bluuebunny/crossref_metadata_2025 huggingface dataset:
HOXA5-Mediated Stabilization of IκBα Inhibits the NF-κB Pathway and Suppresses Malignant Transformation of Breast Epithelial Cells
Authors: Pai Priya , Wang Guannan , Teo Wei Wen , Raez-Rodriguez Diana , Gabrielson Kathleen L. , Győrffy Balázs , Downs Bradley M. , Aggarwal Akanksha , Sukumar Saraswati
Published: September 2022

HOXA5 is a transcription factor and tumor suppressor that promotes differentiation of breast epithelial cells and is frequently lost during malignant transformation. HOXA5 loss alone, however, does not confer tumorigenicity. To determine which molecular alterations combined with loss of HOXA5 expression can transform cells, we examined isogenic derivatives of a nonmalignant breast epithelial cell line containing knock-in or knockout mutations in key breast cancer genes. Knockdown (KD) of HOXA5 in cells harboring double knock-in (DKI) of mutated PIK3CA (E545K) and HER2 (V777L) induced epithelial–mesenchymal transition and migration and promoted invasive tumor outgrowth within mouse mammary ducts. The NF-κB pathway was significantly upregulated in DKI cells following HOXA5 KD. HOXA5 KD upregulated multiple NF-κB target genes, including IL6. IκBα protein, but not RNA, expression was reduced in HOXA5-KD cells. HOXA5 bound and stabilized IκBα, forming a nuclear HOXA5-IκBα complex. Chromatin immunoprecipitation sequencing database queries revealed that HOXA5 and IκBα are co-enriched at 528 genomic loci. In patients with breast cancer, high coexpression of HOXA5 and IκBα conferred a significantly better overall and progression-free survival. Collectively, these data suggest that HOXA5 suppresses malignancy in breast epithelial cells by blunting NF-κB action via stabilization of its inhibitor IκBα.

Significance:

Loss of HOXA5 reduces IκBα stability and increases NF-κB signaling to exacerbate breast cancer aggressiveness, providing new insights into the tumor suppressor functions of HOXA5.
Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy
Authors: Ykema Berbel L.M. , Gini Andrea , Rigter Lisanne S. , Spaander Manon C.W. , Moons Leon M.G. , Bisseling Tanya M. , de Boer Jan Paul , Verbeek Wieke H.M. , Lugtenburg Pieternella J. , Janus Cecile P.M. , Petersen Eefke J. , Roesink Judith M. , van der Maazen Richard W.M. ,   for the DICHOS study group, Aleman Berthe M.P. , Meijer Gerrit A. , van Leeuwen Flora E. , Snaebjornsson Petur , Carvalho Beatriz , van Leerdam Monique E. , Lansdorp-Vogelaar Iris
Published: September 2022

Background:

Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups.

Methods:

The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG).

Results:

Overall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG).

Conclusions:

Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy.

Impact:

Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.
NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy
Authors: Pinter Matthias , Pinato David J. , Ramadori Pierluigi , Heikenwalder Mathias
Published: September 2022

The last 10 years have revolutionized our basic understanding of nonalcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining, or exacerbating nonalcoholic steatohepatitis (NASH)—a disease that has been recently defined as autoaggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carcinoma (HCC). Preliminary data from preclinical studies suggest that immunotherapy efficacy may be reduced in NASH-related HCC compared with viral HCC; however, conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with carcinogenesis and therapeutic resistance is key to prevent progression to cirrhosis, improve monitoring and stratification of NASH according to predicted cancer risk, and ultimately increase survival of patients with NASH-HCC. In this review, we summarize the state of the art in the field of NASH and NASH-HCC with focus on immunobiology. We discuss preclinical and clinical findings underpinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulnerabilities in NASH-associated HCC.
Novel Lymphocyte-Independent Antitumor Activity by PD-1 Blocking Antibody against PD-1+ Chemoresistant Lung Cancer Cells
Authors: Rotolo Ramona , Leuci Valeria , Donini Chiara , Galvagno Federica , Massa Annamaria , De Santis Maria Chiara , Peirone Serena , Medico Giovanni , Sanlorenzo Martina , Vujic Igor , Gammaitoni Loretta , Basiricò Marco , Righi Luisella , Riganti Chiara , Salaroglio Iris Chiara , Napoli Francesca , Tabbò Fabrizio , Mariniello Annapaola , Vigna Elisa , Modica Chiara , D’Ambrosio Lorenzo , Grignani Giovanni , Taulli Riccardo , Hirsch Emilio , Cereda Matteo , Aglietta Massimo , Scagliotti Giorgio Vittorio , Novello Silvia , Bironzo Paolo , Sangiolo Dario
Published: September 2022

Purpose:

Antibodies against the lymphocyte PD-1 (aPD-1) receptor are cornerstone agents for advanced non–small cell lung cancer (NSCLC), based on their ability to restore the exhausted antitumor immune response. Our study reports a novel, lymphocyte-independent, therapeutic activity of aPD-1 against NSCLC, blocking the tumor-intrinsic PD-1 receptors on chemoresistant cells.

Experimental Design:

PD-1 in NSCLC cells was explored in vitro at baseline, including stem-like pneumospheres, and following treatment with cisplatin both at transcriptional and protein levels. PD-1 signaling and RNA sequencing were assessed. The lymphocyte-independent antitumor activity of aPD-1 was explored in vitro, by PD-1 blockade and stimulation with soluble ligand (PD-L1s), and in vivo within NSCLC xenograft models.

Results:

We showed the existence of PD-1+ NSCLC cell subsets in cell lines and large in silico datasets (Cancer Cell Line Encyclopedia and The Cancer Genome Atlas). Cisplatin significantly increased PD-1 expression on chemo-surviving NSCLC cells (2.5-fold P = 0.0014), while the sequential treatment with anti–PD-1 Ab impaired their recovery after chemotherapy. PD-1 was found to be associated with tumor stemness features. PD-1 expression was enhanced in NSCLC stem-like pneumospheres (P < 0.0001), significantly promoted by stimulation with soluble PD-L1 (+27% ± 4, P < 0.0001) and inhibited by PD-1 blockade (−30% ± 3, P < 0.0001). The intravenous monotherapy with anti–PD-1 significantly inhibited tumor growth of NSCLC xenografts in immunodeficient mice, without the contribution of the immune system, and delayed the occurrence of chemoresistance when combined with cisplatin.

Conclusions:

We report first evidence of a novel lymphocyte-independent activity of anti–PD-1 antibodies in NSCLC, capable of inhibiting chemo-surviving NSCLC cells and exploitable to contrast disease relapses following chemotherapy.

See related commentary by Augustin et al., p. 505
B-cell Lymphoma 6 (BCL6): From Master Regulator of Humoral Immunity to Oncogenic Driver in Pediatric Cancers
Authors: McLachlan Tabitha , Matthews William C. , Jackson Evangeline R. , Staudt Dilana E. , Douglas Alicia M. , Findlay Izac J. , Persson Mika L. , Duchatel Ryan J. , Mannan Abdul , Germon Zacary P. , Dun Matthew D.
Published: September 2022

B-cell lymphoma 6 (BCL6) is a protooncogene in adult and pediatric cancers, first identified in diffuse large B-cell lymphoma (DLBCL) where it acts as a repressor of the tumor suppressor TP53, conferring survival, protection, and maintenance of lymphoma cells. BCL6 expression in normal B cells is fundamental in the regulation of humoral immunity, via initiation and maintenance of the germinal centers (GC). Its role in B cells during the production of high affinity immunoglobins (that recognize and bind specific antigens) is believed to underpin its function as an oncogene. BCL6 is known to drive the self-renewal capacity of leukemia-initiating cells (LIC), with high BCL6 expression in acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and glioblastoma (GBM) associated with disease progression and treatment resistance. The mechanisms underpinning BCL6-driven therapy resistance are yet to be uncovered; however, high activity is considered to confer poor prognosis in the clinical setting. BCL6’s key binding partner, BCL6 corepressor (BCOR), is frequently mutated in pediatric cancers and appears to act in concert with BCL6. Using publicly available data, here we show that BCL6 is ubiquitously overexpressed in pediatric brain tumors, inversely to BCOR, highlighting the potential for targeting BCL6 in these often lethal and untreatable cancers. In this review, we summarize what is known of BCL6 (role, effect, mechanisms) in pediatric cancers, highlighting the two sides of BCL6 function, humoral immunity, and tumorigenesis, as well as to review BCL6 inhibitors and highlight areas of opportunity to improve the outcomes of patients with pediatric cancer.
Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade
Authors: Lander Varintra E. , Belle Jad I. , Kingston Natalie L. , Herndon John M. , Hogg Graham D. , Liu Xiuting , Kang Liang-I , Knolhoff Brett L. , Bogner Savannah J. , Baer John M. , Zuo Chong , Borcherding Nicholas C. , Lander Daniel P. , Mpoy Cedric , Scott Jalen , Zahner Michael , Rogers Buck E. , Schwarz Julie K. , Kim Hyun , DeNardo David G.
Published: September 2022

The effects of radiotherapy (RT) on tumor immunity in pancreatic ductal adenocarcinoma (PDAC) are not well understood. To better understand if RT can prime antigen-specific T-cell responses, we analyzed human PDAC tissues and mouse models. In both settings, there was little evidence of RT-induced T-cell priming. Using in vitro systems, we found that tumor–stromal components, including fibroblasts and collagen, cooperate to blunt RT efficacy and impair RT-induced interferon signaling. Focal adhesion kinase (FAK) inhibition rescued RT efficacy in vitro and in vivo, leading to tumor regression, T-cell priming, and enhanced long-term survival in PDAC mouse models. Based on these data, we initiated a clinical trial of defactinib in combination with stereotactic body RT in patients with PDAC (NCT04331041). Analysis of PDAC tissues from these patients showed stromal reprogramming mirroring our findings in genetically engineered mouse models. Finally, the addition of checkpoint immunotherapy to RT and FAK inhibition in animal models led to complete tumor regression and long-term survival.

Significance:

Checkpoint immunotherapeutics have not been effective in PDAC, even when combined with RT. One possible explanation is that RT fails to prime T-cell responses in PDAC. Here, we show that FAK inhibition allows RT to prime tumor immunity and unlock responsiveness to checkpoint immunotherapy.

This article is highlighted in the In This Issue feature, p. 2711
Uterine Lavage Identifies Cancer Mutations and IncreasedTP53Somatic Mutation Burden in Individuals with Ovarian Cancer
Authors: Ghezelayagh Talayeh S. , Kohrn Brendan F. , Fredrickson Jeanne , Manhardt Enna , Radke Marc R. , Katz Ronit , Gray Heidi J. , Urban Renata R. , Pennington Kathryn P. , Liao John B. , Doll Kemi M. , Simons Elise J. , Burzawa Jennifer K. , Goff Barbara A. , Speiser Paul , Swisher Elizabeth M. , Norquist Barbara M. , Risques Rosa Ana
Published: September 2022

Current screening methods for ovarian cancer have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with TP53 ultradeep sequencing for the detection of disseminated ovarian cancer cells has emerged as a promising tool, but this approach has not been tested for early-stage disease or non-serous histologies. In addition, lavages carry multiple background mutations, the significance of which is poorly understood. Uterine lavage was collected preoperatively in 34 patients undergoing surgery for suspected ovarian malignancy including 14 patients with benign disease and 20 patients with ovarian cancer [6 non-serous and 14 high-grade serous-like (serous)]. Ultradeep duplex sequencing (∼3,000×) with a panel of common ovarian cancer genes identified the tumor mutation in 33% of non-serous (all early stage) and 79% of serous cancers (including four early stage). In addition, all lavages carried multiple somatic mutations (average of 25 mutations per lavage), more than half of which corresponded to common cancer driver mutations. Driver mutations in KRAS, PIK3CA, PTEN, PPP2R1A, and ARID1A presented as larger clones than non-driver mutations and with similar frequency in lavages from patients with and without ovarian cancer, indicating prevalent somatic evolution in all patients. Driver TP53 mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with ovarian cancer, suggesting that TP53-specific clonal expansions are linked to ovarian cancer development. Our results demonstrate that lavages capture cancer cells, even from early-stage cancers, as well as other clonal expansions and support further exploration of TP53 mutation burden as a potential ovarian cancer risk factor.

Significance:

Cancer driver mutations are found in uterine lavage DNA in all individuals, but driver TP53 mutations presented as significantly larger clones and with higher frequency in lavages from individuals with ovarian cancer. This suggests that TP53-specific clonal expansion plays a role in tumorigenesis and presents opportunities for early detection.
Delimitação de nascente soterrada utilizando método da eletrorresistividade na cidade de Cuiabá, MT
Authors: Siqueira Neto Antonio Carlos de , Siqueira Flávia Regina Pereira Santos de
Published: September 2022

O município de Cuiabá é recortado por redes de drenagem superficiais e várias nascentes preservadas e soterradas. A cobertura pedológica é majoritariamente composta por neossolos litólicos e afloramentos de rochas metapelíticas de baixo grau metamórfico do Grupo Cuiabá. Nesse contexto, executou-se estudo hidrogeológico aplicando-se método geofísico para o estudo de surgência hídrica observada durante a execução das obras de um condomínio residencial horizontal. Reconheceram-se as formações pedológicas e geológicas presentes na área, estimou-se o contato solo/rocha ao longo de perfis geofísicos, avaliou-se a extensão das zonas de aquíferos e identificaram-se as possíveis nascentes. Aplicou-se o método da eletrorresistividade, usando-se as técnicas de sondagem elétrica vertical e caminhamento elétrico. Coletaram-se também dados diretos, como amostras do solo, e realizou-se o teste de permeabilidade e mapeamento estrutural da área. O padrão de fraturas e foliações obtido é responsável pelo fluxo da água subterrânea, tendo como direção preferencial a área das surgências, indicando que fluxo segue essas estruturas, das mais altas para as mais baixas. Concluiu-se que há uma possível nascente aterrada, cuja ocorrência foi constatada pela abertura de trincheiras e surgência de água, evidenciando-se a existência de zonas aquíferas dentro da área do condomínio.
Effects of Electrode-Tissue Proximity on Cardiac Lesion Formation Using Pulsed Field Ablation
Authors: Howard Brian , Verma Atul , Tzou Wendy S. , Mattison Lars , Kos Bor , Miklavčič Damijan , Onal Birce , Stewart Mark T. , Sigg Daniel C.
Published: September 2022

Background:

Pulsed field ablation (PFA) is a novel energy modality for treatment of cardiac arrhythmias. The impact of electrode-tissue proximity on lesion formation by PFA has not been conclusively assessed. The objective of this investigation was to evaluate the effects of electrode-tissue proximity on cardiac lesion formation with a biphasic, bipolar PFA system.

Methods:

PFA was delivered on the ventricular epicardial surface in an isolated porcine heart model (n=8) via a 4-electrode prototype catheter. An offset tool was designed to control the distance between electrodes and target tissue; deliveries were placed 0 mm (0 mm offset), 2 mm (2 mm offset), and 4 mm away from the tissue (4 mm offset). Lesions were assessed using tetrazolium chloride staining. Numerical models for the experimental setup with and without the offset tool validated and supported results.

Results:

Cardiac lesion dimensions decreased proportional to the distance between epicardial surface and electrodes. Lesion depth averaged 4.3±0.4 mm, 2.7±0.4 mm, and 1.3±0.4 mm for the 0, 2, and 4 mm and lesion width averaged 9.4±1.1 mm, 7.5±0.8 mm and 5.8±1.4 mm for the 0, 2, and 4 mm offset distances, respectively. Numerical modeling matched ex vivo results well and predicted lesion creation with and without the offset tool.

Conclusions:

Using a biphasic, bipolar PFA system resulted in cardiac lesions even in the 0 mm offset distance case. The relationship between lesion depth and offset distance was linear, and the deepest lesions were created with 0 mm offset distance, that is, with electrodes in contact with tissue. Therefore, close electrode-tissue proximity increases the likelihood of achieving transmural lesions by maximizing the electric field penetration into the target tissue.
Sustained Attention as Measured by Reaction Time Variability Is a Strong Modulator for the P600, but Not the N400
Authors: Contier Friederike , Weymar Mathias , Wartenburger Isabell , Rabovsky Milena
Published: September 2022

The functional significance of the two prominent language-related ERP components N400 and P600 is still under debate. It has recently been suggested that one important dimension along which the two vary is in terms of automaticity versus attentional control, with N400 amplitudes reflecting more automatic and P600 amplitudes reflecting more controlled aspects of sentence comprehension. The availability of executive resources necessary for controlled processes depends on sustained attention, which fluctuates over time. Here, we thus tested whether P600 and N400 amplitudes depend on the level of sustained attention. We reanalyzed EEG and behavioral data from a sentence processing task by Sassenhagen and Bornkessel-Schlesewsky [The P600 as a correlate of ventral attention network reorientation. Cortex, 66, A3–A20, 2015], which included sentences with morphosyntactic and semantic violations. Participants read sentences phrase by phrase and indicated whether a sentence contained any type of anomaly as soon as they had the relevant information. To quantify the varying degrees of sustained attention, we extracted a moving reaction time coefficient of variation over the entire course of the task. We found that the P600 amplitude was significantly larger during periods of low reaction time variability (high sustained attention) than in periods of high reaction time variability (low sustained attention). In contrast, the amplitude of the N400 was not affected by reaction time variability. These results thus suggest that the P600 component is sensitive to sustained attention whereas the N400 component is not, which provides independent evidence for accounts suggesting that P600 amplitudes reflect more controlled and N400 amplitudes reflect more automatic aspects of sentence comprehension.
Considering Readout to Understand Working Memory
Authors: Myers Nicholas E.
Published: September 2022

While working memory (WM) allows us to store past information, its function is to guide future behavior. Given this role, the tight link between how WMs are maintained and how they are read out to be transformed into context-appropriate actions remains relatively unexplored. Beyond helping us understand memory-guided behavior, focusing on WM readout may also help us better understand the neural basis of memory maintenance.
Funding COVID-19 research: Insights from an exploratory analysis using open data infrastructures
Authors: Mugabushaka Alexis-Michel , van Eck Nees Jan , Waltman Ludo
Published: September 2022

To analyze the outcomes of the funding they provide, it is essential for funding agencies to be able to trace the publications resulting from their funding. We study the open availability of funding data in Crossref, focusing on funding data for publications that report research related to COVID-19. We also present a comparison with the funding data available in two proprietary bibliometric databases: Scopus and Web of Science. Our analysis reveals limited coverage of funding data in Crossref. It also shows problems related to the quality of funding data, especially in Scopus. We offer recommendations for improving the open availability of funding data in Crossref.
Cortiella yatungense, a new species of Cortiella (Apiaceae) from Xizang, China
Authors: DENG JIAO-JIAO , PENG CHANG , LIU CHANG-KUN , XIE DENG-FENG , GUI LING-JIAN , ZHOU SONG-DONG , HE XING-JIN
Published: September 2022

We identified and described Cortiella yatungense, a new species of Cortiella (Apiaceae) from Xizang, China. This species can be distinguished from other members of this genus (C. hookeri, C. caespitosa, C. lamondiana, and C. cortioides) by fewer umbels (3–6), thinner and longer pedicels than the leaves, ovate to suborbicular fruits, and mericarp without vittae. Molecular phylogenetic analyses based on the internal transcribed space (ITS) region and two chloroplast DNA intron sequences (rpl16 and rps16) showed that C. yatungense was sister to C. hookeri with strong support. Thus, both morphological and phylogenetic evidence suggested that C. yatungense is a distinct species of Cortiella. A comprehensive description of C. yatungense along with morphological characteristics and habitat are provided.
Taxonomic review of the Agrisius guttivitta Walker species group with transfer of the genus Agrisius Walker to the family Nolidae Bruand and descriptions of five new species (Lepidoptera: Nolidae: Eligminae)
Authors: VOLYNKIN ANTON V. , SALDAITIS AIDAS
Published: September 2022

The genus Agrisius Walker, 1855 is transferred from the family Erebidae, subfamily Arctiinae to the family Nolidae, subfamily Eligminae. The Agrisius guttivitta Walker species group is reviewed and five new species are described: Agrisius soror sp. n. (North Vietnam), Agrisius witti sp. n. (China, Yunnan), Agrisius cernyi sp. n. (North and West Thailand), Agrisius kachina sp. n. (North Myanmar), and Agrisius frater sp. n. (China, Shaanxi). A new synonymy is introduced: Agrisius vernalis Dubatolov, Kishida & Wang, 2012 = Agrisius fangchenglaiae Orhant, 2015, syn. n. Adults and male and female genitalia are illustrated.
MDMA-assisted psychotherapy for post-traumatic stress disorder: The devil is in the detail
Authors: Bedi Gillinder , Cotton Susan M , Guerin Alexandre A. , Jackson Henry J
Published: September 2022

Recent years have seen escalating media, public and scientific interest in psychedelic medicine. Australia and New Zealand have been late to this research; however, in the past 2 years, rapid developments suggest that this is changing. Here, we argue for the need to critically review existing evidence in this field to guide future directions. We focus on (±)3,4-methylenedioxymethamphetamine-assisted psychotherapy for post-traumatic stress disorder, currently the most advanced area of clinical psychedelic research. Food and Drug Administration approval of this approach is likely in 2023, based on a series of promising findings. We provide a detailed overview of Phase 2 and 3 studies published to date. We identify several concerns related to this body of evidence, including methodological/design limitations and broader factors – such as robust involvement of advocacy groups in research and reliance on non-government financing leading to simplistic public messaging – that compound the methodological issues identified. We propose steps for future improvement, including the need for large, high-quality, independent efficacy trials with design enhancements, effectiveness trials and for researchers to consider their own engagement with media and public messaging around these modalities. We argue that, notwithstanding promising findings to date, rigorous and dispassionate science is needed to move the field forward and safeguard the welfare of participants.
Paying terrorist ransoms: Frayed consensus, uneven outcomes & undue harm
Authors: Davis Jessica , Wilner Alex
Published: September 2022

Terrorist groups are believed to be financed, in part, by ransoms paid for kidnap victims. As part of global efforts to counter the financing of terrorism and prevent further terrorist attacks (including more kidnappings), the international community has attempted to implement a moratorium on the payment of ransoms. Despite a unified stance, ransom payments to terrorist groups have continued. An exploratory review of 20 countries reveals significant variation between public statements and private practice when it comes to ransom payments. While it is clear that states, organizations, and individuals are paying terrorist ransoms, it is far less clear what effect this has had on terrorism itself. A review of three case studies shows significant variation in the relationship (or perhaps, lack thereof) between ransom payments and terrorist attacks. These findings suggest a need for more study on the effects of ransom payments on terrorist capabilities, and a re-assessment of existing “no-ransom” policies.
The Impact of Social Support on Social Identity Development and Well-Being in International Exchange Students
Authors: Matschke Christina
Published: September 2022

International exchanges have become increasingly common. Although it is an explicit goal of exchange programs that exchange students immerse in another culture and learn to feel like a local, there is no systematic research on the development of one’s social identity during the exchange year. A longitudinal study with German high school students who spend an exchange year in the United States investigates the trajectories of social identification, identity integration of primary and secondary cultural identities, and well-being longitudinally at three measurement times (before departure, N = 556, 3 months, N = 210, and 6 months after arrival, N = 178). As social support is suggested to be an important resource, multilevel analyses tested the impact of three subcomponents of social support (i.e., emotional, instrumental, and compatibility-informational support) on the individual trajectories. It was found that social identification and identity integration increased over time, whereas well-being was high across all times. Identity integration mediated the positive effect of social identification on well-being. Moreover, emotional support was positively related to well-being and compatibility-informational support was positively related to identity integration. Instrumental support fostered early identity integration but diminished its slope when applied at later times. The present data demonstrate that an exchange year stimulates the development of the social self-concept, which is relevant for well-being. Moreover, it shows that the right kind of social support at the right time can foster this development.
Social Class and Socialization Values in the United States and China
Authors: Chen Xiaochen , Wang Zhongwei , Deng Ziqian , Wei Qingwang
Published: September 2022

The psychological correlate of social class across cultures is a topic of debate. Some have argued cross-cultural similarities, while others have maintained culturally divergent manifestations of social class. Using the data from the World Value Survey 2017 to 2020 (Wave 7), the current study examined the associations between social class and socialization values among parents in the United States ( n = 1,615) and China ( n = 2,524). Results indicated that all social class indices (i.e., education level, income, subjective social status, and composite social class) were positively associated with self-oriented socialization values in the United States, whereas such associations were absent in China, except for education level. In addition, higher social class, in terms of higher income, higher subjective social status, and higher composite social class, was associated with greater other-oriented socialization values in China. However, such associations were absent (for income, education level, and composite social class) or even reversed (for subjective social status) in the United States. These findings extend the literature on social class variations in parenting and highlight cultural specificity in the psychological manifestations of social class.
What middle schoolers need: Respect, accountability, and grace
Authors: Vail Kathleen
Published: September 2022

The 2022 National School Counselor of the Year Alma Lopez talks about how her students at California’s Livingston Middle School were impacted by the pandemic. Livingston Middle School is a Title 1 school in California’s Central Valley, with 850 students in 6th, 7th, and 8th grades. Most families in this rural community are farm laborers or food production workers. Livingston Union School District serves about 2,500 students, 80 percent of whom are Latinx. Students and their families suffered losses during the pandemic, and middle schoolers missed out on key opportunities for connection and belonging.
Truly open to all: Three ways to diversify teacher leadership
Authors: Beck Jori S. , Hinton KaaVonia , Butler Brandon M.
Published: September 2022

Teacher leadership recently has gained prominence as an important method for school improvement and reform, yet the ranks of teacher leaders do not match the racial and ethnic diversity of the students they serve. Jori S. Beck, KaaVonia Hinton, and Brandon M. Butler conducted a study of teacher leadership that garnered almost 800 survey responses and included 31 interviews with administrators and teachers. They discovered how the lack of diversity in the teacher workforce, the myth of meritocracy, and the isolation of teachers of color present barriers to diversifying the teacher leader workforce. Potential solutions include equity audits, revisions to hiring practices, and the distribution of teachers of color within school buildings.
How a university and a school district made change together
Authors: Marsh Valerie L. , Nelms Shaun C. , Peyre Sarah , Larson Joanne
Published: September 2022

The University of Rochester and East High School in Rochester, New York, entered into a partnership in 2015, hoping to transform the school to prevent shut down by the state. Both partners were wary because of the district’s failed attempts at reform and the history of similar partnerships elsewhere. A new state-level reform option allowed the partners to form an educational partnership organization (EPO) so that they could become equal partners with some autonomy from the district. The partners decided that to succeed, they would need to involve the community. They learned from listening sessions that the community wanted the school to remain open but also wanted everything about it to change. So, instead of taking an incremental approach, they chose to transform the school’s structures, culture, leadership model, and curriculum and instruction. Valerie L. Marsh, Shaun C. Nelms, Sarah Peyre, and Joanne Larson describe how the university and the school worked together to transform East on all these fronts.
Leading through crisis
Authors: Learned-Miller Carole
Published: September 2022

The COVID-19 pandemic, societal racial reckonings, and pressure from parents and the media have put education leaders in a crisis. Carole Learned-Miller of the Leadership Academy in New York spoke with school and education organization leaders who saw their organizations through a variety of challenges, including the pandemic, racial inequities, a teacher strike, and a financial crisis. These leaders shared some of the principles that helped them through. These include building relationships, communicating clearly, listening to other views, having trusted advisers, being true to their values, and staying hopeful. Leaders describe how these principles helped them weather difficult times.
On Leadership: Getting the community on the path toward equity
Authors: Starr Joshua P.
Published: September 2022

Soon after Xavier Botana took over as superintendent of Maine’s Portland Public Schools, he realized that, despite the district’s professed commitment, efforts to promote equity were embedded in other programs rather than being its own goal. He knew that if he were going to make his vision for equity a reality, he would need to get the community’s commitment to the effort. Joshua Starr discusses why community engagement is essential to the success of equity initiatives and describes how leaders like Botana can build a team of supporters within the school district and across the wider community.
Bookshelf: Kappan authors on their favorite reads
Authors: Deutsch Nancy
Published: September 2022

In this regular column, Kappan authors recommend books and articles that have influenced them. Nancy Deutsch shares an article from Human Development that helped her put a name — m(ai)cro — to the combination of forces that guide people’s development. Steven Wolk shares how Carl Rogers’ Freedom to Learn inspired him to see new possibilities when he was beginning his teaching career.
Concurrent and real-time measurement of fabric liquid moisture management properties using a novel sweating simulator
Authors: Amir Shahzad , Fan Jintu
Published: September 2022

Evaluation of fabric liquid moisture management is an indispensable requirement while making new fabric or choosing the right kind of fabric for developing effective personal moisture management clothing. However, existing methods and instruments for measuring fabric liquid moisture management, though they have been effective in some ways, lack sufficient simulation of fabric-perspiring skin interaction, active body posture, and concurrent determination of dynamic liquid accumulation, evaporation, draining, and drying. This article explains a new instrument, the novel sweating simulator (NSS), for evaluating the fabric dynamic liquid moisture management properties in proximity to true wearing conditions. In addition to investigating the fabric wetting, wicking, and multidimensional liquid transport, thanks to its regional sweating zone and gravimetric measuring principle, the instrument accurately measured the dynamic liquid distribution by recording the real-time changes in mass of liquid supplied, evaporated, and dripped through the fabric. On the NSS, eight different kinds of moisture management knitted fabrics were tested to evaluate and distinguish their dynamic liquid moisture management properties. The findings showed that fabric construction and constituent fiber nature are the most important elements in controlling fabric weight and liquid dynamic distribution. In addition, the liquid distribution of fabric was found to be significantly affected by the effect of the adjustable supply rate and slope of the sweating plane. Owing to its comprehensive testing potential and versatility, it is anticipated that the NSS will be extremely useful in developing and evaluating the next-generation high-performance moisture management fabrics for various clothing and industrial applications.
Wartime, professional military education, and politics
Authors: Fisher Kathryn Marie
Published: September 2022

The 2018 United States (US) National Military Strategy claimed that professional military education (PME) in the US had ‘stagnated’. Since then the 2020 US Joint Chiefs of Staff publication Developing Today’s Joint Officer’s for Tomorrow’s Ways of War can be seen as a direct response to such stagnation. The associated temporal positionings of war from stagnation, to today’s officers, to tomorrow’s ways of war, reinforce the significance of wartime in how professional military education is framed. In this paper I ask: To what extent do professional military education mission statements rely on frames of wartime for a construction of purpose, what are the implications of such framings for goals of minimizing violence and suffering, and how may such potential limitations be addressed in the classroom? A focus on wartime can help us draw out significant strategic and ethical challenges of conflict termination alongside ‘forever wars’, the normalization of exceptional security practices and violence, and the way in which prioritizations of either doing war ‘better’ or minimizing the likelihood of war are in seemingly direct epistemological competition. Given a goal of less insecurity, in an era in which fewer and fewer wars actually ‘end’ or ‘end’ with a sense of victory, I assess the extent to which engaging critical approaches in PME may help or hinder the need to challenge self-propagating dynamics of wartime that may be limiting efforts at lessening violence.
Clinical features, outcomes and predictors of drug resistance and complications in patients admitted with pyelonephritis
Authors: Jacob Amita , Sahni Rani Diana , Bharathy Muruga , George Tina , Rebekah Grace , Sudarsanam Thambu David
Published: September 2022

Drug resistance and the presence of structural complications have significant implications for the treatment of acute pyelonephritis. We aimed to examine the predictors of drug resistance and complications in a retrospective cohort of patients admitted with pyelonephritis. 188 patients were included in this study. Patients who had had a urinary catheterization in the previous month and who lived outside the district in which the hospital was located were more likely to have ESBL infections. Carbapenem resistance was associated with recent urinary catheterization, a positive urine nitrate test, hypotension requiring vasopressors and the need for intensive care. A history of flank pain, urea level >13.3 mmol/L, a differential neutrophil count >75% and a urinalysis with >1000 leucocytes per high power field was associated with an increased risk of complications. A score derived from these variables to predict structural complications of infection had a sensitivity of 77.8% and a specificity of 67.1%
Clinical Pharmacology Studies in Patients with Renal Impairment: Past Experience and Regulatory Perspectives
Authors: Ibrahim Safaa , Honig Peter , Huang Shiew‐Mei , Gillespie Williams , Lesko Lawrence J. , Williams Roger L.
Published: September 2022

The objective of this report is to provide a regulatory perspective on the quality of pharmacokinetic studies in renal impairment (RI) studies submitted in support of new drug applications (NBAs) or supplements to NDAs (sNDAs) submitted to the Food and Drug Administration (FDA). Fifty‐one NDA and 20 sNDA submissions reviewed between 1996 and 1997 by the Office of Clinical Pharmacology and Biopharmaceutics were evaluated for the following: (1) whether an RI study was conducted; (2) contribution of the renal clearance to the overall clearance in subjects without renal impairment; (3) degree of plasma protein binding (%PB) in subjects without renal impairment; (4) dose proportionality of single and multiple doses; (5) study design, including dosing regimen; (6) definition of renal impairment; (7) stratification of renal functions; (8) number of subjects/group; (9) data analysis and interpretation; and (10) impact on labeling. Results of the analysis indicated that 67% of the NDAs and 30% of supplemental NDAs contained RI studies (34/51 for NDAs and 6/20 for sNDAs). No obvious differences in the pharmacokinetic characteristics (e.g., percentage excreted unchanged in urine and %PB) were observed between drugs for which RI studies were conducted versus those not conducted. Most studies conducted were designed as single dose (70%). Seventy‐five percent of the studies used doses within the therapeutic dosage range of the drug. The measured 24‐hour creatinine clearance was most often used to assess the renal function. Stratification of renal function ranged from one to five groups, with 6 to 8 subjects enrolled per group. In most studies conducted (38/40), data were analyzed by point estimate using ANOVA. Results of RI studies were adequately reflected in the labeling. The survey reveals that RI study design can be improved for regulatory review purposes. In part based on this analysis, the FDA has prepared a guidance that provides recommendations on the design, analysis, and impact on dosing and labeling for RI studies to include recommendations on when RI studies do not need to be performed. The guidance proposes an equivalence approach with confidence intervals, as opposed to a point estimate approach, to assess the impact of RI on systemic exposure measures.
Pharmacokinetic and Pharmacodynamic Comparison of Two Calcium Supplements in Postmenopausal Women
Authors: Heller Howard J. , Greer Laura G. , Haynes Sharon D. , Poindexter John R. , Pak Charles Y. C.
Published: September 2022

This randomized crossover study compared the single‐dose bioavailability and effects on parathyroid function of two commercially formulated calcium supplements containing 500 mg of elemental calcium. Twenty‐five postmenopausal women underwent three phases of study wherein they each took a single dose of calcium citrate with a standard breakfast (as Citracal® 250 mg + D), calcium carbonate (as Os‐Cal ®500 mg + D), or placebo at 8 a.m. Blood samples were drawn at baseline and hourly for 4 or 6 hours after each dose. Fasting and postload urine samples were also collected. Compared with calcium carbonate, calcium citrate provided a 46% greater peak‐basal variation and 94% higher change in area under the curve for serum calcium and a 41% greater increment in urinary calcium. Moreover, the decrement in serum parathyroid hormone concentration from baseline was greater after calcium citrate. In conclusion, calcium citrate is more bioavailable than calcium carbonate when given with a meal.
Pharmacokinetics of Single‐Dose Telmisartan 120 mg Given during and between Hemodialysis in Subjects with Severe Renal Insufficiency: Comparison with Healthy Volunteers
Authors: Stangier Joachim , Su Chung‐An P. F. , Brickl Rolf , Franke Holger
Published: September 2022

The pharmacokinetics of oral telmisartan 120 mg evaluated in subjects with severe renal insufficiency between dialyses and during hemodialysis were compared with those observed in healthy male subjects. Between dialyses and during dialysis, the plasma concentration‐time curves of subjects with renal insufficiency were lower than those of healthy subjects. The mean plasma protein binding of telmisartan was 99.5% in healthy subjects, compared with mean values of 99.1% between dialyses and 98.8% during dialysis. Only very small amounts of telmisartan were removed by dialysis. Single doses of telmisartan 120 mg were well tolerated in subjects with severe renal insufficiency when administered either between dialyses or during dialysis, and no clinically relevant changes in vital signs were detected. In conclusion, the maximum plasma concentrations of telmisartan and areas under the plasma concentration‐time curves in subjects with severe renal insufficiency were markedly reduced compared with healthy subjects. The fraction of telmisartan not bound to plasma proteins was increased approximately twofold. Changes in the pharmacokinetic profile in subjects with renal insufficiency did not affect the safety profile of telmisartan, which was well tolerated in these subjects.
Pharmacokinetics and Tolerability of an Antiangiogenic Ribozyme (ANGIOZYME™) in Healthy Volunteers
Authors: Sandberg Jennifer A. , Parker Vann P. , Blanchard Karin S. , Sweedler David , Powell James A. , Kachensky Arlee , Bellon Laurent , Usman Nassim , Rossing Thomas , Borden Ernest , Blatt Lawrence M.
Published: September 2022

The pharmacokinetics and tolerability of a chemically stabilized synthetic ribozyme (ANGIOZYME™) targeting the Flt‐1 VEGF receptor mRNA were evaluated in healthy volunteers. In a placebo‐controlled, single‐dose escalation study, ribozyme was administered as a 4‐hour IV infusion of 10 or 30 mg/m2 or as a SC bolus of 20 mg/m2. Peak ribozyme plasma concentrations of 1.5 and 3.8 μg/mL were observed after the 10 and 30 mg/m2 IV infusions, respectively. When normalized to dose, AUC values as well as peak concentrations increased proportionally as the dose was increased from 10 to 30 mg/m2. Peak concentrations of 0.9 μg/mL were observed approximately 3.25 hours after a 20 mg/m2 SC bolus of ribozyme. The dose‐normalized AUCs obtained after SC dosing were compared to the mean dose‐normalized AUC after IV dosing to estimate an absolute SC bioavailability (f) of approximately 69%. An average elimination half‐life of 28 to 40 minutes was observed after IV administration, which increased to 209 minutes after SC administration. Only 4 of 12 reported adverse events were possibly related to administration of ribozyme (headache and somnolence). Thus, ribozyme administration was well tolerated after a single 4‐hour IV infusion of up to 30 mg/m2 or a single SC bolus of 20 mg/m2.