bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Missense Variant in SORBS2 Is Causative With Familial Alzheimer's Disease
Authors: Wang Qi , Wang Shiyuan , Cao Shuman , Wang Qigeng , Wei Yiping , Li Ying , Wang Yan , Li Yan , Qin Wei , Quan Meina , Jia Jianping
Published: February 2025

Background

Alzheimer's disease (AD) is a common neurodegenerative disorder with a substantial genetic component. Despite advances in elucidating the genetic underpinnings of AD, much of its heritability remains unexplained. Discovering novel genetic variants and understanding their pathogenic roles are crucial challenges in AD research.

Objective

This study aimed to identify pathogenic genes and elucidate their role in familial early‐onset AD (EOAD).

Methods

Blood samples from an EOAD pedigree and Sorbin and SH3 Domain‐Containing Protein 2 (SORBS2) T189M transgenic mice were analyzed. Cognitive function was assessed via the Morris water maze (MWM). Protein expression was evaluated by western blotting, while amyloid‐β (Aβ) levels were quantified via immunohistochemistry and enzyme‐linked immunosorbent assay. Inflammatory markers were measured using immunofluorescence and quantitative reverse transcription polymerase chain reaction (PCR). Neuronal morphology, including dendritic and spine alterations, was examined using Golgi staining.

Results

We identified a novel SORBS2 variant (c. 566C>T, p. T189M) in a Han Chinese family, segregating with AD in a Mendelian fashion. SORBS2 T189M transgenic mice exhibited cognitive deficits, cortical Aβ accumulation, and an increased Aβ42/Aβ40 ratio. Additionally, elevated levels of interleukin (IL)‐1β, IL‐6, tumor necrosis factor α (TNF‐α), and ionized calcium‐binding adaptor molecule 1 (Iba1)‐positive microglia, along with neuronal loss, were observed in the brains of T189M mice.

Conclusion

Our study suggest that the SORBS2 T189M variant is a novel candidate causal mutation associated with familial AD in a Chinese pedigree, contributing to AD pathogenesis by promoting neuroinflammation and neuronal injury. Notably, this study is the first to establish a link between SORBS2 mutations and AD.
Comparison of the efficacy and safety of GLP‐1 receptor agonists on cardiovascular events and risk factors: A review and network meta‐analysis
Authors: An Xuedong , Sun WenJie , Wen Zhige , Duan LiYun , Zhang YueHong , Kang Xiaomin , Ji Hangyu , Sun Yuting , Jiang Linlin , Zhao Xuefei , Gao Qing , Lian Fengmei
Published: February 2025

Objective

This study aims to systematically evaluate and perform a systematic review and network meta‐analysis comparing the comprehensive cardiovascular protective effects of various glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), focusing on cardiovascular events and risk factors.

Methods

We searched PubMed, Embase, Cochrane Library and Web of Science from inception to December 15, 2024. Included studies were published randomized controlled trials (RCTs) comparing GLP‐1RAs to placebo or other GLP‐1RAs. Missing data were standardized, and network meta‐analysis was performed using Stata 17.0. Study heterogeneity, publication bias and evidence quality were assessed using the Cochrane Risk of Bias tool and Confidence in Network Meta‐Analysis (CINeMA).

Results

As of December 15, 2024, a total of 18 313 articles were retrieved. Based on the inclusion and exclusion criteria, 156 high‐quality studies were included, incorporating 144 782 patients and 14 different GLP‐1RAs. The network meta‐analysis demonstrated low heterogeneity, ensuring the reliability of the results. Comprehensive analysis revealed the following: Efpeglenatide was the most effective in reducing major adverse cardiovascular events. Oral semaglutide shows more significant advantages in reducing all‐cause mortality and cardiovascular mortality. Orforglipron excelled in glycaemic control and weight reduction. SC‐Semaglutide showed the greatest efficacy in lowering both systolic blood pressure and diastolic blood pressure, Liraglutide showed the greatest efficacy in lowering total cholesterol, Noiiglutide in triglycerides and Taspoglutide in low‐density lipoprotein cholesterol, but no GLP‐1RAs in high‐density lipoprotein cholesterol. GLP‐1RAs did not significantly increase the incidence of adverse events, but Orforglipron and Taspoglutide significantly increased the incidence of gastrointestinal adverse events compared with placebo.

Conclusion

This study compared the cardiovascular benefits of different GLP‐1RAs, including reductions in cardiovascular events and improvements in multiple cardiovascular risk factors. However, due to limitations in the quantity and quality of the included studies, the conclusions should be interpreted with caution. Future large‐scale, high‐quality clinical trials are needed to validate these findings and further optimize comprehensive cardiovascular management strategies for patients.
Museum collections reveal a global range of Ophryocystis parasites in Danaus butterflies
Authors: Müller‐Theissen Maria L. , Barriga Paola , Yan Katie , Gottdenker Nicole L. , Altizer Sonia M.
Published: February 2025

Understanding the host range, patterns and consequences of parasite infection is essential for detecting and responding to parasite‐mediated insect declines. The debilitating protozoan Ophryocystis elektroscirrha (OE; Neogregarinorida: Ophryocystidae) was identified as a parasite of monarch (Danaus plexippus) and queen (D. gilippus) butterflies in the late 1960s in Florida, USA. Recently, similar parasites were documented in other Danaus species, but their occurrence among the diverse clade of milkweed butterflies (Nymphalidae: Danainae) remains unexplored.

This study used museum collections to systematically investigate the host range and global occurrence of OE and similar Ophryocystis parasites in milkweed butterflies. We examined 2727 museum specimens from 86 countries/areas, spanning 61 milkweed butterfly species across 10 genera, to document parasitism.

Our findings revealed that, among milkweed butterflies, Ophryocystis parasites were confined to hosts in the genus Danaus and were widespread across five continents. Positive specimens dated back to 1909. Lesser wanderers (D. petilia) exhibited the highest percentage of positive specimens (16%), followed by monarchs (12%), plain tigers (D. chrysippus, 11%) and queens (4%). We also present the first documented infections in Jamaican monarchs (D. cleophile, 4%). The patterns of parasite variation in size reflected the relatedness of their host species but not their size.

Overall, this research underscores the value of museum collections for investigating geographic and temporal host–parasite associations and provides foundational ecological data on the relationships between Ophryocystis parasites and their milkweed butterfly hosts.
The Development of a Brief Session‐Level Process Measure for Emotion‐Focused Couple Therapy
Authors: Biran Talmor Shanny , Shahar Ben , A. Sbarra David , Bar‐Kalifa Eran
Published: February 2025

Emotion‐focused therapy for couples (EFT‐C) has a strong tradition of delineating mechanisms of change. These change processes are typically examined using labor‐intensive observational methods, which may not be practical for clinicians or researchers who aim to routinely monitor changes in therapy processes as they unfold across therapy sessions. The current study describes the EFT‐C Process Measure (ECPM), a short, easily administered, eight‐item questionnaire that can complement more traditional observational methods. The ECPM uses a systemic framework (assessing one's experience as well as one's perception of the partner's experience) and can be administered at the end of each session to capture the key processes of change in EFT‐C (cycle understanding, accessing vulnerability, sharing vulnerabilities, responsive expression). We used data from 1033 session reports obtained from 44 couples receiving EFT‐C to examine the validity of this measure. The results indicated that the ECPM evidenced convergent and discriminant validity (it was associated with reports of the therapeutic alliance), criterion validity (it was associated with reports of session evaluation and relationship satisfaction), and incremental validity for its systemic framework. Additionally, the ECPM proved sensitive in tracking change processes from session to session and capturing the expected increase in process engagement throughout the course of therapy. Although a complete validation of this tool requires a larger sample, the ECPM may be used by researchers and clinicians to obtain insights into the change process in EFT‐C.
Thriving or sinking? The emplacement process of Ukrainian refugees in depopulating, peripheral areas in the Netherlands
Authors: Tesorio Jofelle
Published: February 2025

The ‘free‐to‐work, free‐to‐settle’ feature of the EU's temporary protection for Ukrainian refugees has led millions to various locations, with the majority gravitating towards urban areas. However, due to housing shortages, a significant number have moved to peripheral municipalities experiencing depopulation. These refugees often find themselves in villages without a network and where the Ukrainian diaspora is small or non‐existent. Reflecting on their settlement and everyday ‘unproblematic’ encounters (conviviality) with neighbours, colleagues at work, and networks at various institutions in Het Hogeland and Pekela, The Netherlands, this analysis explores the emplacement process of Ukrainian refugees. Based on this reflection, the paper aims to address the question: Which factors facilitate or hinder positive encounters among Ukrainian refugees in these peripheral areas, motivating them to (re)consider taking root in these host localities?
Drought Stress at Different Growth Stages Affects the Capacities of Sinks and Two Carbon Sources of Spring Wheat (Triticum aestivum L.)
Authors: Yang Jingya , Liang Xi
Published: February 2025

Drought stress reduces cereal crop growth and yield due to modifications to interactions between sink and source. However, little research has investigated multiple carbon sources and their relationships with sink capacities, especially in response to drought stress at different growth stages. The objective of this study was thus to examine two major carbon sources (i.e., photosynthetic assimilation in the flag leaf and remobilisation of pre‐anthesis reserves in stems) and their interactions with sink strength in response to drought stress at different phenological stages. A greenhouse experiment was conducted at five water regimes: well‐watered (WW), progressive drought (PD), and drought stress (DS) during vegetative growth (DS‐V), early reproductive growth (DS‐ER), and post‐anthesis (DS‐PA). Compared with the WW regime, the DS‐V treatment reduced shoot biomass, grain yield, number of grains per pot, grain weight, harvest index, and water‐soluble carbohydrates in stems despite the recovered photosynthesis after rehydration. Wheat plants subject to DS‐PA exhibited reduced shoot biomass, grain yield, grain weight, and post‐anthesis photosynthetic rate but greater depletion of water‐soluble carbohydrates in stems during grain filling relative to the WW regime. Grain yield positively correlated with residual water‐soluble carbohydrates in stems and late‐season photosynthetic rates. This study demonstrated yield losses associated with changes in sink and source capacities in response to drought stress at different phenological stages and showcased the predominant role of the two carbon sources in grain filling.
Exploration of the covariation signal between cortical bone and dentine volumes across the upper limb bones and anterior teeth in modern humans and relevance to evolutionary anthropology
Authors: Augoyard Mathilde , Zanolli Clément , Profico Antonio , Thibeault Adrien , Cazenave Marine , Oettlé Anna C. , L′Abbé Ericka N. , Hoffman Jakobus , Bayle Priscilla
Published: February 2025

Cortical bone and dentine are two mineralized tissues sharing a common embryological origin, developmental, and genetic background, distinct from those of enamel. Understanding their relationship is crucial to decipher the factors acting on their postnatal development, and shedding light on the evolutionary patterns of tissue proportions. Here, we investigate the coordinated variation between cortical bone and dentine volumes measured from arm and forearm bones (humeri, ulnae, radii) and upper anterior teeth (central incisors, lateral incisors, canines) of modern humans. Given the shared characteristics of cortical bone and dentine, we expect similarities in their postnatal development, which may lead to covariation between their volumes. The degree of bone‐dentine covariation may be influenced by the physiological response of upper limb bones to mechanical loading. No such covariation is expected with enamel volumes, due to the greater developmental independence of bone and enamel. Our sample includes 55 adults of African and European ancestries from South African osteological collections. Principal component analysis of cortical thickness variation along the shafts of paired humeri, ulnae, and radii is used to assess asymmetry. Bone regions with bilateral asymmetry in cortical bone thickness are considered sensitive to functional loads, while regions with minimal bilateral variation likely reflect genetic influences during bone postnatal development. Statistical analyses reveal strong positive correlations between cortical bone and dentine volumes across all bones and teeth, and weaker correlations between cortical bone and enamel. We outline a complex pattern of bone‐dentine covariation that varies by skeletal location and tooth type. Contrary to our expectations, the presumed functional sensitivity of bone regions does not influence the covariation signal. Additionally, the strength of the covariation appears to align with the developmental sequence of the anterior teeth, with the upper canines showing the strongest correlation with cortical bone volumes, followed by lateral and central incisors. These results provide insights into the functional and biological factors influencing the coordinated variation of cortical bone and dentine volumes during postnatal development. Further research on the cortical bone‐dentine covariation across different skeletal parts, including lower limb elements, would enhance our understanding of the effects of both endogenous and exogenous factors on the development of the mineralized tissues.
Feasibility and Safety of Pulsed‐Field Ablation for Persistent Atrial Fibrillation: A Prospective Study
Authors: Chen Guocai , Gao Mingyang , Lai Yiwei , Huang Lihong , Xia Shijun , Zuo Song , Guo Xueyuan , Liu Nian , Long Deyong , Dong Jianzeng , He Liu , Du Xin , Li Songnan , Sang Caihua , Ma Changsheng
Published: February 2025

Introduction

Pulsed‐field ablation (PFA) is a novel nonthermal ablation approach using rapid electrical pulses to cause cardiac cell apoptosis via electroporation. Our study aims to investigate the feasibility and safety of PFA for persistent atrial fibrillation (PeAF).

Methods

Thirty‐two consecutive patients diagnosed with PeAF were enrolled in our study. All patients underwent PFA treatment using the strategy including pulmonary vein isolation (PVI), left atrial posterior wall (LAPW) isolation, cavotricuspid isthmus (CTI) block, and mitral isthmus (MI) block. Acute and follow‐up procedure outcomes were evaluated, and adverse events related to the ablation procedure were also observed.

Results

One‐year survival free from atrial tachyarrhythmia post‐ablation was 65.6%. Acute success rates for PVI, LAPW isolation, CTI block, and MI block were 100%, 100%, 96.9%, and 81.3%, respectively. Eleven cases (34.4%) experienced atrial tachyarrhythmia recurrence, with eight cases being atrial fibrillation (AF) recurrence and three cases being atrial flutter recurrence. Three patients underwent repeat ablation. Minor complications were encountered in four patients with asymptomatic cerebral lesions. Vagal responses were commonly observed during the procedure. No severe coronary vasospasm or severe hemolysis occurred in our cohort.

Conclusion

PFA with the strategy including PVI, LAPW isolation, CTI block, and MI block is feasible, safe, and associated with a high rate of freedom from atrial tachyarrhythmia recurrence at 1 year in patients with PeAF.

Trial Registration

This study registered at the Chinese Clinical Trial Registry (ChiCTR2300068980).
Analysis of Mitochondrial Sequence Deletion in the atp9 5′UTR Region and Design of Molecular Markers in Cotton (Gossypium spp.)
Authors: Kang Wanlin , Zhang Lanlan , Li Zhiyu , Fang Yuzhu , Yang Jinglong , Song Yan , Liu Shining , Zhang Xiao , Zhang Rui
Published: February 2025

Cotton (Gossypium) is the most important fibre crop in the world, consisting of 45 diploid and 7 tetraploid cotton species. These cotton varieties are valuable for breeding, but their molecular identification methods still need further study. We identified an insert/deletion site (AATTT) at the atp9 5′UTR region in the mitochondrial genome of cotton, which could be used to distinguish different cotton species. In this study, the target fragments of 33 cotton species (29 diploid and 4 tetraploid species) were amplified by PCR, and the PCR products potentially containing an EcoR I restriction site were subsequently digested and analysed. The sequencing results revealed that 27 out of 33 cotton species lacked ‘AATTT’ sequences, while six cotton species (G. longicalyx, G. hirsutum, G. barbadense, G. tomentosum, G. mustillinum and G. darwinii) were found to possess the sequences. Additionally, 39 SNPs were found in this region, and specific molecular markers for G. stocksii, G. bickii and E‐genome were developed, respectively. The comparative analysis of mitochondrial sequences from diploid and tetraploid cotton species elucidated their genetic diversity and evolutionary relationships, and species‐specific markers were able to discriminate among these species, thereby provided a foundation for more targeted use of wild genetic resources in cotton improvement and efforts to ensure their conservation.
TRPV3 Mutation‐Associated Olmsted Syndrome in a Hispanic Patient: Response to Erlotinib and Review of Literature
Authors: Arias‐Berrios Gabriel , Ortiz‐López Laura I. , Sánchez‐Flores Xavier
Published: February 2025

Olmsted syndrome (OS) is a rare genetic condition characterized by severe palmoplantar and periorificial keratoderma, often linked to TRPV3 gene mutations. This case report describes a 23‐month‐old Hispanic boy with TRPV3‐associated OS who initially showed limited improvement with acitretin but experienced substantial recovery with the addition of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor. A review of the literature indicates that erlotinib has shown efficacy in other cases of OS, making it a promising therapeutic option. This report underscores erlotinib's potential to effectively manage TRPV3 mutation‐associated OS, especially when traditional treatments fail.
Life Satisfaction and Healthy Lifestyle Behaviors of Individuals According to Exercise Preferences of Outdoor and Indoor
Authors: Avsar Fatma , Kizilaslan Nildem
Published: February 2025

Objective

Preference for outdoor and indoor exercises is essential when choosing a place to exercise. This study compared adults' healthy lifestyle behaviors and life satisfaction according to physical activity location preferences.

Subject and Methods

The study is conducted using a cross‐sectional design between May and October 2023, with visitors to a gym (n = 270). The study sample included participants in the activities of two outdoor sports groups and two gyms operating. Study. The questionnaire for data collection consists of demographic characteristics, Health Promotion Lifestyle Profile (HPLP), Life Satisfaction Scale (SLS), Three‐Factor Eating Questionnaire‐R (TFEQ). Percentage, mean, standard deviation, t‐test, ANOVA posthoc analysis, and Chi‐square tests were used to analyze the data.

Results

The mean age of the participants was 25.87 ± 8.59 years. The rate of people doing indoor activity is 67.4%. The rate of those who prefer outdoor exercise is 87.8%. Many parameters were significant for indoor and outdoor exercisers compared to those in a single location (p < 0.05).

Conclusion

Healthy lifestyle behaviors are better for those who prefer both locations for exercise. A fuller picture of this study is that balance is important for the preference of outdoor and indoor exercises. Individuals should be encouraged to exercise outdoors and indoors.
The changing nature of Brescia's Romanitas: political rhetoric and material culture in the early modern Venetian mainland☆
Authors: Valseriati Enrico
Published: February 2025

Brescia, a city of Roman origins, became in 1426 a part of the Republic of Venice. Throughout the fifteenth and sixteenth centuries, during both war‐ and peacetime, the ruling class enacted deliberate strategies to re‐functionalize the city's Roman material heritage to convey political meanings that negotiated republican and imperial identities depending on current needs and shifts in the relationship with the Venetian rettori. Public spaces provided the perfect canvas to articulate political messages that helped Brescia find its place in the terraferma state without giving up assertions of its autonomy; in this sense, antiquarianism was configured not just as a cultural phenomenon, but (especially in times of warfare) as instrumental to defining the contours of the city's political identity. The graphic signs of this communicative policy can still be ‘read’ and deciphered today, having left the most visible evidence in the Platea Magna (now Piazza della Loggia). This article aims to analyse how epigraphs, frescoes, sculptures, and the urban fabric in general came to serve as the material tools through which Brescian civic identity was negotiated in public spaces, in constant conversation with the Republic of Venice.
Fenlong tillage accelerates the enrichment of the host‐specific rhizosphere bacterial community of cassava
Authors: Huang Yuanhang , Li Liangwu , Li Guilong , Peng Xiaohui , Ou Guining , Zhou Jia , Qin Fengyan , Yang Weixian , Wei Maogui , Shen Zhangyou
Published: February 2025

As a starch and biofuel feedstock in China, cassava (Manihot esculenta Crantz) is continuously cultivated on marginal land in the south, predominantly in red and yellow soil types. With the prolonged application of conventional tillage (CT) method (mouldboard ploughing once at a depth of 30–35 cm and then raked twice at a depth of 18 cm), the soil became increasingly compact, while the cassava yield decreased year after year. The previous study reported that the cassava yield was significantly increased by Fenlong (FL) tillage, which implements the use of spiral drill bits to replace traditional ploughshares. Thus, the current study aimed to reveal how FL combined with N application affects the bacterial community diversity of cassava rhizosphere soil. The results indicated that Actinobacteria, Proteobacteria, Chloroflexi, Acidobacteria, and Firmicutes were the most abundant phyla in cassava rhizosphere soil. The relative abundances of Actinobacteria, Firmicutes, and Gemmatimonadetes of the CT group were generally higher than the FL group in 2019, while the relative abundances of Actinobacteria, Chloroflexi, and Planctomycetota in the FL treatments were higher than those in the CT treatments in 2020. In addition, the abundance of the phylum Acidobacteria decreased with the N application rate, and its abundance was generally higher in the FL group than in the CT group in 2019. Genera norank_o__Gaiellales, Bryobacter, Pseudolabrys, Acidothermus, Rhodoplanes, Conexibacter, and Paenibacillus were also found higher enriched in the FL treatment than in the CT treatment. These results indicate that FL tillage exhibited stronger abilities than CT for recruiting host‐specific bacteria of cassava by creating better conditions for roots and thus boosting more exudates based on the developed root system.
Effect of Warpage Pattern of Printed Circuit Board on Solder Paste Volume in Stencil Printing Process
Authors: Mohammadhosseinzadeh Majid , Kim Hyeongtae , Ghorbani-Menghari Hossein , Park Jungbin , Kang Namhyun , Jung Myung Keun , Na Seung Ryul , Kim Ji Hoon
Published: February 2025

This study examines the influence of printed circuit board (PCB) warpage patterns on solder paste distribution during the stencil printing process (SPP). A multi-stage numerical model was developed and validated with experimental data, showing a deviation of less than 4%, to simulate the SPP with various warped PCB configurations. Various warpage patterns, including horizontal, vertical, spherical, and diagonal warpage, were analyzed along with key process parameters such as stopper load, squeegee load, and the positioning of clamping plates to identify the conditions that most significantly affect solder paste distribution. Results indicate that increasing the stopper load to 170 N can reduce PCB warpage by approximately 60%, leading to a more even solder paste volume distribution. The squeegee load had minimal impact on gap reduction due to the constraints imposed by the side-clamping plates. Among the warpage patterns, diagonal warpage yielded the most uniform solder paste distribution, with up to 43% better consistency compared to horizontal warpage, which exhibited the greatest variation.
Methan-o-poly: a giant collaborative game to “digest” the microbiology of green biogas production
Authors: Porras-Socias Pau , Mattiussi Raffaello , Silveira Kris Anthony , O'Flaherty Vincent
Published: February 2025

In an era of rapid change and global challenges, impactful educational experiences about sustainability become imperative. Especially in organic waste conversion bioprocess such as anaerobic digestion (AD). Here proposed, is a gamified approach to learn AD and hidden microbial interactions, bringing to real-life size an invisible phenomenon. In Methan-o-poly, participants roleplay cooperating microbes within a bioreactor engaged in four sequential mini-games to mimic organic waste degradation and methane production. Perturbations in the activity simulate real challenges, enhancing adaptability and problem-solving skills. Overall, this cooperative game promotes motivation, collaboration, and experiential learning. Its initial implementation received positive feedback across various age groups, enhancing green education initiatives.
A group-forming course content-focused icebreaker for life science classrooms
Authors: Kleinschmit Adam J. , Sparks-Thissen Rebecca L. , Pandey Sumali
Published: February 2025

Collaboration and communication are important competencies for undergraduate life science education, as noted in the
Vision and Change in Undergraduate Biology Education
report. However, initiating collaboration and communication in the classroom can be an anxiety-inducing experience for many students. In contrast to traditional-style icebreakers, we introduce a course content-focused icebreaker activity that served as a group-forming undertaking on the first day of class. We developed four sets of handouts (icebreaker tickets), each having a common course theme (e.g., microbiology, cell biology, physiological system infections/disorders, virology). Students were randomly provided with a ticket at the beginning of the course, and they worked to establish groups with their peers, based on their own interpretation of the ticket’s content and rationalization of a grouping scheme. Student feedback and engagement data collected from implementation at three independent institutions were largely positive, where students reported the activity to be an effective tool for building a course content-focused community of learners. The icebreaker tickets and instructor’s notes disseminated in this manuscript can be adapted to fit educators’ course goals and help set the tone for the first day of the class and beyond that fosters communication and collaboration among students.
Contrasting roles of PSGL-1 and PD-1 in regulating T-cell exhaustion and function during chronic viral infection
Authors: Viramontes Karla M. , Thone Melissa N. , De La Torre Jamie-Jean , Neubert Emily N. , DeRogatis Julia M. , Garcia Chris , Henriquez Monique L. , Tinoco Roberto
Published: February 2025

Immune checkpoints are critical regulators of T-cell exhaustion, impairing their ability to eliminate antigens present during chronic viral infections. Current immune checkpoint inhibitors (ICIs) used in the clinic aim to reinvigorate exhausted T cells; yet, most patients fail to respond or develop resistance to these therapies, underscoring the need to better understand these immunosuppressive pathways. PSGL-1 (
Selplg
), a recently discovered immune checkpoint, negatively regulates T-cell function. We investigated the cell-intrinsic effects of PSGL-1, PD-1, and combined deletion on CD8
+
T cells during chronic viral infection. We found that combined PSGL-1 and PD-1 (

Selplg
-/-
Pdcd1
-/-

) deficiency in CD8
+
T cells increased their frequencies and numbers throughout chronic infection compared to the wild type. This phenotype was primarily driven by PD-1 deficiency. Furthermore, while PD-1 deletion increased virus-specific T-cell frequencies, it was detrimental to their function. Conversely, PSGL-1 deletion improved T-cell function but resulted in lower frequencies and numbers. The primary mechanism behind these differences in cell maintenance was driven by proliferation rather than survival. Combined PSGL-1 and PD-1 deletion resulted in defective T-cell differentiation, driving cells from a progenitor self-renewal state to a more terminal dysfunctional state. These findings suggest that PD-1 and PSGL-1 have distinct, yet complementary, roles in regulating T-cell exhaustion and differentiation during chronic viral infection. Overall, this study provides novel insights into the individual and combined roles of PSGL-1 and PD-1 in CD8
+
T-cell exhaustion. It underscores the potential of targeting these checkpoints in a more dynamic and sequential manner to optimize virus-specific T-cell responses, offering critical perspectives for improving therapeutic strategies aimed at reinvigorating exhausted CD8
+
T cells.

IMPORTANCE

Our findings provide a comprehensive analysis of how the dual deletion of PD-1 and PSGL-1 impacts the response and function of virus-specific CD8
+
T cells, revealing novel insights into their roles in chronic infection. Notably, our findings show that while PD-1 deletion enhances T-cell frequencies, it paradoxically reduces T-cell functionality. Conversely, PSGL-1 deletion improves T-cell function but reduces their survival. Whereas the combined deletion of PSGL-1 and PD-1 in CD8
+
T cells improved their survival but decreased their function and progenitor-exhausted phenotypes during infection. We believe our study advances the understanding of immune checkpoint regulation in chronic infections and has significant implications for developing more effective immune checkpoint inhibitor (ICI) therapies.
Complete genome sequence of the
Staphylococcus aureus
NCCP 11854 isolated from a food-poisoning patient in the Republic of Korea
Authors: Kim Joon Ki , Choi Chi-Hwan , Yun Mi-ran , Ahn YeWon , Choi Young Sill , Kim Su Yeon
Published: February 2025

Staphylococcus aureus
is the etiological agent of skin diseases and food poisoning. In this study, we report the complete genome sequence of
S. aureus
NCCP 11854, which was originally isolated from the pus of a food-poisoning patient in the Republic of Korea in 2009.
Massively elevated sFlt1/PlGF in a pregnant patient with fetal growth restriction and perinatal death in the context of a systemic lupus erythematosus
Authors: Ndarugendamwo Angélique Mutwenzi , Schlatter Bettina , Surbek Daniel , Radan Anda-Petronela
Published: February 2025

We report a case of confusingly high soluble fms-like tyrosine kinase 1/placental growth factor (sFlt1/PlGF) ratio in a pregnant patient with underlying systemic lupus erythematosus and antiphospholipid syndrome without superimposed pre-eclampsia.
Fish Tank-AssociatedMycobacterium MarinumInfection in an Immunocompromised Host
Authors: Khan Attam , Jain Dimple
Published: February 2025

Mycobacterium marinuminfection can be challenging to diagnose and treat, especially in immunocompromised patients on tumour necrosis factor alpha inhibitors. A patient with collagenous colitis on infliximab presented with ulcerated plaques accompanied by nodules in a sporotrichoid fashion. Initial treatments failed until a biopsy confirmedM. marinum. Multiple antibiotic regimens, including rifampicin and ciprofloxacin, were required due to resistance. The case underscores the importance of patient education on avoiding aquatic environments, considering atypical mycobacterial infections in differentials for immunocompromised patients with sporotrichoid lesions, and prioritising urgent diagnostic biopsies. Treatment can be lengthy, often requiring up to 12 months, emphasising the need for ongoing patient counselling and multidisciplinary management. Current guidelines recommend a combination of ethambutol and macrolides, though further research is necessary to optimise treatment protocols.
Severe hypokalaemia in primary aldosteronism during pregnancy
Authors: Lin Allison , Chan Stephanie J , Crapanzano John P , Kuo Eric J
Published: February 2025

Primary aldosteronism (PA) is rarely seen in pregnancy despite being a common cause of secondary hypertension. Spironolactone, the first-line treatment, is contraindicated in pregnancy due to potential anti-androgenic effects; treatment options are thus limited. We present a case in which severe hypokalaemia associated with PA was discovered during pregnancy. Eplerenone was used as a short-term treatment without adverse effects to the fetus before unilateral laparoscopic adrenalectomy was performed in the second trimester after the patient was refractory to medical treatment. This case report adds to the limited literature on management of PA in pregnancy, which could influence future risk-benefit discussions regarding surgical versus medical management of this condition.
Predictors of ATF inspections of FFLs and subsequent violations
Authors: Reeping Paul , Killian Grace , Gobaud Ariana N , Mehranbod Christina , Rajan Sonali
Published: February 2025

Background

The Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) conducts inspections of Federal Firearms Licensees (FFLs) to ensure compliance with federal laws in an effort to keep the public safe from firearm violence. However, the criteria for which FFLs are inspected lacks transparency, potentially signalling inefficiencies or biases.

Methods

We extracted data on FFL inspections and violations (2016–2017) requiring remedial action from theGun Store Transparency Projectdatabase and the ATF’s FFLs listings. Using a generalised linear mixed model with a random effect for states and robust SE, we estimated the census tract and state level predictors of 1) the likelihood of the ATF inspecting an FFL and 2) among those inspected, the likelihood of a violation.

Results

Of the 93,420 FFLs, 22 921 were inspected and 2392 had violations requiring remedial action. Increased likelihood of inspection was statistically significantly associated with higher levels of poverty, lower median income, greater non-White population percentages, and older census tract median ages. The sole predictor of an FFL receiving a violation requiring remedial action was the state’s firearm law permissiveness.

Discussion

ATF inspections disproportionately targeted communities with higher poverty, lower median income, larger non-White populations, and older demographics. This indicates potential racial and socioeconomic biases, diverting attention from jurisdictions with more lenient firearm laws where violations were more likely to occur.

Conclusion

The ATF needs to reassess the influence of potential biases on its strategies for selecting FFLs for inspections and instead focus on risk-based assessments in order to promote public safety.
Susac’s syndrome: diagnostic challenges
Authors: Elsabbagh Khuloud , Elrayes Mai , Herwadkar Amit , Stylianides Amira , Gosal David , Sharaf Nazar
Published: February 2025

A 39-year-old woman presented with headaches, slurred speech, facial weakness and brief altered sensations, together with non-specific visual disturbances, unsteadiness and falls. Despite initial treatment with intravenous methylprednisolone, her condition worsened with cognitive decline, confusion, ataxia and incontinence. We diagnosed Susac’s syndrome having excluded other causes. Her management was difficult, taking 4 months to achieve remission with corticosteroids, rituximab, cyclophosphamide and intravenous immunoglobulin (Ig). She continues to be on aspirin, intravenous Ig and mycophenolate mofetil to maintain remission, with cyclophosphamide planned for possible relapses.
BLOW-UP SOLUTIONS FOR FRACTIONAL DIFFERENTIAL EQUATIONS WITH NONLINEAR MEMORY
Authors: MEDKOUR MOHAMMED , REBIAI BELGACEM , ALKHALAF SALEM , ALHARBI ASMA
Published: February 2025

In this paper, we consider the nonlinear cauchy problem [Formula: see text] where [Formula: see text] and [Formula: see text] [Formula: see text]. We will study the equation for [Formula: see text] We demonstrate the local existence and uniqueness of the solution to this problem by the Banach fixed-point principle. Then, it is shown that local solutions experience blow-up. Finally, we present the blow-up rate when [Formula: see text]
A Guide to Choosing Polymers for Use in Lithium-Ion Cells
Authors: Adamson Anu , Abeysooriya Shanika , Chisholm Sam , Johnson Michel B. , Bötticher Tom , Metzger Michael
Published: February 2025

Every commercial Li-ion cell contains several inactive components, most of which are composed of polymers. Many of these polymer-based inactive components, such as cell gaskets, jellyroll tapes, or even current collectors, utilize ester-based plastics. This study presents chemical screening experiments on ester-based plastics used in lithium-ion cells, specifically in the presence of alkoxides, which are common electrolyte degradation products generated in cells without effective electrolyte additives. These experiments demonstrate that ester-based polymers used in Li-ion cells can negatively impact their safety and performance as ester bonds are vulnerable to degradation by alkoxides. There is increasing interest in the battery industry to use metallized polymer current collectors, which typically consist of an ester-based polymer film coated on both sides with Cu or Al. This study demonstrates that the chemical stability of these metallized polymer current collectors in Li-ion cells is compromised when alkoxides are created. Finally, we provide recommendations for alternative polymers based on their chemical stability and market availability.
A Case of Nocardia kroppenstedtii Infection Successfully Treated With a Multidisciplinary Approach
Authors: Foglia Francesco , Ambrosino Annalisa , Greco Giuseppe , Chianese Annalisa , Zannella Carla , Cinone Francesca , Reginelli Alfonso , Giordano Diego Sandro , Tortorella Giovanni , Laieta Maria Teresa , De Filippis Anna , Galdiero Massimiliano , Greco Rita , Finamore Emiliana
Published: February 2025

Nocardia species constitute a diverse group of microorganisms classified as aerobic actinomyces. Among these species, many have been implicated as causative agents of severe human infections, particularly in immunocompromised patients, affecting lungs, skin, and nervous system. Here, we described a rare species, identified as Nocardia kroppenstedtii, isolated at the Complex Operative Unit of Virology and Microbiology from the subxiphoid formation and pseudonodular formation in the left leg of a 69‐year‐old immunocompetent patient, who was hospitalized and treated at the Complex Operative Unit of Internal Medicine and Geriatrics of the University Hospital of Campania “Luigi Vanvitelli” in an antimicrobial diagnostic stewardship context. This rare pathogen was first isolated in 2014 from a bronchoalveolar lavage sample obtained from a lung transplant recipient. Since then, only five cases of clinical interest have been described in literature.
Supplementary table 4 from Mammographic Density in Relation to Breast Cancer Risk Factors among Chinese Women
Authors: Koka Hela , Tian Yuan , Deng Lu , Yu Kai , Li Er-Ni , Guo Changyuan , Guida Jennifer L. , Sung Hyuna , Chan Ariane , Hu Nan , Lu Ning , Gierach Gretchen L. , Li Jing , Yang Xiaohong R.
Published: February 2025

Distributions of risk factors and Volpara mamographic density measurements by menopausal status and body mass index in women from Beijing, China.
Supplementary table 3 from Mammographic Density in Relation to Breast Cancer Risk Factors among Chinese Women
Authors: Koka Hela , Tian Yuan , Deng Lu , Yu Kai , Li Er-Ni , Guo Changyuan , Guida Jennifer L. , Sung Hyuna , Chan Ariane , Hu Nan , Lu Ning , Gierach Gretchen L. , Li Jing , Yang Xiaohong R.
Published: February 2025

Associations between lifestyle factors and absolute dense volume (ADV), non-dense volume (NDV), and percent dense volume (PDV).
Supplementary figure 1 from Mammographic Density in Relation to Breast Cancer Risk Factors among Chinese Women
Authors: Koka Hela , Tian Yuan , Deng Lu , Yu Kai , Li Er-Ni , Guo Changyuan , Guida Jennifer L. , Sung Hyuna , Chan Ariane , Hu Nan , Lu Ning , Gierach Gretchen L. , Li Jing , Yang Xiaohong R.
Published: February 2025

Distributions of mammographic density measurements: total breast volume(TBV), absolute dense volume (ADV), non-dense volume (NDV), and percent dense volume (PDV) in each BI-RADS category and their correlations with one another.
Supplemental Figure S7 from Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
Authors: Huang Xiaosong , Lott Paul C. , Hu Donglei , Zavala Valentina A. , Jamal Zoeb N. , Vidaurre Tatiana , Casavilca-Zambrano Sandro , Navarro Vásquez Jeannie , Castañeda Carlos A. , Valencia Guillermo , Morante Zaida , Calderón Mónica , Abugattas Julio E. , Fuentes Hugo A. , Liendo-Picoaga Ruddy , Cotrina Jose M. , Neciosup Silvia P. , Rioja Viera Patricia , Salinas Luis A. , Galvez-Nino Marco , Huntsman Scott , Sanchez Sixto E. , Williams Michelle A. , Gelaye Bizu , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe , Echeverry Magdalena , Velez Alejandro , Carmona-Valencia Jenny A. , Bohorquez-Lozano Mabel E. , Torres Javier , Cruz Miguel , Ho Weang-Kee , Teo Soo Hwang , Tai Mei Chee , John Esther M. , Haiman Christopher A. , Conti David V. , Chen Fei , Torres-Mejía Gabriela , Kushi Lawrence H. , Neuhausen Susan L. , Ziv Elad , Carvajal-Carmona Luis G. , Fejerman Laura
Published: February 2025

Supplemental Figure S7 shows performance of PRS panels in H/L samples with matched age in cases and controls.
Supplemental Figure S6 from Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
Authors: Huang Xiaosong , Lott Paul C. , Hu Donglei , Zavala Valentina A. , Jamal Zoeb N. , Vidaurre Tatiana , Casavilca-Zambrano Sandro , Navarro Vásquez Jeannie , Castañeda Carlos A. , Valencia Guillermo , Morante Zaida , Calderón Mónica , Abugattas Julio E. , Fuentes Hugo A. , Liendo-Picoaga Ruddy , Cotrina Jose M. , Neciosup Silvia P. , Rioja Viera Patricia , Salinas Luis A. , Galvez-Nino Marco , Huntsman Scott , Sanchez Sixto E. , Williams Michelle A. , Gelaye Bizu , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe , Echeverry Magdalena , Velez Alejandro , Carmona-Valencia Jenny A. , Bohorquez-Lozano Mabel E. , Torres Javier , Cruz Miguel , Ho Weang-Kee , Teo Soo Hwang , Tai Mei Chee , John Esther M. , Haiman Christopher A. , Conti David V. , Chen Fei , Torres-Mejía Gabriela , Kushi Lawrence H. , Neuhausen Susan L. , Ziv Elad , Carvajal-Carmona Luis G. , Fejerman Laura
Published: February 2025

Supplemental Figure S6 shows performance of PRS panels in H/L samples excluding samples in discovery GWAS.
Supplemental Figure S5 from Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
Authors: Huang Xiaosong , Lott Paul C. , Hu Donglei , Zavala Valentina A. , Jamal Zoeb N. , Vidaurre Tatiana , Casavilca-Zambrano Sandro , Navarro Vásquez Jeannie , Castañeda Carlos A. , Valencia Guillermo , Morante Zaida , Calderón Mónica , Abugattas Julio E. , Fuentes Hugo A. , Liendo-Picoaga Ruddy , Cotrina Jose M. , Neciosup Silvia P. , Rioja Viera Patricia , Salinas Luis A. , Galvez-Nino Marco , Huntsman Scott , Sanchez Sixto E. , Williams Michelle A. , Gelaye Bizu , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe , Echeverry Magdalena , Velez Alejandro , Carmona-Valencia Jenny A. , Bohorquez-Lozano Mabel E. , Torres Javier , Cruz Miguel , Ho Weang-Kee , Teo Soo Hwang , Tai Mei Chee , John Esther M. , Haiman Christopher A. , Conti David V. , Chen Fei , Torres-Mejía Gabriela , Kushi Lawrence H. , Neuhausen Susan L. , Ziv Elad , Carvajal-Carmona Luis G. , Fejerman Laura
Published: February 2025

Supplemental Figure S5 shows effect of adding only one H/L SNP to Asian PRS panels on performance in H/L samples.
Supplemental Figure S3 from Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
Authors: Huang Xiaosong , Lott Paul C. , Hu Donglei , Zavala Valentina A. , Jamal Zoeb N. , Vidaurre Tatiana , Casavilca-Zambrano Sandro , Navarro Vásquez Jeannie , Castañeda Carlos A. , Valencia Guillermo , Morante Zaida , Calderón Mónica , Abugattas Julio E. , Fuentes Hugo A. , Liendo-Picoaga Ruddy , Cotrina Jose M. , Neciosup Silvia P. , Rioja Viera Patricia , Salinas Luis A. , Galvez-Nino Marco , Huntsman Scott , Sanchez Sixto E. , Williams Michelle A. , Gelaye Bizu , Estrada-Florez Ana P. , Polanco-Echeverry Guadalupe , Echeverry Magdalena , Velez Alejandro , Carmona-Valencia Jenny A. , Bohorquez-Lozano Mabel E. , Torres Javier , Cruz Miguel , Ho Weang-Kee , Teo Soo Hwang , Tai Mei Chee , John Esther M. , Haiman Christopher A. , Conti David V. , Chen Fei , Torres-Mejía Gabriela , Kushi Lawrence H. , Neuhausen Susan L. , Ziv Elad , Carvajal-Carmona Luis G. , Fejerman Laura
Published: February 2025

Supplemental Figure S3 shows performance of combinations of European and Asian PRS panels in H/L samples.
Supplementary Figure S2 from Timeliness of Lung Cancer Care and Area-Level Determinants in Victoria: A Bayesian Spatiotemporal Analysis
Authors: Tesema Getayeneh Antehunegn , Tessema Zemenu Tadesse , Heritier Stephane , Stirling Rob G. , Earnest Arul
Published: February 2025

The proportion of diagnostic and treatment delays among lung cancer patients in Victoria, 2011-2022
Supplementary Table S1 from Socioeconomic Inequalities in Participation in Colorectal Cancer Screening in Ontario, Canada: A Decomposition Analysis
Authors: Jalili Faramarz , Austin Nichole , Lavergne M. Ruth , Hajizadeh Mohammad
Published: February 2025

Supplementary Table S1: Definition of variables used in the study. This table provides detailed definitions of the variables used in the study
Supplementary Table 4 from Significant Disparities in Hepatocellular Carcinoma Outcomes by Race/Ethnicity and Sociodemographic Factors
Authors: Patel Shyam , Khalili Mandana , Singal Amit G. , Pinheiro Paulo S. , Jones Patricia D. , Kim Rebecca G. , Kode Vishwajit , Thiemann Anna , Zhang Wei , Cheung Ramsey , Wong Robert J.
Published: February 2025

Supplementary Table 4 shows the results from the adjusted multivariable logistic regression analyses evaluating for predictors of delays in HCC treatment (≥3 months vs. <3 months), stratified by race/ethnicity.
Supplementary Table S7 from Polygenic Risk Score, Healthy Lifestyle Score, and Colorectal Cancer Risk: A Prospective Cohort Study
Authors: Shen Yuefan , Chen Weiwei , Fu Chengqu , Liu Xinyi , Miao Junyan , Li Jiacong , Li Ni , Hang Dong
Published: February 2025

Association between lifestyle and colorectal cancer risk after excluding cases within the first year of follow-up
Table S2 from CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis
Authors: MacLehose Richard F. , Ahern Thomas P. , Collin Lindsay J. , Li Aixin , Lash Timothy L.
Published: February 2025

Supplementary Table S2: Search Terms used in systematic review
Table S1 from CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis
Authors: MacLehose Richard F. , Ahern Thomas P. , Collin Lindsay J. , Li Aixin , Lash Timothy L.
Published: February 2025

Supplementary Table S1: Meta-analysis results stratified by outcome and DNA source.