bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-sensitive fluorescence-activated droplet single-cell sorting based on Tetramer-HCR-EvaGreen amplification
Authors: Chen Long , Xu Yi , Zhou Lele , Ma Ding , Zhang Rong , Liu Yifan , Mi Xianqiang 
Published: January 2025

Abstract
The current single-cell analysis technologies such as fluorescence-activated cell sorting (FACS) and fluorescence-activated droplet sorting (FADS) could decipher the cellular heterogeneity but were constrained by low sorting performance and cell viability. Here, an ultra-sensitive single-cell sorting platform has been developed by integrating the FADS technology with Tetramer-HCR-EvaGreen (THE) fluorescence signal amplification. The THE system produced much higher fluorescence signal than that of the single Tetramer or Tetramer-HCR signal amplification. Upon application to target MCF-7 cells, the platform exhibited high efficacy and selectivity while maintaining more than 95% cell viability. The THE-FADS achieved sorting efficiencies of 55.5% and 50.3% with purities of 91% and 85% for MCF-7 cells in PBS solutions and simulated serum samples, respectively. The sorted MCF-7 cells showed similar proliferation together with CK19 and EGFR mRNA expression compared with the control cells. The established THE-FADS showed the promising prospects to cellular heterogeneity understanding and personalized medicine.
GILT stabilizes cofilin to promote the metastasis of prostate cancer
Authors: Han Dunsheng , Wu Zhiming , Zhang Cong , Wei Ziwei , Chao Fan , Xie Xuefeng , Liu Jinke , Song Yufeng , Song Xiaoming , Shao Dingchang , Wang Shiyu , Xu Guoxiong , Chen Gang 
Published: January 2025

Abstract
Gamma-interferon-induced lysosomal thiol reductase (GILT), known for catalyzing disulfide bond reduction, is involved in various physiological processes. While the involvement of GILT in the development of various tumors has been demonstrated, the mechanisms underlying its regulation in prostate cancer (PCa) are not fully understood. In the present study, we confirmed that GILT was significantly upregulated in PCa and facilitated tumor metastasis. Mechanistically, GILT stabilized the cofilin protein by competitively binding to cofilin with Src family tyrosine kinase (SRC), inhibiting SRC-mediated tyrosine phosphorylation of cofilin, thereby suppressing the ubiquitination pathway degradation of cofilin. GILT overexpression stabilized and increased the protein level of cofilin in PCa cells and promoted the metastasis of PCa cells by accelerating actin dynamics through cofilin-mediated actin severing. Our findings reveal a novel mechanism of GILT in PCa and provide a new potential target for the diagnosis and treatment of PCa patients.
Polar mesospheric ozone loss initiates downward coupling of solar signal in the Northern Hemisphere
Authors: Seppälä Annika , Kalakoski Niilo , Verronen Pekka T. , Marsh Daniel R. , Karpechko Alexey Yu. , Szelag Monika E. 
Published: January 2025

Abstract
Solar driven energetic particle precipitation (EPP) is an important factor in polar atmospheric ozone balance and has been linked to ground-level regional climate variability. However, the linking mechanism has remained ambiguous. The observed and simulated ground-level changes start well before the processes from the main candidate, the so-called EPP-indirect effect, would start. Here we show that initial reduction of polar mesospheric ozone and the resulting change in atmospheric heating rapidly couples to dynamics, transferring the signal downwards, shifting the tropospheric jet polewards. This pathway is not constrained to the polar vortex. Rather, a subtropical route initiated by a changing wind shear plays a key role. Our results show that the signal propagates downwards in timescales consistent with observed tropospheric level climatic changes linked to EPP. This pathway, from mesospheric ozone to regional climate, is independent of the EPP-indirect effect, and solves the long-standing mechanism problem for EPP effects on climate.
Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei
Authors: Krasiļņikova Marija , Marques Catarina A. , Briggs Emma M. , Lapsley Craig , Hamilton Graham , Beraldi Dario , Crouch Kathryn , McCulloch Richard 
Published: January 2025

Abstract
The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub-megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise to many telomeres. DNA replication dynamics have only been described in the megabase chromosome cores, and in the single active VSG transcription site. Using a Nanopore genome assembly, we show that megabase chromosome subtelomeres display a paucity of replication initiation events relative to the core, correlating with increased instability. In addition, replication of the active VSG transcription site is shown to originate from the telomere, likely causing targeted VSG recombination. Lastly, we provide evidence that the 177 bp repeats act as conserved DNA replication origins, explaining submegabase chromosome stability. Compartmentalized DNA replication therefore explains how T. brucei balances stable genome transmission with localised instability driving immune evasion.
A CD26+ tendon stem progenitor cell population contributes to tendon repair and heterotopic ossification
Authors: Chen Siwen , Lin Yingxin , Yang Hao , Li Zihao , Li Sifang , Chen Dongying , Hao Wenjun , Zhang Shuai , Chao Hua , Zhang Jingyu , Wang Jianru , Li Zemin , Li Xiang , Zhan Zhongping , Liu Hui 
Published: January 2025

Abstract
Inadequate tendon healing and heterotopic bone formation result in substantial pain and disability, yet the specific cells responsible for tendon healing remain uncertain. Here we identify a CD26+ tendon stem/progenitor cells residing in peritendon, which constitutes a primitive stem cell population with self-renewal and multipotent differentiation potentials. CD26+ tendon stem/progenitor cells migrate into the tendon midsubstance and differentiation into tenocytes during tendon healing, while ablation of these cells led to insufficient tendon healing. Additionally, CD26+ tendon stem/progenitor cells contribute to heterotopic ossification and Tenascin-C-Hippo signaling is involved in this process. Targeting Tenascin-C significantly suppresses chondrogenesis of CD26+ tendon stem/progenitor cells and subsequent heterotopic ossification. Our findings provide insights into the identification of tendon stem/progenitor cells and illustrate the essential role of CD26+ tendon stem/progenitor cells in tendon healing and heterotopic bone formation.
A human oral commensal-mediated protection against Sjögren’s syndrome with maintenance of T cell immune homeostasis and improved oral microbiota
Authors: Tseng Yu-Chao , Liao Kai-Sheng , Lin Wei-ting , Li Chin , Chang Chia-Bin , Hsu Jie-Wei , Chan Chin-Pui , Chen Chun-Ming , Wang Hon-Pin , Chien Hsiu-Chuan , Wang Jann-Tay , Hsieh Song-Chou , Wu Shu-Fen 
Published: January 2025

Abstract
Sjögren’s syndrome (SS) is a prevalent systemic autoimmune disease with substantial impacts on women’s health worldwide. Although oral Haemophilus parainfluenzae is reduced in SS, its significance remains unclear. This study aimed to elucidate the pathophysiological role of H. parainfluenzae in SS. Reduced salivary H. parainfluenzae levels in SS patients were confirmed through quantitative PCR. Oral H. parainfluenzae inoculation in NOD mice alleviated focal sialadenitis, improved salivary function, and reduced IFN-γ+CD3+ and IFN-γ+CD8+ T cells in salivary gland-draining lymph nodes, maintaining immune homeostasis against a biased type 1 response. Inoculation also enhanced salivary microbiota diversity, balanced the Firmicutes-to-Proteobacteria ratio, and reduced the overwhelming presence of Pseudomonas mendocina. In vitro, H. parainfluenzae-preconditioned A253 cells limited CD8 T cell expansion with reduced IFN-γ production. These findings suggest that H. parainfluenzae improves oral microbial diversity, promotes homeostatic T-cell immunity, and protects against SS, supporting its potential as a next-generation probiotic.
RED light promotes flavonoid and phenolic accumulation in Cichorium spp. callus culture as anti-candida agent
Authors: Abdelhamid Sayeda Abdelrazek , Marzouk Alaa I. , Asker Mohsen S. , El Shabrawi Hattem M. 
Published: January 2025

Abstract
Chicory species, particularly Cichorium endive Supp. Pumillum, also, known as Egyptian chicory, are globally recognized for their rich content of bioactive secondary metabolites such as flavonoids and phenolics. These metabolites are highly valued for their pharmaceutical, dietary, and commercial applications. Light exposure, particularly through red and blue wavelengths, is a potent natural elicitor that influences the biosynthesis of secondary metabolites and impacts plant morphology. This study investigates the effects of red and blue LED light exposure on the callus culture of Egyptian chicory (Cichorium endive Supp. Pumillum), with the aim of enhancing flavonoid accumulation for potential use as an anti-Candida agent. Callus cultures of Cichorium intybus, Cichorium endive Supp. Pumillum, and Taraxacum officinale (Italian chicory) were grown on MS media supplemented with 4 mg/L 2iP and 0.5 mg/L NAA for 4 weeks. The cultures were then exposed to 12 days of red and blue LED light. After extraction using liquid nitrogen and methanol, the resulting callus extracts were tested against Candida albicans NRRL477 at various concentrations (1/8, 1/4, and 1/2 MIC) for 20 to 120 min. The antifungal activity was assessed by determining the effects on acid-soluble phosphorus, total lipids, and soluble proteins in the Candida cells. Our results demonstrate that the red LED light-exposed Cichorium endive Supp. Pumillum callus extract exhibited the most potent antifungal activity, significantly inhibiting the growth of Candida species compared to blue light and control treatments. Notably, the red light-treated callus culture accumulated higher concentrations of flavonoids and phenolic compounds, which contributed to its effectiveness as an anti-Candida agent. These findings suggest that LED red light elicitation is an effective method for enhancing the production of bioactive compounds in Egyptian chicory, offering potential for its use in natural antifungal therapies. Future research will explore the mechanistic pathways of flavonoid accumulation under different light conditions and investigate the broader applications of this elicitation technique for other medicinal plants.
Treatment of patients with tumor/treatment-related hypothalamic obesity in the first two years following surgical treatment or radiotherapy
Authors: Müller Hermann L. , Witte Julian , Surmann Bastian , Batram Manuel , Braegelmann Kylie , Flume Mathias , Beckhaus Julia , Touchot Nicolas , Friedrich Carsten 
Published: January 2025

Abstract
Survivors of sellar/suprasellar tumors involving hypothalamic structures face a risk of impaired quality of life, including tumor- and/or treatment-related hypothalamic obesity (TTR-HO) defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment related damage of the hypothalamus. We analyze German claims data to better understand treatment pathways for patients living TTR-HO during the two years following the index surgical treatment. A database algorithm identified patients with TTR-HO in a representative German payer claims database between 2010 and 2021 (n = 5.42 million patients). Claims from 37 patients with TTR-HO were analyzed on a quarterly basis over 2 years. The analysis considered inpatient, outpatient, and prescription data. In the follow-up period, patients with TTR-HO are hospitalized 3.68 times on average; 37% of hospitalizations in year 1 and 31% in year 2 are due to TTR-HO. On average, patients see a general practitioner 12.27 times and various specialists 20.45 times. The need for complex neuroendocrine therapy develops quickly, with most patients having 2–3 neuroendocrine prescriptions in any given quarter. The management of patients with TTR-HO requires frequent inpatient and outpatient visits for tumor follow-up and management of incident comorbidities, and most patients with TTR-HO require intense polytherapy.
Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
Authors: Biswas Kazal Boron , Kawai Yuka , Nakagawa Satoshi , Kanai Kyoko , Kojima Hiroyuki , Masutani Teruaki , Oyama Masayoshi , Iddamalgoda Arunasiri , Sakamoto Kotaro 
Published: January 2025

Abstract
Hyaluronic acid (HA) is an important component of the skin’s extracellular matrix, and its degradation leads to wrinkles. Hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID) is the main factor responsible for HA degradation in dermis. This study aimed to identify natural plant materials that can effectively suppress HYBID expression and protect HA from degradation. Screening of various plant extracts was performed for the inhibition of histamine-induced mRNA expression of HYBID in normal human dermal fibroblasts (NHDF). The molecular size distribution of HA was evaluated by incubating fluorescein isothiocyanate (FITC)-labeled large HA (1200–1600 kDa) in NHDF for certain time followed by measuring different sizes of FITC-labeled HA in the cultured medium by HPLC. Among 380 plant extracts, we found that Artemisia capillaris flower extract (ACFE) was the most effective agent in both suppressing HYBID expression as well as protecting large HA from degradation. Subsequent mechanism elucidation studies showed that ACFE epigenetically regulates the expression of HYBID by modulating the expression of a specific miRNA, miR-486-5p, which is known to directly target and inhibit HYBID expression. Our active compound search identified 1-caffeoyl-3-hydroxybutane and 3-caffeoyl-1-hydroxybutane in ACFE as new compounds, which we named Kawarayomogin I and Kawarayomogin II, respectively. This is the first report to show that Artemisia capillaris with two novel active compounds inhibits HYBID expression as well as hyaluronic acid degradation, and therefore, could be used as possible agent for cosmeceutical potential.
Direct observation of small molecule activator binding to single PR65 protein
Authors: Yang-Schulz Annie , Zacharopoulou Maria , Yilmaz Sema Zeynep , Banerjee Anupam , Saha Satyaki , Nietlispach Daniel , Ohlmeyer Michael , Gur Mert , Itzhaki Laura S. , Bahar Ivet , Gordon Reuven 
Published: January 2025

Abstract
The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.6 ± 2.5 μM, consistent with ensemble fluorescence anisotropy results but challenging to achieve with other methods due to low affinity. Single-molecule NOT measurements reveal that binding increases optical scattering, indicating PR65 elongation. This interpretation is supported by all-atom molecular dynamics simulations showing PR65 adopts more extended conformations upon binding. This work highlights NOT’s utility in quantifying binding kinetics and structural impact, offering insights valuable for drug discovery.
Pre-chewing of infant food – expectations towards an old, traditional
feeding habit for potential allergy prevention
Authors: Meixner Lara , Kalb Birgit , Schnadt Sabine , Sturmfels Meral , Blumchen Katharina , Beyer Kirsten , Ahrens Birgit 
Published: January 2025

AbstractPremastication is a traditional feeding method whereby
solids are pre-chewed by the mother or sometimes by other relatives and then
given to the infant along with the oral microbiota. The aim of this study
was to assess if premastication is known or performed among the German
population as well as to evaluate the expectations regarding this feeding
method, particularly in the context of allergy prevention. Two surveys about premastication were conducted. For the
survey of the “general population (GP)” 10,000 participants (18 to 65 years
old) were randomly selected from the official population register of Berlin.
The survey of the “selected population (SP)” was conducted by the patient
organization German Allergy and Asthma Association (DAAB). 526 people from the GP and 220 participants from the SP
completed the questionnaire. 15.3% (n=114) of all respondents had previously
heard of premastication, 1.5% (n=7/455) of the people with children reported
that they have performed premastication for their child. 42.8% (n=225) of
the GP as well as 36.4% (n=80) of the SP could imagine performing
premastication for their future child or grandchild. 59.3% (n=312) of the GP
stated that they at least partially think premastication may help to prevent
the development of allergies.Premastication appears to be barely known and practiced
among the German population. However, a considerable proportion of
participants would consider giving pre-chewed food to their infant. A high
rate of respondents, especially among the GP, believed that premastication
may have a positive impact on the prevention of allergies.
Ein praxisnahes PJ-Logbuch in digitaler Form: Erfahrungen aus einem Pilotprojekt
Authors: Meyer Frank , Wippermann Jens , Wacker Max , Awad George , Scherner Maximilian , Fakundiny Bastian , Walles Thorsten , Choritz Lars , Hansen Michael , Cukaz Hatice , Herrmann Tim , Helm André 
Published: January 2025

ZusammenfassungDigitale Lehrinhalte sind nicht zuletzt vor dem Hintergrund der für 2025 geplanten Reform der humanmedizinischen Approbationsordnung gefordert und im Trend. Im Rahmen eines Pilotprojektes haben wir ein Logbuch für Studierende im „Praktischen Jahr“ (PJ) digitalisiert und evaluiert.Ziel der vorliegenden Arbeit ist es, das digitale und nicht digitale PJ-Logbuch zu evaluieren.Basierend auf einem gedruckten PJ-Logbuch wurde ein digitales PJ-Logbuch als Web-App entwickelt. Die Umsetzung erfolgte mit dem kommerziellen Enterprise-Wissensmanagementsystem Confluence (Atlassian Corporation, Sydney, Australien), das responsives Design, Anbindung an das Nutzerverzeichnis der Universität und Integration des Corporate Designs ermöglicht. Die Zufriedenheit der Studierenden (n = 34) wurde mit Fragebogen und einer 5-stufigen Likert-Skala bewertet. Zudem bewerteten die Studierenden vor (n = 49) und nach (n = 34) Einführung des digitalen Logbuches ihre Fähigkeiten zu Beginn und Ende des Tertials mit Schulnoten.Die Mehrzahl der Studierenden schätzte das digitale Logbuch als intuitiv bedienbar und sinnvolle Ergänzung ein. Im stationären Bereich zeigte sich nach Einführung des digitalen Logbuches eine signifikante Verbesserung der selbst eingeschätzten Fähigkeiten um 0,73 Schulnoten zu Beginn (p < 0,001) und um 0,78 Schulnoten zum Ende des Tertials (p < 0,001). Im OP-Bereich zeigte sich lediglich zu Beginn des Tertials eine signifikante Verbesserung um 0,47 Schulnoten (p = 0,027).Die Evaluation zeigt, dass das digitale PJ-Logbuch bei Studierenden „gut ankommt“, angenommen und akzeptiert wird. Die beobachtete Zunahme der Handlungssicherheit könnte auf die Einführung des digitalen Logbuches und dessen Inhalte zurückzuführen sein, auch wenn andere Faktoren, wie z. B. das Engagement der Lehrenden, nicht ausgeschlossen werden können. Zukünftige Modifikationen sind geplant, um das Logbuch sukzessive zu optimieren und Alltagsanforderungen gemäß noch attraktiver zu machen.
Complete Hearing Recovery after Retrosigmoid Resection of Jugular Foramen Schwannoma with Concurrent Ipsilateral Vestibular Schwannoma
Authors: Kanaris Achilles A. , Hac Nicholas E.F. , Magill Stephen T. , Zhan Kevin Y. 
Published: January 2025

Abstract
Introduction Cerebellopontine angle (CPA) tumors frequently present with hearing loss, which influences whether a hearing-preservation versus hearing ablative surgical approach is chosen. We discuss a case of complete hearing recovery after resection of a jugular foramen schwannoma (JFS) in a patient who also had a small intracanalicular vestibular schwannoma (VS).
Case A 46-year-old woman presented with left ear fullness, tinnitus, and imbalance for 9 months. She had no lower cranial nerve dysfunction. Audiometry demonstrated Class D hearing with 4% word recognition on the left. Vestibular testing showed absent caloric response on the left and subtle central findings. Magnetic resonance imaging demonstrated a left 3.3-cm JFS and separate left 1-cm intracanalicular VS. A retrosigmoid approach was performed for a radical subtotal resection of the JFS, relieving the mass effect on the vestibulocochlear nerve. The small intracanalicular VS was not manipulated. Pathology confirmed schwannoma with neurofibromatosis type 2 (NF2) mutation in the tumor but normal NF2 germline. Postoperative audiometry at 6 weeks showed normal audiometric thresholds with 100% discrimination. Subtle left caloric response was noted on postoperative vestibular testing and central oculomotor findings improved.
Discussion The presented case describes the management of concurrent ipsilateral VS and JFS in the absence of NF2 and demonstrates a unique complete and rapid recovery of hearing following JFS resection without manipulation of concurrent VS. This case supports the use of a hearing-preservation approach in similar cases and corroborates previous reports of hearing recovery following resection of non-VS CPA tumors with hearing-preservation approaches.
Exploiting the Impact of Sociodemographics in the Diagnosis of Central Nervous System Tumors in Childhood
Authors: Leroy Marcela Yasmin , Lopes Luiz Fernando , Faria Raniela Ferreira , Faria Thaissa Maria Veiga , Prado Denise Leonardi Queiroz , Hirai Welinton Yoshio , Mançano Bruna Minniti 
Published: January 2025

Abstract
Introduction Central nervous system (CNS) tumors are the most common solid tumors in childhood, comprising 20% of all neoplasms in that age. Besides, they constitute the biggest cause of morbidity and mortality among childhood tumors, and about two thirds of the surviving patients have sequelae. The build-up of sequelae due to neoplastic growth is directly related with the time until diagnosis. Therefore, late diagnosis has a negative influence on the prognosis.
Objective To analyze the journey of the pediatric patients with CNS tumors and their families to the reference center.
Materials and Methods The present is a retrospective, prospective cohort study based on chart analyses and questionnaire application.
Results The mean age of the patients was 8.39 years, most were male (58%), white (56%), and originated from the Southeast of Brazil (56%). A total of 83% of the patients were accompanied by their mothers, and the family income obtained was below 3 minimum wages (20%). The average time until perception of the first signs or symptoms was 48 days, the mean time from symptom perception until the first medical appointment was 30 days, and the mean time between the first medical appointment and referral to Hospital de Amor Infantojuvenil de Barretos was 315 days. The most frequently present signs and symptoms were neurological manifestations (72%), such as headaches (14.8%) and projectile vomiting (6.5%). There was an association between the medical service (public or private service) where the first medical appointment took place and the first medical specialty consulted, although it did not relate to a shorter time until diagnosis.
Conclusion The difficulties in the journey of CNS tumor pediatric patients occurred mainly due to health system flaws and medical professionals' hardships. Thus, it is essential to reinforce the importance of continued medical education and to encourage new studies that may reveal precisely where these system flaws are taking place.