bluuebunny/crossref_metadata_2025 huggingface dataset:
Approximate Computing Survey, Part II: Application-Specific & Architectural Approximation Techniques and Applications
Authors: Leon Vasileios , Hanif Muhammad Abdullah , Armeniakos Giorgos , Jiao Xun , Shafique Muhammad , Pekmestzi Kiamal , Soudris Dimitrios
Published: January 2025

The challenging deployment of compute-intensive applications from domains such as Artificial Intelligence (AI) and Digital Signal Processing (DSP), forces the community of computing systems to explore new design approaches.
Approximate Computing
appears as an emerging solution, allowing to tune the quality of results in the design of a system in order to improve the energy efficiency and/or performance. This radical paradigm shift has attracted interest from both academia and industry, resulting in significant research on approximation techniques and methodologies at different design layers (from system down to integrated circuits). Motivated by the wide appeal of Approximate Computing over the last 10 years, we conduct a two-part survey to cover key aspects (e.g., terminology and applications) and review the state-of-the-art approximation techniques from all layers of the traditional computing stack. Part II of the survey classifies and presents the technical details of application-specific and architectural approximation techniques, which both target the design of resource-efficient processors/accelerators and systems. Moreover, it reports a quantitative analysis of the techniques and a detailed analysis of the application spectrum of Approximate Computing, and finally, it discusses open challenges and future directions.
Research Directions in Software Supply Chain Security
Authors: Williams Laurie , Benedetti Giacomo , Hamer Sivana , Paramitha Ranindya , Rahman Imranur , Tamanna Mahzabin , Tystahl Greg , Zahan Nusrat , Morrison Patrick , Acar Yasemin , Cukier Michel , Kästner Christian , Kapravelos Alexandros , Wermke Dominik , Enck William
Published: January 2025

Reusable software libraries, frameworks, and components, such as those provided by open-source ecosystems and third-party suppliers, accelerate digital innovation. However, recent years have shown almost exponential growth in attackers leveraging these software artifacts to launch software supply chain attacks. Past well-known software supply chain attacks include the SolarWinds, log4j, and xz utils incidents. Supply chain attacks are considered to have three major attack vectors: through vulnerabilities and malware accidentally or intentionally injected into open-source and third-party
dependencies/components/containers
; by infiltrating the
build infrastructure
during the build and deployment processes; and through targeted techniques aimed at the
humans
involved in software development, such as through social engineering. Plummeting trust in the software supply chain could decelerate digital innovation if the software industry reduces its use of open-source and third-party artifacts to reduce risks. This paper contains perspectives and knowledge obtained from intentional outreach with practitioners to understand their practical challenges and from extensive research efforts. We then provide an overview of current research efforts to secure the software supply chain. Finally, we propose a future research agenda to close software supply chain attack vectors and support the software industry.
HumanEvalComm: Benchmarking the Communication Competence of Code Generation for LLMs and LLM Agent
Authors: Wu Jie Jw , Fard Fatemeh H.
Published: January 2025

Large language models (LLMs) have significantly improved their ability to perform tasks in the field of code generation. However, there is still a gap between LLMs being capable coders and being top-tier software engineers. The most recent trend is using LLM-based agents to iterate the code generation process. Based on the observation that top-level software engineers often ask clarifying questions to reduce
Ambiguity
in both requirements and coding solutions, we argue that the same should be applied to LLMs for code generation tasks. For this purpose, we define the communication skills of LLMs as “being able to ask clarifying questions when the description of the code generation problem has issues”. In this study, we restrict these issues to three matters from the software requirement engineering field: inconsistent requirements, ambiguous requirements, and incomplete requirements. By asking probing questions about the requirements of problem descriptions before generating the final code, the challenges of programming with LLMs, such as unclear intent specification may be alleviated, resulting to a correct code in the initial iterations.

In this work, we conducted an empirical study on the benchmark and analysis of the communication skills of LLMs for code generation. We created a new benchmark, HumanEvalComm, by modifying problem descriptions according to three issues mentioned above,
Inconsistency
,
Ambiguity
,
Incompleteness
. We then experimented on HumanEvalComm with different Code LLMs, and a new LLM agent approach,

C
o
de
C
l
a
rificatio
n
a
nd
G
eneration
A
ge
n
t

(Okanagan), to identify and ask questions in ambiguous parts from code and descriptions for further refining the generated code. In the evaluation, we introduced an
LLM-based evaluator
and created
Communication Rate
and
Good Question Rate
as the evaluation metrics to represent the ratio of questions asked and questions with good quality in responses. We found that more than 60% of responses from Code LLMs still generate code rather than ask questions when the problem descriptions are manually modified according to different clarification categories. The Pass@1 and Test Pass Rate of most Code LLMs drop by 35%

\(\sim\)

52% and by 17%

\(\sim\)

35% respectively, with statistical significance in each category for over 75% numbers. Okanagan, as an LLM agent approach that uses LLM such as ChatGPT 3.5, effectively increases the Communication Rate and Good Question Rate by an absolute 58% and 38%, respectively. Thus, Okanagan boosts Pass@1 and Test Pass Rate by an absolute 8% and 7%, respectively, when the problem descriptions are modified based on given clarification categories. This result indicates the potential for achieving more effective communication capability using LLM agent. Our benchmark and full code are publicly available at
https://github.com/jie-jw-wu/human-eval-comm
.
Relating the Salt Thermodynamic Factor to Solvent Activities in Ternary Multi-Solvent Electrolytes
Authors: Self Julian , Al-Salih Hilal , Abu-Lebdeh Yaser
Published: January 2025

The activities of individual solvent species in multi-solvent ternary liquid electrolytes dictate liquid-solid equilibria and are pertinent to transport phenomena. Nonetheless, considerable scholarship has assumed that such electrolytes can be modeled as single-solvent electrolytes. Relaxing this assumption, we show in the present work that knowledge of the activity of ionic species, described by the salt thermodynamic factor and the transfer activity coefficients at infinite dilution, is sufficient to calculate activity changes of individual solvent species for ternary multi-solvent electrolytes. We also propose measurements of an individual solvent species activity as a method to study (ionic) solvent transfer energies. We apply the derived relationships to the well-characterized liquid electrolyte system LiCl in H2O-EtOH. We also study a non-aqueous electrolyte solution, LiPF6 in EC-EMC, which is important for lithium-ion battery technology. For the latter, we show that in the studied composition space there are non-negligible transfer activity coefficients, highlighting the importance of a multisolvent description of the ternary electrolytes.
Adaptive changes in balance control strategies under continuous exposure to visual-somatosensory conflicts
Authors: Hua An-Ke , Bai Jing-Yuan , Wang Guo-Zheng , Hao Zeng-Ming , Meng Jun , Wang Jian
Published: January 2025

Lower limb muscle coordination plays a vital role when facing continuous perturbation by updating sensorimotor mappings. However, it is unclear how muscle coordination adapts to visual-somatosensory congruent and incongruent perturbations. Here, we found that muscle coordination showed context-specific adaptive changes to visual-somatosensory congruent or incongruent environment.
Cooking‐Induced Lipid–Protein Oxidation in Kavurma (a Cooked Meat Product)
Authors: Babaoglu Melike , Aktas Nesimi , Igci Nasit , Ertul Seref
Published: January 2025

Optimizing the nutritional quality of cooked meat requires a better understanding of the mechanisms responsible for lipid–protein changes caused by cooking. In this study, the aim was to determine the levels of protein–lipid oxidation that could occur during the kavurma production process. For this purpose, cooking was performed at 100°C for 30, 60, 90, and 120 min, and protein oxidation was determined by measuring carbonyl content, sulfhydryl (S‐H) group levels, and Schiff base formation, while lipid oxidation was assessed by measuring thiobarbituric acid reactive substances (TBARS), peroxide, p‐anisidine, and free fatty acid (FFA) values. Also, the changes in protein structure were identified by Fourier‐transform infrared spectroscopy (FT‐IR). Carbonyl, formation of Schiff bases, peroxide, p‐anisidine, and FFA values significantly increased throughout the cooking time (p < 0.05). TBARS values showed a significant increase within the first 30 min, followed by a decrease. The level of S‐H groups significantly decreased with increasing cooking time (p < 0.05). FT‐IR analysis of the myofibrillar extract revealed 13 major peaks, with peak areas decreasing depending on the cooking time. Analysis of the secondary structure indicated higher relative intensities of α‐helix and random coil up to 90 min of cooking time. Results indicate that protein–lipid oxidation is dependent on the cooking time, which point out to an effect on the nutritional quality of proteins and lipids in kavurma. Also, these results not only enhance our comprehension of the complex relationship between cooking time and product quality but also present encouraging prospects for fostering healthier and safer cooking methods.
Some Novel Inequalities for Godunova–Levin Preinvex Functions via Interval Set Inclusion (⊆) Relation
Authors: Khan Zareen A. , Afzal Waqar , Abbas Mujahid , Nantomah Kwara
Published: January 2025

In this note, we introduce the concept of ℏ‐Godunova–Levin interval‐valued preinvex functions. As a result of these novel notions, we have developed several variants of Hermite–Hadamard and Fejér‐type inequalities under inclusion order relations. Furthermore, we demonstrate through suitable substitutions that this type of convexity unifies a variety of other convex classes. To further support our main findings, we formulated several remarks and nontrivial examples.
VAX014 Activates Tumor-Intrinsic STING and RIG-I to Promote the Development of Antitumor Immunity
Authors: Nelson Kinsey L. , Reil Katherine A. , Tsuji Shingo , Parikh Amanda M. , Robinson Mikella , House Carrie D. , McGuire Kathleen L. , Giacalone Matthew J.
Published: January 2025

In situ immunization (ISI) has emerged as a promising approach to bolster early phases of the cancer immunity cycle through improved T-cell priming. One class of ISI agents, oncolytic viruses (OV), has demonstrated clinical activity, but overall benefit remains limited. Mounting evidence suggests that due to their inherent vulnerability to antiviral effects of type I IFN, OVs have limited activity in solid tumors expressing stimulator of interferon genes (STING) and/or retinoic acid–inducible gene I (RIG-I). Here, using a combination of pharmacologic, genetic, and in vivo approaches, we demonstrate that VAX014, a bacterial minicell–based oncolytic ISI agent, activates both STING and RIG-I and leverages this activity to work best in STING-positive and/or RIG-I–positive tumors. Intratumoral treatment of established syngeneic tumors expressing STING and RIG-I with VAX014 resulted in 100% tumor clearance in two mouse models. Antitumor activity of VAX014 was shown to be dependent on both tumor-intrinsic STING and RIG-I with additive activity stemming from host-intrinsic STING. Analysis of human solid tumor datasets demonstrated STING and RIG-I co-expression is prevalent in solid tumors and associates with clinical benefit in many indications, particularly those most amenable to intratumoral administration. These collective findings differentiate VAX014 from OVs by elucidating the ability of this agent to elicit antitumor activity in STING-positive and/or RIG-I–positive solid tumors and provide evidence that STING/RIG-I agonism is part of VAX014’s mechanism of action. Taken together, this work supports the ongoing clinical investigation of VAX014 treatment as an alternative to OV therapy in patients with solid tumors.
THG-1/TSC22D4 Promotes IL-1 Signaling through Stabilization of TRAF6 in Squamous Cell Carcinoma
Authors: Okano Yasuhito , Suzuki Hiroyuki , Watanabe Yukihide , Abdelaziz Mohammed , Manevich Lev , Kawanishi Kunio , Ozaki Haruka , Ishii Ryota , Matsumoto Shin , Goto Nohara , Zheng Ling , Okita Yukari , Hwang Jongchan , Nakayama Masahiro , Shima Yoshihide , Sakamoto Noriaki , Noguchi Masayuki , Tabuchi Keiji , Kato Mitsuyasu
Published: January 2025

Malignant neoplasms arise within a region of chronic inflammation, which is a key factor in all aspects of tumorigenesis including initiation, proliferation, invasion, angiogenesis, and metastasis. IL-1 plays critical functions in tumor development by influencing the tumor microenvironment and promoting cancer progression. However, the mechanism of continuous activation of the IL-1–mediated inflammatory pathway in tumors has not been fully elucidated. This study provides a novel mechanism of the autocrine activation of IL-1 signaling in squamous cell carcinoma (SCC) through a novel oncoprotein, TSC-22 homologous gene-1 (THG-1, also known as TSC22D4). The RNA sequencing analysis revealed that THG-1 overexpression enhances the transcription of NF-κB targets including IL1A, IL1B, TNFA, and IL8. Furthermore, THG-1 knockdown reduced the responsiveness to IL-1 through the suppression of NF-κB nuclear translocation. To elucidate the mechanism, we focused on a THG-1 interacting protein, NRBP1. We found that NRBP1 facilitates the degradation of TNF receptor–associated factor 6 (TRAF6) through its E3 ubiquitin ligase activity. THG-1 bound to NRBP1 and suppressed the degradation of TRAF6. Furthermore, THG-1 knockdown reduced TRAF6 abundance and NF-κB activity in SCC cells. Public database analyses of head and neck SCC revealed that high expression of THG-1 is associated with the activation of the IL-1 and TNF pathways, which share TRAF6 in the signal transductions. Finally, THG-1 abundance in laryngeal SCC specimens is elevated in patients with recurrence. These results indicated that THG-1 drives the self-sufficiency of IL-1–mediated inflammatory pathway, which could contribute to the future diagnosis and immunotherapy of SCCs.

Implications: An oncoprotein, THG-1/TSC22D4 activates the IL-1–mediated inflammatory pathway through the suppression of TRAF6 degradation, which mediates the continuous inflammation in tumors.
MiR-211 regulates cutaneous wound healing through inhibiting inflammatory reactions and oxidative stress by binding SOX11
Authors: Chen Yun , Zhang Xinyi , Wu Fangfang , Wang Lixia , Zuo Hongju , Tian Hanbing , Chen Huan
Published: January 2025

Introduction: Loss of skin integrity due to a wound or disease can lead to severe disability or even life threat. The highly expressed microRNAs in the skin are of great significance for skin development. The investigation purposed to explore the effect and mechanism of miR-211 on inflammation, oxidative stress and migration in keratinocytes.
Methods: The HaCaT keratinocytes were treated with hydrogen peroxide (H2O2) to establish a wound-healing model. The expression of miR-211 was examined by quantitative real-time PCR (qRT-PCR). The cell function was reflected in proliferative ability, migration, apoptosis, and inflammation, which were evaluated by Cell Counting Kit-8 (CCK-8) assay, Transwell test, flow cytometry technique, and enzyme-linked immunosorbent assay (ELISA). The target of miR-211 was verified by luciferase luminescence measurements.
Results: H2O2 inhibited HaCaT cell proliferation, migration, and promoted cell apoptosis, accompanied with the downregulation of miR-211. H2O2 led to inflammatory response and oxidative damage to HaCaT. MiR-211 promoted proliferation and migration, but improved cell apoptosis of HaCaT. The role of H2O2 on inflammatory response and oxidative stress was alleviated by miR-211. SRY-box transcription factor 11 (SOX11) was a targeted mediator of miR-211. SOX11 reversed the influence of miR-211 on cell proliferation, migration, apoptosis, inflammatory response and oxidative stress.
Conclusion: MiR-211 regulated proliferation, migration, apoptosis, inflammation and oxidative stress of keratinocytes by mediating SOX11, thus participating in cutaneous wound healing.
Multiple Primary Cutaneous Anaplastic Large Cell Lymphoma: A Case Report
Authors: Al Saud Aljoharah , Alsergani Reem , Alhumidi Ahmed , Aleisa Abdullah
Published: January 2025

Introduction: Anaplastic large cell lymphomas (ALCL) are a subtype of non-Hodgkin lymphoma categorized into systemic and cutaneous (cALCL) subtypes. cALCL are frequently characterized by their lack of ALK receptor expression, which differentiates them from their systemic counterparts. cALCLs present as solitary or grouped skin lesions. Due to their rarity, cALCLs are frequently misdiagnosed as other skin conditions.
Case presentation: We report the case of a female with a 30-year history of expanding skin lesions on the upper and lower limbs, abdomen, and back. During her initial presentation, the lesions were thought to be due to an arthropod bite. However, lesion biopsy revealed ALK-negative cALCL and methicillin-resistant Staphylococcus aureus. A full workup excluded systemic ALCL and, therefore, confirmed the diagnosis of primary cALCL. The patient was placed on methotrexate to treat the lesions and sulfamethoxazole/trimethoprim to treat the infection.
Conclusion: Our case highlights the need to consider cALCL in the differential diagnosis of patients with persistent skin lesions.
Exploring factors behind patient non-adherence to intravitreal anti-VEGF
injections in macular diseases
Authors: Naaman Efrat , Yanir-Prat Noa , Shair Diana , Bar Nitai , Miller Beata , Fishman Anna , Zayit-Soudry Shiri
Published: January 2025

Introduction: In recent years, intravitreal injections (IVT) of vascular endothelial growth factor (VEGF) inhibitors have become the standard of care for several macular disorders. Frequently, the therapeutic course requires numerous injections, posing a burden on patients. Non-adherence to treatment may result in reduced visual outcomes, therefore understanding and addressing the underlying causes is imperative.
Methods: A cross-sectional study of patients who missed their scheduled appointment for anti-VEGF IVT as part of the routine management of their macular disease at a single tertiary center between November 2020 and February 2021. A telephone survey was conducted and patient medical charts were reviewed for ophthalmological data.
Results: A total of 100/556 (18%) patients who failed to attend their scheduled anti-VEGF IVT appointments were documented. Among these subjects, the average age was 66 (SD ±14) years with a nearly equal gender distribution of 49:51 F:M ratio. Reported no-show reasons included concurrent illness (39%), administrative issues such as missing financial coverage forms or scheduling problems (28%), and lack of motivation (11%). Additionally, 73% of patients who missed appointments expressed a need for accompaniment, and 74% resided outside the hospital city.
Conclusions: Study results highlight modifiable factors contributing to no-shows to anti-VEGF IVT, such as poor transportation access, complicated administrative processes, and difficulty rescheduling missed appointments. Understanding potential obstacles to anti-VEGF IVT therapy, particularly those that are preventable, can enhance adherence and potentially improve the clinical outcome.
Fortgeschrittenes Plattenepithelkarzinom, das sich auf einer chronischen Hidradenitis suppurativa entwickelt hat und erfolgreich mit Cemiplimab behandelt wurde: ein Fallbericht
Authors: Ruggiero Angelo , Lauro Wanda , Miano Chiara , Villani Alessia , Fabbrocini Gabriella , Marasca Claudio
Published: January 2025

Hidradenitis suppurativa (HS) ist eine entzündliche Hauterkrankung mit chronisch-remittierendem Verlauf. Selten wurde berichtet, dass eine langfristige Entzündung bei HS zu ernsthaften Komplikationen wie Plattenepithelkarzinomen der Haut führen kann. Cemiplimab ist eine Immuntherapie mit einem vollständig humanen Antikörper, der PD-1 (Programmed Cell Death Protein 1) hemmt und für die Behandlung von lokal fortgeschrittenen Plattenepithelkarzinomen oder metastasierten Plattenepithelkarzinomen bei Patienten zugelassen ist, die für eine kurative Operation oder Strahlentherapie nicht infrage kommen. Wir berichten über den Fall eines 56-jährigen Patienten, bei dem sich ein invasives Plattenepithelkarzinom auf seit langem bestehenden und nicht ansprechenden HS-Läsionen entwickelte und das erfolgreich mit Cemiplimab behandelt wurde.
A Case-Control Study of Trichotillomania Patients Using a National Database
Authors: Parikh Aarushi , Musolff Noah , Tchack Madeline , Rao Babar
Published: January 2025

Introduction: Trichotillomania (TTM) is a body-focused repetitive disorder linked to psychiatric comorbidities. Comprehensive studies mapping its associations with a range of conditions remain limited. This study examines TTM’s associations with psychiatric, neurodevelopmental, substance-related, reproductive, and social factors using a national database.
Methods: We performed a case-control study using the All of Us Research Program database. TTM cases (n=40) were matched to controls (n=400) based on age, sex, and ethnicity. Multivariate logistic regression was used to examine associations with comorbidities and lifestyle factors, controlling for demographic variables.
Results: TTM was significantly associated with OCD (OR 18.3), BPD (OR 15), anxiety disorders (OR 10.2), alcohol abuse (OR 6.13), depression (OR 5.89), and vitamin D deficiency (OR 4.2) (all p < 0.01). Other significant associations included fatigue, social anxiety, PTSD, ADHD, and difficulty running errands alone.
Conclusion: Our findings highlight the strong association between TTM and a wide range of psychiatric and behavioral conditions, emphasizing the need for integrated treatment strategies addressing both psychiatric and physical aspects.
Bullous Lichen Planus Treated with Adalimumab: A Case Report
Authors: Alhubayshi Bashayr S. , Alnoshan Abdulaziz A. , AlHumidi Ahmed A. , Shadid Asem
Published: January 2025

Introduction: Bullous lichen planus is a rare variant of lichen planus that is characterized by vesiculobullous lesions developing in the setting of preexisting LP lesions with a burning and painful feeling. Bullous lichen planus treatment is difficult since so few examples of the condition have been documented in the literature. Case Presentation: A 46-year-old female presented to our outpatient clinic with pruritic violaceous bullae involving lower extremities and oral mucosa for 8 years. After extensive investigations, a diagnosis of bullous lichen planus was made and successfully treated with adalimumab after failure of other treatment options. Conclusion: Adalimumab may represent a promising, efficacious, and safe monotherapy option for the management of bullous lichen planus. The therapeutic value of this novel off-label use should be assessed in controlled clinical trials.
Die Rolle von Staphylococcus aureus bei der atopischen Dermatitis verstehen: Stammvielfalt, Mikroevolution und Prophageneinfluss
Authors: Wang Zhongjie , Hülpüsch Claudia , Traidl-Hoffmann Claudia , Reiger Matthias , Schloter Michael
Published: January 2025

Atopische Dermatitis (AD) ist eine weit verbreitete entzündliche Hauterkrankung, die durch chronische Entzündung, eine gestörte Hautbarriere und mikrobielle Dysbiose gekennzeichnet ist, wobei Staphylococcus aureus eine wichtige Rolle in der Pathogenese spielt. Diese Übersichtsarbeit untersucht die Stammvielfalt und Mikroevolution von S. aureus bei AD-Patienten und zeigt, wie sich bestimmte Stämme an das veränderte Hautmilieu anpassen und die Erkrankung verschlimmern. Die Übersichtsarbeit unterstreicht die Bedeutung der Variation spezifischer funktioneller Gene bei S. aureus-Stämmen, die ihre Fähigkeit zur Anpassung an unterschiedliche Mikroumgebungen verbessert und ihr pathogenes Potenzial prägt. Darüber hinaus wird diskutiert, wie mobile genetische Elemente, insbesondere Prophagen, zur genetischen Diversität beitragen und die Virulenz und Antibiotikaresistenz von S. aureus bei AD fördern. Die klinischen Herausforderungen, die diese stammspezifischen Faktoren für die Behandlung der Krankheit darstellen, werden hervorgehoben. Die Arbeit plädiert für die Integration fortgeschrittener Genomikinstrumente wie vollständige Genomsequenzierung und maschinelles Lernen, um zielgerichtete Therapien zu entwickeln. Durch die Fokussierung auf die genetische Anpassungsfähigkeit von S. aureus und ihre Auswirkungen auf die AD unterstreicht diese Übersichtsarbeit den Bedarf an stammspezifischer Diagnostik und personalisierten Behandlungsstrategien, um die Ergebnisse für die Patienten zu verbessern.
A Rare Case of Calciphylaxis: A Case Report
Authors: Lafrid Maria , Labioui Narjiss , Hallak Mohamed , Bahadi Abdelaali , El Kabbaj Driss , Allaoui Mohamed , Zajjari Yassir
Published: January 2025

Introduction: Calciphylaxis is a rare and severe disorder characterized by obstructive small vessel disease in the subcutaneous adipose tissue and skin, leading to necrotic skin lesions. The condition poses a significant risk of mortality due to infectious and ischemic complications. Case Presentation: We present the case of a 60-year-old woman, with a history of renal lithiasis, hypertension, and end-stage renal disease on hemodialysis complicated by hyperparathyroidism and aortic valve replacement. She developed extensive necrotic lesions on both lower limbs and upper extremities, prompting a diagnosis of calciphylaxis. Radiographic and biopsy findings supported the diagnosis, revealing characteristic calcifications. Treatment involved antibiotics, oral thiosulfate, daily hemodialysis, hyperbaric oxygen therapy, and discontinuation of calcium and alfacalcidol, with alendronate initiation. Unfortunately, despite these interventions, the patient experienced a rapid clinical decline, developing septic shock necessitating bilateral leg amputations. Regrettably, she succumbed to the disease 10 days later. Conclusion: This case underscores the challenging prognosis of calciphylaxis and the need for effective therapeutic options, including surgical intervention and access to injectable thiosulfate.
World Health Organization´s Well-Being Index - WHO-5: psychometric performance of the Portuguese version for adolescents
Authors: Carvalho Paula Saraiva , Vieira Martins Miguel , Azevedo Isabel , Rodrigues Ricardo , Ferreira Sofia
Published: January 2025

Introduction: The World Health Organization Well-Being Index (WHO-5) is a five-item scale designed to measure psychological well-being and is considered effective in detecting depressive symptoms. This scale was translated and validated in more than 30 languages and is used in clinical practice and research worldwide. In Portugal, validation of this scale has yet to be done. This study aims to analyse the psychometric performance of the WHO-5 scale in the setting of a Portuguese adolescent population.
Methods: An observational cross-sectional survey-based study was carried out to assess the emotional state of adolescents resorting to the WHO-5 scale. A sample of 1916 elementary and secondary school students from grades 7-12 was used.
Results: The WHO-5 median score was 17 [14-20], and the best scores were found in males (p<0,001), in those with no health issues (p<0,001), those who slept well (p<0,001), those who practised sports (p<0,001) and those who had no difficulties making friends (p<0,001). Results from the answers to the WHO-5 questionnaire showed good internal consistency with a Cronbach alpha value of 0,80, and a confirmatory factor analysis supported the unidimensional structure of the questionnaire, which was consistent with a valid scale for the study sample.
Conclusion: This study showed that the Portuguese version of the WHO-5 is capable of assessing psychological well-being in adolescents.
The WHO-5 is a simple and readily usable scale that can be applied in routine consultations for screening the emotional state of adolescents and early detection of signs of mental health problems.
Eyebrow microblading: Science, art and complications
Authors: Shishak Mansak , Kuthial Madhu
Published: January 2025

Eyebrows are a distinct facial feature and any shift in its appearance impacts self-perception of external beauty attributes. There may be loss of hairs, or changes in pigment and texture due to primary or secondary causes. A surge in demand for microblading in recent years majorly for aesthetic value, has driven curiosity and requests for the procedure. This has translated to subjective dissatisfaction of cosmetic outcomes while also increasing the risk of complications, and immunogenically driven adverse events. Understanding the nuances of the technique and undertaking basic precautions will enable safe and desirable results in this common procedure.
A novel X-linked variant c.1772delG (p.G591fs*20) in IRS4 in two related patients with central hypothyroidism
Authors: Köprülü Özge , Tozkir Hilmi
Published: January 2025

Introduction: Central hypothyroidism (CeH) is characterized by thyroid hormone deficiency due to impairment of pituitary thyroid stimulating hormone (TSH) or hypothalamic TRH biosynthesis. It is extremely rare and affects approximately 1:16,000-100,000 individuals. Diagnosis, especially of isolated CeH, may be challenging. CeH is often seen as a part of multiple pituitary hormone deficiencies, but it can also be seen as isolated CeH. To date, some variants that can cause CeH have been identified; although in a number of patients the cause has not been clarified. Recently, variants of the insulin receptor substrate 4 (IRS4) gene have been reported to be the cause of isolated CeH. Herein, we report two related patients and their family with carriers with a novel X-linked frameshift variant in the IRS4 gene. It has also been shown that thyroid function may be slightly affected in the heterozygous female carriers in our study. Case Presentation: Herein, we reported two Turkish male patients with CeH due to a hemizygous variant in IRS4. The index case was a 15-year-and-2-month male who presented with a low serum free thyroxin level, which was incidentally detected. Conclusion: Isolated CeH should kept in mind in insistent low fT4 levels without an increase in TSH levels. Genetic testing can aid in identifying the underlying cause of CeH in such cases. This report demonstrates the significance of providing comprehensive laboratory and molecular features of the patients and carriers with the IRS4 variants.
Estrogen receptors and platelet-activating acetylhydrolase activity in the pathogenesis of systemic lupus erythematosus
Authors: Sato Akira , Ogawa Yuta , Yabuki Ayano , Sato Genta , Nemoto Hina , Ohira Makoto
Published: January 2025

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects various body systems, including the skin and facial features. Estrogen promotes lupus in human and mouse models of SLE. In this study, we conducted an in vivo study to investigate the relationship between two estrogen receptors (ERα and ERβ) and platelet-activating factor acetylhydrolase (PAF-AH) on the symptoms of SLE. Methods: Skin and facial features, serum PAF-AH activity, tumor-necrosis factor-alpha (TNF-α), and anti-double-stranded DNA (anti-dsDNA) antibody titer, all of which are central to the classification and pathogenesis of SLE, were measured in SLE model mice injected with various ER antagonists. Results: In SLE mice, the injection of an ERβ antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidine-3-yl]-phenol induced the expression of facial erythema (especially around a cheek). The injection of an ERα/β antagonist tamoxifen induced hair-loss on the head and the neck. The injection of an ERα antagonist methylpiperidino pyrazole or tamoxifen increased PAF-AH activity and decreased TNF-α levels and anti-dsDNA antibody in mouse serum. Conclusions: The activation of ERα and inactivation of ERβ can cause inflammatory and cutaneous symptoms of SLE, respectively, implying that ERα antagonists and/or ERβ agonists can be useful for the prevention and treatment of SLE.
Association Between Liver Fibrosis and Risk of Incident Stroke and Mortality: A Large Prospective Cohort Study
Authors: Wang Zijie , Gong Zhitao , Wen Jianshang , Zhang Shanyu , Hu Xiao , Guo Wenliang , Tian Yanghua , Li Qi
Published: January 2025

Background

There is a well‐established relationship between liver conditions and cardiovascular diseases. However, uncertainty persists regarding the contribution of liver fibrosis to major stroke types including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage at the population level.

Methods

In this large prospective cohort study, participants without previous stroke or coronary heart disease at baseline from the UK Biobank were included. We identified participants at high probability of advanced liver fibrosis using the Fibrosis‐4 index >2.67 or aspartate aminotransferase to platelet ratio index ≥1.0. Multivariable Cox proportional hazard regression analyses were conducted to estimate hazard ratios (HRs) for liver fibrosis with the incidence of major stroke types, stroke‐related death, and all‐cause death.

Results

Among 379 953 participants (mean age, 56.2 [SD, 8.1] years; 44.6% men), 7396 (1.9%) had a Fibrosis‐4 index >2.67 at baseline. During a median follow‐up of 12.75 (interquartile range, 12.03–13.48) years, 7143 (1.9%) incident stroke cases were documented. Advanced liver fibrosis assessed by the Fibrosis‐4 index was associated with an increased risk of ischemic stroke (HR, 1.94 [95% CI, 1.70–2.22]), intracerebral hemorrhage (HR, 2.14 [95% CI, 1.63–2.81]), subarachnoid hemorrhage (HR, 1.90 [95% CI, 1.27–2.84), stroke‐related death (HR, 2.20 [95% CI, 1.73–2.80]), and all‐cause death (HR, 2.59 [95% CI, 2.46–2.73]). Using the aspartate aminotransferase to platelet ratio index as an alternative score, liver fibrosis was correlated with magnified risk of intracerebral hemorrhage (HR, 3.76 [95% CI, 2.38–5.93]) and subarachnoid hemorrhage (HR, 3.05 [95% CI, 1.51–6.13]) compared with ischemic stroke (HR, 1.58 [95% CI, 1.17–2.14]). Restricted cubic spline analysis showed nonlinear associations of the Fibrosis‐4 index and aspartate aminotransferase to platelet ratio index with stroke incidence and all‐cause death.

Conclusions

Liver fibrosis is associated with increased risk of incident stroke and death among people without previous stroke or cardiovascular events, with particularly greater risk of intracerebral hemorrhage and subarachnoid hemorrhage. Noninvasive indices of liver fibrosis may serve as an easily accessible marker to detect individuals facing elevated risk of stroke and death in the primary prevention settings.
Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality
Authors: Louwe Mieke C. , Gialeli Chrysostomi , Michelsen Annika E. , Holm Sverre , Edsfeldt Andreas , Skagen Karolina , Lekva Tove , Olsen Maria Belland , Bjerkeli Vigdis , Schjørlien Therese , Stø Kristine , Kong Xiang Yi , Dahl Tuva B. , Nilsson Per H. , Libby Peter , Aukrust Pål , Mollnes Tom Eirik , Ueland Thor , Skjelland Mona , Gonçalves Isabel , Halvorsen Bente
Published: January 2025

Background

Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce.

Methods and Results

We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H in patients with advanced carotid atherosclerosis in a
Discovery
(n=324) and in a
Validation
(n=206) cohort in relation to adverse outcome (mean follow‐up 7.8 and 6.6 years, respectively). Our major findings were as follows. Compared with healthy controls, patients with carotid atherosclerosis had increased plasma levels of factor D, properdin, and C3bBbP (
P
<0.001), but not factor H, an inhibitor of the alternative complement pathway, compared with controls. Although patients with carotid atherosclerosis had elevated levels of properdin compared with controls, within these patients, low plasma levels of properdin (ie, <median levels of properdin in the patient group) were significantly associated with cardiovascular mortality. This was seen in both the
Discovery
(HR 2.31,
P
=0.019) and the
Validation
cohort (hazard ratio [HR], 2.81,
P
=0.014). In contrast to the low circulating levels, high intraplaque properdin levels (assessed by ELISA) correlated with markers of plaque vulnerability and symptomatology.

Conclusions

We show a strong and independent association of low plasma properdin levels with cardiovascular mortality in 2 cohorts. Conversely, the plaque properdin levels linked to features of plaque vulnerability, potentially reflecting increased deposition at the site of inflammation or local production of properdin in the atherosclerotic lesion indicating local enhanced alternative complement pathway activation.
Ide
Copy Number Variant Does Not Influence Stroke Severity in 2 C57BL/6J Mouse Models nor in Humans: An Exploratory Study
Authors: Foddis Marco , Blumenau Sonja , Mueller Susanne , Messerschmidt Clemens , Rocca Clarissa , Pagnamenta Alistair T. , Winek Katarzyna , Endres Matthias , Meisel Andreas , Tucci Arianna , Bras Jose , Guerreiro Rita , Beule Dieter , Dirnagl Ulrich , Sassi Celeste
Published: January 2025

BACKGROUND:

Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning
Ide
locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory. Given
IDE
critical role in vascular plasticity, we hypothesized
Ide
CNV may have explained PcomA variability in C57BL/6J inbred mice.

METHODS:

We applied a combination of techniques (T2-weighted magnetic resonance imaging, time-of-flight angiography, cerebral blood flow imaging, and histology) to characterize the collaterome in 77 C57BL/6J bilateral common carotid artery stenosis, middle cerebral artery occlusion, naive, and sham mice and performed on these Taqman genotyping, exome sequencing, and RNA sequencing. We then investigated the hypothesis that
IDE
structural variants (CNVs, gain/loss of function mutations) may have influenced the cerebrovascular phenotype in a large cohort of 454 040 cases and controls (UK Biobank, Genomics England).

RESULTS:

We detected an
Ide
CNV in a bilateral common carotid artery stenosis mouse with 2 patent PcomAs (minor allele frequency, 1.3%), not segregating with the PcomA patency phenotype. In addition, 2 heterozygous
IDE
CNVs, resulting in loss of function were found in 1 patient with hereditary ataxia, a patient with hereditary congenital heart disease, and 2 healthy individuals (minor allele frequency 9×10
-6
). Moreover, we report 4
IDE
loss of function point mutations (p.Leu5X, p.Met394ValfsX29, p.Pro14SerfsX26, p.Leu889X, minor allele frequency 0.02%) present also in controls or inherited from healthy parents.

CONCLUSIONS:

Ide
CNV and loss of function variants are rare, do not crucially influence PcomA variability in C57BL/6J inbred mice, and do not cause a vascular phenotype in humans.
Specifying Precision in Visual-orthographic Prediction Error Representations for a Better Understanding of Efficient Reading
Authors: Fu Wanlu , Gagl Benjamin
Published: January 2025

Efficient visual word recognition presumably relies on orthographic prediction error (oPE) representations. On the basis of a transparent neurocognitive computational model rooted in the principles of the predictive coding framework, we postulated that readers optimize their percept by removing redundant visual signals, allowing them to focus on the informative aspects of the sensory input (i.e., the oPE). Here, we explore alternative oPE implementations, testing whether increased precision by assuming all-or-nothing signaling and more realistic word lexicons results in adequate representations underlying efficient word recognition. We used behavioral and electrophysiological data (i.e., EEG) for model evaluation. More precise oPE representations (i.e., implementing a binary signaling and a frequency-sorted lexicon with the 500 most common five-letter words) explained variance in behavioral responses and electrophysiological data 300 msec after stimulus onset best. The original less-precise oPE representation still best explains early brain activation. This pattern suggests a dynamic adaption of represented visual-orthographic information, where initial graded prediction errors convert into binary representations, allowing accurate retrieval of word meaning. These results offer a neuro-cognitive plausible account of efficient word recognition, emphasizing visual-orthographic information in the form of prediction error representations central to the transition from perceptual processing to the access of word meaning.
Synopsis of Barra Jordan, 1904 (Coleoptera: Anthribidae) with description of a new species from Brazil with an updated key to the genus
Authors: VILHENA POLIANA DE MESQUITA , LOPES MARCELA PAES DE AZEVEDO MACHADO , MERMUDES JOSÉ RICARDO MIRAS
Published: January 2025

Barra tocantinensis Vilhena, Lopes & Mermudes sp. nov. (Anthribinae: Piesocorynini) is described from Serra do Lajeado Ecological Reserve (Fazenda Céu), a threatened biome in central-western Brazil. A key to the all known species of Barra is presented. New data on the distribution of the genus are provided.
The Art of Becoming Infinite
Authors: Stanchina Gabriella
Published: January 2025

Mou Zongsan is arguably the most important Chinese philosopher of the twentieth century. This work delves into the philosopher's exploration of self and subjectivity, setting Mou Zongsan’s theories against Western paradigms. Mou contrasts Western ‘horizontal’ model, based on the separation of subject and object, and aimed at cognitive enhancement, with the ‘vertical’ view dominant in the Confucian and Daoist tradition. The vertical model has, at its core, a practical-performative interpretation of the subject, based on the moral self-cultivation. This spiritual cultivation enables the finite human being to ‘become infinite,’ embodying the original unlimited moral mind that constitutes the Self and the universe.

In addressing fundamental questions of self-consciousness and self-identity, the book contextualizes Mou's philosophy within contemporary discussions in neuroscience and cognitive science. By placing Mou's ideas in dialogue with Western thought—examining thinkers like Husserl, Kant, Hegel, and Lévinas—as well as with Daoist and Confucian vision of mind, this work opens a pathway to understanding selfhood beyond purely epistemological boundaries.

This book will be of interest to readers and scholars interested in the contemporary debate about mind and the Self, as well as those intrigued by the new horizons opened by a cross-cultural Western-Chinese approach to subjectivity.
Pixels and Predictions: Potential of GPT-4V in Meteorological Imagery Analysis and Forecast Communication
Authors: Lawson John R. , Trujillo-Falcón Joseph E. , Schultz David M. , Flora Montgomery L. , Goebbert Kevin H. , Lyman Seth N. , Potvin Corey K. , Stepanek Adam J.
Published: January 2025

Generative artificial intelligence (AI), such as OpenAI’s GPT-4V large-language model, has rapidly entered mainstream discourse. Novel capabilities in image processing and natural-language communication may augment existing forecasting methods. Large language models further display the potential to better communicate weather hazards in a style honed for diverse communities and different languages. This study evaluates GPT-4V’s ability to interpret meteorological charts and communicate weather hazards appropriately to the user, despite challenges of hallucinations, where generative AI delivers coherent, confident, but incorrect responses. We assess GPT-4V’s competence in two tasks: 1) generating a severe-weather outlook from weather-chart analysis and conducting self-evaluation, revealing an outlook that corresponds well with a Storm Prediction Center human-issued forecast, and 2) producing hazard summaries in Spanish and English from weather charts. Responses in Spanish, however, resemble direct (not idiomatic) translations from English to Spanish, yielding poorly translated summaries that lose critical idiomatic precision required for optimal communication. Our findings advocate for cautious integration of tools like GPT-4V in meteorology, underscoring the necessity of human oversight and development of trustworthy, explainable AI.

Significance Statement

The integration of generative AI such as GPT-4V into meteorology brings opportunity for improving forecast communication of weather hazards across languages and communities. This study evaluates GPT-4V’s capacity to create plausible severe-weather outlooks and communicate hazards in both Spanish and English, from inputs of weather charts and texts. The weather outlook generally aligns with a human-generated forecast product but displays vagueness and incorrect reasoning. Further, translations lack idiomatic precision and display poor grasp of cultural nuance. Despite this, GPT-4V shows the potential for advancement in meteorological application. We advocate for cautious AI integration, emphasizing the need for human oversight and reliable, trustworthy output.