bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trefoil factor 1 suppresses stemness and enhances chemosensitivity of pancreatic cancer
Authors: Yamaguchi Junpei , Kokuryo Toshio , Yokoyama Yukihiro , Oishi Shunsuke , Sunagawa Masaki , Mizuno Takashi , Onoe Shunsuke , Watanabe Nobuyuki , Ogura Atsushi , Ebata Tomoki 
Published: June 2024

AbstractBackground and AimsPancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial‐mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor‐suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer.MethodsTo investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1‐Cre/LSL‐KRASG12D/LSL‐p53R172H/TFF1−/−) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model.ResultsThe deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine‐induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells in vitro. In vivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness.ConclusionThese results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.
An unusual clinical presentation of a plunging ranula—The plunging ranula with extension to the vallecula
Authors: Schmitz Lisa , Büscheck Franziska , Betz Christian Stefan , Böttcher Arne 
Published: June 2024

Key Clinical MessageA plunging ranula may present initially as an extensive vallecular cyst and correct diagnosis may be reached with the use of ultrasound, fluid aspiration for amylase detection, and MRI imaging.AbstractThe ranula is a pseudocyst of the sublingual salivary gland and can be divided into two known subtypes. The simple ranula and plunging ranula. While the simple type can be found in the floor of the mouth, the plunging ranula usually pervades the mylohoid muscle and presents as a cervical swelling. The presented case should outline the difficulties in diagnostic and treatment of an uncommon expression of a mucocele above the mylohoid muscle without presenting either a cervical or an intraoral swelling, only extending towards the vallecula. We present a previously unreported clinical manifestation of a ranula of an 18‐year old male, which extends posteriorly, remaining confined in the supramylohyoid muscle space. The cystic lesion protrudes in the oropharynx, and clinically appears as an extensive vallecular cyst. On magnetic resonance imaging the initial suspected diagnosis of a vallecular cyst was changed to the final diagnosis of a plunging ranula. The marsupialization of the cyst sac was performed. Outpatient follow‐up revealed a persisting ostium, indicating a continuous extravasation of the sublingual gland. The present case report describes an unusual clinical presentation of a plunging ranula, remaining above the mylohyoid muscle and protruding into the oropharynx, misdirecting to the first suspected diagnosis of a vallecular cyst. The case highlights the useful contribution of the MRI imaging for differential diagnoses and the need for criteria to indicate further investigations.
Successful management of a multiple endocrine neoplasia type 1‐associated thymic neuroendocrine neoplasms with acute chest pain as initial symptom: A rare case report
Authors: Li Xuesong , Gu Liangbiao , Zhao Wenhui , Yu Zhuo , Xiao Jianzhong , Cao Chenxiang 
Published: June 2024

Key Clinical MessageAcute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)‐associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1‐associated NEN.AbstractMultiple endocrine neoplasia type 1(MEN1)‐associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor MEN1 gene. Patients with MEN1‐associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45‐year‐old man who developed MEN1‐associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of MEN1 gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67‐positive cells (2%) in MEN1‐associated NEN. Further evaluation unveiled MEN1‐associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc‐HYNIC‐TOC scintigraphy showed that focally increased radioactivity in the mid‐upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6‐month follow‐up. Thus, acute chest pain can be the first manifestation of MEN1‐associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1‐associated NEN.
Coexistence of myasthenia gravis and lichen planus: A case report and systematic review of related case reports from 1971 to 2024
Authors: Jameie Melika , Amanollahi Mobina , Ahli Bahareh , Farahmand Ghasem , Magrouni Hana , Sarraf Payam 
Published: June 2024

Key Clinical MessageThe co‐occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases.AbstractMyasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co‐occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co‐occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67‐year‐old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti‐AchR‐Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late‐onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x‐ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co‐occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases.
Total Synthesis of (15R)‐ and (15S)‐Prostaglandin A2
Authors: Lackner Justus , Alberti Christoph , Bock Theresa , Neßmerak Katharina , Urban Ernst , Khom Sophia , Schützenmeister Nina 
Published: June 2024

AbstractFrom both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABAA receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators.
Flavonoid‐Quinoxaline Hybrid Compounds as Cathepsin Inhibitors Against Fascioliasis
Authors: Ferraro Florencia , Merlino Alicia , Gil Jorge , Pérez‐Silanes Silvia , Corvo Ileana , Cabrera Mauricio 
Published: June 2024

AbstractFasciola hepatica is a parasitic trematode that infects livestock animals and humans, causing significant health and economic burdens worldwide. The extensive use of anthelmintic drugs has led to the emergence of resistant parasite strains, posing a threat to treatment success. The complex life cycle of the liver fluke, coupled with limited funding and research interest, have hindered progress in drug discovery. Our group has been working in drug development against this parasite using cathepsin proteases as molecular targets, finding promising compound candidates with in vitro and in vivo efficacy. Here, we evaluated hybrid molecules that combine two chemotypes, chalcones and quinoxaline 1,4‐di‐ N‐oxides, previously found to inhibit F. hepatica cathepsin Ls and tested their in vitro activity with the isolated targets and the parasites in culture. These molecules proved to be good cathepsin inhibitors and to kill the juvenile parasites at micromolar concentrations. Also, we performed molecular docking studies to analyze the compounds‐cathepsins interface, finding that the best inhibitors interact at the active site cleft and contact the catalytic dyad and residues belonging to the substrate binding pockets. We conclude that the hybrid compounds constitute promising scaffolds for the further development of new fasciolicidal compounds.
Relay strip intercropping of wheat and cotton under limited water conditions
Authors: Çakaloğulları Uğur , Tatar Özgür 
Published: June 2024

AbstractWheat (Triticum aestivum L.)–cotton (Gossypium hirsutum L.) relay strip intercropping involves cultivating wheat sown in autumn and cotton sown in spring, allowing the two crops to grow together for ∼2 months. Despite its prevalence in cotton‐growing regions globally, this agricultural practice remains untapped in Turkey, where the emphasis on resource use efficiency and the competition between staple and cash crops are paramount. To address this, we conducted a study comparing three cropping systems under both well‐watered and limited water conditions: sole wheat with a row spacing of 13.5 cm, sole cotton with a row spacing of 70 cm, and an intercropping system consisting of four rows of wheat and two rows of cotton, with row spacings of 13.5 cm and 40.5 cm, respectively. In intercropped wheat and cotton, the relative wheat yield was 0.68, while the relative cotton yield was 0.73, resulting in a combined relative yield of 1.41 when compared to monoculture. The land equivalent ratio (1.44) and area time equivalent ratio (1.08) consistently exceeded 1.0, particularly under limited watering conditions and concurrent heat stress observed in the second year of the experiment. Our findings indicate that wheat–cotton relay intercropping holds significant potential as a highly effective approach to enhance the production of both cotton and wheat in Turkey, particularly in stressful conditions such as limited water availability.
Pharmaceutical company payments to Japanese breast cancer practice guideline authors
Authors: Murayama Anju , Higuchi Kenichi , Byreddy Keerthana R. , Hinari Kugo , Senoo Yuki 
Published: June 2024

AbstractBackgroundThe creation of breast cancer practice guidelines requires proper management of financial relationships with drug companies, as they can introduce conflicts of interest (COIs) among guideline authors. However, little is known about the specific landscape and fraction of financial interactions between the authors of the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, edition 2022 (JBCS2022) and drug companies.MethodsUsing payment data publicly disclosed by major drug companies in Japan, this study analysed the personal payments made to the authors of JBCS2022 between 2016 and 2020. We performed descriptive analyses on the payment data.ResultsOf the 149 JBCS2022 authors, 115 (77.2%) received at least one personal payment totaling $3 828 455 from drug companies between 2016 and 2020. The average and median payment amounts per author were $25 772 (standard deviation: $58 197) and $2761 (interquartile range: $322‒$15 828), respectively. The total annual payments per JBCS2022 authors between 2016 and 2019 increased from $588 054 in 2016 to $967 802 in 2019. The JBCS2022 chairperson and vice‐chairperson received $246 936 (fourth highest) and $216 744 (fifth highest) over the 5 years. More than 60% of personal payments to the JBCS2022 authors were not declared by the authors as they were below the declaration threshold set by the Japanese Breast Cancer Society. However, nine authors undeclared personal payments summing $594 615 even though these payments were higher than the thresholds.ConclusionThis study demonstrated that the majority of the breast cancer guideline authors received personal payments from drug companies in Japan. Furthermore, the majority of payments were not declared because of the less transparent COI policy.
Serum AZD7442 (tixagevimab–cilgavimab) concentrations and in vitroIC50 values predict SARS‐CoV‐2 neutralising antibody titres
Authors: Clegg Lindsay E , Stepanov Oleg , Matthews Sam , White Tom , Seegobin Seth , Thomas Steven , Tuffy Kevin M , Någård Mats , Esser Mark T , Streicher Katie , Cohen Taylor S , Aksyuk Anastasia A 
Published: June 2024

AbstractObjectivesThe evolution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus‐neutralising antibody (nAb) titres in serum. However, authentic virus‐based assays pose inherent practical challenges for measuring nAb titres against emerging SARS‐CoV‐2 variants (e.g. storing infectious viruses and testing at biosafety level‐3 facilities). Here, we demonstrate the utility of pseudovirus neutralisation assay data in conjunction with serum mAb concentrations to robustly predict nAb titres in serum.MethodsSARS‐CoV‐2 nAb titres were determined via authentic‐ and lentiviral pseudovirus‐based neutralisation assays using serological data from three AZD7442 (tixagevimab–cilgavimab) studies: PROVENT (NCT04625725), TACKLE (NCT04723394) and a phase 1 dose‐ranging study (NCT04507256). AZD7442 serum concentrations were assessed using immunocapture. Serum‐based half‐maximal inhibitory concentration (IC50) values were derived from pseudovirus nAb titres and serum mAb concentrations, and compared with in vitro IC50 measurements.ResultsnAb titres measured via authentic‐ and lentiviral pseudovirus‐based neutralisation assays were strongly correlated for the ancestral SARS‐CoV‐2 virus and SARS‐CoV‐2 Alpha. Serum AZD7442 concentrations and pseudovirus nAb titres were strongly correlated for multiple SARS‐CoV‐2 variants with all Spearman correlation coefficients ≥ 0.78. Serum‐based IC50 values were similar to in vitro IC50 values for AZD7442, for ancestral SARS‐CoV‐2 and Alpha, Delta, Omicron BA.2 and Omicron BA.4/5 variants.ConclusionsThese data highlight that serum mAb concentrations and pseudovirus in vitro IC50 values can be used to rapidly predict nAb titres in serum for emerging and historical SARS‐CoV‐2 variants.
Associations between multiple neurological biomarkers and distal sensorimotor polyneuropathy: KORA F4/FF4 study
Authors: Herder Christian , Thorand Barbara , Strom Alexander , Rathmann Wolfgang , Heier Margit , Koenig Wolfgang , Morrison Helen , Ziegler Dan , Roden Michael , Peters Annette , Bönhof Gidon J. , Maalmi Haifa 
Published: June 2024

AbstractAimsThe aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).Materials and MethodsCross‐sectional analyses were based on 1032 participants aged 61–82 years from the population‐based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1‐SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini–Hochberg procedure.ResultsHigher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB‐H = 0.044) and PDGFRα (platelet‐derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB‐H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM‐B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB‐H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB‐H>0.05).ConclusionsThis study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.
Potentiation of the axis involving pentose phosphate pathway/NADPH oxidase/reactive oxygen species drives higher IL‐10 production in monocytes of Sub‐Saharan Africans
Authors: Ongwe Madeleine Eunice Betouke , Mouwenda Yoanne D. , Manurung Mikhael D. , Heieis Graham , Azimi Shohreh , Adegnika Ayola A. , Kremsner Peter G. , Kuijpers Taco W. , Yazdanbakhsh Maria , Everts Bart 
Published: June 2024

AbstractCellular metabolism is a key determinant of immune cell function. Here we found that CD14+ monocytes from Sub‐Saharan Africans produce higher levels of IL‐10 following TLR‐4 stimulation and are bioenergetically distinct from monocytes from Europeans. Through metabolomic profiling, we identified the higher IL‐10 production to be driven by increased baseline production of NADPH oxidase‐dependent reactive oxygen species, supported by enhanced pentose phosphate pathway activity. Together, these data indicate that NADPH oxidase‐derived ROS is a metabolic checkpoint in monocytes that governs their inflammatory profile and uncovers a metabolic basis for immunological differences across geographically distinct populations.
Muti‐Responsive Flexible Ln‐MOFs Paper Based on Cellulose Fibers for Sensing Humidity, pH and Phenylenediamine
Authors: Liu Kunyang , Jia Hongfei , Fang Ran , Yang Lizi 
Published: June 2024

AbstractThe natural polymer cellulose exhibits significant potential for various applications due to its unique optical, electronic, and chemical properties. However, the use of cellulose materials in luminescent applications has been relatively limited. This study aims to develop a simple and efficient method to enhance the fluorescence of cellulose materials by incorporating rare earth elements, thereby expanding their range of applications. In this work, we synthesized hybrid cellulose materials by grafting Eu‐bpy (H2bpydc=2,2‐bipyridine‐5,5‐dicarboxylic acid) onto the surface of cellulose fibers through a straightforward post‐processing procedure, resulting in materials with excellent fluorescence properties. By leveraging the abundant hydroxyl groups on the surface of cellulose fibers, Eu‐bpy@CF exhibits high luminescence in response to relative humidity and pH changes, with a noticeable color shift from light red to red visible to the naked eye. Consequently, these materials were further applied in the construction of smart fluorescent switches for the highly accurate and selective detection of phenylenediamine. Our research provides a simple approach to creating environmentally responsive handheld fluorescent papers and expands the diversity of rare‐earth cellulose fibers for developing new fluorescent materials with smart functions.
Ligand Assisted Cleavage of H2 Across a Ru−N Bond within a Four‐membered Metallacycle and the Catalytic Hydrogenation of CO2 to Formate
Authors: Bag Ranjit , Tizzard Graham J. , Coles Simon J. , Owen Gareth R. 
Published: June 2024

AbstractThe catalytic hydrogenation of CO2 to formate was achieved using the previously reported dichloro(η6‐p‐cymene){diphenyl(3‐methyl‐2‐indolyl)phosphine}ruthenium (1) as a catalyst under mild conditions. In this complex, the phosphorus‐based ligand adopts a κ1‐P coordination mode. The catalytic activity was achieved in the presence of DBU as a base providing a TONmax value of 3,800. In order to explore potential transformations occurring within the catalytic reactions, a series of stoichiometric tests were performed. Complex 1 was reacted with DBU to form chloro(η6‐p‐cymene){diphenyl(3‐methyl‐2‐indolide)phosphine}ruthenium (2). Structural characterization of complex 2 confirmed a κ2‐P,N coordination mode for the ligand resulting in a four membered metallacycle. Reaction of 2 with H2 led to the formation of hydrochloro(η6‐p‐cymene){diphenyl(3‐methyl‐indolyl)phosphine}ruthenium (3), albeit not with a clean conversion. This is the product resulting from the formal addition of hydrogen across the Ru−N bond of the metallacycle. Complex 3 was also synthesized via an alternative route involving the reaction of complex 1 with Me2NH • BH3 as a means of converting Ru−Cl to Ru−H