bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns and Cofactors of Polyfunctional Mycobacteria-Specific T-Cell Response Restoration Following 6-Month Antiretroviral Treatment in Children With HIV
Authors: Day Cheryl L , Njuguna Irene N , Cranmer Lisa Marie , Whatney Wendy E , Pearson Rachel A , Lindestam Arlehamn Cecilia S , Sette Alessandro , LaCourse Sylvia M , Escudero Jaclyn N , Sasser Loren E , Mugo Cyrus , Okinyi Hellen Moraa , Maleche-Obimbo Elizabeth , Wamalwa Dalton C , John-Stewart Grace C
Published: December 2024

Background

Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children with HIV (CHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CHIV.

Methods

CD4 and CD8 T-cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells from CHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya. T-cell expression of cytokines and activation-induced markers were measured following stimulation of peripheral blood mononuclear cells with a pool of 300 peptides from TB (MTB300) or staphylococcal enterotoxin B.

Results

Among 47 CHIV (median age, 1.5 years), staphylococcal enterotoxin B–induced Th1 cytokine+ and activation-induced marker+ CD4 cell frequencies increased significantly after 6 months of ART. Although MTB300-specific CD4 and CD8 cell frequency did not increase after ART, polyfunctional capacity of MTB300-specific CD4 cells expressing combinations of Th1 cytokines with CD40L increased significantly after ART. Baseline age, immune activation, and effector memory CD4 levels were associated with less restoration of MTB300-specific polyfunctional CD4 cells, whereas CD4 percentage and levels of naive CD4 cells following ART were associated with improved MTB300-specific polyfunctional capacity.

Conclusions

Despite increases in Th1 cytokine production, deficits in mycobacteria-specific CD4 cells persisted 6 months after ART, with higher deficits in older CHIV with more immunosuppression, higher immune activation, and lower proportion of naive CD4 cells. These findings may explain persistent TB risk during early ART among CHIV and identify those at highest risk.
Candida albicans Recovered From Persistent Candidemia Exhibits Enhanced Virulence Traits
Authors: Ribeiro Felipe de Camargo , Kemmerich Karoline Kristina , Gonçale Juliana Caparroz , Junqueira Juliana Campos , Mannan Mohammad , Nabeela Sunna , Colombo Arnaldo Lopes , Uppuluri Priya
Published: December 2024

Candida albicans catheter-related candidemia is largely driven by microbial adhesion and biofilm formation on central venous catheters. Cells that disperse from these biofilms can enter the bloodstream, spread to distant organs, and sustain the cycle of infection. In this study, we investigated the virulence potential of C. albicans isolates obtained from the blood of catheterized patients experiencing persistent candidemia, comparing them to isolates that were cleared from the bloodstream early in the infection. Our results show that isolates persisting in the bloodstream for 4 days or longer, despite antifungal treatment, exhibited enhanced adherence, filamentation, and biofilm formation in vitro, along with increased expression of key virulence-related genes. Notably, cells dispersed from second-generation biofilms formed by these persistent isolates displayed even more pronounced pathogenic characteristics, including improved immune evasion. Furthermore, in vivo experiments using Galleria mellonella revealed that persistent isolates were significantly more virulent than their nonpersistent counterparts.
A systematic review and individual bacterial species level meta-analysis of in vitro studies on the efficacy of ceftazidime/avibactam combined with other antimicrobials against carbapenem-resistant Gram-negative bacteria
Authors: Assefa Getnet M , Roberts Jason A , Aslan Abdullah T , Mohammed Solomon A , Sime Fekade B
Published: December 2024

Background

Carbapenem-resistant Gram-negative bacteria (CR-GNB) develop resistance to many antimicrobials. To effectively manage infections caused by these organisms, novel agents and/or combinations of antimicrobials are required.

Objectives

Evaluated the in vitro efficacy of ceftazidime/avibactam in combination with other antimicrobials against CR-GNB.

Methods

PubMed, Web of Science, Embase and Scopus were searched. Study outcomes were quantified by counting the number of isolates exhibiting synergy, defined as a fractional inhibitory concentration index ≤ 0.5 for checkerboard and Etest, and a >2 log cfu/mL reduction for time-kill studies. The proportion of synergy was calculated as the ratio of isolates exhibiting synergy to the total number of isolates tested. These proportions were analysed using a random-effects model, following the Freeman–Tukey double-arcsine transformation.

Results

Forty-five in vitro studies were included. A total of 734 isolates were tested, and 69.3% of them were resistant to ceftazidime/avibactam. The combination of ceftazidime/avibactam with aztreonam showed a high synergy rate against carbapenem-resistant Klebsiella pneumoniae (effect size, ES = 0.91–0.98) and Escherichia coli (ES = 0.75–1.00). Ceftazidime/avibactam also demonstrated a high synergy rate (ES = 1) in time-kill studies when combined with azithromycin, fosfomycin and gentamicin against K. pneumoniae. Compared to ceftazidime/avibactam alone, a higher bactericidal rate was reported when ceftazidime/avibactam was combined with other antimicrobials against carbapenem-resistant K. pneumoniae (57% versus 31%) and E. coli (93% versus 0%).

Conclusions

Ceftazidime/avibactam frequently demonstrates synergistic bactericidal activity when combined with various antimicrobials against CR-GNB in in vitro tests. Further pre-clinical and clinical studies are warranted to validate the utility of ceftazidime/avibactam-based combination regimens for CR-GNB infections.
Leveraging local public health to advance antimicrobial stewardship (AMS) implementation and mitigate antimicrobial resistance (AMR): a scoping review
Authors: Leung Valerie , Ashiru-Oredope Diane , Hicks Lauri , Kabbani Sarah , Aloosh Mehdi , Armstrong Irene E , Brown Kevin A , Daneman Nick , Lam Kevin , Meghani Hamidah , Nur Mahad , Schwartz Kevin L , Langford Bradley J
Published: December 2024

Objective

To explore the role of local public health organisations in antimicrobial stewardship (AMS) and antimicrobial resistance (AMR) surveillance.

Methods

A scoping review was conducted. Peer-reviewed and grey literature from countries within the organisation for economic co-operation and development was searched between 1999 and 2023 using the concepts of local public health, AMR and AMS. Thematic analysis was performed to identify themes.

Results

There were 63 citations illustrating 122 examples of AMS and AMR surveillance activities with local public health involvement. Common AMS activities (n = 105) included healthcare worker education (n = 22), antimicrobial use (AMU) evaluation (n = 21), patient/public education (n = 17), clinical practice guidelines (n = 10), and antibiograms (n = 10). Seventeen citations described local public health activities in AMR surveillance; the majority focussed on communicable diseases (n = 11) and/or AMR organisms (n = 6).

Conclusions

Local public health capabilities should be leveraged to advance high-impact activities to mitigate AMR, particularly in the areas of knowledge translation/mobilisation, optimising surveillance and establishing strategic collaborations.

Policy implications

Future work should focus on better understanding barriers and facilitators, including funding, to local public health participation in these activities.
‘Some patients demand for a prescription of an antibiotic’: an assessment of barriers and facilitators to rational antimicrobial use in a private health facility in Uganda
Authors: Kizito Mark , Lalitha Rejani , Kajumbula Henry , Muhumuza Richard , Kintu Moses Grace , Muyanja David , Byakika-Kibwika Pauline
Published: December 2024

Background

Antimicrobial misuse and overuse propagate antimicrobial resistance, yet data on factors influencing antibiotic prescription decisions in low-resource settings are limited. We describe factors influencing antimicrobial prescription at a large tertiary care private not-for-profit hospital in Uganda.

Methods

We conducted a descriptive phenomenology qualitative study involving face-to-face in-depth interviews of 12 purposively selected prescribers (four intern doctors, six medical officers and two Internal Medicine physicians) in a private not-for-profit hospital in Kampala, Uganda. Audio recordings and filed notes were transcribed verbatim and analysed manually by content analysis. Emerging themes and sub-themes were recorded and reported.

Results

Three broad themes emerged: experience with antimicrobial use in Uganda, barriers and facilitators to rational antimicrobial prescription and measures to address irrational antimicrobial use. Participants recognized that antibiotics are often used irrationally, prescribed even when there is uncertainty regarding clinical evidence for infection, and influenced by drug promoters, and noted high levels of antibiotic resistance. Patients’ symptoms and clinical signs, previous experience using antibiotics, fear of bad outcomes, patient demand and expectations, influence from senior colleagues, the turnaround time of clinical investigations and drug marketers were the barriers and facilitators to antimicrobial prescription. Prescribers also acknowledged the need to update clinical guidelines, set up hospital antibiograms, and provide continuous medical education on rational antimicrobial use.

Conclusions

A complex interplay of intrinsic and extrinsic factors influences antibiotic prescribing decisions in this hospital. Targeted interventions through continuous education and training for prescribers, providing local prescription guidelines and antibiograms and implementing regulations on over-the-counter antibiotic sales are needed to implement robust antimicrobial stewardship programmes to curb antimicrobial resistance successfully.
Short-term outcomes of periacetabular osteotomy versus periacetabular osteotomy with concomitant femoral osteochondroplasty: a propensity matched analysis
Authors: Houlihan Nathan V , Sucato Daniel J , Thornton Tanner , Nepple Jeffrey J , Clohisy John C , Sankar Wudbhav N
Published: December 2024

This study compared outcomes of periacetabular osteotomy (PAO) with and without femoral osteochondroplasty (OCP) in treating symptomatic acetabular dysplasia through propensity score matching. Data from a prospective multicenter cohort of patients undergoing PAO from 2007 to 2014 were analyzed. Inclusion criteria were a lateral center edge angle <25°. The exclusion criteria were history of previous procedure and age >45 years. A 2- to 5-year follow-up interval was utilized; patients outside this follow-up window were excluded. Propensity matching variables included sex, baseline hip internal rotation at 90° flexion, preoperative alpha angle, lateral center edge angle, modified Harris Hip score (mHHS), and arthroscopy at the time of surgery. Propensity scores were calculated using logistic regression with treatment as the dependent variable. Clinical failure was defined as failure to meet the minimal clinically important difference and patient acceptable symptom state for mHHS or a need for reoperation. There were 219 patients that met the inclusion criteria. Of these, 116 patients were matched, representing 58 pairs (PAO/OCP = 58; PAO without OCP = 58). Preoperative functional scores were similar between groups. At mean 4.1 years follow-up, there were no significant differences in the rates of clinical failure or reoperation between the two groups [PAO/OCP = 13 (22%), PAO without OCP = 8 (14%); P = .23] Similarly, the final mHHS was 83.2 ± 16.2 for the PAO/OCP group and 84.1 ± 15.9 for the isolated PAO group, with no significant difference (P = .74). In the treatment of symptomatic acetabular dysplasia, isolated PAO is noninferior to combined PAO/OCP at short-term follow-up in patients who are likely to be treated by either method.
The spatiotemporal patterns of the beet webworm (Lepidoptera: Crambidae) in China and possible dynamics under future climate scenarios
Authors: Zhang Jinping , Yang Qin , Zhao Zhengxue , Yu Xiaofei , Wei Jianzhou , Cheng Hua , Zhao Xuechun , Yang Maofa , Jin Baocheng
Published: December 2024

The beet webworm (BWW), Loxostege sticticalis (L.), is a notorious migratory agriculture pest of crops and fodder plants, inducing sudden outbreaks and huge losses of food and forage production. Quantifying its spatiotemporal patterns and possible dynamics under future climate scenarios may have significant implications for management policies and practices against this destructive agriculture pest. In this paper, a database containing nearly 7,000 occurrence records for the spatiotemporal distribution of BWW in China was established and its possible dynamics under future climate scenarios predicted using Maxent. We found that BWW could affect a vast geographic range of Northern China, about one third of the country’s land area. The beet webworm overwintered in most of its distribution regions. Maxent model found a northward movement and distribution reduction for BWW in China under future climate scenarios. The occurrence and overwintering regions will move northward about 0.3°N–0.9°N under warming climate scenarios, and about 40%–70% of the suitable habitat and overwintering habitat will disappear by 2100. Most of the northward movement and suitable area reduction likely will happen in 2 decades. Given the vast affected area, the abrupt outbreaks, the diverse host plants, the sensitivity to climate change, as well as their long-distance migration capacity, global scale research, and monitoring the population dynamics of BWW are essential for developing effective management strategies and mitigating its impact on agriculture and ecosystems.
Physical activity and incident cardiovascular disease in breast cancer survivors: the Pathways Study
Authors: Kresovich Jacob K , Richards Alicia R , Ergas Isaac J , Cannioto Rikki , Thomsen Catherine , Laurent Cecile A , Shariff-Marco Salma , Rillamas-Sun Eileen , Kolevska Tatjana , Yao Song , Ambrosone Christine , Kushi Lawrence , Greenlee Heather , Kwan Marilyn L
Published: December 2024

Background

Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail.

Methods

The Pathways Study is a prospective cohort study of 4504 women diagnosed with invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their physical activities during the previous 6 months, which were dichotomized as meeting the Centers for Disease Control and Prevention’s Physical Activity Guidelines for Americans (≥150 minutes of moderate-intensity or ≥75 minutes of vigorous-intensity activity per week) vs not. Incident CVD events (heart failure, cardiomyopathy, cardiac arrest, ischemic heart disease, stroke) occurring between enrollment and December 2021 were identified from electronic health records. Covariate-adjusted, competing-risks Cox regression models estimated associations between meeting physical activity guidelines and CVD risk.

Results

Compared with women who did not meet physical activity guidelines at their diagnosis, those who did had a 25% lower risk of CVD (HR = 0.75, 95% CI = 0.60 to 0.94). Among the individual CVD outcomes, meeting physical activity guidelines was protective against incident cardiomyopathy (hazard ratio [HR] = 0.54, 95% CI = 0.31 to 0.95), heart failure (HR = 0.66, 95% CI = 0.50 to 0.87), and cardiac arrest (HR = 0.68, 95% CI = 0.49 to 0.99).

Conclusions

Meeting physical activity guidelines at breast cancer diagnosis was associated with lower risk of CVD after diagnosis. Studies investigating changes in physical activity after a breast cancer diagnosis and CVD risk are warranted.
Compliance under distrust: do people comply less when they feel distrusted?
Authors: Mendoza Juan P , Wielhouwer Jacco L
Published: December 2024

Several studies indicate that people are less compliant when they feel distrusted. This can pose a challenge for public administration, as some forms of control may signal distrust towards people and could undermine their motivation to comply. In this study, we question whether feeling distrusted is necessarily negative for compliance. In two experiments on tax compliance (N = 239), we examine the case in which the individual is distrusted by the authority. Mediation analyses indicate that distrust reduces opportunism, and this is in turn associated with higher compliance. In a survey experiment on compliance with COVID-19 rules (N = 590), we examine the case in which the individual’s group is distrusted by other members of society. A mediation analysis indicates that distrust increases opportunism, but only for participants who already see themselves as less compliant than average, and this is in turn associated with a lower willingness to comply in the near future. These findings challenge the notion that distrust necessarily leads to retaliation or negative reciprocity, and indicate that the cautious communication of distrust may even be positive in some cases.
Multi-source inference via mixture of hidden Markov models: application to regional labour statistics in Italy
Authors: Filipponi Danila , Guarnera Ugo , Varriale Roberta
Published: December 2024

The increased availability of a large amount of administrative information suggests investigating new methodological approaches for the production of estimates, based on integrating and combining administrative and statistical survey data. We show how latent variable models can be used for estimating employment proportions in the Italian regions using survey and administrative data, taking into account the deficiencies in the corresponding measurement process and the longitudinal structure of the data. To this purpose, we adopt a mixture of hidden Markov models, a longitudinal extension of latent class analysis; in the model specification, we consider covariates and unobserved heterogeneity of the latent process among the units of the population. The mixture of hidden Markov model is used to evaluate the accuracy of the available administrative sources, to define their use in the statistical production, and to produce statistics on employment status at both regional and national levels of aggregation of the entire population.
Design, validation, and implementation of multiplex digital PCR assays for simultaneous quantification of multiple targets
Authors: de Korne-Elenbaas Jolinda , Caduff Lea , Lison Adrian , McLeod Rachel , Pitton Melissa , Gan Charles , Julian Timothy R
Published: December 2024

Quantitative polymerase chain reaction (qPCR) and digital PCR (dPCR) are applied for quantifying molecular targets in disease diagnostics, pathogen detection, and ecological monitoring. Uptake of dPCR is increasing due to its higher quantification accuracy relative to qPCR, which stems from its independence from standard curves and its increased resistance to PCR inhibitors. Throughput can be increased through multiplexing, which allows simultaneous quantification of multiple targets. However, multiplexing with dPCR faces unique challenges relative to qPCR. Here, we describe the three-phase development process of non-competing multiplex dPCR assays using target-specific fluorescently labeled hydrolysis probes. We highlight common challenges encountered, along with recommended solutions. Phase 1: In silico assay design; target-specific primers and probes are selected or designed, potential issues with primer and probe interactions are identified, and fluorophores and quenchers are chosen based on dPCR instrumentation. Phase 2: Wet-lab validation; assays are benchmarked using positive controls. Insufficient performance leads to assay redesign, as needed. Phase 3: Assay implementation; assay specificity and sensitivity are validated on relevant sample matrices. Finally, we provide recommendations on the future design and standardization of multiplexed dPCR assays, highlighting the need for better in silico predictions of assay performance, standardizing positive controls, and automating partition classification systems.
Antibacterial, antibiofilm, and gene expression assessment of ajwain (Trachyspermum ammi) essential oil on drug-resistant gastrointestinal pathogens and its combination effect with ampicillin
Authors: Ozma Mahdi Asghari , Alileh Niloofar Fallahi , Abbasi Amin , Mahdavi Sina , Fadaee Manouchehr , Nezhadi Javad , Ozma Masoud Asghari , Asgharzadeh Mohammad , Kafil Hossein Samadi
Published: December 2024

Essential oils are natural substances used as therapeutic agents and food preservatives to inhibit harmful microorganisms. This study aimed to assess the synergistic effect of Trachyspermum ammi essential oil and ampicillin on antibiotic-resistant gastrointestinal pathogens, including Escherichia coli, Enterococcus faecalis, Shigella flexneri, and Salmonella serotype Typhimurium. Using gas chromatography–mass spectrometry (GC-MS), the main components of T. ammi essential oil were identified as thymol, gamma terpenes, and cymene. The antibacterial and antibiofilm properties were evaluated by minimum inhibitory concentration (MIC), disk diffusion, and microtiter plate methods, revealing MIC values of 2, 1, 4, and 4 mg ml−1 for E. coli, E. faecalis, S. flexneri, and S. Typhimurium, respectively, and inhibition zones between 10 and 14 mm. Pathogens were examined for their biofilm-related virulence genes, including aggR, esp, icsA, and fliC, using real-time polymerase chain reaction (RT-PCR) in E. coli, E. faecalis, S. flexneri, and S. Typhimurium, respectively. The methyl thiazole tetrazolium (MTT) assay was used to evaluate the essential oil’s effect on the viability of human embryonic kidney 293 (HEK293) cells, which showed cell viability of over 80%. The combination of T. ammi oil and ampicillin demonstrated a synergistic effect, and biofilm formation was inhibited. E. faecalis exhibited the greatest sensitivity, while S. flexneri exhibited the lowest sensitivity.
‘With a Gesture, a Smile, a Glance’: Felix Salten Performing Vienna and Decoding Acculturation
Authors: Eisele Theresa
Published: December 2024

This article accompanies Felix Salten, author of Bambi and popular journalist in fin-de-siècle Vienna, in his efforts to observe, negotiate, and perform social role performances in the modern city. Linking Jewish Cultural Studies with theatre theory, it argues that Salten developed an understanding for the performative qualities of society through his sensibility as a theatre critic, and that he positioned Jewish belonging within this performative framework as thoroughly corporeal. His writings, thus, articulate his Jewish experiences for his Vienna contemporaries as a physical practice of socialization—thereby decentring acculturation as a merely Jewish practice, while also unravelling a praxeology of belonging via attention, gaze, and posture.
Gathering Validity Evidence for the Bushmaster Assessment Tool
Authors: Elkins Ethan , Lee Yen , Dong Ting , Durning Steven J , Barry Erin S
Published: December 2024

Introduction

The education of military medical providers typically relies on assessments with established passing parameters to help ensure individuals are equipped to care for those in harm’s way. Evaluations of medical knowledge are often provided by governing bodies and are supported by strong validity evidence. In contrast, assessing an individual’s leadership skills presents a challenge, as tools with robust validity evidence for leadership evaluation are not yet as widely available as clinical assessment tools. This challenge becomes even more complex in simulated environments designed to mimic intense operational conditions.

Materials and Methods

An instrument has been implemented to assess students explicitly in a variety of graded roles with varying responsibilities. Faculty rate each student on their character, context, leadership-transcendent skills, communication, and competence using a 4-point Likert scale. This project used confirmatory factor analyses to assess the validity evidence of the instrument used during Bushmaster with data gathered from 645 School of Medicine students and 170 faculty evaluators from 2021 to 2023 resulting in 2863 evaluations.

Results

Overall, the one-factor structure was confirmed with Tucker Lewis Index >0.95, Root Mean Square Error of Approximation <0.03, and Standardized Root Mean Square Residual <0.03; student or faculty assessment had a small effect on item scores (interclass correlation <0.19) while the assigned position significantly affected the item score. The evaluation score of behavioral health officer and platoon leader was higher than the evaluation score of surgeon.

Conclusions

This study provides validity evidence for the Bushmaster leader assessment tool, confirming its ability to measure leader performance in military medical education. The findings highlight the importance of standardized faculty training in ensuring consistent evaluations, as variations in scores were influenced more by evaluation conditions than by differences among students or evaluators.
The Impact of Critical Speed and Lean Body Mass on Load Carriage Performance for Army Reserve Officers’ Training Corps Cadets
Authors: Dicks Nathan D , Mahoney Sean J , Barry Allison M , Christensen Bryan K , Pettitt Robert W , Hackney Kyle J
Published: December 2024

Introduction

Load carriage is an inherent part of tactical operations. Critical speed (CS) has been associated with technical and combat-specific performance measures (e.g., loaded running). The 3-min all-out exercise test provides estimates of CS and the maximal capacity to displace the body (Dʹ) at speeds above CS. The current study investigated the contributions of CS, Dʹ, lean body mass (LBM), thigh lean mass (TLM), and lower body isokinetic strength and endurance parameters related to load carriage time trials (LCTTs).

Methods

Twenty-two Reserve Officers’ Training Corps cadets (6 = females, age = 20.82 ± 1.59 years) underwent various assessments that included a running 3-minute all-out test to determine CS and Dʹ, isokinetic knee extension (KE) muscle strength and endurance, body composition assessed by dual-energy X-ray absorption, and two 21-kg LCTTs of 400 and 3,200 m, respectively. Pearson’s product-moment correlations investigated relationships between selected predictor variables. Stepwise multiple linear regression analyses were used to determine the relationship between variables that predicted LCTT performance.

Results

Significant correlations were as follows: LBM and CS (r = 0.651, P < .001), KE endurance work and CS (r = 0.645, P < .001), TLM and CS (r = 0.593, P < .05), and KE peak torque and CS (r = 0.529, P < .05). The stepwise regression analyses indicated that CS and LBM contributed significantly to predicting 3,200-m LCTT (F [2,19] = 81.85, R2 = 0.90, P < .001) with standardized β coefficients (−0.723 and −0.301, respectively). Thigh lean mass contributed significantly to predicting the 400-m LCTT (F [1,20] = 46.586, R2 = 0.70, P < .001) with a standardized β coefficient (−0.836).

Conclusion

The results of this study highlight that CS and LBM were the best predictors of the 3,200-m LCTT, and TLM was the best predictor of the 400-m LCTT. The findings of this study support that CS and LBM, including TLM, are important in predicting load carriage task completion in the time trial tasks.
Combination checkpoint blockade and laser interstitial thermal therapy in radiographically progressive non-small cell lung cancer brain metastases
Authors: Haskell-Mendoza Aden P , Srinivasan Ethan S , Gonzalez Ariel T , Reason Ellery H , Jackson Joshua D , Flusche Ann Marie , Wachsmuth Lucas P , Lerner Emily , Underwood Delaney , Buckley Evan D , Zaidi Saif E , Herndon James E , Fecci Peter E
Published: December 2024

Background

Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment being employed frequently for radiographically progressive brain metastases. Considerable interest exists in combining LITT-mediated in situ vaccination to license immune checkpoint blockade (ICB). No studies have examined the clinical feasibility of this combination in brain metastases.

Methods

All patients receiving LITT for radiographically progressive non-small cell lung carcinoma (NSCLC) brain metastases at a single center from 2015 to 2023 were retrospectively reviewed. Combination therapy was defined as ICB within 6 weeks of LITT. Clinical data, post-LITT freedom from local progression, and overall survival (OS) were collected. Adverse events (AEs) were evaluated according to Common Terminology Criteria.

Results

Eighteen patients received LITT + ICB for a total of 19 lesions. The median time between therapies was 2.29 weeks (range 0.85–5.98). In comparison to NSCLC patients receiving LITT alone or with targeted therapy (LITT only) (n = 25), there was no decrement in procedural outcomes. Patients receiving LITT + ICB discontinued steroids at a median of 11 (4–147) days post-LITT vs. 24 (3–242) days for patients receiving LITT only (P = .62). At study cutoff, the local control rate was 18/19 (94.7%) lesions in the LITT + ICB group and 22/25 (88.0%) in the LITT only group. There were 3 and 5 AEs ≥Grade 3 in the LITT + ICB and LITT-only groups, respectively.

Conclusions

Combination of LITT and ICB does not compromise procedural outcomes or time to steroid discontinuation in NSCLC. Prospective studies are needed to assess biomarkers of immune response.
Core factor of NEXT complex, ZCCHC8, governs the silencing of LINE1 during spermatogenesis
Authors: Yan Rushuang , Qi Meijie , Zhang Pengfei , Shen Bin , Yin Jiqing , Chen Chuan , Tian Silin , Chen Lin , Huang Xingxu , Wang Hong , Gao Shaorong , Wu You , Gao Yawei
Published: December 2024

The overactivation of transposable elements (TEs) is a significant threat to male reproduction, particularly during the delicate process of spermatogenesis. Here, we report that zinc finger protein ZCCHC8—a key component of the nuclear exosome targeting (NEXT) complex that is involved in ribonucleic acid (RNA) surveillance—is required for TE silencing during spermatogenesis. Loss of ZCCHC8 results in delayed meiotic progression and reduced production of round spermatids (RS). We observed that young long-interspersed nuclear element (LINE1, L1) subfamilies that are targeted by ZCCHC8 were upregulated in both spermatogonial stem cells (SSC) and pachytene spermatocytes (PS) of Zcchc8 null testes. Further study found that a reduced H3K9me3 modification in SSC and elevated H3 lysine 4 trimethylation in the PS of Zcchc8 KO mice occurred upon young L1, especially L1Md_A, which may have contributed to impairment of the chromatin condensation from PS to RS during spermatogenesis. This study highlights the crucial role of RNA surveillance-mediated chromatin repression by the NEXT complex during spermatogenesis.
Intuiting the Archive: When the Women Are Unidentified
Authors: Masola Athambile
Published: December 2024

This chapter begins with the problem of erasure: captions on a photograph render a group of black women at Lovedale Girls Institution in South Africa “unidentified.” Using photographs as a starting point, the chapter considers the historical implications of erasing black women’s names and stories. Rather than offering a chronological and historiographical account of these women’s lives, the chapter considers the research methodology of intuiting the archive to find the names of the unidentified women. By focusing on the friendship between Tause Soga and Martha Kwatsha, the chapter offers a way of reading a scattered archive, which includes listening to photographs that provide glimpses of aliveness and interiority. At the heart of this methodology is the creation of imbali enobuntu, a historiography that humanizes black women. This chapter also makes use of personal narrative and historical imagination as a response to the marginality and erasure that dehumanize black women. It is through imbali enobuntu that we can center black women’s aliveness and not merely bodies who passed through history. This centering insists on voice and relationality, which challenge the erasure, and marginality, which silences black women’s stories. This chapter challenges the carelessness when it comes to black women’s names, stories, and personhood.
Adorno’s Theory of Film, Radio, and Television
Authors: Powell Larson
Published: December 2024

Although Adorno’s thoughts on media, which were never stated in systematic form, were long marginalized by the dominance of Medientheorie (especially in Friedrich Kittler’s influential version), they have recently been subject to reconsideration. In particular, the clichéd view of him as an enemy of film has been corrected by increased attention to his later essays on that medium. Adorno’s view of film, defined partly against Walter Benjamin’s preference for montage, turns out to have surprising kinship to André Bazin. His work on radio, first in the United States and then in postwar Germany, is at once critical of commercial music broadcasting and also imagines the medium in experimental ways. The establishment of a definitive edition of his work on film music with Hanns Eisler has stimulated new thought on that work as well. Even television may be used as a pedagogical medium for Adorno. The conclusion considers the extension of Adorno’s critique to digitalization.
The Cities of Lycia
Authors: Hülden Oliver
Published: December 2024

Although influenced by Greek culture since the Archaic period, the main part of Lycia was not part of the Greek world in pre-Hellenistic times and there were only a few Greek colonies in the east of the region. The larger Lycian settlements were turned into poleis after the decline of the dynasts, the aristocratic Lycian ruler elite, around the middle of the 4th century bc. In the Hellenistic period, institutions based on the Greek model were gradually adopted and a phase of urbanization of the Lycian settlements set in. In ad 43 the region became a province of the Roman Empire and the development of the urban infrastructure continued to progress, only interfered by heavy earthquakes in the 1st and 2nd centuries ad. Despite the increase of Roman influence in the Imperial period, Lycia remained rooted in the Greek world and its own cultural heritage.
The Cities of Egypt
Authors: van Minnen Peter
Published: December 2024

This chapter surveys the cities in Roman Egypt with a focus on their inhabitants and their civic institutions. The establishment of the Roman province of Egypt eventually led to growth and prosperity. This resulted in material and structural changes in cities and in a new relation with their hinterland. In the 2nd century ad, Egyptian cities monumentalized, and new civic institutions (magistrates and, after ad 200, a council) eventually dominated urban life as well as the administration of the immediate hinterland. By the 4th century ad, cities in Roman Egypt had become very much like cities elsewhere in the Roman East—and vice versa.
Ambushing the Wild and Following the Herds: Archaeozoological Review of Human Occupation of the Iranian Mountains from the Middle Palaeolithic to the Late Neolithic
Authors: Mashkour Marjan , Davoudi Hossein
Published: December 2024

The intricate and long-standing relationship between human communities and highland areas is a fundamental aspect of the archaeology of the Iranian Plateau characterized by two major mountain ranges: the Zagros to the west and the Alborz to the north. The altitudinal range of these mountains served as natural habitats for the wild ancestors of herbivores such as the goat that were later domesticated in the Zagros. This paper provides a comprehensive overview of subsistence economies and the different trajectories of human settlement from the Middle Palaeolithic to Late Neolithic, along these two mountain ranges, based on archaeozoological data of sixty sites composed of caves, rock shelters, and artificial mounds. While Zagros has the most abundant data from the Middle and Late Palaeolithic to the late Neolithic, the Alborz region is distinguished by its Epipalaeolithic settlements. Settlements in higher altitudinal zones are documented in the Zagros up to more than 2,000 m ASL while around 1,500 m ASL in the Alborz. In both regions the presence of caprines, first wild and then domesticated, is a major feature of subsistence economies of highland areas. Differences in the biodiversity and environmental settings are also visible in the two regions. Among wild herbivores, besides caprines, the continuous presence of gazelles should be highlighted in the Alborz versus the presence of equids and red deer in the Zagros. A major shift in the acquisition of faunal resources is expressed by the significant increase in sheep and goat with the transition from Palaeolithic to the Neolithic and the advent of domestication.
The Invention of the Sonnet
Authors: Pich Federica
Published: December 2024

The chapter reflects on the transnational fortune of the sonnet, and in particular of the “Italian sonnet,” from the time of its invention to the present. After an introductory section, the argument is organized into three parts, each addressing an opposition that is essential to what a sonnet is and does. The self-contained shape of the sonnet allows for both monody and dialogue, for both closure and connections within larger poetic structures. Similarly, the narrowness suggested by its fourteen-line measure and rhyme schemes proves inseparable from the wealth of discursive possibilities sparked by the infinitely varied balance between its internal partitions. Finally, the recognizable visual shape and object-like character of the sonnet coexist with its lyric and dynamic quality, dominated by voice and address. While acknowledging the enduring connection between the sonnet and Petrarch, the conclusion questions the persistence of a deep cultural perception of the assumed “Italianness” of the form.
The Matter of “Race”: Race-Thinking, Racism, and the Construction of “Italianness”
Authors: Patriarca Silvana
Published: December 2024

Drawing on a variety of different texts, the essay underlines the longue durée of the racial or descent-based idea of Italianness, an idea that we can trace back to the national patriotism of the Risorgimento and that continues to exist even today in our supposedly post-racial era. This occurs notwithstanding the fact that Italians cannot claim any kind of ethnic homogeneity, if such a thing exists anywhere. The struggle for national unification and independence constituted the beginning of a national “raciology,” namely of a discourse on race that made the Italians into a distinctive group of people, and contrasted this people to others, often in a hierarchical fashion. Race-thinking was followed by the institutionalization of practices of racial discrimination first in the colonies and then, under Fascism, also against the small minority of Italians of Jewish background. Italianness also continued to be implicitly understood in somatic/chromatic terms after the fall of the dictatorship and the (slow) process of decolonization. Ideas and stereotypes of racial differences (as well as hierarchies of race) continued to circulate in Italian society, and even today a color line—although contested—defines in the eyes of most Italians who “truly” belongs in the nation and who does not.
Intermedial Literature: From Cinema through Television to the Internet
Authors: Brook Clodagh
Published: December 2024

The rapid rise of intermedial border crossings has unsettled literature and transformed its position in the world. Italian literature’s relations with other arts are mobile and in constant transformation, meaning that its position in what Eugenio d’Ors calls the “gravitation of the arts” shifts over time, forcing us to confront anew how we define and understand it. With the rise of new forms of art and media over the twentieth century (especially cinema, television, and the Internet), the interconnectedness of literature has reached unprecedented levels of complexity. This article explores Italian literature’s life on its boundaries, especially where cinema and Internet butt up against it, as well as mass media more widely, an obligatory point of reference. What has the fragmenting of literature’s boundaries and its increasing entanglement with technological media meant for literature? Case studies in this chapter are Italo Calvino’s Palomar (1983), Fango (1996) by “Cannibale” writer Niccolò Ammaniti, Wu Ming’s Manituana and its website (2007), and literary examples from 2010 to 2020.
Mary Magdalene in the Gospel of Mary, Gospel of Thomas, Gospel of Philip, First Apocalypse of James, Sophia of Jesus Christ, and Dialogue of the Savior
Authors: King Karen L.
Published: December 2024

This essay discusses the representations of Mary (Magdalene) in the Gospel of Mary, Gospel of Thomas, Gospel of Philip, First Apocalypse of James, Sophia of Jesus Christ, and Dialogue of the Savior. Composed in the second to third centuries ce, these texts were rediscovered in the modern period and offer striking portraits of Mary as a leading disciple, often connecting her with discussions of women’s roles, gender, and salvation. After asking whether the modern classification of these texts as Gnostic is appropriate and why that matters, the essay builds on the widely noted mixing of Marys and uses interfigural analysis to help sharpen those observations and insights. It concludes with a brief reflection on the diversity of portraits of Mary in her “third life” beyond history and memory.
Ethical Anxiety in Global Politics
Authors: Steele Brent J.
Published: December 2024

Anxiety is a central feature of late modernity. It plays a central role in political psychological approaches in international relations. Often considered a burden or obstacle to political action, or one that can be manipulated for populist politics, this chapter evaluates the productive possibilities of what it calls “ethical anxiety.” It canvasses insights from ontological security studies, as well as philosophical resources from communitarian ethics, to explore the embodied mobilization of ethical anxiety for productive political action. It provides illustrations of how ethical anxiety is transformed into action via two political movements—the fight to stem climate change and for Black Lives Matter(ing).
Transitional Justice in the Arab Region
Authors: Aboueldahab Noha
Published: December 2024

This chapter discusses transitional justice in the Arab region. It begins with a brief background about the ways in which transitional justice practices were pursued in the Arab states that experienced mass anti-government uprisings, and the ouster of their leaders, in 2011. This period is often referred to as the Arab Uprisings, or the Arab Spring. The chapter then highlights the importance of distinguishing, while also recognizing the link, between political transitions, revolutions, and counter-revolutions disguised as political transitions. It also addresses the three areas to which the Arab regional context contributes empirical and theoretical value: the relevance of the transitional justice imaginary; the question of whether transitional justice is better placed to focus on process over outcome; and the role of Arab knowledge production in transitional justice research and praxis. The chapter argues that transitional justice, as an intellectual and practical project, lacks significantly in empirically grounded material from underrepresented parts of the world—the Arab region being one of them.
Formal Theory
Authors: Paine Jack , Tyson Scott A.
Published: December 2024

An autocrat’s power depends on gaining support, managing agents, and preventing the opposition from mobilizing. The language of game-theoretic modeling is designed specifically to study strategic interactions among rulers, regime agents/elites, and opposition actors. Consequently, in the past two decades, game theory has become an indispensable tool for studying authoritarian politics. Recent contributions in applied modeling have advanced our understanding of the main problems that autocrats confront, including commitment problems, agency problems, and coordination problems. We highlight both canonical models and very recent advances to showcase insights from formal theory that inform how autocrats address these problems.
The Horizontal Effect of Fundamental Rights
Authors: Haupt Claudia
Published: December 2024

This chapter examines in comparative perspective the constitutional doctrine of horizontal effect as it relates to speech and data privacy on social media platforms. Whereas protecting private speech against government restrictions is the core concern of the First Amendment, other constitutional regimes go beyond applying individual rights only ‘vertically’ as between individual and state. Fundamental rights may also have ‘horizontal’ effect between private parties. Absent a constitutional framework capturing private interactions, courts and scholars in the United States developed various approaches to address the social relationships between users and social media platforms. Most prominent in the speech context, where the state action doctrine prevents enforcement of free speech rights by users against private platforms, is the idea of platforms as common carriers. With respect to data privacy, by contrast, the concept of information fiduciaries, and related duties such as data loyalty, have gained traction. A global perspective illustrates that a strict public/private divide in enforcing fundamental rights hinders capturing the social relationships between users and social media platforms, because modern speech and privacy conflicts there do not manifest between the individual and the state. The horizontal effect doctrine, as this chapter illustrates, is one way to better capture these relationships.
Expansion of the MutS gene family in plants
Authors: Sloan Daniel B , Broz Amanda K , Kuster Shady A , Muthye Viraj , Peñafiel-Ayala Alejandro , Marron Jennifer R , Lavrov Dennis V , Brieba Luis G
Published: December 2024

The widely distributed MutS gene family functions in recombination, DNA repair, and protein translation. Multiple evolutionary processes have expanded this gene family in plants relative to other eukaryotes. Here, we investigate the origins and functions of these plant-specific genes. Cyanobacterial-like MutS1 and MutS2 genes were ancestrally gained via plastid endosymbiotic gene transfer. MutS1 was subsequently lost in seed plants, whereas MutS2 was duplicated in Viridiplantae (i.e., land plants and green algae). Viridiplantae also have two anciently duplicated copies of the eukaryotic MSH6 gene and acquired MSH1 via horizontal gene transfer - potentially from a nucleocytovirus. Despite sharing a name, "plant MSH1" is not directly related to the MSH1 gene in some fungi and animals, which may be an ancestral eukaryotic gene acquired via mitochondrial endosymbiosis and subsequently lost in most eukaryotes. There has been substantial progress in understanding the functions of plant MSH1 and MSH6 genes, but the cyanobacterial-like MutS1 and MutS2 genes remain uncharacterized. Known functions of bacterial homologs and predicted protein structures, including fusions to diverse nuclease domains, provide hypotheses about potential molecular mechanisms. Because most plant-specific MutS proteins are mitochondrial and/or plastid-targeted, the expansion of this family has played a large role in shaping plant organelle genetics.