Bindu , Xu Qing , Shen Guoxiang , Li Liang , Ma Lian , Okusanya Olanrewaju O. , Simpson Natalie E. , Nguyen Wanda , Theoret Marc R. , Pazdur Richard , Gormley Nicole J.
Published: July 2022

On August 5, 2020, the FDA granted accelerated approval to belantamab mafodotin-blmf (BLENREP; GlaxoSmithKline) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Substantial evidence of effectiveness was obtained from the phase II, multicenter DREAMM-2 trial. Patients received belantamab mafodotin 2.5 or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. The trial demonstrated an overall response rate of 31% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort. Keratopathy was the most frequent adverse event, occurring in 71% and 77% of patients, respectively. Other ocular toxicities included changes in visual acuity, blurred vision, and dry eye. The U.S. prescribing information for belantamab mafodotin includes a boxed warning for ocular toxicity, and belantamab mafodotin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy. This article summarizes the data and the FDA review process supporting accelerated approval of belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Anti-GD2 Antibodies Conjugated to IL15 and IL21 Mediate Potent Antitumor Cytotoxicity against Neuroblastoma
Authors: Nguyen Rosa , Zhang Xiyuan , Sun Ming , Abbas Shahroze , Seibert Charlie , Kelly Michael C. , Shern Jack F. , Thiele Carol J.
Published: July 2022

Purpose:

Half of the patients with high-risk neuroblastoma who receive GD2-targeted mAb do not achieve long-term remissions. Recently, the antibody hu14.18 has been linked to IL2 (hu14.18-IL2) to enhance its efficacy and shown promising preclinical and clinical activity. We developed two new immunocytokines (IC) by linking two other γc cytokines, IL15 and IL21, to hu14.18. The purpose of this study was to compare hu14.18-IL15 and -IL21 with hu14.18-IL2 in their ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC) against neuroblastoma.

Experimental Design:

We assessed ADCC of hu14.18-IL15 and -IL2 (human cytokines, cross-reactive to mouse) against GD2low and GD2high neuroblastoma cell lines in vitro. T-cell–deficient mice with orthotopic patient-derived xenografts (PDX) and immunocompetent mice with transplantable orthotopic neuroblastoma were used to test all three ICs, including hu14.18-IL21 (murine IL21, not cross-reactive to human). Mechanistic studies were performed using single-cell RNA-sequencing (scRNA-seq).

Results:

hu14.18-IL15 and hu14.18-IL2 mediated equivalent in vitro ADCC by human NK cells. When combined with chemotherapy, all three ICs similarly controlled the growth of PDXs in nude mice with murine NK effector cells. However, hu14.18-IL15 and -IL21 outperformed hu14.18-IL2 in immunocompetent mice with syngeneic neuroblastoma, inducing complete tumor regressions and extending survival. scRNA-seq data revealed an increase in CD8+ T cells and M1 tumor-associated macrophages and decreased regulatory T cells and myeloid-derived suppressor cells in the tumor microenvironment.

Conclusions:

Hu14.18-IL15 and Hu14.18-IL21 exhibit robust preclinical activity, warranting further consideration for clinical testing in patients with GD2-expressing neuroblastoma.
Enhancing PD-L1 Degradation by ITCH during MAPK Inhibitor Therapy Suppresses Acquired Resistance
Authors: Yang Zhentao , Wang Yan , Liu Sixue , Deng Weixian , Lomeli Shirley H. , Moriceau Gatien , Wohlschlegel James , Piva Marco , Lo Roger S.
Published: July 2022

MAPK inhibitor (MAPKi) therapy in melanoma leads to the accumulation of tumor-surface PD-L1/L2, which may evade antitumor immunity and accelerate acquired resistance. Here, we discover that the E3 ligase ITCH binds, ubiquitinates, and downregulates tumor-surface PD-L1/L2 in MAPKi-treated human melanoma cells, thereby promoting T-cell activation. During MAPKi therapy in vivo, melanoma cell–intrinsic ITCH knockdown induced tumor-surface PD-L1, reduced intratumoral cytolytic CD8+ T cells, and accelerated acquired resistance only in immune-competent mice. Conversely, tumor cell–intrinsic ITCH overexpression reduced MAPKi-elicited PD-L1 accumulation, augmented intratumoral cytolytic CD8+ T cells, and suppressed acquired resistance in BrafV600MUT, NrasMUT, or Nf1MUT melanoma and KrasMUT-driven cancers. CD8+ T-cell depletion and tumor cell–intrinsic PD-L1 overexpression nullified the phenotype of ITCH overexpression, thereby supporting an in vivo ITCH–PD-L1–T-cell regulatory axis. Moreover, we identify a small-molecular ITCH activator that suppresses acquired MAPKi resistance in vivo. Thus, MAPKi-induced PD-L1 accelerates resistance, and a PD-L1–degrading ITCH activator prolongs antitumor response.

Significance:

MAPKi induces tumor cell–surface PD-L1 accumulation, which promotes immune evasion and therapy resistance. ITCH degrades PD-L1, optimizing antitumor T-cell immunity. We propose degrading tumor cell–surface PD-L1 and/or activating tumor-intrinsic ITCH as strategies to overcome MAPKi resistance.

This article is highlighted in the In This Issue feature, p. 1825
miR-181a Improved Renal Inflammation by Targeting TNF-α in a Diabetic Nephropathy Animal Model
Authors: Liu Dan , Chen Ruoxin , Ni Haifeng , Liu Hong
Published: July 2022

Introduction: Recent studies have elucidated that miR-181a plays a vital role in various inflammation-associated diseases; however, its role in the pathogenesis of diabetic nephropathy (DN) has not been elucidated clearly. Hence, we investigated the involvement of miR-181a in the pathogenesis of DN in patients and animal models. Methods: miR-181a levels were measured in the kidneys of DN patients and a DN mouse model (db/db mice) by RT-PCR. The interaction of miR-181a with the 3′-UTR of potential target transcripts was investigated using luciferase reporter assays. miR-181a-GFP-AAV and miR-181a inhibitor were used to overexpress or downregulate miR-181a in the kidney of db/db mice, respectively. The expression of inflammatory proteins and target genes was measured in the kidneys of the animals. Results: In DN patients and DN mouse models, expression analyses showed a significant decrease in miR-181a levels in the kidney. In addition, a negative linear correlation between miR-181a and proinflammatory gene (IL-1β and TNF-α) levels was observed in the kidneys of DN patients. Overexpression of miR-181a reduced IL-1β and TNF-α expression, whereas suppression of miR-181a worsened these changes, which was attenuated by combined treatment with TNF-α neutralizing antibody in db/db mice. Moreover, luciferase assays revealed that TNF-α is a direct target of miR-181a. Conclusion: Our data emphasized the anti-inflammatory actions of miR-181a by targeting TNF-α in the context of renal inflammation in DN. Hence, we concluded that miR-181a could be a potential therapeutic option for minimizing renal inflammation in DN.
Intravitreal Cotton Fiber Foreign Body after Intravitreal Injection
Authors: Drnovšek Fran , Lumi Xhevat
Published: July 2022

Iatrogenic intraocular foreign bodies (IOFBs) are rare findings to be associated with sterile intraocular procedures. They are usually observed in the anterior chamber, introduced during cataract surgery, while IOFBs in the posterior segment of the eye are very rare. We report a case of a patient with intravitreal cotton fiber foreign body associated with intravitreal anti-VEGF injection. An 86-year-old male patient presented with sudden, painless loss of vision in his right eye. Examination of the fundus revealed dense subretinal hemorrhage (SRH) involving the macula and causing deterioration of vision. Examination also revealed a fiber foreign body in the posterior vitreous of the same eye. The patient had known neovascular age-related macular degeneration and had been treated with regular anti-VEGF intravitreal injections for the past 6 years. Due to SRH in his right, the only functioning eye, we decided to perform a pars plana vitrectomy. During the surgery, we were able to touch the intraocular fiber foreign body with surgical instruments and it proved to be soft, flexible, and relatively compact. Given the white color and composition, our conclusion was that it was a cotton fiber thread. Identical material is an integral part of cotton tips used to disinfect the conjunctiva with povidone iodine just before administering an intravitreal injection. We hypothesize that such a cotton tip was the source of the foreign body. Careful preparation of the operative field and selection of high-quality surgical materials are mandatory in avoiding such a complication.
Efficacy of Intrabronchial Voriconazole Instillation for Inoperable Pulmonary Aspergilloma: A Pilot Randomized Controlled Trial
Authors: Hadda Vijay , Doddamani Sachin , Mittal Saurabh , Tiwari Pavan , Madan Karan , Mohan Anant , Khan Maroof Ahmad , Bhalla Ashu Seith , Guleria Randeep
Published: July 2022

Background: Endobronchial administration of voriconazole is a potential therapeutic option for inoperable aspergilloma. Objective: This study aimed to assess the efficacy of endobronchial instillation of voriconazole for inoperable pulmonary aspergilloma. Method: Patients with mild to moderate hemoptysis, due to inoperable aspergilloma, were randomized to receive either medical therapy (MT) alone or bronchoscopic instillation of voriconazole with MT and followed up till 3 months. The primary objective of this study was to compare the percentage of patients achieving reduction in the severity of hemoptysis assessed on visual analogue scale (VAS) in intervention and control arm at 3 months. Results: This study included 60 patients (female = 47) with mean (SD) age of 40.6 (13.2) years who were randomized to receive either bronchoscopic instillation of voriconazole (n = 30) or MT alone (n = 30). At 3-month follow-up, the primary objective was achieved in 26/30 (86.7%) patients in intervention group as compared to 11/30 (36.7%) in the control group (p value <0.0001). The VAS score at 3 months was significantly lower in voriconazole group 13.9 (9.3) mm as compared to MT alone group 22.3 (11.5) mm, p value of 0.003. Bronchoscopic instillation of voriconazole was also associated with reduction in cough severity and size of the aspergilloma; however, there was no benefit of this therapy in terms of requirement of hospitalization and BAE. Conclusions: Our study shows that for nonoperable aspergilloma, bronchoscopic instillation of voriconazole is associated with reduction in the severity of hemoptysis. This therapy should be evaluated in large multi-center trials.
Bilateral Orbital Inflammation as a Manifestation of Paraneoplastic Syndrome
Authors: Yoshida Miyo , Suda Kenji , Oishi Akio , Fujimoto Masahiro , Nakano Eri , Kashii Satoshi , Ohsumi Akihiro , Tsujikawa Akitaka
Published: July 2022

Paraneoplastic neurologic syndromes (PNS) constitute a rare group of disorders whose optimal treatment is yet to be established. We report a patient with bilateral orbital inflammation associated with PNS, who responded well to surgical resection of the primary tumor. An 83-year-old woman was referred to our department for treatment of a progressive reduction in visual acuity and palpebral swelling in both eyes for the past 2 months. She was scheduled to undergo thoracic surgery for lung cancer. The best-corrected visual acuity (BCVA) in the right and left eye had worsened from 0.3 to 0.5 one month before she was referred to our department to 0.03 and 0.07, respectively. A slit-lamp examination revealed edema in both eyelids. Goldmann perimetry revealed several paracentral scotomas with constriction of the peripheral visual fields of both eyes, along with central absolute scotomas in V-4e isopter in the right eye. Magnetic resonance imaging revealed swelling of the bilateral extraocular muscles, which compressed the bilateral optic nerves at the orbital apex. Seven days after the resection of the lung cancer, the BCVA improved to 0.07 and 0.15 in the right and left eyes, respectively, without concomitant immunotherapy. Intravenous methylprednisolone (500 mg/day) was administered for 3 days to treat the residual orbital inflammation. Fourteen days after surgery, the BCVA further improved to 0.4 and 0.5 in the right and left eyes, respectively. Swelling of the bilateral extraocular muscles and the visual field abnormalities improved dramatically. Early diagnosis is crucial for the management of PNS.
Discriminatory Changes in Circulating Metabolites as a Predictor of Hepatocellular Cancer in Patients with Metabolic (Dysfunction) Associated Fatty Liver Disease
Authors: Lu Haonan , George Jacob , Eslam Mohammed , Villanueva Augusto , Bolondi Luigi , Reeves Helen L. , McCain Misti , Chambers Edward , Ward Caroline , Sartika Dewi , Sands Caroline , Maslen Lynn , Lewis Matthew R. , Ramaswami Ramya , Sharma Rohini
Published: July 2022

Introduction: The burden of metabolic (dysfunction) associated fatty liver disease (MAFLD) is rising mirrored by an increase in hepatocellular cancer (HCC). MAFLD and its sequelae are characterized by perturbations in lipid handling, inflammation, and mitochondrial damage. The profile of circulating lipid and small molecule metabolites with the development of HCC is poorly characterized in MAFLD and could be used in future studies as a biomarker for HCC. Methods: We assessed the profile of 273 lipid and small molecule metabolites by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry in serum from patients with MAFLD (n = 113) and MAFLD-associated HCC (n = 144) from six different centers. Regression models were used to identify a predictive model of HCC. Results: Twenty lipid species and one metabolite, reflecting changes in mitochondrial function and sphingolipid metabolism, were associated with the presence of cancer on a background of MAFLD with high accuracy (AUC 0.789, 95% CI: 0.721–0.858), which was enhanced with the addition of cirrhosis to the model (AUC 0.855, 95% CI: 0.793–0.917). In particular, the presence of these metabolites was associated with cirrhosis in the MAFLD subgroup (p < 0.001). When considering the HCC cohort alone, the metabolic signature was an independent predictor of overall survival (HR 1.42, 95% CI: 1.09–1.83, p < 0.01). Conclusion: These exploratory findings reveal a metabolic signature in serum which is capable of accurately detecting the presence of HCC on a background of MAFLD. This unique serum signature will be taken forward for further investigation of diagnostic performance as biomarker of early stage HCC in patients with MAFLD in the future.
Hsa_circ_0016070/micro‐340‐5p Axis Accelerates Pulmonary Arterial Hypertension Progression by Upregulating TWIST1 Transcription Via TCF4/β‐Catenin Complex
Authors: Huang Chun‐Xia , Jiang Zhi‐Xin , Du Da‐Yong , Zhang Zhi‐Min , Liu Yang , Li Yun‐Tian
Published: July 2022

Background

Hypoxia is considered a major leading cause of pulmonary hypertension (PH). In this study, the roles and molecular mechanism of circ_0016070 in PH were studied.

Methods and Results

The expression of circ_0016070 in serum samples, human pulmonary artery smooth muscle cells and hypoxia/monocrotaline‐treated rats was determined by real‐time quantitative polymerase chain reaction. Cell viability, migration, and apoptosis were analyzed by Cell Counting Kit‐8, wound healing, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays, respectively. The molecular interactions were validated using RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase reporter assays. The levels of phenotype switch‐related proteins were evaluated by Western blot and immunohistochemistry. The pathological characteristics were assessed using hematoxylin and eosin staining. circ_0016070 was highly expressed in the serum samples, hypoxia‐induced pulmonary artery smooth muscle cells and pulmonary arterial tissues of PH rats. Downregulation of circ_0016070 ameliorated the excessive proliferation, migration, vascular remodeling, and phenotypic transformation but enhanced cell apoptosis in the PH rat model. In addition, micro (miR)‐340‐5p was verified as a direct target of circ_0016070 and negatively regulated TCF4 (transcription factor 4) expression. TCF4 formed a transcriptional complex with β‐catenin to activate TWIST1 (Twist family bHLH transcription factor 1) expression. Functional rescue experiments showed that neither miR‐340‐5p inhibition nor TWIST1 or TCF4 upregulation significantly impeded the biological roles of circ_0010670 silencing in PH.

Conclusions

These results uncovered a novel mechanism by which circ_0016070 play as a competing endogenouse RNA of miR‐340‐5p to aggravate PH progression by promoting TCF4/β‐catenin/TWIST1 complex, which may provide potential therapeutic targets for PH.
Utility of Provocative Testing in the Diagnosis and Genotyping of Congenital Long QT Syndrome: A Systematic Review and Meta‐Analysis
Authors: Yang Ying , Lv Ting‐ting , Li Si‐yuan , Liu Peng , Gao Qing‐gele , Zhang Ping
Published: July 2022

Background

Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards.

Methods and Results

A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library through October 14, 2021. The fixed effects model was used to assess the effect of the provocative testing on QTc interval. A total of 22 studies with 1137 patients with LQTS were included. At baseline, QTc interval was 40 ms longer in patients with LQTS than in controls (mean difference [MD], 40.54 [95% CI, 37.43–43.65];
P
<0.001). Compared with the control group, patients with LQTS had 28 ms longer ΔQTc upon standing (MD, 28.82 [95% CI, 23.05–34.58];
P
<0.001), nearly 30 ms longer both at peak exercise (MD, 27.31 [95% CI, 21.51–33.11];
P
<0.001) and recovery 4 to 5 minutes (MD, 29.85 [95% CI, 24.36–35.35];
P
<0.001). With epinephrine infusion, QTc interval was prolonged both in controls and patients with QTS, most obviously in LQT1 (MD, 68.26 [95% CI, 58.91–77.60];
P
<0.001) and LQT2 (MD, 60.17 [95% CI, 50.18–70.16];
P
<0.001). Subgroup analysis showed QTc interval response to abrupt stand testing and exercise testing varied between LQT1, LQT2, and LQT3, named Type Ⅰ, Type Ⅱ, and Type Ⅲ.

Conclusions

QTc trend Type Ⅰ and Type Ⅲ during abrupt stand testing and exercise testing can be used to propose a prospective evaluation of LQT1 and LQT3, respectively. Type Ⅱ QTc trend combined epinephrine infusion testing could distinguish LQT2 from control. A preliminary diagnostic workflow was proposed but deserves further evaluation.
Single‐Center Experience of Hybrid Pulmonary Valve Replacement Using Left Anterior Thoracotomy With Pulmonary Artery Plication in Patients With Large Right Ventricular Outflow Tract
Authors: Carr Kaitlin , Mohammad Nijres Bassel , Windsor Jimmy J. , Nakamura Yuki , Karimi Mohsen , Ricci Marco , Aldoss Osamah
Published: July 2022

Background

Until recently, a large right ventricle outflow tract interfered with the feasibility of standard transcatheter pulmonary valve replacement (PVR). We are describing our experience using a hybrid approach for PVR using a left anterior thoracotomy approach to allow for plication of the main pulmonary artery followed by a transcatheter PVR using a Sapien S3 valve.

Methods and Results

This is a single‐center, retrospective review of patients who were evaluated to be appropriate for a hybrid PVR approach. The patients' demographics, procedure details, and follow‐up data were collected. Between May 2018 and April 2021, a total of 11 patients presented for hybrid transcatheter PVR. The median age and weight were 24 years (interquartile range, 19–43 years) and 81.8 kg (interquartile range, 69–91 kg), respectively. Nine out of 11 patients received a transcatheter PVR after main pulmonary artery plication. There were no procedurally related deaths. One major complication was encountered in which the valve was malpositioned requiring successful surgical PVR. Minor complications included acute kidney injury (n=1) and a broken rib (n=1). The median length of stay was 4 days (interquartile range, 2–4 days), with median follow‐up of 7 months (interquartile range, 3–18 months). A well‐functioning pulmonary valve was observed in all patients at the last follow‐up.

Conclusions

A hybrid approach using left anterior thoracotomy with pulmonary artery plication followed by transcatheter Sapien S3 PVR provides a less‐invasive option for patients with an enlarged right ventricular outflow tract. Preliminary results demonstrated this to be a safe option with good short‐term outcomes.
When A Nonnative Accent Lets You Spot All the Errors: Examining the Syntactic Interlanguage Benefit
Authors: Gosselin Leah , Martin Clara D. , González Martín Ana , Caffarra Sendy
Published: July 2022

In our continuously globalizing world, cross-cultural and cross-linguistic communications are far from exceptional. A wealth of research has indicated that the processing of nonnative-accented speech can be challenging for native listeners, both at the level of phonology. However, few online studies have examined the underpinnings of accented speech recognition from the perspective of the nonnative listener, even though behavioral studies indicate that accented input may be easier to process for such individuals (i.e., the interlanguage speech intelligibility benefit. The current EEG study first examined the phonological and syntactic analysis of nonnative-accented speech among nonnative listeners. As such, 30 English learners of Spanish listened to syntactically correct and incorrect Spanish sentences produced in native and nonnative-accented Spanish. The violation in the incorrect sentences was caused by errors that are typical (i.e., gender errors; *la color) or atypical (i.e., number errors; *los color) for English learners of Spanish. Results indicated that nonnative listeners elicit a phonological mismatch negativity (PMN) when attending to speech produced by a native Spanish speaker. Furthermore, the nonnative listeners showed a P600 for all grammatical violations, indicating that they repair all errors regardless of their typicality or the accent in which they are produced. Follow-up analyses compared our novel data to the data of native listeners from the methodologically identical precursor study. These analyses showed that native and nonnative listeners exhibit directionally opposite PMN effects; whereas natives exhibited a larger PMN for English-accented Spanish, nonnatives displayed a larger PMN in response to native Spanish utterances (a classic interlanguage speech intelligibility benefit). An additional difference was observed at the syntactic level: Whereas natives repaired only atypical number errors when they were English-accented, nonnative participants exhibited a P600 in response to all English-accented syntactic errors, regardless of their typicality (a syntactic interlanguage speech intelligibility benefit). Altogether, these results suggest that accented speech is not inherently difficult to process; in fact, nonnatives may benefit from the presence of a nonnative accent. Thus, our data provide some of the first electrophysiological evidence supporting the existence of the classic interlanguage speech intelligibility benefit and its novel syntactic counterpart.
Scrutinizing Whether Mere Group Membership Influences the N170 Response to Faces: Results from Two Preregistered Event-Related Potential Studies
Authors: Hong Youngki , Mayes Matthew S. , Munasinghe Anudhi P. , Ratner Kyle G.
Published: July 2022

A socially consequential test of the cognitive penetrability of visual perception is whether merely sharing a group membership with another person influences how you encode their face. Past research has examined this issue by manipulating group membership with techniques from social psychology and then measuring the face-sensitive N170 ERP. However, methodological differences across studies make it difficult to draw conclusions from this literature. In our research, we conducted two large-scale, preregistered ERP studies to address how critical methodological decisions could influence conclusions about top–down effects of group membership on face perception. Specifically, we examined how mere group membership, perceptual markers that signify group membership, number of trials included in the study design, the racial/ethnic identity of face stimuli, and the data analytic approach affect inferences about the N170 response to faces. In Study 1, we found no evidence that mere group membership significantly influenced the N170. However, we found that the background color used to signify group membership modulated the magnitude and latency of the N170. Exploratory analyses also showed effects of stimulus race/ethnicity. In Study 2, we dissociated background color from face encoding by presenting background color before the faces. In this second study, we found no main effect of group membership, background color, or stimulus race/ethnicity. However, we did see an unhypothesized mere group membership effect on trials toward the end of the study. Our results inform debates about social categorization effects on visual perception and show how bottom–up indicators of group membership can bias face encoding.
HIF-1α Stabilization Boosts Pulp Regeneration by Modulating Cell Metabolism
Authors: Han Y. , Koohi-Moghadam M. , Chen Q. , Zhang L. , Chopra H. , Zhang J. , Dissanayaka W.L.
Published: July 2022

Stem cell–based therapeutics is a promising strategy in dental pulp regeneration. However, low cell viability after transplantation in vivo due to the ischemic microenvironment is still a critical challenge for future clinical application. With the aim of improving postimplantation cell survival and pulp tissue regeneration, stem cells from human exfoliated deciduous teeth (SHED) were preconditioned to a hypoxic condition by hypoxia-inducible factor 1α (HIF-1α) stabilization via knockdown of prolyl hydroxylase domain-containing protein 2 (PHD2) using lentiviral short hairpin RNA. HIF-1α–stabilized SHED were encapsulated in PuraMatrix hydrogel, injected into root canals of human tooth fragments, and implanted in the subcutaneous space of immunodeficient mice. After 28 d, enhanced dental pulp–like tissue formation was observed with a significantly higher level of vascularization, which could be attributed to both endothelial differentiation of SHED and recruitment of host blood vessels. Furthermore, dentin-like tissue formation in vivo and accelerated odontogenic/osteogenic differentiation both in vivo and in vitro were observed. At 7 d postimplantation, significantly less DNA damage and higher Ki67 expression were detected in the HIF-1α–stabilized SHED group compared with the control SHED. Accordingly, cell viability assay and staining for Ki67 and apoptotic cells in vitro showed that HIF-1α stabilization could decrease cell apoptosis and enhance cell survival significantly. We demonstrated that PI3K/AKT pathway activation had resulted in low caspase 3 expression in HIF-1α–stabilized SHED in hypoxic conditions. Furthermore, we found that HIF-1α–induced cell survival could also be attributed to the upregulated expression of PDK1, HK2, and Glut1, which contributes to the maintenance of reactive oxygen species homeostasis and metabolic adaptation in hypoxia. In addition, we identified Smad7 as 1 of the top 3 upregulated genes through RNA sequencing in HIF-1α–stabilized SHED and demonstrated its essential role in HK2 and Glut1 upregulation. Taken together, HIF-1α stabilization enhances cell survival of SHED through modulating various target genes and potential signaling pathways, as well as odontogenic tissue formation during dental pulp regeneration, which could benefit stem cell–based therapy in general.
(Un)Standardizing Emotions: An Ethical Critique of Social and Emotional Learning Standards
Authors: Clark Caroline T. , Chrisman Alyssa , Lewis Suzanne G.
Published: July 2022

Background:

This study took place within a policy context in which the state of Ohio, echoing moves across the country, adopted a set of K–12 Social and Emotional Learning (SEL) standards based in the work of the Collaborative for Academic and Social Emotional Learning (CASEL) and its core competencies: self-awareness, self-management, social awareness, relationship skills, and responsible decision-making. As one of the first states to make such standards part of the state reporting system for school progress, and considering recent critiques of the hegemonic, normative impacts of SEL, we engaged in a systematic analysis of these standards to consider how they affect and further exacerbate the systemic oppressions experienced by multiply-marginalized people in schools.

Purpose:

This article reports on the normative assumptions in the Ohio SEL standards, using critical discourse analysis (CDA) and the DisCrit tenets to engage in an ethical critique of the real and potential social effects of these standards. Situating these standards relative to existing scholarship on race and dis/abilities in school, we show how the Ohio SEL standards and the CASEL competencies ignore racism, ableism, and other oppressions; privilege civility over productive conflict; and focus on behaviors over emotions, especially when expressed by Black, Brown, dis/abled, and queer people.

Research Design:

This is a qualitative study whose data were derived from an analysis of the Ohio K–12 Social and Emotional Learning Standards and the CASEL core competencies.

Conclusions/Recommendations:

Our ethical critique of the Ohio K–12 SEL standards and CASEL core competencies demonstrates how benign acquiescence to their expressed assumptions may negatively affect the experiences of multiply-marginalized people in schools. By ignoring racism, ableism, and other oppressions; privileging civility over productive conflict; and focusing on behaviors over emotions, especially when expressed by Black, Brown, dis/abled, and queer people, SEL standards may undermine or erase the critically productive role that emotions have played in movements for social justice. If we truly want to prioritize the actual social and emotional learning of all students in schools, we need a framework that explicitly names inequities, allows for collective agency, and acknowledges and enables access to emotions. Making space for these emotions, although considered by some to be outside the “norm” of acceptable classroom behaviors, would allow all students to be seen for who they are, to truly express how they feel, and to create and take up opportunities, themselves, for social change and justice.
SEA-PS: Semantic embedding with attention to measuring patent similarity by leveraging various text fields
Authors: Wang Zihong , Liu Yufei
Published: July 2022

Similarity metrics are critical to identifying the relationships between patents. While many bibliometric methods such as co-citation and co-classification fail to use the vast majority of technical information existing in the text, most text mining methods focus on keywords in only one text field of the patent document. This article aims to leverage various text fields to measure pairwise patent similarity according to their technological bases. A novel approach called semantic embedding with attention for patent similarity (SEA-PS) is proposed. First, the method identifies technological bases and models the semantic relatedness. To achieve this, we put forward an additional patent stop-word list to help extract technical terms with an n-gram-based statistical method. The technical terms are then mapped into a vector space using word embedding. Second, we propose a graph-based method to allocate weights to distinguish the technical focus, considering the linkages between technologies. Finally, we assess the feasibility of the text fields, and integrate their semantics at the patent-level with an attention layer to conduct similarity metrics. The validations are from two perspectives: content validity (coverage of technical information, the validity of semantic representations and effectiveness of text field combinations), and external validity against existing methods via an expert panel. The results demonstrate the superiority of SEA-PS to existing methods, and suggest that ‘abstracts’, ‘claims’ and ‘technical descriptions’ are more effective than ‘titles’. SEA-PS is a fundamental tool for patent retrieval and classification. It also has a broad range of practical applications in innovation and strategy studies, including identifying technological frontiers and studying knowledge spillovers.
Predictors of Relationship Satisfaction Across the Transition to Parenthood: Results from the Norwegian Mother, Father, and Child Cohort Study (MoBa)
Authors: Kingsbury Mila , Clayborne Zahra , Nilsen Wendy , Torvik Fartein Ask , Gustavson Kristin , Colman Ian
Published: July 2022

The purpose of the study was to describe trajectories of relationship satisfaction across the transition to parenthood, and identify predictors of these trajectories. This study is based on the Norwegian Mother, Father, and Child Cohort Study (MoBa). Mothers (N = 43,517) reported on their relationship satisfaction at five timepoints from 17 weeks gestation to 5 years postpartum, as well as sociodemographic, psychological, and behavioral covariates. Latent Trajectory Modeling revealed 5 trajectories of relationship satisfaction: “stable very high” (18.05%), “stable high” (43.47%); “stable moderate” (17.21%); “high falling” (3.38%); and “low falling” (4.02%). Predictors of group membership were identified using multinomial logistic regression. Significant predictors included unplanned pregnancy, maternal social support, maternal history of depression, maternal history of abuse, postnatal depression, financial stress, sexual satisfaction, and child negative emotionality. These results may help identify families at risk of declining relationship satisfaction, and aid in targeting interventions aimed at improving satisfaction during this vulnerable transition.
Causes of Mortality and Profile of Spontaneous Tumors in Young CD-1 Mice
Authors: Apreutese Ancuta , Levi Michela , Taylor Ian , Apreutese Radu , Mukaratirwa Sydney , Mowat Vasanthi
Published: July 2022

A retrospective study was performed to establish the causes of mortality and incidence patterns of tumors in young (<50 weeks) control CD-1® mice from Charles River Laboratories. Tumor incidences (fatal and nonfatal) and nonneoplastic causes of death observed during the first 50 weeks of the study were collected from 48 thirteen-week toxicity studies conducted between 2009 and 2018 and from 43 carcinogenicity studies conducted between 2005 and 2018. Thirteen-week studies had a mortality rate of 8/620 (1.3%) in males and 4/620 (0.65%) in females. The major factors contributing to death were integument lesions in males (3/8) and experimental procedure–related injuries in females (3/4). All tumors recorded were nonfatal. Bronchiolo-alveolar adenoma was the commonest tumor with the same incidence in both males and females (4/620, 0.65%); a single lymphoma (0.16%) and uterine leiomyosarcoma (1/620 0.16%) were reported in females. The mortality rates of males and females that died or were euthanized during the first 50 weeks in carcinogenicity studies were 192/2830 (6.8%) and 198/2830 (7%), respectively. The most common fatal tumor in this age group was lymphoma in both sexes, with an incidence of 18/192 (9.3%) and 41/198 (20.7%) in males and females, respectively. In males tumors were responsible for fewer deaths than in females (17% vs. 32.3%). The major nonneoplastic causes of death or moribundity were cutaneous lesions (44/192, 22.9%), and obstructive uropathy (39/192, 20.3%) in males, and chronic progressive nephropathy (40/198, 20.2%) in females. Only minor differences were evident compared to a similar study performed 15 years ago; these might reflect changes in terminology and diagnostic criteria, and stricter animal welfare endpoints.
Divine Proportions in the Assessment of Facial Esthetics—Antiquity vs Contemporary: A Systematic Review
Authors: Chaitanya A. S. Krishna , Reddy G. Ramya , Reddy A. Kaladhar , Rachala Madhukar Reddy , Reddy G. Prabhandh , Reddy S. N. Praveenkanth
Published: July 2022

Objective:

The objective of this research was to systematically evaluate evidence regarding the correlation between divine proportions and facial esthetics.

Materials and Methods:

An extensive literature search was performed in multiple electronic databases such as PubMed, Medline, Embase, ScienceDirect, and ProQuest which included articles published from May 1982 to March 2021 in the English language. Furthermore, only randomized clinical trials and original research studies were included. The risk of bias in the included studies was assessed by using the Cochrane risk-of-bias tool ROBVIS (Risk-of-bias VISualization tool).

Results:

A total of 2,736 articles were retrieved and 974 duplicate records were eliminated; subsequently, articles were screened based on title and abstracts, inclusion and exclusion criteria from which a total of 14 original articles were included in the systematic review. Of the 14 included studies, 5 studies showed a low risk of bias, 6 studies showed a moderate risk of bias, and 3 showed a high risk of bias. Four studies showed a positive correlation and 10 studies showed a negative correlation between divine proportions and facial esthetics.

Conclusion:

The evidence from this study suggests that there exists a weak correlation between divine proportions and facial esthetics. Hence, divine proportions are not absolute determinants and are only partially related to facial attractiveness. Further high-quality cross-sectional studies with a strong methodology are needed to establish the correlation between divine proportions and facial esthetics and to support this evidence. Trial registration number: PROSPERO CRD42022302308
Built Environment and Loneliness Among Older Adults in South East Queensland, Australia
Authors: Lam Jack , Wang Siqin
Published: July 2022

Objective: To examine characteristics of the built environment and investigate associations with loneliness among older adults. Methods: Drawing on geocoded data from the Household, Income and Labour Dynamics in Australia Survey and measures of neighborhood features retrieved from multiple publicly available sources, we conducted principal component and regression analyses to examine the associations between characteristics of the built environment and loneliness among older adults in South East Queensland, Australia. Results: Older adults living in compact neighborhoods with higher population and housing density, smaller land parcels, and more access to green space reported lower levels of loneliness. Compact and mixed land-use neighborhoods may increase people’s exposure to and social interactions with surrounding people and the environment. Conclusion: The built environment provides the context for social interactions. Our study and findings inform research and suggest the development of interventions surrounding the built environment that could potentially help tackle loneliness in older adults.
Combined effect of circumferential roughness and squeeze velocity on ferrofluid squeeze film with rotating sphere and rough plate
Authors: Patel Darshana A , Kataria Ramesh C
Published: July 2022

Based on the Jenkins model for ferrofluid flow regarding the performance of squeeze-film lubrication between rotating upper spherical surface and circumferentially rough lower plate is presented. Here, for hydrodynamic lubrication, we have adopted the ferrohydrodynamic theory. Further, using Christensen’s stochastic model, surface roughness is examined. In the paper, in the presence of a radially variable magnetic field, rotations of both the upper and lower surfaces as well as roughness of the surface, the Reynolds type equation for the squeeze-film bearing is established. By using the Reynolds type equation, expressions for the non-dimensional film pressure and load-carrying capacity are obtained for circumferential roughness pattern. Neuringer–Rosensweig (NR) model results are computed using the Jenkins model. The results show that non-dimensional film pressure increases remarkably when the non-dimensional radial parameter ( R) increases. Also, as the nominal minimum film thickness increases, load-carrying capacity decreases in the Jenkins model. However, as a result of Tables 5 and 6, the non-dimensional load-carrying capacity of the Jenkins model is improved compared to that of the NR model.
Effect of nano-Sized Al2O3 Particles on Microstructure and Mechanical Properties of Aluminum Matrix Composite Fabricated by Multipass FSW
Authors: Rani Preety , Misra R.S. , Mehdi Husain
Published: July 2022

Powder metallurgy is versatile in fabricating the reinforced aluminum matrix composite (AMCs) by combining aluminum alloy with various nanoparticles. However, the AMCs fabricated by the powder metallurgy generally lack ductility due to processing-related factors such as undesirable microstructure, oxygen content, and porosity. In this work, the effect of multipass friction stir welding and Al2O3 nanoparticles of friction stir welded joint of AA5083 and AA6061 was investigated. The results demonstrated that multipass FSW significantly impacts the Al2O3 nanoparticles’ distribution. Furthermore, the dispersion pattern of Al2O3 nanoparticles in the stir zone strongly influenced the microstructure and mechanical properties. The tensile strength, % strain, and microhardness of the AMCs were improved after implementing multipass FSW. The improvement in the mechanical properties was observed via higher grain refinement by pinning effect and dynamic recrystallization (DRX) by Al2O3 nanoparticles.
Enhancing data locality of the conjugate gradient method for high-order matrix-free finite-element implementations
Authors: Kronbichler Martin , Sashko Dmytro , Munch Peter
Published: July 2022

This work investigates a variant of the conjugate gradient (CG) method and embeds it into the context of high-order finite-element schemes with fast matrix-free operator evaluation and cheap preconditioners like the matrix diagonal. Relying on a data-dependency analysis and appropriate enumeration of degrees of freedom, we interleave the vector updates and inner products in a CG iteration with the matrix-vector product with only minor organizational overhead. As a result, around 90% of the vector entries of the three active vectors of the CG method are transferred from slow RAM memory exactly once per iteration, with all additional access hitting fast cache memory. Node-level performance analyses and scaling studies on up to 147k cores show that the CG method with the proposed performance optimizations is around two times faster than a standard CG solver as well as optimized pipelined CG and s-step CG methods for large sizes that exceed processor caches, and provides similar performance near the strong scaling limit.
Physical Activity, Inflammation, and Physical Function in Older Adults: Results From the Health & Retirement Study
Authors: Hlebichuk Jeanne L. , Gretebeck Randall J. , Garnier-Villarreal Mauricio , Piacentine Linda B. , Singh Maharaj , Gretebeck Kimberlee A.
Published: July 2022

Physical function declines with aging due to physical and biological changes. The biological process of aging has been associated with increases in systemic inflammation and a greater risk for chronic conditions. In older adults, physical activity aids in maintenance of function. However, the influence of inflammatory biomarkers and adiposity on physical activity and physical function needs to be further explored. Methods: A cross-sectional secondary data analysis from Wave 13 of the Health & Retirement Study (HRS) core biennial data and Venous Blood Study (VBS) was conducted. Structural equation modeling was used to establish the model and test the relationships. Results: Chronic low-level inflammation was moderately negatively correlated with physical activity (r = −0.326) and function (r = −0.367). Latent regressions showed that higher physical activity is associated with better physical function (unstandardized estimate = 0.600, p < .001) while inflammation negatively affects physical function (unstandardized estimate = −0.139, p < .001), and adiposity was not a predictor in the model ( p = 0.055). Conclusion: For older adults, preserving physical function by participation in physical activity and decreasing chronic inflammation are key preventive health strategies for older adults to maintain independence, with a need to further explore pro and anti-inflammatory biomarkers.