bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of anxiety symptoms and disorders in older adults: a diagnostic accuracy systematic review
Authors: Atchison Kayla , Wu Pauline , Samii Leyla , Walsh Michael , Ismail Zahinoor , Iaboni Andrea , Goodarzi Zahra
Published: July 2024

Background

Anxiety symptoms and disorders are common in older adults and often go undetected. A systematic review was completed to identify tools that can be used to detect anxiety symptoms and disorders in community-dwelling older adults.

Methods

MEDLINE, Embase and PsycINFO were searched using the search concepts anxiety, older adults and diagnostic accuracy in March 2023. Included articles assessed anxiety in community-dwelling older adults using an index anxiety tool and a gold standard form of anxiety assessment and reported resulting diagnostic accuracy outcomes. Estimates of pooled diagnostic accuracy outcomes were completed.

Results

Twenty-three anxiety tools were identified from the 32 included articles. Pooled diagnostic accuracy outcomes were estimated for the Geriatric Anxiety Inventory (GAI)-20 [n = 3, sensitivity = 0.89, 95% confidence interval (CI) = 0.70–0.97, specificity = 0.80, 95% CI = 0.67–0.89] to detect generalized anxiety disorder (GAD) and for the GAI-20 (n = 3, cut off ≥ 9, sensitivity = 0.74, 95% CI = 0.62–0.83, specificity = 0.96, 95% CI = 0.74–1.00), Beck Anxiety Inventory (n = 3, sensitivity = 0.70, 95% CI = 0.58–0.79, specificity = 0.60, 95% CI = 0.51–0.68) and Hospital Anxiety and Depression Scale (HADS-A) (n = 3, sensitivity = 0.78, 95% CI = 0.60–0.89, specificity = 0.76, 95% CI = 0.60–0.87) to detect anxiety disorders in clinical samples.

Conclusion

The GAI-20 was the most studied tool and had adequate sensitivity while maintaining acceptable specificity when identifying GAD and anxiety disorders. The GAI-20, GAI-Short Form and HADS-A tools are supported for use in detecting anxiety in community-dwelling older adults. Brief, self-rated and easy-to-use tools may be the best options for anxiety detection in community-dwelling older adults given resource limitations. Clinicians may consider factors including patient comorbidities and anxiety prevalence when selecting a tool and cut off.
Characterizing reward and relief/habit drinking profiles in a study of naltrexone, varenicline, and placebo
Authors: Kady Annabel , Grodin Erica N , Ray Lara A
Published: July 2024

Introduction

This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo.

Methods

Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals’ drinking outcomes on each medication versus placebo.

Results

Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P’s < .05). Reward individuals’ tension decreased on naltrexone, while relief/habit individuals’ tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001).

Discussion

This study suggests relief/habit individuals’ mood worsens during early abstinence. Our finding that reward individuals’ tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.
Effects of Optimal Temperature Control in Body Contouring Surgery: A Nonrandomized Controlled Clinical Trial
Authors: Hoyos Alfredo E , Perez Pachon Mauricio E , Benavides Jorge E , Eljaiek Anet , Borras Osorio Mariana , Ramirez Brian
Published: July 2024

Background

Perioperative hypothermia in plastic surgery has underestimated risks, including increased risk of infection, cardiac events, blood loss, prolonged recovery time, and increased nausea, pain, and opioid usage. Inadequate preventive measures can result in up to 4 hours of normothermia restoration.

Objectives

The aim was to compare the impact of different strategies for normothermia during plastic surgery procedures and their relationship with clinical outcomes.

Methods

A nonrandomized clinical trial was conducted in a single center in Bogota, Colombia. We enrolled adult patients undergoing body contouring surgery and divided them into 4 intervention groups with different measures to control body temperature. Univariate and bivariate analyses were performed, comparing several clinical symptoms to evaluate outcomes.

Results

A total of 197 patients were analyzed. Most of them were females (84.3%). Mean age was 38.6 years, and the median procedure duration was 260 minutes. Demographic and clinical characteristics did not exhibit significant differences between the groups. There were notable variations in temperature measurements at crucial moments during the surgical procedure among the groups, attributed to the implementation of distinct thermal protective strategies. Group comparisons showed a relationship between hypothermia and increased nausea, vomiting, shivering, pain, and additional analgesia requirements.

Conclusions

Incorporation of active thermal protective measures, such as Blanketrol or HotDog, during body contouring procedures, markedly diminishes the risk of hypothermia and enhances overall clinical outcomes. Implementing these active measures to maintain the patient in a state of normothermia not only improves operating room efficiency but also leads to a reduction in recovery room duration.

Level of Evidence: 3
Revisiting the biogeographical regionalization of the Pacific Lowlands biogeographical province using bird distributional data
Authors: Morrone Juan J , García-Trejo Erick A
Published: July 2024

The individual tracks of 47 bird species endemic to the Pacific Lowlands biogeographical province, which belongs to the Mesoamerican dominion of the Neotropical region, were used to revise its biogeographical regionalization. As a result, the six biogeographical districts previously recognized are classified in two subprovinces: the Coastal Lowlands of Nayarit-Sinaloa subprovince, stat. nov., which includes the Sinaloan, Tres Marías Islands, Revillagigedo Islands, and Guerreran districts; and the Coastal Lowlands of Southwestern Mexico subprovince, stat. nov., which includes the Tehuanan and Tapachultecan districts. Bird species supporting the biogeographical subprovinces and districts recognized are listed. The recognition of the subprovinces encompassing the districts represents an improvement of this biogeographical regionalization.
Becoming an Ex-Extremist: Stopping the Hate and Embracing a New Identity
Authors: DeMichele Matthew , Simi Pete , Blee Kathleen
Published: July 2024

Domestic radicalization to violent extremism has evolved into the most urgent terrorism threat facing the West. We contribute to research on extremism and role exit processes by demonstrating how identity transformations are linked to the pursuit and avoidance of possible future selves motivated by negative emotional states of shame, embarrassment and guilt. The data are drawn from in-depth life history interviews with 47 former members of US domestic violent extremist groups. The interviewees, who had detailed accounts of childhood maltreatment, abuse and neglect, were vulnerable and looking for belonging, acceptance and significance in their lives. The interviews revealed that the extremist role identity conflicted with other emerging aspects of their selves (e.g. parent, spouse) that created an interaction between negative emotional states (i.e. shame, guilt and embarrassment) and doubts about their group involvement. The internal conflicts and emotional awareness opened individuals to embrace non-extremist versions of themselves. These processes diverted their extremist trajectory by creating doubts, engaging in anticipatory socialization and avoiding a feared possible self.
Realities on Participation of Scheduled Caste in India: The Benefits of Social Inclusion in Higher Education through Social Work Interventions
Authors: Das Gadha M , Lalitha S
Published: July 2024

Education plays a crucial role in empowering individuals and building a society that is driven by knowledge. In India, higher education focuses on instilling values, attitudes and skills in students for their personal growth and the betterment of society. The core principles of higher education in India revolve around social justice, equality, democratic participation and equity. However, despite the constitutional promise of equality and social justice, the Indian social structure still adheres to the Caste system. This leads to social exclusion and creates a significant gap in access to quality education for marginalised groups, particularly the Scheduled Castes (SCs). This article examines the participation trends of SC students in higher education, highlighting the challenges within the education system and policies. It emphasises the need for inclusive education to empower SC students and uphold the principles enshrined in the Indian Constitution. Moreover underscores the value of social work intervention in encouraging the active involvement of SCs in higher education.
Seed quality and germination performance increase with cross-pollination in members of subtribe Orchidinae (Orchidaceae)
Authors: Bazzicalupo Miriam , Masullo Ilaria , Duffy Karl J , Fay Michael F , Calevo Jacopo
Published: July 2024

Over half of angiosperms have self-incompatibility systems to avoid self-pollination and inbreeding depression. Many members of Orchidaceae are self-compatible, but they may be prone to negative consequences of self-pollination. We investigated the effects of both within-flower (autogamy) and within-plant (geitonogamy) self-pollination, and cross-pollination on fruit set, seed quality, and germination rates in 11 related orchid taxa of subtribe Orchidinae. We hand-pollinated flowers and measured fruit set to estimate pre- and postzygotic barriers. We collected morphometric data on embryos and seeds and calculated the percentage of seeds with embryos and seed viability. We then calculated inbreeding depression values for each treatment for each taxon. Ten taxa produced fruits when self-pollinated, but germination rates and seed size increased with cross-pollination. Higher seed viability was correlated with larger embryos/seeds. However, geitonogamous pollination generally resulted in the lowest seed quality compared with autogamy and cross-pollination, with high values of inbreeding depression being detected. Only seven of the 11 taxa (Anacamptis papilionacea, Himantoglossum adriaticum, Ophrys apifera, Ophrys bertolonii, Orchis patens subsp. brevicornis, Orchis provincialis, and Serapias vomeracea) were confirmed as self-compatible. These results show that cross-pollination improves overall seed quality, and that the assessment of self-compatibility in orchids should be based on postfruiting stages.
Elevated cutaneous expression of stem cell factor in chronic spontaneous urticaria: a prospective cohort study
Authors: Mostmans Yora , De Smedt Katleen , Feoli Francesco , Waelput Wim , De Maertelaer Viviane , Olemans Cathérine , Meiers Isabelle , Cielen Thierry , Corazza Francis , Michel Olivier , Richert Bertrand
Published: July 2024

Background

Tissue expression of endothelial cell markers of microcirculatory changes in chronic spontaneous urticaria (CSU) is poorly understood.

Objectives

To explore the expression of specific endothelial cell markers [stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)] in lesional and nonlesional CSU skin through immunohistochemistry (IHC) and in serum.

Methods

Lesional and nonlesional skin biopsies from patients with CSU (n = 23) and healthy controls (n = 9) were studied by IHC for expression of SCF, VEGF and MAC. In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity and markers of autoimmune CSU. The study was registered at ClinicalTrials.gov (NCT03443362).

Results

Epidermal SCF reactivity was significantly higher in CSU lesional skin than in healthy skin (P = 0.026). In the dermis, SCF immunoreactivity was seen particularly in endothelial, perivascular and epithelial cells. In CSU lesional skin, the mean perivascular SCF staining was significantly more intense than in healthy controls (P < 0.001). Furthermore, CSU nonlesional skin also showed significantly higher SCF staining in dermal perivascular cells than in healthy controls (P < 0.001). Patients with CSU had the highest SCF immunoreactivity scores in the epidermis and/or on dermal endothelial cells. These patients did not have significantly higher SCF serum levels.

Conclusions

To our knowledge, this is the first study to show elevated cutaneous expression of SCF in CSU. These findings underline the potential therapeutic possibilities of anti-Kit antibodies in CSU treatment.
Et3N-catalyzed [3 + 2] annulation reaction of β-oxo-acrylamides with diethyl 2-oxomalonates: facile access to oxazolidin-4-one derivatives
Authors: Wu Lingang , Guan Baochuan , Wang Zhaoxue , Xie Lei
Published: July 2024

A new and effective method for the [3 + 2] annulation of β-oxo-acrylamides with diethyl 2-oxomalonate, catalyzed by NEt3, has been developed to be carried out under mild reaction conditions. This approach offers a direct route to synthesize oxazolidin-4-one derivatives with yields ranging from 58% to 76%. The process is notable for being highly atom-efficient and operationally simple.
Rapid Wane and Recovery of XBB Sublineage Neutralization After Sequential Omicron-based Vaccination in Solid Organ Transplant Recipients
Authors: Johnston Trevor S , Hage Camille , Abedon Aura T , Panda Snigdha , Alejo Jennifer L , Eby Yolanda , Segev Dorry L , Tobian Aaron A R , Cox Andrea L , Werbel William A , Karaba Andrew H
Published: July 2024

Durability of variant neutralization in solid organ transplant recipients following Omicron-containing boosters is unknown. We report wane in XBB.1.5 neutralization by 3 months following a first bivalent booster, improved by a second booster; hybrid immunity improved peak, and duration of neutralization. Boosting at 3 to 6 months appears necessary to maintain neutralization.
2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Appendicitis in Adults, Children, and Pregnant People
Authors: Bonomo Robert A , Tamma Pranita D , Abrahamian Fredrick M , Bessesen Mary , Chow Anthony W , Dellinger E Patchen , Edwards Morven S , Goldstein Ellie , Hayden Mary K , Humphries Romney , Kaye Keith S , Potoski Brian A , Rodríguez-Baño Jesús , Sawyer Robert , Skalweit Marion , Snydman David R , Donnelly Katelyn , Loveless Jennifer
Published: July 2024

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America (IDSA). In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Intra-abdominal Abscess in Adults, Children, and Pregnant People
Authors: Bonomo Robert A , Tamma Pranita D , Abrahamian Fredrick M , Bessesen Mary , Chow Anthony W , Dellinger E Patchen , Edwards Morven S , Goldstein Ellie , Hayden Mary K , Humphries Romney , Kaye Keith S , Potoski Brian A , Rodríguez-Baño Jesús , Sawyer Robert , Skalweit Marion , Snydman David R , Donnelly Katelyn , Loveless Jennifer
Published: July 2024

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this article, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Intra-abdominal Fluid Cultures in Adults, Children, and Pregnant People
Authors: Bonomo Robert A , Humphries Romney , Abrahamian Fredrick M , Bessesen Mary , Chow Anthony W , Dellinger E Patchen , Edwards Morven S , Goldstein Ellie , Hayden Mary K , Kaye Keith S , Potoski Brian A , Rodríguez-Baño Jesús , Sawyer Robert , Skalweit Marion , Snydman David R , Tamma Pranita D , Donnelly Katelyn , Loveless Jennifer
Published: July 2024

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
Secondary tricuspid regurgitation: incidence, types, and outcomes in atrial fibrillation vs. sinus rhythm
Authors: Naser Jwan A , Castrichini Matteo , Ibrahim Hossam H , Scott Christopher G , Lin Grace , Lee Eunjung , Mankad Rekha , Siontis Konstantinos C , Eleid Mackram F , Pellikka Patricia A , Michelena Hector I , Pislaru Sorin V , Nkomo Vuyisile T
Published: July 2024

Background and Aims

Incidence and types of secondary tricuspid regurgitation (TR) are not well defined in atrial fibrillation (AFib) and sinus rhythm (SR). Atrial secondary TR (A-STR) is associated with pre-existing AFib; however, close to 50% of patients with A-STR do not have AFib. The aim of this study was to assess incidence, types, and outcomes of ≥ moderate TR in AFib vs. SR.

Methods

Adults with and without new-onset AFib without structural heart disease or ≥ moderate TR at baseline were followed for the development of ≥ moderate TR. Tricuspid regurgitation types were pacemaker, left-sided valve disease, left ventricular (LV) dysfunction, pulmonary hypertension (PH), isolated ventricular, and A-STR.

Results

Among 1359 patients with AFib and 20 438 in SR, 109 and 378 patients developed ≥ moderate TR, respectively. The individual types of TR occurred more frequently in AFib related to the higher pacemaker implantation rates (1.12 vs. 0.19 per 100 person-years, P < .001), larger right atrial size (median 78 vs. 53 mL, P < .001), and higher pulmonary pressures (median 30 vs. 28 mmHg, P < .001). The most common TR types irrespective of rhythm were LV dysfunction-TR and A-STR. Among patients in SR, those with A-STR were older, predominantly women with more diastolic abnormalities and higher pulmonary pressures. All types of secondary TR were associated with all-cause mortality, highest in PH-TR and LV dysfunction-TR.

Conclusions

New-onset AFib vs. SR conferred a higher risk of the individual TR types related to sequelae of AFib and higher pacemaker implantation rates, although the distribution of TR types was similar. Secondary TR was universally associated with increased mortality.
The relationship between psychological burden and providing assistance with taking medication among caregivers of patients with dementia: a cross-sectional study
Authors: Fuga Habuchi , Yamaoka Erika , Ishida Natsuko , Shitanda Koji , Hashimoto Masako , Matushita Ryo
Published: July 2024

Objectives

Previous studies have examined the psychological burden of caregivers of patients with dementia. However, although many caregivers struggle to assist patients with dementia with medication management, the relationship between assisting such patients with taking their medicines and the caregiver psychological burden is understudied. Therefore, this study identified the association between caregivers’ psychological burden and assisting patients with dementia with taking medication.

Methods

A cross-sectional survey was conducted among caregivers of patients with dementia in Japan. The survey questionnaire included questions that assessed the symptoms of patients with dementia, their status of taking medication through medication assistance from caregivers, and caregivers’ psychological burden using the Kessler Psychological Distress Scale and the Japanese version of the Perceived Stress Scale.

Key findings

A total of 57 caregivers participated in the study. Higher Kessler Psychological Distress Scale scores were significantly associated with unsuccessful assistance with taking regular medication (β = 0.35, 95% confidence interval [CI]: 2.23–12.0, P < .05), depressive symptoms (β = 0.26, 95% CI: 0.10–8.53, P < .05), and irritability (β = 0.38, 95% CI: 2.71–11.5, P < .05). Likewise, higher scores on the Japanese version of the Perceived Stress Scale were significantly associated with irritability (β = 0.37, 95% CI: 1.87–12.5, P < .05) among patients with dementia.

Conclusion

The findings suggest that caregiver psychological burden is associated with unsuccessful assistance with taking regular medication for patients with dementia.
Do Pregnant Persons Want Influenza Vaccines? Knowledge, Attitudes, Perceptions, and Practices Toward Influenza Vaccines in 8 Low- and Middle-Income Countries
Authors: McCarron Margaret , Yau Tat S , Griffin Chelsey , Marcenac Perrine , Ebama Malembe S , Lafond Kathryn E , Igboh Ledor S , Duca Lindsey M , Bino Silvia , Bettaieb Jihene , Dhaouadi Sonia , Sahakyan Gayane , Cherkaoui Imad , Alj Loubna , Coulibaly Daouda , Lutwama Julius J , Douba Alfred , N’Gattia Anderson , Khanthamaly Viengphone , Tengbriacheu Chankham , Patthammavong Chansay , Lambach Philipp , Otorbaeva Dinagul , Azziz-Baumgartner Eduardo , Bresee Joseph S
Published: July 2024

Background

Vaccination is the most effective way to prevent influenza infection and adverse outcomes; despite global recommendations to vaccinate pregnant persons, access to influenza vaccines remains low. We explored knowledge, attitudes, and practices of pregnant persons to inform actions to improve vaccine uptake.

Methods

We pooled data from cross-sectional surveys assessing pregnant persons’ attitudes toward influenza vaccines in 8 low- and middle-income countries. Countries used standard methods to measure attitudes and intents toward influenza vaccination. We stratified by presence/absence of a national influenza vaccination program, income group, geographic region, and individual-level factors.

Results

Our analysis included 8556 pregnant persons from 8 countries. Most pregnant persons (6323, 74%) were willing to receive influenza vaccine if it was offered for free. Willingness differed by presence of an existing influenza vaccination program; acceptance was higher in countries without programs (2383, 89%) than in those with programs (3940, 67%, P < .001).

Conclusions

Most pregnant persons in middle-income countries, regardless of influenza vaccination program status, were willing to be vaccinated against influenza if the vaccine was provided free of charge. National investments in influenza vaccination programs present an opportunity to avert illness both in pregnant persons themselves and in their newborn babies.
Diverse roles of dendritic cell and regulatory T cell crosstalk in controlling health and disease
Authors: Yamazaki Sayuri
Published: July 2024

Dendritic cells (DCs) are specialized antigen-presenting cells for lymphocytes, including regulatory T (Treg) cells, a subset of CD4+ T cells expressing CD25 and Foxp3, a transcription factor. Treg cells maintain immunological self-tolerance in mice and humans, and suppress autoimmunity and other various immune responses such as tumor immunity, transplant rejection, allergy, responses to microbes, and inflammation. Treg-cell proliferation is controlled by antigen-presenting DCs. On the other hand, Treg cells suppress the function of DCs by restraining DC maturation. Therefore, the interaction between DCs and Treg cells, DC–Treg crosstalk, could contribute to controlling health and disease. We recently found that unique DC–Treg crosstalk plays a role in several conditions. First, Treg cells are expanded in ultraviolet B (UVB)-exposed skin by interacting with DCs, and the UVB-expanded Treg cells have a healing function. Second, manipulating DC–Treg crosstalk can induce effective acquired immune responses against severe acute respiratory syndrome coronavirus 2 antigens without adjuvants. Third, Treg cells with a special feature interact with DCs in the tumor microenvironment of human head and neck cancer, which may contribute to the prognosis. Understanding the underlying mechanisms of DC–Treg crosstalk may provide a novel strategy to control health and disease.
The Dynamic Effects of UN SEA Reporting on the Actions of Peacekeeping Contributing Countries
Authors: Torres-Beltran Angie , Mailhot Cameron
Published: July 2024

Abstracts

What effect does sexual exploitation and abuse (SEA) reporting by the United Nations (UN) have on the actions of peacekeeping missions’ troop and police contributing countries (TPCCs)? While past scholarship has studied the effect of naming and shaming for states’ human rights records, we examine the relationship between the UN’s reporting on human rights abuses committed by its Member States’ personnel and their policy and personnel responses. Focusing on SEA reporting within peacekeeping missions, we theorize the ways in which the UN’s reporting of SEA may lead to two distinct responses: TPCCs may issue legal frameworks to demonstrate compliance and address SEA, or they may withdraw from peacekeeping missions by reducing their personnel commitments. Using an original, cross-national dataset of UN reporting on SEA allegations and the patterns of framework issuance and personnel commitments among TPCCs (2010–2020), we find that TPCCs with SEA reports are more likely to issue legal frameworks and to reduce personnel contributions than their nonreported counterparts, and that this relationship is particularly strong following the first instance of reporting. With targeted TPCCs demonstrating both greater policy compliance and personnel withdrawal, our findings highlight the dynamic impact that UN reporting for SEA can have on the actions of TPCCs.
Revealing the effect of X-ray or proton brain irradiation on systemic inflammation and leukocyte subpopulation interplay in rodents
Authors: Pham Thao-Nguyen , Coupey Julie , Rousseau Marc , Thariat Juliette , Valable Samuel
Published: July 2024

The absolute lymphocyte count (ALC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR) offer convenient means to assess systemic inflammation post-cancer treatment, which influences treatment outcomes. Understanding these biomarker variations and leukocyte subpopulation interplay is crucial for optimizing radiotherapy. Herein, leukocyte subpopulations (T-CD4+, T-CD8+, B cells, NK cells, neutrophils, monocytes) during and after brain irradiation (using X-rays or protons) in tumor-free mice were used to compute ALC, LMR, and NLR, on which radiation parameter influence was assessed by principal component analysis (PCA). NLR kinetics was further examined using modeling. Leukocyte subpopulation interplays and their response to radiation parameters were examined using PCA and correlation analysis. Under X-rays, ALC and LMR decreased, with ALC recovered to baseline after irradiation, but not LMR. Both X-rays and protons increased the NLR during irradiation, recovering in protons but not X-rays. Both irradiation volume and dose rate had a pronounced effect on the NLR. Leukocyte subpopulation interplay was observed under X-rays and protons, normalizing in the proton group by day 28. Lymphopenia was observed in all lymphocyte subpopulations under X-ray irradiation but not protons. The recovery patterns varied among the subpopulations. Neutrophil counts increased during irradiation, with the recovery of protons, but not X-rays, by day 28. Interplays between NK cells and myeloid subpopulations were evident under X-rays but not protons. Importantly, no interplay was detected between myeloid cells and T/B cells, indicating that LMR and NLR variations were primarily due to independent responses to brain irradiation. A tumor-free experimental mouse model was used to study the effects of brain radiotherapy on systemic immunity. When administering fractionated irradiation with a total dose of 20 Gy using a vertical beam to either the whole brain or hemi-brain, proton irradiation had fewer adverse impacts on the immune system compared to X-rays in tumor-free rodents.
Measuring the ejecta velocities of type Ia supernovae from the pan-STARRS1 medium deep survey
Authors: Pan Y -C , Jheng Y -S , Jones D O , Lee I -Y , Foley R J , Chornock R , Scolnic D M , Berger E , Challis P M , Drout M , Huber M E , Kirshner R P , Kotak R , Lunnan R , Narayan G , Rest A , Rodney S , Smartt S
Published: July 2024

There is growing evidence that Type Ia supernovae (SNe Ia) may originate from multiple explosion channels. Previous studies have indicated that the ejecta velocity of SNe Ia is one powerful tool to discriminate between different channels. In this work, we study ∼400 confirmed SNe Ia discovered by the Pan-STARRS1 Medium Deep Survey (PS1-MDS), and obtain a sample of ∼50 SNe Ia that have near-peak $\mathrm{Si}\, {\small II}\, \lambda 6355$ velocity ($v_{\mathrm{Si}\, {\small II}}$) measurements. We investigate the relationships between $v_{\mathrm{Si}\, {\small II}}$ and various parameters, including SN light-curve width, colour, host galaxy properties, and redshift. No significant trends are identified between $v_{\mathrm{Si}\, {\small II}}$ and light-curve parameters. Regarding the host-galaxy properties, we see a significant trend that high-velocity (HV) SNe Ia ($v_{\mathrm{Si}\, {\small II}}\gtrsim 12000$  km s$^{-1}$) tend to reside in more massive galaxies compared to normal velocity (NV) SNe Ia ($v_{\mathrm{Si}\, {\small II}}\lt 12000$  km s$^{-1}$) when combining both the PS1-MDS data set and those from previous low-z studies. While we do not see a significant trend between $v_{\mathrm{Si}\, {\small II}}$ and redshift, HV SNe Ia appear to be more prevalent in low-z samples than in high-z samples. We discuss several possibilities that could potentially contribute to this trend. Furthermore, we investigate the potential bias on SN Ia distances and find no significant difference in Hubble residuals between HV and NV subgroups.
Inference of Locus-Specific Population Mixtures from Linked Genome-Wide Allele Frequencies
Authors: Reyna-Blanco Carlos S , Caduff Madleina , Galimberti Marco , Leuenberger Christoph , Wegmann Daniel
Published: July 2024

Admixture between populations and species is common in nature. Since the influx of new genetic material might be either facilitated or hindered by selection, variation in mixture proportions along the genome is expected in organisms undergoing recombination. Various graph-based models have been developed to better understand these evolutionary dynamics of population splits and mixtures. However, current models assume a single mixture rate for the entire genome and do not explicitly account for linkage. Here, we introduce TreeSwirl, a novel method for inferring branch lengths and locus-specific mixture proportions by using genome-wide allele frequency data, assuming that the admixture graph is known or has been inferred. TreeSwirl builds upon TreeMix that uses Gaussian processes to estimate the presence of gene flow between diverged populations. However, in contrast to TreeMix, our model infers locus-specific mixture proportions employing a hidden Markov model that accounts for linkage. Through simulated data, we demonstrate that TreeSwirl can accurately estimate locus-specific mixture proportions and handle complex demographic scenarios. It also outperforms related D- and f-statistics in terms of accuracy and sensitivity to detect introgressed loci.
TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice
Authors: Tresky Roland , Miyamoto Yuta , Nagayoshi Yu , Yabuki Yasushi , Araki Kimi , Takahashi Yukie , Komohara Yoshihiro , Ge Huicong , Nishiguchi Kayo , Fukuda Takaichi , Kaneko Hitomi , Maeda Nobuko , Matsuura Jin , Iwasaki Shintaro , Sakakida Kourin , Shioda Norifumi , Wei Fan-Yan , Tomizawa Kazuhito , Chujo Takeshi
Published: July 2024

In higher eukaryotes, tRNA methyltransferase 10A (TRMT10A) is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs. Pathogenic mutations in TRMT10A cause intellectual disability, microcephaly, diabetes, and short stature in humans, and generate cytotoxic tRNA fragments in cultured cells; however, it is not clear how TRMT10A supports codon translation or brain functions. Here, we generated Trmt10a null mice and showed that tRNAGln(CUG) and initiator methionine tRNA levels were universally decreased in various tissues; the same was true in a human cell line lacking TRMT10A. Ribosome profiling of mouse brain revealed that dysfunction of TRMT10A causes ribosome slowdown at the Gln(CAG) codon and increases translation of Atf4 due to higher frequency of leaky scanning of its upstream open reading frames. Broadly speaking, translation of a subset of mRNAs, especially those for neuronal structures, is perturbed in the mutant brain. Despite not showing discernable defects in the pancreas, liver, or kidney, Trmt10a null mice showed lower body weight and smaller hippocampal postsynaptic densities, which is associated with defective synaptic plasticity and memory. Taken together, our study provides mechanistic insight into the roles of TRMT10A in the brain, and exemplifies the importance of universal tRNA modification during translation of specific codons.
Machine learning enables pan-cancer identification of mutational hotspots at persistent CTCF binding sites
Authors: Chen Wenhan , Zeng Yi C , Achinger-Kawecka Joanna , Campbell Elyssa , Jones Alicia K , Stewart Alastair G , Khoury Amanda , Clark Susan J
Published: July 2024

CCCTC-binding factor (CTCF) is an insulator protein that binds to a highly conserved DNA motif and facilitates regulation of three-dimensional (3D) nuclear architecture and transcription. CTCF binding sites (CTCF-BSs) reside in non-coding DNA and are frequently mutated in cancer. Our previous study identified a small subclass of CTCF-BSs that are resistant to CTCF knock down, termed persistent CTCF binding sites (P-CTCF-BSs). P-CTCF-BSs show high binding conservation and potentially regulate cell-type constitutive 3D chromatin architecture. Here, using ICGC sequencing data we made the striking observation that P-CTCF-BSs display a highly elevated mutation rate in breast and prostate cancer when compared to all CTCF-BSs. To address whether P-CTCF-BS mutations are also enriched in other cell-types, we developed CTCF-INSITE—a tool utilising machine learning to predict persistence based on genetic and epigenetic features of experimentally-determined P-CTCF-BSs. Notably, predicted P-CTCF-BSs also show a significantly elevated mutational burden in all 12 cancer-types tested. Enrichment was even stronger for P-CTCF-BS mutations with predicted functional impact to CTCF binding and chromatin looping. Using in vitro binding assays we validated that P-CTCF-BS cancer mutations, predicted to be disruptive, indeed reduced CTCF binding. Together this study reveals a new subclass of cancer specific CTCF-BS DNA mutations and provides insights into their importance in genome organization in a pan-cancer setting.
Directed evolution of hyperactive integrases for site specific insertion of transgenes
Authors: Hew Brian E , Gupta Sabranth , Sato Ryuei , Waller David F , Stoytchev Ilko , Short James E , Sharek Lisa , Tran Christopher T , Badran Ahmed H , Owens Jesse B
Published: July 2024

The ability to deliver large transgenes to a single genomic sequence with high efficiency would accelerate biomedical interventions. Current methods suffer from low insertion efficiency and most rely on undesired double-strand DNA breaks. Serine integrases catalyze the insertion of large DNA cargos at attachment (att) sites. By targeting att sites to the genome using technologies such as prime editing, integrases can target safe loci while avoiding double-strand breaks. We developed a method of phage-assisted continuous evolution we call IntePACE, that we used to rapidly perform hundreds of rounds of mutagenesis to systematically improve activity of PhiC31 and Bxb1 serine integrases. Novel hyperactive mutants were generated by combining synergistic mutations resulting in integration of a multi-gene cargo at rates as high as 80% of target chromosomes. Hyperactive integrases inserted a 15.7 kb therapeutic DNA cargo containing von Willebrand Factor. This technology could accelerate gene delivery therapeutics and our directed evolution strategy can easily be adapted to improve novel integrases from nature.
Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing
Authors: Schep Ruben , Trauernicht Max , Vergara Xabier , Friskes Anoek , Morris Ben , Gregoricchio Sebastian , Manzo Stefano G , Zwart Wilbert , Beijersbergen Roderick L , Medema René H , van Steensel Bas
Published: July 2024

The efficiency and outcome of CRISPR/Cas9 editing depends on the chromatin state at the cut site. It has been shown that changing the chromatin state can influence both the efficiency and repair outcome, and epigenetic drugs have been used to improve Cas9 editing. However, because the target proteins of these drugs are not homogeneously distributed across the genome, the efficacy of these drugs may be expected to vary from locus to locus. Here, we systematically analyzed this chromatin context-dependency for 160 epigenetic drugs. We used a human cell line with 19 stably integrated reporters to induce a double-stranded break in different chromatin environments. We then measured Cas9 editing efficiency and repair pathway usage by sequencing the mutational signatures. We identified 58 drugs that modulate Cas9 editing efficiency and/or repair outcome dependent on the local chromatin environment. For example, we find a subset of histone deacetylase inhibitors that improve Cas9 editing efficiency throughout all types of heterochromatin (e.g. PCI-24781), while others were only effective in euchromatin and H3K27me3-marked regions (e.g. apicidin). In summary, this study reveals that most epigenetic drugs alter CRISPR editing in a chromatin-dependent manner, and provides a resource to improve Cas9 editing more selectively at the desired location.
Geochemical Evidence of Water-Fluxed Crustal Melting in the Northern Colombian Andes
Authors: Errázuriz-Henao Carlos , Parolari Mattia , Gómez-Tuena Arturo , Gutiérrez-Aguilar Fabian , García-RodrÍguez Hermes
Published: July 2024

The compositions of crustal magmas are powerful tools for understanding the formation and differentiation of continents. However, the geochemical fingerprints that distinguish the two dominant mechanisms of crustal melting, namely dehydration and water-fluxed melting, are still controversial. To provide new insights into this problem, we discuss the petrogenesis of the Paipa Volcanic Complex (PVC), an isolated Quaternary volcanic field in the Colombian Eastern Cordillera. The PVC is characterized by peraluminous trondhjemite-like rhyolites with exceptionally high Na2O contents (~6 wt %), super-chondritic Nb/Ta (~27), elevated Sr/Y ratios (~120), spoon-shaped REE patterns, and enriched isotopic compositions that overlap with those of the local basement. They also exhibit high pre-eruptive H2O contents (~up to 9.5 wt %) and abundant Paleozoic zircon inheritances. We demonstrate that these characteristics are inconsistent with a process of intra-crustal differentiation from a mafic or intermediate mantle-derived precursor. Instead, we propose that the origin of the PVC is best explained by melting the local (meta)sedimentary basement under H2O-saturated conditions, at middle-crustal pressures (~1.3 GPa) and relatively low temperatures (~690–740°C), following the complete breakdown of plagioclase and biotite, and the formation of reactive peritectic amphibole. This scenario differs from the high-temperature dehydration melting conditions that have been widely proposed for the Andes and globally, which result in the production of water undersaturated magmas in equilibrium with anhydrous lithologies rich in plagioclase and/or garnet. Accordingly, we speculate that an external H2O flux was ultimately sourced from a buoyant, cold, and hydrated mantle wedge that was extensively metasomatized by fluids derived from the Nazca and Caribbean flat-slab fronts. These conditions depressed the asthenospheric mantle potential temperature, likely inhibiting mantle melting. In turn, they facilitated the infiltration and ascent of mantle-derived H2O through pre-existing crustal faults and shear zones. Our results indicate that water-fluxed melting could be a plausible mechanism for generating crustal magmas in orogenic regions where the availability of free H2O has been difficult to confirm.
Meeting expectations? Response of policy innovation labs to sustainable development goals
Authors: Hoss-Golan Esti , Gofen Anat , Wellstead Adam M
Published: July 2024

Introduced by the United Nations, Sustainable Development Goals (SDGs) aim at facilitating inclusive sustainable development. Responsiveness to SDGs is considered a key to addressing pressing development problems. The current literature focuses on the responsiveness of varied public organizations to SDGs, whereas SDGs’ responsiveness of policy innovation labs (PILs) is understudied. Aiming to address both persistent and emerging social and environmental problems, PILs are aligned with SDGs. On the other hand, PILs seek innovative ways to generate policy solutions in collaboration with citizens through experimental methods and thus are more committed to the local public rather than international organizations. This paper investigates to what extent and in what way PILs respond to SDGs during policy formulation processes, both implicitly and explicitly. Data draws on a database the authors developed, identifying 211 European PILs. Thematic coding of PILs’ websites reveals that 62.1% of the PILs implicitly promote at least one SDG. Additionally, sustainable cities and communities (SDG11) and good health and well-being (SDG3) are the two SDGs with the highest implicit-response rates, respectively. We apply grounded theory analysis from semi-structured interviews with senior PIL employees of 31 PILs to gauge their explicit views of SDGs. This inductive approach reveals three dimensions to SDGs: levels of responsiveness, different practices, and considerations that guide PILs on whether to comply with SDGs. A better understanding of PILs’ response to SDGs provides a more nuanced portrayal of PILs as organizations aiming to craft innovative policy solutions that align with international frameworks.
Partisan Poll Watchers and Americans’ Perceptions of Electoral Fairness
Authors: Cohen Mollie J , Sheagley Geoffrey
Published: July 2024

Poll watchers play an increasingly visible role in American elections, yet there is little research into how their presence shapes beliefs about electoral integrity. On the one hand, poll watchers—like other election observers—may lead voters to be more trusting in elections. On the other hand, poll watchers who expressly represent political parties may contribute to polarized views of electoral integrity. We address this gap with two conjoint experiments and one vignette experiment administered on large national samples. The conjoint experiments vary several features of election polling locations, including the presence of poll watchers, voter identification requirements, and other election regulations. We find that regulations around poll watchers shape views of election fairness, but that the nature of this influence depends on the type and partisanship of poll watchers who are present. The vignette experiment shows that perceptions of poll watchers decline when these individuals act in bad faith; effects are especially large for Republican respondents. These findings help identify the potential that poll watchers have to shape Americans’ beliefs about election fairness and integrity.
Missing Financial Data
Authors: Bryzgalova Svetlana , Lerner Sven , Lettau Martin , Pelger Markus
Published: July 2024

We document the widespread nature and structure of missing observations of firm fundamentals and show how to systematically handle them. Missing financial data affects more than 70% of firms that represent about half of the total market cap. Firm fundamentals have complex systematic missing patterns, invalidating traditional approaches to imputation. We propose a novel imputation method to obtain a fully observed panel of firm fundamentals that exploits both time-series and cross-sectional dependency of data to impute missing values and allows for general systematic patterns of missingness. We document important implications for risk premiums estimates, cross-sectional anomalies, and portfolio construction. (JEL C14, C38, C55, G12)