bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-induced renal tubular acidosis in a patient receiving trimethoprim-sulfamethoxazole
Authors: Tan Hui Lin , Ee Samuel Cheng Ee , Zhao Yue , Lew Pei Shi
Published: January 2025

An Asian woman in her 70s was started on trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of her left fourth toe osteomyelitis. During the course of her therapy, she developed renal tubular acidosis despite being immunocompetent with no known renal disease. Cessation of TMP-SMX and supportive care resulted in resolution of her condition.
Insights from 1096 clinical cases: pioneering a universal grading system for vernal keratoconjunctivitis management
Authors: Chandrasekar Ambika , Agarwal Shweta , Chauhan Gaurav , Srinivasan Bhaskar , Chavda Varsha Bhambani , Iyer Geetha
Published: January 2025

Aim

To analyse the clinical and demographic profiles of patients with vernal keratoconjunctivitis (VKC) and propose a grading for VKC based on corneal status and symptom periodicity rather than disease activity.

Methods

Retrospective observational study from January 2015 to January 2020 in India. VKC grading was based on past/present clinical signs and frequency of symptoms rather than disease activity. The electronic medical records were screened and details of VKC patients diagnosed by cornea specialists were recorded and analysed.

Results

1096 VKC patients with a mean age of onset of 7.05±5.3 with 8.39% having adult onset were analysed. Symptoms included; itching (50.55%) and decreased vision (15.44%). Mixed VKC (52.04%) was the most common presentation with 49.1% having active disease. Complications included; keratoconus (18.43%), steroid-induced cataract (11.41%), glaucoma (10.95%) and limbal stem cell deficiency (5.29%). Dual-acting antiallergics (69.39%) were most commonly used, followed by topical immunomodulators.

The patients were graded as, grade I: mild—presence of mild and seasonal symptoms and/or signs. Grade II: moderate—presence of persistent symptoms/and/or signs without corneal involvement. Grade III: severe—chronic persistent symptoms/and/or intermittent signs with corneal involvement or asymptomatic to mild symptoms with corneal pathognomonic signs. Grade IV: very severe—chronic persistent symptoms and/or corneal pathognomonic signs or active involvement/complication or asymptomatic with complications.

Conclusion

VKC is a chronic disease that often causes visual complications. The new grading system based on the cornea status and symptom periodicity rather than disease activity might help plan the management better.
Acceptability and feasibility of shared medical appointments to support self-management of anxiety and depression in primary care in England: a qualitative study of service user/patient perspectives
Authors: Hanrahan Megan , Graham Fiona , Tang Mei Yee
Published: January 2025

Objective

Shared medical appointments (SMAs) are an innovative care delivery method that provides delivery of clinical care while also supporting self-management. Their usefulness for mental health conditions has only briefly been explored, though early evidence demonstrates their utility for supporting mental health management. Therefore, this study set out to better understand the views that adults with anxiety and depression have towards SMAs as a way of receiving care to support self-management in primary care.

Design and methods

A qualitative study using 1:1 semi-structured interviews which were analysed thematically following Braun and Clarke’s six-phase reiterative process. We employed a deductive, theory-informed approach to thematically analyse the data.

Participants

The final sample consisted of 17 predominantly White ethnic adults with a clinical diagnosis of anxiety and/or depression from five different regions in England. Participants represented a broad age group (22–74 years) and a range of socioeconomic backgrounds.

Results

Three main themes were established: (1) motivation to attend an SMA, (2) barriers and challenges to SMA engagement and (3) implementation preferences. The concept of SMAs was largely acceptable to participants, although participants reported several factors that would influence their decision to attend an SMA. Participants held some reservations but were on the whole receptive to the idea. The main benefits reported were peer support, support for self-management and quicker access to care. Drawbacks reported included risks to patient confidentiality, negative impact on emotional well-being and the unsuitability of the group setting for some patients. Some salient preferences identified included face-to-face/hybrid delivery formatting and mental health specialist involvement.

Conclusions

SMAs in primary care to support anxiety and depression self-management would be acceptable to patients, contingent on the mode of delivery of the SMAs. Future acceptability research should explore SMA appropriateness for diverse patient populations of different ethnic backgrounds, to inform their potential wider roll-out in English primary care.
How does the first index mode of birth in public or private hospitals predict subsequent births? A 16-year Australian population-based linked data study
Authors: Peters Lilian , de Jonge Ank , de Boer Michiel , Downe Soo , Dahlen Hannah G
Published: January 2025

Objectives

In this descriptive study, we aimed to assess how the index mode of birth and subsequent birth modes vary over time for public and private hospital maternity care funding models. The second aim was to determine to what extent the index mode of birth predicts subsequent birth modes in general and whether this differs in public versus private hospital maternity care funding models. With our aim, we have an innovative approach, specifically the women’s life course approach, which is hypothesis-generating and can be assessed in future studies.

Design, setting and participants

New South Wales population-linked data of low-risk women were analysed (2001–2016). Demographics and public/private care were recorded. Modes of the index birth and subsequent modes of second and third births (ie, spontaneous vaginal, instrumental vaginal elective/emergency caesarean birth) were registered. For those with 2 births and 3 births, 16 and 64 subsequent births patterns were created.

Primary and secondary outcome measures

Trend of index modes of birth and subsequent modes of birth over time and the prediction of subsequent birth modes based on the index birth. These outcomes were stratified for the initial maternity care funding model.

Results

In total, 172 041 low-risk nulliparous women were included in the initial cohort, 54.1% had a spontaneous index vaginal birth and 71% had their index birth in public hospitals. During the study period, 131 675 women had 2 births and 44 677 of these women had 3 births, respectively. Among women birthing in public hospitals, higher proportions of index and subsequent vaginal births were observed than in private hospitals, with fewer instrumental vaginal births and caesarean sections. Large differences were observed for birth patterns: vaginal-vaginal (public 55.8% vs private 36.8%) and vaginal-vaginal-vaginal (public 57.2% vs private 38.8%). Women with an index spontaneous vaginal birth showed a high probability (91.3%) of subsequent spontaneous vaginal births. When stratified by maternity care funding model, the probabilities were similar: 91.6% in public hospitals and 90.2% in private hospitals.

Conclusions

Our study of low-risk Australian women (2001–2011) found that those giving birth in public hospitals had higher proportions of spontaneous vaginal births compared with private hospitals, where caesarean sections were more common. Women with an index spontaneous vaginal birth had a very high probability to have subsequent vaginal births. These findings suggest that index mode of birth may be a predictor for subsequent modes of birth.
Understanding the impact of racism on surgical outcomes in settler nation-states USA and Canada: a protocol for a systematic review and meta-analysis
Authors: Adedipe Ifeoluwa , Marchand Tyara , Aziz Saffa , Matta Mirna , Brindle Mary , Daodu Oluwatomilayo
Published: January 2025

Introduction

To improve surgical quality and safety, health systems must prioritise equitable care for surgical patients. Racialised patients experience worse postoperative outcomes when compared with non-racialised surgical patients in settler colonial nation-states. Identifying preventable adverse outcomes for equity-deserving patient populations is an important starting point to begin to address these gaps in care. To derive literature-based estimates of the outcome gap for racialised surgical patients, we will systematically review and meta-analyse rates of adverse postoperative events associated with common and/or high-risk operations performed in Canada and the USA.

Methods and analysis

An electronic search of Medline, Embase, Web of Science, Cochrane Central, CINAHL and Scopus will be conducted to identify studies reviewing complication rates of racialised compared with non-racialised patients from inception to December 2023. We will include publications from the USA and Canada comparing surgical outcomes of racialised and non-racialised patients. The procedures of interest will be the four most common (hip arthroplasty, knee arthroplasty, appendectomy and cholecystectomy), and the five highest risk (oesophagectomy, abdominal aortic aneurysm, aortic valve replacement, coronary artery bypass graft and pancreatectomy) surgical procedures performed in these countries. The outcomes will be mortality, length of stay in hospital, readmission, reoperation, wound dehiscence, surgical site infection, pulmonary embolism, sepsis or septic shock, pneumonia, blood transfusion, stroke, myocardial infarction and bile duct injury. Summary estimates of cumulative incidence, prevalence, incidence rate and occurrence rate of complications using DerSimonian and Laird random effects models will be calculated for the systematic review and meta-analysis. Heterogeneity in these estimates will be examined using subgroup analyses and meta-regression.

Ethics and dissemination

This study uses secondary data and, therefore, does not require ethics approval. This study will be communicated through presentations at international conferences and published in peer-reviewed literature. The results from this study will inform the development of future surgical equity tools and quality improvement programmes and provide benchmarks on the impact of racism on surgical outcomes.

PROSPERO registration number

CRD42024491439.
Impact of out-of-home nutrition labelling on people with eating disorders: a systematic review and meta-synthesis
Authors: Trompeter Nora , Duffy Fiona , Peebles Imogen , Wadhera Emily , Chambers Kate , Sharpe Helen , Maloney Ellen , Nicholls Dasha , Schmidt Ulrike , Serpell Lucy , Jewell Tom
Published: January 2025

Objectives

Mandatory nutrition labels for out-of-home food consumption have been introduced in several countries to curb rising obesity levels. However, concerns have been raised about the potential negative impacts of such policies on individuals with eating disorders. This review aimed to summarise the literature on the impact of out-of-home nutrition labels on individuals with eating disorders or disordered eating.

Design

A systematic search across eight databases was conducted on 11 October 2023.

Data sources

MEDLINE, EMBASE, APA PsycINFO, Web of Science, ProQuest Dissertations and Theses Global, Scopus and CINAHL. Unpublished studies were searched for on Google Scholar and PsyArXiv.

Eligibility criteria

Studies were included if they assessed the impact of out-of-home nutrition labelling policies on individuals with eating disorders or disordered eating.

Data extraction and synthesis

538 studies were screened, of which 16 studies met inclusion criteria.

Results

The reviewed studies included five experimental/quasi-experimental studies, five cross-sectional studies and six qualitative/mixed-methods studies. Across studies, eating disorder pathology was associated with noticing labels more frequently, paying more attention to caloric intake and more frequent behaviour changes due to caloric values. The metasynthesis identified five themes based on the qualitative findings,being drawn to calories,facilitating the eating disorder,reassurance,social eatingandfrustration.

Conclusions

The current review summarised the existing literature on the impact of out-of-home nutrition label policies on individuals with eating disorders. The evidence suggests that there is cause for concern regarding negative impacts, particularly for those with restrictive eating disorders, which should be explored further by research and considered by policymakers when making decisions on public health policies.
Inpatient versus outpatient diagnosis of heart failure across the spectrum of ejection fraction: a population cohort study
Authors: Wang Huan , Gao Chuang , Guignard-Duff Magalie , Cole Christian , Hall Christopher , Baruah Resham , Das Shikta , Gao He , Mamza Jil Billy , Lang Chim C , Mordi Ify R
Published: January 2025

Background

Early heart failure (HF) diagnosis is crucial to ensure that optimal guideline-directed medical therapy (GDMT) is administered to reduce morbidity and mortality. Limited access to echocardiography could lead to a later diagnosis for patients, for example, during an HF hospitalisation (hHF). This study aimed to compare the incidence and outcomes of inpatient versus outpatient diagnosis of HF.

Methods

Electronic health records were linked to echocardiography data between 2015 and 2021 from patients in Tayside, Scotland (population~450 000). Incident HF diagnosis was classified into inpatient or outpatient and stratified by ejection fraction (EF). A non-HF comparator group with normal left ventricular function was also defined. The primary outcome was time to cardiovascular death or hHF within 12 months of diagnosis.

Results

In total, 5223 individuals were identified, 4231 with HF (1115 heart failure with reduced ejection fraction (HFrEF), 666 heart failure with mildly reduced ejection fraction, 1402 heart failure with preserved ejection fraction and 1048 HF with unknown EF) and 992 with non-HF comparators. Of the 4231 HF patients, 2169 (51.3%) were diagnosed as inpatients. The primary outcome was observed in 1193 individuals with HF (28.1%) and 32 (3.2%) non-HF comparators and was significantly more likely to occur in individuals diagnosed as inpatients than outpatients (809 vs 384 events; adjusted HR: 1.62 (1.39–1.89), p<0.001), and this was consistent regardless of EF. For HFrEF patients first diagnosed as inpatients, those discharged on ≥2 GDMT had a reduced incidence of the primary outcome compared with those discharged on <2 GDMT (303 vs 175 events; adjusted HR: 0.72 (0.55–0.94), p=0.016).

Conclusions

Individuals whose first presentation was a HF hospitalisation had a significantly worse outcome than those who were diagnosed in the community. Among hospitalised individuals, higher use of GDMT was associated with improved outcomes. Our results highlight the importance of improving diagnostic pathways to allow for earlier identification and treatment of HF.
The prevalence of PD-L1 expression in patients with advanced oesophageal cancer: the EXCEED observational study
Authors: Xue Liyan , Wang Jiaqi , Kuang Dong , Yun Jingping , Li Yuan , Jiang Lili , Wu Daoyuan , Duan Pei , Lu Shixun , Jin Yan , He Du , Qian Jing , Tang Wenmin , Wang Yan , Li Jielin , Ying Jianming
Published: January 2025

Aims

There are limited data on programmed death ligand 1 (PD-L1) expression in oesophageal cancer (OC) from multicentre studies conducted across China. We aimed to determine the prevalence of high PD-L1 expression in patients with advanced OC.

Methods

The EXCEED study was a multicentre, retrospective analysis of data from six tertiary hospitals that evaluated PD-L1 expression in adults with advanced OC or advanced head and neck squamous cell carcinoma. PD-L1 expression was evaluated at each site according to a standardised protocol. The primary outcome was the prevalence of high PD-L1 expression (Combined Positive Score (CPS) ≥10) in surgical or tumour biopsy samples. Low PD-L1 expression was defined as CPS <10. Patient demographic and baseline factors associated with high PD-L1 expression were also investigated. This report presents the results for the OC cohort only.

Results

Overall, 482 patients were included, the majority were male (87.6%) and the mean age at diagnosis was 63.3 years; 207 had high PD-L1 expression (42.9%; 95% CI 38.5, 47.5) and 275 had low expression (57.1%; 95% CI 52.5, 61.5). There were significant differences in high PD-L1 expression prevalence between subgroups by sex (p=0.044), number of distant metastases (p=0.020), and if chemotherapy (p=0.004) was received prior to the collection of biological samples (ie, biopsy or surgery).

Conclusions

These real-world data provide a robust estimate of the prevalence of high PD-L1 expression in patients with advanced OC and identify clinicopathological and treatment features related to PD-L1 expression that can inform treatment selection.
Prediction of long-term drug-free outcomes in ACPA-positive and ACPA-negative rheumatoid arthritis by combined clinical and ultrasound assessment of residual disease: a 5-year prospective study
Authors: Manzo Antonio , Bozzalla Cassione Emanuele , Montecucco Carlomaurizio , Sakellariou Garifallia , Xoxi Blerina , Luvaro Terenzj , Sammali Ylenia , De Stefano Ludovico , Alpini Claudia , Klersy Catherine , Bugatti Serena
Published: January 2025

Objective

To delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission on long-term drug-free (DF) outcomes.

Methods

RA patients, referring to the Pavia early arthritis clinic (EAC) between 2009 and 2021 and achieving remission after Disease Activity Score-driven methotrexate (MTX) monotherapy, were recruited. Eligible patients underwent DF follow-up at 3-month intervals over 5 years after MTX discontinuation. Pre-selected clinical, serological and ultrasound (US) exposure variables at MTX withdrawal were analysed using multivariable Cox regression to predict time-to-flare.

Results

Of 761 EAC patients with RA, 132 started DF follow-up (person-months: 3678). 62 experienced a flare after a median (range) of 9 (3–60) months, resulting in a progressive decline in flare-free survival throughout the observation period. Whole-cohort multivariate Cox regression identified anti-citrullinated protein antibody (ACPA) positivity (HR: 4.20, 95% CI 2.37 to 7.44) and hands’ joints with grey scale (US-GS) alterations (GS>1; HR: 2.18, 95% CI 1.20 to 3.93) as independent predictors. ACPA-positive patients in Simplified Disease Activity Index (SDAI) remission displayed a flare-free survival estimate at 5 years of 6.4% (95% CI 1.2 to 35.7) versus 78.2% (95% CI 67.4 to 90.8) for ACPA-negative patients in SDAI remission without residual US-GS alteration in hands’ joints (n=59); the latter group showing no evidence of radiographic progression and functional deterioration.

Conclusions

Long-term DF remission is attainable in a niche subset of ACPA-negative RA. Examining clinical and subclinical residual synovial abnormalities during remission allows for effective preemptive identification of this subset in real life.
Large CP violation in flavor violating muon decays
Authors: Redigolo Diego , Tammaro Michele , Tesi Andrea
Published: January 2025

We identify new room for CP violation in lepton flavor violating observables not bound by the electric dipole moment of leptons. By focusing on new physics in the muon-electron sector, we show that CP violation can make its first appearance in lepton flavor violating muon decays rather than in the electric dipole moment of the electron, further motivating the experimental program of Mu3e. We tackle this issue by performing the full one-loop running and matching from the low energy observables at the muon scale, including the T-odd asymmetry in

$$\mu \rightarrow 3e$$

μ
→
3
e

decays, to the Standard Model effective field theory above the electroweak scale. We then sketch a simple UV model that can give rise to these patterns.
Dirac fermions in graphene under curved spacetime: a study of Beltrami geometry and $${{\mathcal {CPT}}}$$ symmetry
Authors: Kouachi Ikram Imane , Yeşiltaş Özlem
Published: January 2025

We analyze the dynamics of Dirac fermions in graphene set within Beltrami spacetime, characterized by a negative curvature. This research investigates how both curvature and external electromagnetic fields influence electron motion, particularly in terms of Landau level quantization and the quantum Hall effect. By utilizing Darboux transformations, we construct novel solvable potentials along with their associated solutions. Furthermore, we assess the role of

$${\mathcal {CPT}}$$

CPT

symmetry in shaping the Hamiltonian and derive the metric operator

$$\eta $$

η

within the framework of pseudo-Hermitian quantum mechanics. This study sheds light on the intricate relationship between curvature, symmetry, and quantum behavior in graphene-based systems. We have tested our results using numerical calculations.
Relativistic Einstein rings of Reissner–Nordström black holes nonminimally coupled to electrodynamics
Authors: Maier Rodrigo
Published: January 2025

In this paper we examine the relativistic Einstein rings assuming a nonminimal coupling between gravitation and electromagnetism in a Reissner–Norström background. Starting from a general action of a nonminimal coupled electrodynamics we show that an unstable effective photon sphere may be obtained in the regime of eikonal approximation. Restricting ourselves to the unstable photon sphere domain we examine the expected angular positions of the first and second relativistic Einstein rings. To compare our results with previous studies in the literature we model the lens as a Galactic supermassive black hole. For fixed coupling parameters we show that such angular positions decrease as the charge parameter increases. The angular separation between the first and second rings is also evaluated. We show that such separation increases as the charge parameter increases. These patterns are not followed by nearly extremal configurations. In this case we show that there is an overlap domain so that the angular position and the corresponding coupling parameter do not allow one to differ extremal cases from complementary configurations which satisfy the cosmic censorship hypothesis.
Dissipative gravitational collapse in f(R) gravity with anisotropy and inhomogeneity density
Authors: Mardan S. A. , Maha  , Manzoor Rubab , Riaz Muhammad Bilal
Published: January 2025

In this article, we will explore the collective impact of Starobinsky model and horizon function in the proximity of f(R) the theory of gravity (R is the Ricci scalar) in the dissipative gravitational collapse. Our investigation delves into the radiating stellar model with string density accompanied by an exterior Vaidya spacetime in f(R) gravity. We precisely explain the boundary conditions and non-vanishing radial pressure due to heat flux in the presented model. In the model presented here, we have used the horizon function with Starobinsky and Krori and Barua assumptions in the presence of strings to demonstrate the end states of black hole collapse. Graphical analysis is also presented to strengthen our arguments.
Do Not Stay in Denial for long: AI's Influence on Workforce Dynamics
Authors: El-Deeb Ahmed
Published: January 2025

The premise of the Software Industry column is to bring to readers reflections on current issues going in the software industry. However, over this year, each time I get to prepare for writing the new column and I start by reflecting on hot issues being discussed, I always find it related to AI. This is not repetitive. First, this pattern is a true reflection in itself: AI is just in air and all over the place in the software industry. Second, there are many angles to AI - AI is not just one thing. In previous issue; for instance, we discussed Trust issue about AI. In this issue, we will talk about how the tech market is influenced by AI.
Quantum Software Engineering: Roadmap and Challenges Ahead
Authors: Murillo Juan M. , Garcia-Alonso Jose , Moguel Enrique , Barzen Johanna , Leymann Frank , Ali Shaukat , Yue Tao , Arcaini Paolo , Pérez-Castillo Ricardo , García Rodríguez de Guzmán Ignacio , Piattini Mario , Ruiz-Cortés Antonio , Brogi Antonio , Zhao Jianjun , Miranskyy Andriy , Wimmer Manuel
Published: January 2025

As quantum computers advance, the complexity of the software they can execute increases as well. To ensure this software is efficient, maintainable, reusable, and cost-effective —key qualities of any industry-grade software— mature software engineering practices must be applied throughout its design, development, and operation. However, the significant differences between classical and quantum software make it challenging to directly apply classical software engineering methods to quantum systems. This challenge has led to the emergence of Quantum Software Engineering as a distinct field within the broader software engineering landscape. In this work, a group of active researchers analyse in depth the current state of quantum software engineering research. From this analysis, the key areas of quantum software engineering are identified and explored in order to determine the most relevant open challenges that should be addressed in the next years. These challenges help identify necessary breakthroughs and future research directions for advancing Quantum Software Engineering.
Time Series Forecasting with LLMs: Understanding and Enhancing Model Capabilities
Authors: Tang Hua , Zhang Chong , Jin Mingyu , Yu Qinkai , Wang Zhenting , Jin Xiaobo , Zhang Yongfeng , Du Mengnan
Published: January 2025

Large language models (LLMs) have been applied in many fields and have developed rapidly in recent years. As a classic machine learning task, time series forecasting has recently been boosted by LLMs. Recent works treat large language models as zero-shot time series reasoners without further fine-tuning, which achieves remarkable performance. However, some unexplored research problems exist when applying LLMs for time series forecasting under the zero-shot setting. For instance, the LLMs' preferences for the input time series are less understood. In this paper, by comparing LLMs with traditional time series forecasting models, we observe many interesting properties of LLMs in the context of time series forecasting. First, our study shows that LLMs perform well in predicting time series with clear patterns and trends but face challenges with datasets lacking periodicity. This observation can be explained by the ability of LLMs to recognize the underlying period within datasets, which is supported by our experiments. In addition, the input strategy is investigated, and it is found that incorporating external knowledge and adopting natural language paraphrases substantially improves the predictive performance of LLMs for time series. Our study contributes insight into LLMs' advantages and limitations in time series forecasting under different conditions.
µOpTime: Statically Reducing the Execution Time of Microbenchmark Suites Using Stability Metrics
Authors: Japke Nils , Grambow Martin , Laaber Christoph , Bermbach David
Published: January 2025

Performance regressions have a tremendous impact on the quality of software. One way to catch regressions before they reach production is executing performance tests before deployment, e.g., using microbenchmarks, which measure performance at subroutine level. In projects with many microbenchmarks, this may take several hours due to repeated execution to get accurate results, disqualifying them from frequent use in CI/CD pipelines. We propose µOpTime, a static approach to reduce the execution time of microbenchmark suites by configuring the number of repetitions for each microbenchmark. Based on the results of a full, previous microbenchmark suite run, µOpTime determines the minimal number of (measurement) repetitions with statistical stability metrics that still lead to accurate results. We evaluate µOpTime with an experimental study on 14 open-source projects written in two programming languages and five stability metrics. Our results show that (i) µOpTime reduces the total suite execution time (measurement phase) by up to 95.83% (Go) and 94.17% (Java), (ii) the choice of stability metric depends on the project and programming language, (iii) microbenchmark warmup phases have to be considered for Java projects (potentially leading to higher reductions), and (iv) µOpTime can be used to reliably detect performance regressions in CI/CD pipelines.
Assessing the Robustness of Test Selection Methods for Deep Neural Networks
Authors: Hu Qiang , Guo Yuejun , Xie Xiaofei , Cordy Maxime , Ma Wei , Papadakis Mike , Ma Lei , Le Traon Yves
Published: January 2025

Regularly testing deep learning-powered systems on newly collected data is critical to ensure their reliability, robustness, and efficacy in real-world applications. This process is demanding due to the significant time and human effort required for labeling new data. While test selection methods alleviate manual labor by labeling and evaluating only a subset of data while meeting testing criteria, we observe that such methods with reported promising results are simply evaluated, e.g., testing on original test data. The question arises: are they always reliable? In this paper, we explore when and to what extent test selection methods fail. First, we identify potential pitfalls of 11 selection methods based on their construction. Second, we conduct a study to empirically confirm the existence of these pitfalls. Furthermore, we demonstrate how pitfalls can break the reliability of these methods. Concretely, methods for fault detection suffer from data that are: 1) correctly classified but uncertain, or 2) misclassified but confident. Remarkably, the test relative coverage achieved by such methods drops by up to 86.85%. Besides, methods for performance estimation are sensitive to the choice of intermediate-layer output. The effectiveness of such methods can be even worse than random selection when using an inappropriate layer.
Genomic Analysis Reveals Racial and Age-Related Differences in the Somatic Landscape of Breast Cancer and the Association with Socioeconomic Factors
Authors: Van Alsten Sarah C. , Love Michael I. , Calhoun Benjamin C. , Butler Eboneé N. , Perou Charles M. , Hoadley Katherine A. , Troester Melissa A.
Published: January 2025

Cancer genomics consortia have identified somatic drivers of breast cancer subtypes. However, these studies have predominantly included older, non-Black women, and the related socioeconomic status (SES) data is limited. Increased representation and depth of social data are crucial for understanding how health inequity is intertwined with somatic landscapes. Here, we conducted targeted sequencing on primary tumors from the Carolina Breast Cancer Study (N = 357; 52% Black, 47% <50) and compared the results to The Cancer Genome Atlas (N = 948; 18% Black, 27% <50). Race (Black vs. non-Black), age, and SES were evaluated in association with mutations, copy number alterations, and aneuploidy using generalized linear models. Pathway dysfunction was also assessed by aggregating mutation and copy number alterations. Adjusting for age, Black participants (N =350) were significantly more likely to have TP53 and FAT1 mutations and less likely to have PIK3CA, CDH1, DDR2, and GATA3 mutations than non-Black participants. Younger participants had more GATA3 alterations and fewer KMT2C, PTEN, MAP3K1 and CDH1 alterations. Black participants had significant enrichment for MYC (8q) and PIK3CA (3q26) amplifications and higher total aneuploidy, but age was not associated with copy number variation. SES was associated with different patterns of alteration in Black versus non-Black women. Overall, Black participants showed modest differences in TP53, PIK3CA, and other alterations that further varied by SES. Race is a social construct, and varying distributions of etiologic factors across social strata may predispose Black, young, and low SES women to cancer subtypes characterized by these alterations.
Breaking the Rhythm: Harnessing the Menstrual Cycle for Better Chemotherapy.
Authors: Dey Pranay , Brisken Cathrin
Published: January 2025

A recent publication by Bornes and colleagues explored the impact of the estrous cycle on mammary tumor response to neoadjuvant chemotherapy (NAC). Using genetically engineered mouse models, Bornes and colleagues revealed that chemotherapy is less effective when initiated during the diestrus stage compared to during the estrus stage. A number of changes during diestrous were identified that may reduce chemosensitivity of mammary tumors: an increased mesenchymal state of breast cancer cells during diestrous, decreased blood vessel diameters, and higher numbers of macrophages in the tumor microenvironment. Macrophage depletion was sufficient to mitigate this resistance. To translate these findings to humans, retrospective analyses of premenopausal breast cancer patients were conducted. Serum progesterone levels served to determine the menstrual cycle phases, which revealed that treatment efficacy is reduced in women receiving NAC during the luteal (progesterone-high) phase compared to those treated during the follicular (progesterone-low) phase. The findings show that physiological hormone fluctuations may influence chemosensitivity through tumor cell-extrinsic mechanisms with the important implication that aligning treatment initiation with the menstrual cycle improves therapeutic outcomes and that consideration of systemic factors may improve therapy outcome.
CAR-T entering a new “phase”: Improving CAR-T function by harnessing phase separation
Authors: Su Xiaolei
Published: January 2025

Biomolecular condensation has emerged as a general principle in organizing biological processes, including immune response. Xu and colleagues recently reported that the cytoplasmic tail of the CD3ɛ subunit of TCR complex, when fused to CAR, can promote CAR condensation by liquid-liquid phase separation. Through sequence engineering, the authors identified modified CD3ɛ sequences that enhance the maturation of the immunological synapse and co-receptor signaling, leading to an improvement of cytotoxicity in vitro and anti-tumor effects in mouse xenograft models. These results demonstrated that biomolecular condensation could be exploited to improve the function of CAR-T cells, highlighting an exciting strategy for developing next-generation cell therapies.
A bifunctional antibody targeting PD-1 and TGF-β signaling has antitumor activity in combination with radiotherapy and attenuates radiation-induced lung injury
Authors: Wang Sheng , Xu Duo , Wang Yuan , Zhou Yuehua , Xiao Lingyan , Li Fang , Tu Jingyao , Qin Wan , Tian Sidan , Zheng Bolong , Wang Yihua , Yuan Xiang-lin , Liu Yuanhui , Liu Bo
Published: January 2025

Radio-immunotherapy has antitumor activity but also causes toxicity, which limits its clinical application. JS-201 is a dual antibody targeting PD-1 and TGF-β signaling. We investigated the antitumour effect of JS-201 combined with radiotherapy and the effect on radiation-induced lung injury (RILI). Different tumor models were established to detect the antitumor effects of the combination of JS-201 and RT, and RILI models were established to observe the effects of JS-201. Transcriptome sequencing showed that JS-201 optimized the TME by inhibiting extracellular matrix formation and angiogenesis. Combining JS-201 with radiotherapy further increased the inflammatory response and immune infiltration and showed great abscopal effects in LLC-luc models. Single-cell sequencing demonstrated that JS-201 reduced fibroblast proliferation by inhibiting the TGF-β/Smad pathway and the release of neutrophil extracellular traps mediated by ROS, thereby relieving radiation-induced pulmonary fibrosis. In conclusion, the JS-201 and radiotherapy combination enhances antitumor effects while mitigating acute and chronic RILI, and it may have potential for translational investigation as a cancer treatment strategy.
Manual dilution of CRRT fluids in anuric patients with severe hyponatremia: a case report and systematic review
Authors: Koning Mark V. , Reijnen Lassima , Kemperman Femy , Schipper-Reintjes Eugenie
Published: January 2025

Introduction: When a patient with severe hyponatremia requires renal replacement therapy, a too rapid correction of sodium levels may occur. Manual dilution of the fluids during continuous renal replacement therapy (CRRT) is a method that can lead to a controlled correction of sodium. We present a case and add a systematic review to determine the feasibility of this method.
Case presentation: A female was admitted to the Intensive Care Unit (ICU) with acute kidney failure due to anti-GBM antibody glomerulonephritis, anuria and an initial sodium level of 100 mmol/L. She received CRRT with manually diluted fluids for 6 days, in which sodium levels increased from 108 mmol/L to 130 mmol/L. A search in Medline, Web of Science and Google Scholar was added for the systematic review. The search yielded 49 cases, including the current report, of which 47 were anuric or oliguric, in which the fluids were diluted to a median of 8 mmol/L (interquartile range 5-11)[range 0-17] above the serum sodium, the median CRRT dose was 27 ml/kg/hr (22-30)[13-77.5]. This led to an increase in serum sodium of 0.2 mmol/L/hr (0.1-0.3)[0-0.7].
Conclusion: CRRT with manually diluted fluids in patients with severe hyponatremia and anuria can lead to a controlled increase serum sodium, while allowing sufficient RRT dose and fluid removal. Still, errors in dilution may occur and we recommend 4 hourly monitoring of serum sodium levels to timely detect an inadvertent increase in sodium.
Albert Bensoussan: escrever de margem a margem
Authors: Krausz Luis Sergio
Published: January 2025

This article discusses the work of the Jewish writer of Algerian origin Albert Bensoussan (1935-), and the memories of his movements between languages ​​and continents: Arabic and French; Spanish; his origins in colonial Algeria and his present in Brittany. Bensoussan's trajectory is emblematic of the destiny of an entire generation and an entire group: the Jews born in the Islamic world in the 19th and 20th centuries, who were marked, on the one hand, by the experience of the colonization of their home countries by European nations and, on the other, by the persecutions and expulsions that took place after the founding of the State of Israel in 1948. The article also discusses the issues of mother tongue and language as homeland.
The Aspiring Confucian: Long-Term Transformation in the Analects
Authors: Connolly Tim
Published: January 2025

Aspiration, according to Agnes Callard, is the long-term process of learning new values. Confucian self- cultivation as presented in the Analects is also aimed at the reorientation of one’s values, so that instead of being guided by pleasure, comfort, or profit, we become devoted to learning, ritual, and caring for others. According to the text, this process is a long and arduous one that involves a lifelong commitment as well as a total reorganization of one’s daily pursuits. Yet for both Callard and the early Confucians a puzzle arises: how does one aspire toward values that one currently lacks at every level? In this paper, I look at some resources within the Analects for responding to this puzzle.
Indigenous Collective Rights to Consultation and Representative Speech
Authors: Lupin Dina , Townsend Leo
Published: January 2025

Indigenous participatory rights, as set out in the United Nations Declaration on the Rights of Indigenous Peoples (undrip), are collective rights for Indigenous Peoples to have a say in decisions affecting them – something these communities are envisaged as doing “through their own representative institutions” (Article 19). However, the conditions of group representation are not clearly spelled out in the undrip or in commentaries on its provisions. Our article addresses this in two inter-connected ways. First, we distinguish genuine spokesperson speech from three other kinds of representative speech (speaking about the group, speaking as a group member, and speaking in behalf of a group). Second, we identify two minimal conditions of genuine spokesperson speech: that the spokesperson be authorised by the group in whose name they speak, and that the spokesperson speaks for the group willingly and knowingly. While relatively simple in theory, each of these conditions throws up a number of questions, such as who gets to authorise a spokesperson and how individuals might be compelled into acting as spokesperson. We conclude the paper by turning briefly to the issue of how states and the law ought to better ensure that Indigenous Peoples are able to have a say through their proper spokespersons.
British Foreign Policy and the Silencing of Mass Atrocity Crimes against the Rohingya, the Uyghurs, and in Yemen
Authors: Rall Jenni , Heinle Julia , Stahl Bernhard
Published: January 2025

The United Kingdom (UK), like many countries, vowed to the prevention and condemnation of mass atrocity crimes. Yet mass atrocity crimes seem to have flourished in the last decade, and little has been done to prevent and stop them. The article starts from the assumption that action on the international level looks bleak because important states increasingly silence mass atrocity crimes. Considering the UK’s former prestige as a ‘leading hawk’ in the Kosovo crisis and regarding the responsibility to protect and humanitarian intervention, the country looks like a difficult case for our thesis. Theoretically, the emerging concept of ‘silencing’ will be employed to understand how foreign policy inaction is backed up in the domestic political discourse. We will examine three proven cases (committed against the Rohingya, the Uyghurs, and in Yemen) and show to what extent not only the government but also the entire political class has been silencing mass atrocity crimes.
The phylogenetic position of Tshangla
Authors: GERBER Pascal , GROLLMANN Selin
Published: January 2025

In the past, linguists such as Shafer (1955), Bradley (1997) and Noonan (2008) repeatedly assigned the Tshangla branch of the Trans-Himalayan language family a position close to Tibetan. However, no empirical evidence for this subgrouping has been brought forth, let alone shared innovations. Based on empirical data and the application of neogrammarian principles, this paper provides a reevaluation of the phylogenetic position of Tshangla. First, it is shown that Tshangla does not share the diagnostic innovations of Bodish sensu Hill (2019), i.e. Tibetan and East Bodish. Second, some first phonological, morphological and lexical innovations that define Tshangla as a subgroup of Trans-Himalayan are presented and the non-participation of Bodish in those is demonstrated. Finally, potential cognates for certain innovative features of Tshangla in other branches of Trans-Himalayan are discussed.
Malayāḷa Islam and Modernity: Being ‘Muslim’ and Being ‘Modern’ in Colonial Kerala
Authors: Ashraf Muhammed Niyas
Published: January 2025

This paper analyses the contours of the vision of Islamic modernity in Kerala as articulated in the work of Sayyid Sanaullah Makti Taṅṅaḷ, a reformer, thinker, writer, polemist, printer, and publisher of the nineteenth century. He was regarded as the first Muslim reformer to make an influential presence in the modern Malayalam sphere. Hence, the study would offer an assessment of Makti’s reformist initiatives and writings in Malayalam between the closing decades of the nineteenth century. Locating him as a central figure in the new public arena, this study seeks to analyze his multi-faceted efforts to the emergence of a Mappila/Muslim modernist discourse along with the realms of religion, language and education.
Exploring the potential of crossbreeding to enhance black soldier fly (Hermetia illucens) production
Authors: Meyermans R. , Broeckx L. , Mondelaers J. , Gorssen W. , Frooninckx L. , Janssens S. , Van Miert S. , Buys N.
Published: January 2025

The increasing world population leads to a growing demand for animal protein, calling for sustainable solutions. Insects, such as the black soldier fly (Hermetia illucens, BSF), will therefore play a crucial role due to their fast growth, high protein content, good bioconversion efficiency and their ability to thrive on diverse feed substrates. Selective breeding has proven valuable in plants and livestock and holds great potential for farmed insects. Moreover, crossbreeding is a successful strategy to improve the genetic value of progeny, for example by exploiting heterosis. Nevertheless, crossbreeding experiments in BSF remain scarce. In this exploratory study, we present the outcome of a crossbreeding experiment in BSF. Four strains (F0) were used to set up reciprocal crosses (F1). Subsequently, four second generation populations (F2) were created. All populations were reared at pilot scale on chicken feed in triplicate. Each generation (F0, F1, and F2) was evaluated for growth, feed conversion, bioconversion efficiency, mating behaviour and egg production. The mean final larval mass of the F2 generations did not significantly differ from the mean of the F0s, although the development speed of the larvae was higher, resulting in a higher percentage of prepupae at the end of the rearing phase. Interestingly, some F1 crosses showed reciprocal differences (i.e. reversing maternal and paternal lines) in maximal larval weight of 32%. Furthermore, egg production was 19% higher in the F2 generations compared to the average F0s. Taking both production and reproduction traits into account, we calculated an increase of 16.5% in total larval mass production and an increase of 19.1% dried larval mass production for the F2s compared to the F0s. These findings explore the potential for crossbreeding in future BSF rearing programmes and highlight the need for further investigation into reciprocal differences between parental lines.
Semantics and Religion: Christian Themes, the nsm Approach
Authors: Wierzbicka Anna
Published: January 2025

This introduction to Cognitive Semantics and Religion provides an overview of the contributions to this special issue. It explains how nsm, and its more recent development Minimal Languages (e.g. Minimal English) can shed light on problems of translation in biblical linguistics, and in understanding Christian concepts and ideas. The paper points to the long nsm tradition of exploring Christianity through universal human concepts and discusses how this tradition seeks to bring a new clarity to the understanding of Christian faith.
Genitals on Screen: Extremism and the Crisis of Representation
Authors: Batori Anna
Published: January 2025

The article examines the international phenomenon of extreme art cinema with explicit genital content, with a particular focus on Lukas Moodysson’s A Hole in My Heart (Sweden 2004), Srdan Spasojevic’s A Serbian Film (2010), Michael Winterbottom’s 9 songs (UK 2005), and György Pálfi’s Hungarian Taxidermia (2006). The paper sets up three main understandings of these films, distinguishing between those that lack narrative justification for the in-your-face representation of genitals; films in which the pornographic content is integrated into narratives about a crisis in domestic relations, and, finally, films that use the explicit highlighting of genitals as a cornerstone in allegorical representations of broader social-cultural and political contexts.