bluuebunny/crossref_metadata_2025 huggingface dataset:
Susceptibility-Associated Genetic Variation in NEDD9 Contributes to Prostate Cancer Initiation and Progression
Authors: Han Dong , Owiredu Jude N. , Healy Bridget M. , Li Muqing , Labaf Maryam , Steinfeld Jocelyn S. , Patalano Susan , Gao Shuai , Liu Mingyu , Macoska Jill A. , Zarringhalam Kourosh , Siegfried Kellee R. , Yuan Xin , Rebbeck Timothy R. , Cai Changmeng
Published: February 2021

Although American men of European ancestry represent the largest population of patients with prostate cancer, men of African ancestry are disproportionately affected by prostate cancer, with higher prevalence and worse outcomes. These racial disparities in prostate cancer are due to multiple factors, but variations in genomic susceptibility such as SNP may play an important role in determining cancer aggressiveness and treatment outcome. Using public databases, we have identified a prostate cancer susceptibility SNP at an intronic enhancer of the neural precursor expressed, developmentally downregulated 9 (NEDD9) gene, which is strongly associated with increased risk of patients with African ancestry. This genetic variation increased expression of NEDD9 by modulating the chromatin binding of certain transcription factors, including ERG and NANOG. Moreover, NEDD9 displayed oncogenic activity in prostate cancer cells, promoting prostate cancer tumor growth and metastasis in vitro and in vivo. Together, our study provides novel insights into the genetic mechanisms driving prostate cancer racial disparities.

Significance:

A prostate cancer susceptibility genetic variation in NEDD9, which is strongly associated with the increased risk of patients with African ancestry, increases NEDD9 expression and promotes initiation and progression of prostate cancer.

See related commentary by Mavura and Huang, p. 3764
Association of Fusobacterium nucleatum with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment
Authors: Borowsky Jennifer , Haruki Koichiro , Lau Mai Chan , Dias Costa Andressa , Väyrynen Juha P. , Ugai Tomotaka , Arima Kota , da Silva Annacarolina , Felt Kristen D. , Zhao Melissa , Gurjao Carino , Twombly Tyler S. , Fujiyoshi Kenji , Väyrynen Sara A. , Hamada Tsuyoshi , Mima Kosuke , Bullman Susan , Harrison Tabitha A. , Phipps Amanda I. , Peters Ulrike , Ng Kimmie , Meyerhardt Jeffrey A. , Song Mingyang , Giovannucci Edward L. , Wu Kana , Zhang Xuehong , Freeman Gordon J. , Huttenhower Curtis , Garrett Wendy S. , Chan Andrew T. , Leggett Barbara A. , Whitehall Vicki L.J. , Walker Neal , Brown Ian , Bettington Mark , Nishihara Reiko , Fuchs Charles S. , Lennerz Jochen K. , Giannakis Marios , Nowak Jonathan A. , Ogino Shuji
Published: February 2021

Purpose:

While evidence indicates that Fusobacterium nucleatum (F. nucleatum) may promote colorectal carcinogenesis through its suppressive effect on T-cell–mediated antitumor immunity, the specific T-cell subsets involved remain uncertain.

Experimental Design:

We measured F. nucleatum DNA within tumor tissue by quantitative PCR on 933 cases (including 128 F. nucleatum–positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on Bifidobacterium, microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages [TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay]. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between F. nucleatum and T-cell subsets.

Results:

The amount of F. nucleatum was inversely associated with tumor stromal CD3+ lymphocytes [multivariable OR, 0.47; 95% confidence interval (CI), 0.28–0.79, for F. nucleatum–high vs. -negative category; Ptrend = 0.0004] and specifically stromal CD3+CD4+CD45RO+ cells (corresponding multivariable OR, 0.52; 95% CI, 0.32–0.85; Ptrend = 0.003). These relationships did not substantially differ by MSI status, neoantigen load, or exome-wide tumor mutational burden. F. nucleatum was not significantly associated with tumor intraepithelial T cells or with M1 or M2 TAMs.

Conclusions:

The amount of tissue F. nucleatum is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells.
Independent Validation of the PAM50-Based Chemo-Endocrine Score (CES) in Hormone Receptor–Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti–HER2-Based Therapy
Authors: Pascual Tomás , Fernandez-Martinez Aranzazu , Tanioka Maki , Dieci M. Vittoria , Pernas Sonia , Gavila Joaquin , Guarneri Valentina , Cortes Javier , Villagrasa Patricia , Chic Núria , Vidal Maria , Adamo Barbara , Muñoz Montserrat , Griguolo Gaia , Llombart Antonio , Conte Pierfranco , Oliveira Mafalda , Conte Benedetta , Paré Laia , Galvan Patricia , Carey Lisa A. , Perou Charles M. , Prat Aleix
Published: February 2021

Purpose:

We do not yet have validated biomarkers to predict response and outcome within hormone receptor–positive/HER2-positive (HR+/HER2+) breast cancer. The PAM50-based chemo-endocrine score (CES) predicts chemo-endocrine sensitivity in hormone receptor–positive/HER2-negative (HR+/HER2−) breast cancer. Here, we evaluate the relationship of CES with response and survival in HR+/HER2+ breast cancer.

Experimental Design:

Intrinsic subtype and clinicopathologic data were obtained from seven studies in which patients were treated with HER2-targeted therapy either with endocrine therapy (ET) or with chemotherapy (CTX). CES was evaluated as a continuous variable and categorically from low to high scores [CES-C (chemo-sensitive), CES-U (uncertain), and CES-E (endocrine-sensitive)]. We first analyzed each dataset individually, and then all combined. Multivariable analyses were used to test CES association with pathologic complete response (pCR) and disease-free survival (DFS).

Results:

A total of 457 patients were included (112 with ET and 345 with CTX). In the combined cohort, CES-C, CES-U, and CES-E were identified in 60%, 23%, and 17% of the patients, respectively. High CES (i.e., CES-E) was associated with a lower probability of achieving pCR independently of clinical characteristics, therapy, intrinsic subtype, and study (adjusted OR = 0.42; P = 0.016). A total of 295 patients were analyzed for DFS with a median follow-up of 66 months. High CES was also associated with better DFS (adjusted HR, 0.174; P = 0.003) independently of pCR, clinical characteristics and intrinsic subtype. In patients with residual disease, the adjusted DFS HR of CES was 0.160 (P = 0.012).

Conclusions:

In HER2+/HR+ breast cancer, CES is useful for predicting chemo-endocrine sensitivity and provides additional prognostication beyond intrinsic subtype and clinicopathologic characteristics.
FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation
Authors: Pulte E. Dianne , Norsworthy Kelly J. , Wang Yaping , Xu Qing , Qosa Hisham , Gudi Ramadevi , Przepiorka Donna , Fu Wentao , Okusanya Olanrewaju O. , Goldberg Kirsten B. , De Claro R. Angelo , Farrell Ann T. , Pazdur Richard
Published: February 2021

On November 28, 2018, the FDA approved gilteritinib (Xospata; Astellas), a small-molecule FMS-like tyrosine kinase 3 (FLT3) inhibitor, for treatment of relapsed or refractory acute myeloid leukemia with a FLT3 mutation as detected by an FDA-approved test. In the ADMIRAL study, patients were randomized 2:1 to receive gilteritinib or standard chemotherapy and stratified by response to first-line treatment and intensity of prespecified chemotherapy. Efficacy was established on interim analysis on the basis of complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion from transfusion dependence to transfusion independence in 138 patients in the gilteritinib arm. With median follow-up of 4.6 months [95% confidence interval (CI), 2.8–15.8 months] at interim analysis, the CR + CRh rate was 21% (95% CI, 15%–29%), median duration of CR + CRh was 4.6 months (range, 0.1–15.8+), and conversion from transfusion dependence to transfusion independence was 31%. Revised labeling approved on May 29, 2019 included the results of the final analysis, showing an improvement in overall survival (OS) with gilteritinib compared with chemotherapy (HR, 0.64; 95% CI, 0.49–0.83; one-sided P = 0.0004; median OS, 9.3 vs. 5.6 months). The OS benefit was observed in both high and low chemotherapy intensity subgroups. Labeling includes a boxed warning for differentiation syndrome and warnings for posterior reversible encephalopathy syndrome, QT prolongation, pancreatitis, and embryo-fetal toxicity. Safe use requires frequent monitoring of electrocardiograms and blood chemistries. Assessments of long-term safety are pending.
FDA Approval Summary: Nivolumab with Ipilimumab and Chemotherapy for Metastatic Non–small Cell Lung Cancer, A Collaborative Project Orbis Review
Authors: Vellanki Paz J. , Mulkey Flora , Jaigirdar Adnan A. , Rodriguez Lisa , Wang Yibo , Xu Yuan , Zhao Hong , Liu Jiang , Howe Grant , Wang Jian , Choo Qiuyi , Golding Sarah J. , Mansell Victoria , Korsah Kwadwo , Spillman Dianne , de Claro R. Angelo , Pazdur Richard , Beaver Julia A. , Singh Harpreet
Published: February 2021

On May 26, 2020, the FDA approved nivolumab with ipilimumab and two cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non–small cell lung cancer (NSCLC), with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. The approval was based on results from Study CA2099LA (CheckMate 9LA), an open-label trial in which 719 patients with NSCLC were randomized to receive nivolumab with ipilimumab and two cycles of chemotherapy (n = 361) or four cycles of platinum-doublet chemotherapy (n = 358). Overall survival (OS) was improved for patients who received nivolumab with ipilimumab and chemotherapy, with a median OS of 14.1 months [95% confidence interval (CI), 13.2–16.2] compared with 10.7 months (95% CI, 9.5–12.5) for patients who received chemotherapy (HR, 0.69; 96.71% CI, 0.55–0.87; P = 0.0006). Progression-free survival and overall response rate per blinded independent central review were also statistically significant. This was the first NSCLC application reviewed under FDA's Project Orbis, in collaboration with Singapore's Health Sciences Authority, Australia's Therapeutic Goods Administration, and Health Canada. The benefit–risk analysis supports FDA's approval of nivolumab with ipilimumab and chemotherapy.
Robust Antitumor Activity and Low Cytokine Production by Novel Humanized Anti-CD19 CAR T Cells
Authors: Dwivedi Alka , Karulkar Atharva , Ghosh Sarbari , Srinivasan Srisathya , Kumbhar Bajarang Vasant , Jaiswal Ankesh Kumar , Kizhakeyil Atish , Asija Sweety , Rafiq Afrin , Kumar Sushant , Nisar Albeena , Patil Deepali Pandit , Poojary Minal Vivek , Jain Hasmukh , Banavali Shripad D. , Highfill Steven L. , Stroncek David F. , Shah Nirali N. , Fry Terry J. , Narula Gaurav , Purwar Rahul
Published: February 2021

Recent studies have described the remarkable clinical outcome of anti-CD19 chimeric antigen receptor (CAR) T cells in treating B-cell malignancies. However, over 50% of patients develop life-threatening toxicities associated with cytokine release syndrome which may limit its utilization in low-resource settings. To mitigate the toxicity, we designed a novel humanized anti-CD19 CAR T cells by humanizing the framework region of single-chain variable fragment (scFv) derived from a murine FMC63 mAb and combining it with CD8α transmembrane domain, 4-1BB costimulatory domain, and CD3ζ signaling domain (h1CAR19-8BBζ). Docking studies followed by molecular dynamics simulation revealed that the humanized anti-CD19 scFv (h1CAR19) establishes higher binding affinity and has a flexible molecular structure with CD19 antigen compared with murine scFv (mCAR19). Ex vivo studies with CAR T cells generated from healthy donors and patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) expressing either h1CAR19 or mCAR19 showed comparable antitumor activity and proliferation. More importantly, h1CAR19-8BBζ T cells produced lower levels of cytokines (IFNγ, TNFα) upon antigen encounter and reduced the induction of IL6 cytokine from monocytes than mCAR19-8BBζ T cells. There was a comparable proliferation of h1CAR19-8BBζ T cells and mCAR19-8BBζ T cells upon repeated antigen encounter. Finally, h1CAR19-8BBζ T cells efficiently eliminated NALM6 tumor cells in a preclinical model. In conclusion, the distinct structural modification in CAR design confers the novel humanized anti-CD19 CAR with a favorable balance of efficacy to toxicity providing a rationale to test this construct in a phase I trial.
The Monoacylglycerol Lipase Inhibitor JZL184 Inhibits Lung Cancer Cell Invasion and Metastasis via the CB1 Cannabinoid Receptor
Authors: Prüser Jan Lukas , Ramer Robert , Wittig Felix , Ivanov Igor , Merkord Jutta , Hinz Burkhard
Published: February 2021

A targeted modulation of the endocannabinoid system is currently discussed as a promising strategy for cancer treatment. An important enzyme for the endocannabinoid metabolism is the monoacylglycerol lipase (MAGL), which catalyzes the degradation of 2-arachidonoylglycerol (2-AG) to glycerol and free fatty acids. In this study, we investigated the influence of MAGL inhibition on lung cancer cell invasion and metastasis. Using LC-MS, significantly increased 2-AG levels were detected in A549 cells treated with the MAGL inhibitor JZL184. In athymic nude mice, JZL184 suppressed metastasis of A549 cells in a dose-dependent manner, whereby the antimetastatic effect was cancelled by the CB1 receptor antagonist AM-251. In vitro, JZL184 induced a time- and concentration-dependent reduction of A549 cell invasion through Matrigel-coated membranes, which was likewise reversed by AM-251. An MAGL inhibition–associated reduction of free fatty acids as a cause of the anti-invasive effect could be excluded by add-back experiments with palmitic acid. Both JZL184 and the MAGL substrate 2-AG led to an increased formation of the tissue inhibitor of metalloproteinase-1 (TIMP-1), whereby a TIMP-1 knockdown using siRNA significantly attenuated the anti-invasive effects of both substances. Decreased invasion and TIMP-1 upregulation was also caused by the MAGL inhibitors JW651 and MJN110 or transfection with MAGL siRNA. A CB1- and TIMP-1–dependent anti-invasive effect was further confirmed for JZL184 in H358 lung cancer cells. In conclusion, MAGL inhibition led to a CB1-dependent decrease in human lung cancer cell invasion and metastasis via inhibition of 2-AG degradation, with TIMP-1 identified as a mediator of the anti-invasive effect.
A Novel Antibody–IL15 Fusion Protein Selectively Localizes to Tumors, Synergizes with TNF-based Immunocytokine, and Inhibits Metastasis
Authors: Corbellari Riccardo , Stringhini Marco , Mock Jaqueline , Ongaro Tiziano , Villa Alessandra , Neri Dario , De Luca Roberto
Published: February 2021

IL15 is an immunostimulatory cytokine that holds promises for cancer therapy, but its performance (alone or as partner for fusion proteins) has often been limited by suboptimal accumulation in the tumor and very rapid clearance from circulation. Most recently, the Sushi Domain (SD, the shortest region of IL15 receptor α, capable of binding to IL15) has been fused to IL15-based anticancer products to increase its biological activity. Here, we describe two novel antibody fusion proteins (termed F8-F8-IL15 and F8-F8-SD-IL15), specific to the alternatively spliced EDA domain of fibronectin (a marker of tumor neoangiogenisis, expressed in the majority of solid and hematologic tumors, but absent in normal healthy tissues) and featuring the F8 antibody in single-chain diabody format (with a short linker between VH and VL, thus allowing the domains to pair with the complementary ones of another chain). Unlike previously described fusions of the F8 antibody with human IL15, F8-F8-IL15 and F8-F8-SD-IL15 exhibited a preferential uptake in solid tumors, as evidenced by quantitative biodistribution analysis with radioiodinated protein preparations. Both products were potently active in vivo against mouse metastatic colon carcinomas and in sarcoma lesion in combination with targeted TNF. The results may be of clinical significance, as F8-F8-IL15 and F8-F8-SD-IL15 are fully human proteins, which recognize the cognate tumor-associated antigen with identical affinity in mouse and man.
Comunicação e Mediações: novas perspectivas
Authors:   Universidade Federal do Mato Grosso do Sul
Published: February 2021

O Programa de Cooperação Acadêmica (PROCAD), financiado pela Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), com o tema “Comunicação e Mediações em contexto regionais: usos midiáticos, culturais e linguagens” permitiu a reunião entre pesquisadores de três universidades de três estados diferentes: Universidade de São Paulo - USP, Universidade Federal do Mato Grosso do Sul - UFMS e Universidade Federal do Rio Grande do Norte - UFRN. Foram cinco anos entre projetos de pesquisa, seminários, aulas e bancas que contribuíram com os mestrandos, doutorandos e graduandos, e que ainda nutriram iniciações científicas e ações em projetos de extensão universitária nas três universidades. Este é o segundo livro realizado pelo PROCAD/CAPES e, a partir dele, é possível refletir o social, o político e o cultural de cada região. As pesquisas realizadas e presentes neste livro apresentam esse Brasil de dimensão continental, assim como a cultura, comunicação e mediação de cada estado envolvido, já que as mediações em contextos regionais permitem compreender o sujeito na dinâmica dos processos comunicacionais com suas apropriações diante das realidades de cada estado.
Vascular Hypothesis of Alzheimer Disease
Authors: Scheffer Sanny , Hermkens Dorien M.A. , van der Weerd Louise , de Vries Helga E. , Daemen Mat J.A.P.
Published: February 2021

Alzheimer disease (AD) is marked by profound neurodegeneration, neuroinflammation, and cognitive decline. Pathologically, AD is characterized by the accumulation of extracellular amyloid and intraneuronal tangles, consisting of hyperphosphorylated tau. To date, factors leading to disease onset and progression are still an important topic of investigation. Various epidemiological studies revealed cardiovascular disease as an important contributor to the development and progression of AD, leading to the so-called vascular hypothesis. Vascular risk factors, such as hypertension, diabetes, and hyperhomocysteinemia, are associated with a significantly increased chance of developing AD, suggesting an additive or even synergistic effect. These vascular risk factors are often linked to a reduction in cerebral blood flow and the resulting chronic cerebral hypoperfusion is suggested to play a key role in the onset of AD. However, the causal effects of such vascular risk factors for AD onset remain largely unknown. Evidence from animal studies support that chronic cerebral hypoperfusion induction causes a strong aggravation of AD-related pathology, but a comprehensive overview of how the various cardiovascular disease risk factors contribute to disease is lacking. Therefore, we here critically review current literature, to unravel the existing evidence derived from in vivo mouse studies and define the role of cardiovascular disease and chronic cerebral hypoperfusion in AD development. We conclude that, although many aspects of the vascular hypothesis are well supported by observational studies, in-depth mechanistic studies and well-designed randomized controlled trials are highly needed to establish temporal and causal relationships. Described new insights can have major prospective potential for therapeutic interventions.
Carotid Atherosclerosis in Predicting Coronary Artery Disease
Authors: Bytyçi Ibadete , Shenouda Rafik , Wester Per , Henein Michael Y.
Published: February 2021

Objective:

This meta-analysis aims to compare the relationship between phenotypic manifestation of coronary and carotid atherosclerosis using available imaging techniques.

Approach and Results:

We searched all electronic databases until October 2020 for studies which reported relationship between carotid and coronary atherosclerosis. The primary end point was correlation between carotid intima-media thickness (CIMT) and carotid plaque features (calcification and lipid-rich necrotic core) with coronary artery disease (CAD). Secondary end points included carotid pathology that predicts CAD. Eighty-nine papers with 22 683 patients comparing carotid and coronary atherosclerosis were included in the analysis. CIMT was increased linearly with severity of CAD irrespective of its significance (
P
<0.001), mono versus 2 vessel disease (
P
=0.003), and 2 versus multivessel disease (
P
<0.001). Carotid plaque presence and calcification were less, and lipid-rich necrotic core was highly prevalent in nonsignificant versus significant CAD (
P
<0.001,
P
=0.03,
P
<0.001, respectively). Moderate correlation was found between CIMT and severity of CAD (
r
=0.60,
P
<0.001) and the number of diseased vessels (
r
=0.49,
P
<0.001). There was a moderate correlation between carotid and coronary stenosis (
r
=0.53,
P
<0.001) and between carotid and coronary calcification (
r
=0.61,
P
<0.001). CIMT ≥1.0 mm with a summary sensitivity of 77% and summary specificity of 72% and respective values of 80% and 67% for carotid plaque were the best predictors of CAD, irrespective of the technique used for its diagnosis.

Conclusions:

These results support the concept that atherosclerosis affects both carotid and coronary systems, although not always in identical phenotypic manner. These findings highlight the beneficial examination of carotid arteries whenever CAD is suspected.
Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients
Authors: Kim Moinay , Byun Joonho , Chung Yeongu , Lee Si Un , Park Ji Eun , Park Wonhyoung , Park Jung Cheol , Ahn Jae Sung , Lee Seungjoo
Published: February 2021

Background and Purpose:

Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH.

Methods:

This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 µg/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups.

Results:

In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90±17.63 versus 30.66±32.35,
P
<0.01) and PHE ratio (1.19±0.73 versus 2.05±1.27,
P
<0.01). Among clinical factors, time to reach target Richmond Agitation Sedation Scale (5.98 hours [95% CI, 4.82–7.241 versus 8.42 hours], [95% CI, 6.57–10.77],
P
<0.01) and the length of intensive care unit stays (6.46 days [95% CI, 2.38–10.55 versus 12.66 days], [95% CI, 8.47–16.85],
P
<0.01) were significantly shortened among patients who received ROS scavengers than among patients who did not receive ROS scavenger.

Conclusions:

ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study.

Registration:

URL:
https://cris.nih.go.kr/cris/en
; Unique identifier: KCT0004628.
Can Technology Transform Communication Between Schools, Teachers, and Parents? Evidence from a Randomized Field Trial
Authors: Kraft Matthew A. , Bolves Alexander J.
Published: February 2021

We study the adoption and implementation of a new mobile communication application (app) among a sample of 132 New York City public schools. The app provides a platform for sharing general announcements and news, as well as engaging in personalized two-way communication with individual parents. We provide participating schools with free access to the app and randomize schools to receive intensive support (training, guidance, monitoring, and encouragement) for maximizing the efficacy of the app. Although user supports led to higher levels of communication within the app in the treatment year, overall usage remained low and declined in the following year when treatment schools no longer received intensive supports. We find few subsequent effects on perceptions of communication quality or student outcomes. We leverage rich internal user data to explore how take-up and usage patterns varied across staff and school characteristics. These analyses help to identify early adopters and reluctant users, revealing both opportunities and obstacles to engaging parents through new communication technology.
A new species of lac insect in the genus Kerria Targioni Tozzetti (Hemiptera: Coccomorpha: Tachardiidae) on Samanea saman (Fabaceae) from India
Authors: RAJGOPAL N. N. , MOHANASUNDARAM ARUMUGAM , SHARMA KEWAL KRISHAN
Published: February 2021

A new species of lac insect (Hemiptera: Coccomorpha: Tachardiidae), Kerria canalis Rajgopal sp. nov., collected from Rain Tree, Samanea saman (Jacq.) Merr. (Fabaceae), from India (Tamil Nadu, Madurai), is described and illustrated. Detailed line diagrams and photographs, and a key for the identification of all known Kerria species are provided. Variations in the taxonomic characters of K. canalis and its congeners are discussed.
Cryptotermes camelus (Isoptera: Kalotermitidae), a new drywood termite species from the Bolivian Chaco
Authors: SCHEFFRAHN RUDOLF H.
Published: February 2021

Cryptotermes Banks, 1906 is the third most diverse kalotermitid genus worldwide after Glyptotermes Froggatt, 1897 and Neotermes Holmgren, 1911, with its greatest diversity found in the Neotropics (Krishna et al. 2013a). Furthermore, the greatest number of species of Cryptotermes are known from the Caribbean Basin (Scheffrahn & Křeček 1999, Casala et al. 2016, Scheffrahn 2019). Although Araujo (1977) and Bacchus (1987) list Cryptotermes domesticus (Haviland, 1898) from Trinidad (treated as mainland) and Panama, respectively, Scheffrahn & Křeček (1999) and Scheffrahn et al. (2009) doubt the existence of this Asian species in the New World. Without C. domesticus, the total extant Neotropical diversity of Cryptotermes is 29 endemic and three exotic species (Constantino 2020).
Simulation of the Water Table Elevation in Shallow Unconfined Aquifers by means of the ERA5 Soil Moisture Dataset: The Umbria Region Case Study
Authors: Cerlini Paolina Bongioannini , Silvestri Lorenzo , Meniconi Silvia , Brunone Bruno
Published: February 2021

This paper concerns the simulation of the water table elevation in shallow unconfined aquifers where infiltration is assumed as the main mechanism of recharge. The main aim is to provide a reliable tool for groundwater management that satisfies water supply managers. Such a tool is a candidate as a physically based alternative to the use of empirical methods or general circulation models. It is based on the use of two widely available sets of data: the water table elevation measurements and soil moisture time series. In fact, the former are usually provided by government agencies on public websites whereas the latter are included in the atmospheric global datasets (reanalysis). It is notable that data from reanalysis are accessible to any citizen and organization around the world on an open-access basis (e.g., Copernicus). In the proposed method, the measured water table elevations are correlated quantitatively with the water fluxes toward the aquifer evaluated using the soil moisture data from ERA5 reanalysis (provided by ECMWF) within a Richards equation–based approach. The analysis is executed using data from the Umbria region (Italy) on both a daily and monthly scale. In fact, these are the time intervals of interest for a proper management of groundwater resources. The proposed relationships include both a logarithmic and linear term and point out the possible different regimes of the shallow aquifers with regard to the recharge due to infiltration. These different mechanisms reflect in the different role played by the water fluxes toward the aquifer in terms of water table elevation changes according to the considered time scale.
Seasonal, Interannual, and Interdecadal Variations of the East Asian Summer Monsoon: A Diurnal-Cycle Perspective
Authors: Chen Guixing , Du Yu , Wen Zhiping
Published: February 2021

This study revisits the long-term variabilities of the East Asian summer monsoon (EASM) in 1958–2017 through examination of diurnal cycles. We group monsoon days into four dynamic quadrants (Q1 to Q4), with emphasis on the strong daily southerlies coupled with a large (Q1) or small (Q4) diurnal amplitude over Southeast China. The occurrence day of Q1 increases in June–July with the seasonal progress of the EASM. It is most pronounced in the 1960s to the 1970s and declines to the lowest in the 1980s to the 1990s, whereas the Q4 occurrence increases notably from the 1970s to the 1990s; both groups return to normal in recent years. The interdecadal decrease (increase) of Q1 (Q4) occurrence corresponds well to the known weakening of EASM in the twentieth century, and it also coincides with the rainfall anomalies over China shifting from a “north flooding and south drought” to a “north drought and south flooding” mode. The rainfall under Q1 (Q4) can account for ~60% of the interannual variance of summer rainfall in northern (southern) China. The contrasting effects of Q1 and Q4 on rainfall are due to their remarkably different regulation on water vapor transport and convergence. The interannual/interdecadal variations of Q1 (Q4) occurrence determine the anomalous water vapor transports to northern (southern) China, in association with the various expansion of the western Pacific subtropical high. In particular, Q1 conditions can greatly intensify nighttime moisture convergence, which is responsible for the long-term variations of rainfall in northern China. The results highlight that the diurnal cycles in monsoon flow act as a key regional process working with large-scale circulation to regulate the spatial distributions and long-term variabilities of EASM rainfall.
Role of Short-Term Neoadjuvant Chemoradiotherapy for Potentially Resectable Pancreatic Cancer
Authors: Okano Keiichi , Suto Hironobu , Oshima Minoru , Ando Yasuhisa , Matsukawa Hiroyuki , Kamada Hideki , Kobara Hideki , Masaki Tsutomu , Suzuki Yasuyuki
Published: February 2021

Although the efficacy of neoadjuvant therapies for pancreatic cancer (PDAC) is reported in recent years, ideal neoadjuvant treatment for patients with potentially resectable (R) PDAC remains uncertain. We conducted the retrospective study about the effect of short-term neoadjuvant chemoradiotherapy (sNACRT) on R PDAC. The 94 patients received curative intent pancreatectomy for R PDAC between 2000 and 2016. Among them, 31 patients received sNACRT (S1 60 mg/m2/day for 2w and RTx 30 Gy/2w). Clinical outcomes of the 31 patients with sNACRT were analyzed in comparison with 63 patients without sNACRT. The 1-, 3-, and 5-year overall survival (OS) rates were 93, 71, and 62% in the patients with sNACRT and 78, 35, and 26% in the patients without sNACRT ( P = .0007), respectively. Lymph node metastasis was found in 41.9% of patients with sNACRT and 56.5% of patients without sNACRT ( P = .09). Microscopic tumor infiltration at resection margins (R1) was found in no patient with sNACRT and 5 patients (7.9%) without sNACRT ( P=.042). Retropancreatic infiltration ( P = .04), lymphatic invasion ( P = .002), plexus invasion ( P = .042), and main pancreatic duct extension ( P = .004) were significantly fewer in patients with sNACRT than the patients without sNACRT. The recurrences were found in 64% of patients with sNACRT (39% distant, 16% local, and 10% mix pattern) and 68% in patients without sNACRT (28% distant, 21% local, and 19% mix pattern). The recurrence patterns were significantly different ( P = .008) between the groups. Short-term neoadjuvant chemoradiotherapy decreased R1 resection rate and improved OS. Short-term neoadjuvant chemoradiotherapy may provide ideal local control during the short term and improve clinical outcome of R PDAC.
Advanced Endoscopic Evaluation of Gastroesophageal Reflux Disease in Morbidly Obese Patients in a Rural Setting
Authors: Fanous Medhat , Wei Wei , Lorenson David , Gould Jamison
Published: February 2021

Introduction

Obesity is a known risk factor for gastroesophageal reflux disease (GERD). Morbidly obese patients in rural areas are usually referred to the local surgeon for endoscopic evaluation. This situation poses significant challenges given the increased risk for perioperative complications due to anatomical and metabolic factors. This study aims to evaluate the safety of performing GERD diagnostic workup studies in a rural setting.

Methods

Institutional review board approval was obtained for a retrospective chart review of patients who presented with GERD symptoms to a rural antireflux clinic between August 2015 and October 2020. Patients were included if their body mass index (BMI) was over 35 with comorbidities or over 40 kg/m2 who underwent upper gastrointestinal endoscopy with or without concomitant placement of wireless pH probe and/or functional luminal imaging probe.

Results

A total of 117 patients met the inclusion criteria. There were 94 (80.3%) females and 23(19.7%) males. The average age was 56.0 ± 13.4 years. The average BMI was 40.4 (35-66.4). Proton pump inhibitor use was noted in 97/117 (82.9%) with an average duration of 12.0 ± 9.2 years. The average GERD-Health Related Quality of Life, Reflux Symptom Index and GERD Symptom Score (GERSS) were 29.8 ± 20, 24.5 ± 14.2 and 21.3 ± 15.4 respectively. There were no procedural complications. All the endoscopic examinations were successfully completed and patients were discharged.

Conclusion

Performing diagnostic studies for GERD for morbidly obese patients in critical access hospitals is safe. Patient selection, proper training and adequate preparation are critical prerequisites for good outcomes.
Colonic Stenting for Nonmalignant Large Bowel Obstruction to Avoid Emergency Decompressive Surgery
Authors: Zhornitskiy Alex , Zhornitsky Felicia , Chen Formosa C. , Tabibian James H.
Published: February 2021

Self-expanding metallic stents (SEMSs) are frequently used to decompress malignant large bowel obstruction (LBO) and avoid emergent surgery with often permanent colostomy creation. However, limited data are available on the use and outcomes of SEMS in patients with nonmalignant LBO. We present a case series of 4 patients who were found to have nonmalignant LBO for which they underwent emergent colonic stenting as a bridge to elective surgery following interdisciplinary discussion between gastroenterology, colorectal surgery, and radiology. Through each patient vignette, we illustrate the use of SEMSs as a potential alternative to emergent surgery. 2 of 4 patients avoided stoma creation at the time of surgery, and 1 patient avoided surgery altogether; overall, however, the outcomes of this approach were mixed in this series, indicating a need for further investigation to better identify the patient population that would benefit most from initial SEMS placement for decompression of nonmalignant LBO.
Current Status of Handheld Otoscopy Training: A Systematic Review
Authors: Frithioff Andreas , Guldager Mads Juhl , Andersen Steven Arild Wuyts
Published: February 2021

Objective:

Otoscopy is a frequently performed procedure and competency in this skill is important across many specialties. We aim to systematically review current medical educational evidence for training of handheld otoscopy skills.

Methods:

Following the PRISMA guideline, studies reporting on training and/or assessment of handheld otoscopy were identified searching the following databases: PubMed, Embase, OVID, the Cochrane Library, PloS Medicine, Directory of Open Access Journal (DOAJ), and Web of Science. Two reviewers extracted data on study design, training intervention, educational outcomes, and results. Quality of educational evidence was assessed along with classification according to Kirkpatrick’s model of educational outcomes.

Results:

The searches yielded a total of 6064 studies with a final inclusion of 33 studies for the qualitative synthesis. Handheld otoscopy training could be divided into workshops, physical simulators, web-based training/e-learning, and smartphone-enabled otoscopy. Workshops were the most commonly described educational intervention and typically consisted of lectures, hands-on demonstrations, and training on peers. Almost all studies reported a favorable effect on either learner attitude, knowledge, or skills. The educational quality of the studies was reasonable but the educational outcomes were mostly evaluated on the lower Kirkpatrick levels with only a single study determining the effects of training on actual change in the learner behavior.

Conclusion:

Overall, it seems that any systematic approach to training of handheld otoscopy is beneficial in training regardless of learner level, but the heterogeneity of the studies makes comparisons between studies difficult and the relative effect sizes of the interventions could not be determined.
Interplay for change in equality, diversity and inclusion studies
Authors: Gagnon Suzanne , Augustin Tomke , Cukier Wendy
Published: February 2021

In equality, diversity and inclusion studies, there is often an underlying assumption that research will advance equality and inclusion. Yet scholars increasingly point to a gap between theory and practice to achieve change. While paradigmatic differences in how change is framed may in part account for this gap, we argue that ‘action knowledges’ drawn from different paradigms are both important and ‘commensurable’ once a change agenda is adopted. Placing these in tension, we develop an interplay requiring scholars to engage differences in both ontology and ideology to ‘see’ the change knowledge in other paradigms. A ‘fifth knowledge’ for research to combat inequality and contribute to more equitable organizations can result from engaging with the dynamic tensions identified in our analysis.
Prone restraint cardiac arrest: A comprehensive review of the scientific literature and an explanation of the physiology
Authors: Steinberg Alon
Published: February 2021

Deaths occurring among agitated or violent individuals subjected to physical restraint have been attributed to positional asphyxia. Restraint in the prone position has been shown to alter respiratory and cardiac physiology, although this is thought not to be to the degree that would cause asphyxia in a healthy, adult individual. This comprehensive review identifies and summarizes the current scientific literature on prone position and restraint, including experiments that assess physiology on individuals restrained in a prone position. Some of these experimental approaches have attempted to replicate situations in which prone restraint would be used. Overall, most findings revealed that individuals subjected to physical prone restraint experienced a decrease in ventilation and/or cardiac output (CO) in prone restraint. Metabolic acidosis is noted with increased physical activity, in restraint-associated cardiac arrest and simulated encounters. A decrease in ventilation and CO can significantly worsen acidosis and hemodynamics. Given these findings, deaths associated with prone physical restraint are not the direct result of asphyxia but are due to cardiac arrest secondary to metabolic acidosis compounded by inadequate ventilation and reduced CO. As such, the cause of death in these circumstances would be more aptly referred to as “prone restraint cardiac arrest” as opposed to “restraint asphyxia” or “positional asphyxia.”
When young children grieve: Supporting daycare children following bereavement—A parent’s perspective
Authors: Lytje Martin , Dyregrov Atle
Published: February 2021

Thirteen parents who lost the mother or father to their child were interviewed, using semi-structured interviews. Participants reflect on their young children’s (3–6) grief, support needs, and what they learned from this trying time. The event scarred all participants. While some moved on, others were still struggling years after. The study uncovers difficulties associated with informing a young child, with a limfited understanding of illness and loss, in a life-situation where parents themselves are clinging to hope. While support is available from daycare, it can be better organised and structured. Proactive support that assists the child through illness and death relieves the parental care burden.
Linkages of Multi-Dimensional Vulnerabilities with Infant and Child Mortality Rates in India and Its Specific Regions: Are Social Determinants of Health still Relevant?
Authors: Mishra Prem Shankar , Sinha Debashree , Kumar Pradeep , Srivastava Shobhit , Syamala T. S.
Published: February 2021

The present study investigated linkages between multiple socio-economic vulnerabilities with infant and child mortality in India and its specific regions. Data from the National Family Health Survey (2015–16) was used for calculating the key-outcome variables, namely infant mortality and child mortality. The effective sample size for the study was 259,627. Bivariate analysis and binary logistic regression analysis were employed to examine three dimensions of vulnerabilities such as education, wealth, and caste on infant and child mortality. Children born to women with multiple-vulnerabilities were more likely to die than those born to non-vulnerable women. Women who were vulnerable in all the three-dimensions were more likely to have their children die as infants than those who were not vulnerable in any dimensions (predicted probabilities; 0.054 vs 0.026). The predicted probability for child mortality was 0.063 for women who were vulnerable and 0.028 for non-vulnerable women.
Responsiveness and Relationship Satisfaction in Couples Coping With Parkinson’s Disease: A Pilot Study
Authors: Champagne Eden Rose , Muise Amy
Published: February 2021

Parkinson’s disease (PD) is a neurodegenerative disorder which impacts the person’s physical, psychological and relational well-being, and the well-being of their romantic partner, who is often in a caregiving role. People with PD may struggle to empathize with and respond to their partner’s emotional states, which can hinder relationship satisfaction for both partners. Care partners, who may feel burnt out from caring for their partner’s physical and cognitive needs, may be limited in their ability to be responsive to their spouse’s relational needs, which can hinder satisfaction. Despite the challenges faced by couples coping with PD, little work has considered the interpersonal factors associated with relationship satisfaction for affected couples. In the current study, we investigated individual differences in the motivation to be responsive to a partner’s needs (i.e., communal strength), as well as perceptions of a partner’s responsiveness (i.e., the extent to which a person perceives their partner to care for, validate, and understand them). We recruited 20 couples in which one partner was diagnosed with PD and their romantic partner self-identified as a full-time caregiver, in order to examine how responsiveness is associated with both partners’ relationship satisfaction. When partners with PD reported higher communal strength, they reported higher relationship satisfaction and so did their care partner. When partners with PD perceived their care partner to be more responsive, they reported higher relationship satisfaction. These findings provide some preliminary evidence for responsiveness as one interpersonal factor worthy of further consideration for helping couples cope with PD.
Anchor Point Selection: Scale Alignment Based on an Inequality Criterion
Authors: Strobl Carolin , Kopf Julia , Kohler Lucas , Oertzen Timo von , Zeileis Achim
Published: February 2021

For detecting differential item functioning (DIF) between two or more groups of test takers in the Rasch model, their item parameters need to be placed on the same scale. Typically this is done by means of choosing a set of so-called anchor items based on statistical tests or heuristics. Here the authors suggest an alternative strategy: By means of an inequality criterion from economics, the Gini Index, the item parameters are shifted to an optimal position where the item parameter estimates of the groups best overlap. Several toy examples, extensive simulation studies, and two empirical application examples are presented to illustrate the properties of the Gini Index as an anchor point selection criterion and compare its properties to those of the criterion used in the alignment approach of Asparouhov and Muthén. In particular, the authors show that—in addition to the globally optimal position for the anchor point—the criterion plot contains valuable additional information and may help discover unaccounted DIF-inducing multidimensionality. They further provide mathematical results that enable an efficient sparse grid optimization and make it feasible to extend the approach, for example, to multiple group scenarios.
The Older, the Happier?: A Cross-Sectional Study on the “Paradox of Aging” in China
Authors: Li Jia , Lai Daniel W. L. , Chappell Neena L.
Published: February 2021

The “paradox of aging” refers to the phenomenon that even though people’s physical health and functions may decline when they enter later adulthood, their happiness does not necessarily. Previous studies have shown that older adults’ better emotional regulation skills may contribute to the maintenance of their happiness. This study aims to examine the relationship between age, health, and happiness, and the moderating role of emotional stability. We adopted a nationally representative sample (n = 10,968) from the Chinese General Social Survey (CGSS) and performed weight-adjusted regression models with interaction terms. There is generally an S-shaped age-happiness relationship with significant urban-rural differences. Emotional stability buffers the negative association between health and happiness, and this moderating effect was stronger among older than younger adults, especially in rural China. This study calls for special attention paid to the oldest-old population in rural China and older adults’ emotional regulation skills.