bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and prognostic significance of circulating secreted frizzled‐related protein 5 in colorectal cancer
Authors: Li Runhao , Liu Saifei , Yeo Kenny , Edwards Suzanne , Li Man Ying , Santos Ryan , Rad Sima Kianpour , Wu Fangmeinuo , Maddern Guy , Young Joanne , Tomita Yoko , Townsend Amanda , Fenix Kevin , Hauben Ehud , Price Timothy , Smith Eric
Published: June 2024

Background

Secreted Frizzled‐Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC)

Methods

Plasma cSFRP5 concentrations were measured using enzyme‐linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64).

Results

Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II‐III CRC (univariate: HR 1.82, 95% CI: 1.02–3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12–4.88, p = 0.015).

Conclusion

This study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II‐III disease.
Fertility preservation in male adolescents with cancer (2011–2020): A retrospective study in China
Authors: Liu Shasha , Wang Qiling , Zhu Wenbing , Zhang Zhou , Tang Wenhao , Sheng Huiqiang , Yang Jigao , Li Yushan , Liang Xiaowei , Meng Tianqing , Wang Zhiqiang , Lin Faxi , Dong Hao , He Xiaojin , Jiang Xianglong , Dai Shanjun , Zhang Aiping , Song Chunying , Liang Zuowen , Zhang Feng , Wang Xiaojun , Liang Peiyu , Gong Guihua , Huai Xiaohong , Wang Yanyun , Li Fuping , Zhang Xinzong
Published: June 2024

Background

According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long‐term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices.

Methods

From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation.

Results

The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13–14 years and 262 cases (95.3%) aged 15–19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%).

Conclusions

The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.
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

Background and Aims

Pancreatic 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.

Methods

To 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.

Results

The 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.

Conclusion

These 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 Message

A 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.

The 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 Message

Acute 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.

Multiple 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 Message

The 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.

Myasthenia 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

From 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

Fasciola 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.
Dual checkpoint inhibition in gallbladder cancer: Bridging new hope with the need for biomarkers
Authors: Saj Fen , Wu Y. Linda , Pant Shubham , Goyal Lipika
Published: June 2024

Dual checkpoint blockade with nivolumab plus ipilimumab in patients with advanced, refractory gallbladder cancer showed activity in select patients in cohort 48 of the SWOG 1609 DART trial. Optimizing patient selection for this regimen will require validating predictive biomarkers of response and understanding the role of the regimen after chemoimmunotherapy in the frontline.
Relay strip intercropping of wheat and cotton under limited water conditions
Authors: Çakaloğulları Uğur , Tatar Özgür
Published: June 2024

Wheat (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

Background

The 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.

Methods

Using 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.

Results

Of 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.

Conclusion

This 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

Objectives

The 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.

Methods

SARS‐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.

Results

nAb 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.

Conclusions

These 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

Aims

The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).

Materials and Methods

Cross‐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.

Results

Higher 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).

Conclusions

This 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

Cellular 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

The 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

The 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
The effect of 12 weeks of aerobic exercise training with or without saffron supplementation on diabetes‐specific markers and inflammation in women with type 2 diabetes: A randomized double‐blind placebo‐controlled trial
Authors: Rajabi Ali , Akbar Nezhad Gharehlo Ali , Madadizadeh Elham , Basereh Aref , Khoramipoor Kimya , Pirani Hossein , Khoramipour Karen , Moser Othmar , Khoramipour Kayvan
Published: June 2024

This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m2, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double‐blind, placebo‐controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post‐evaluation, homeostatic model assessment of insulin resistance value (HOMA‐IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin‐6 (IL‐6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12‐week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers.
Thermal spray coatings for molten salt facing structural parts and enabling opportunities for thermochemical cycle electrolysis
Authors: Faisal Nadimul Haque , Rajendran Vinooth , Prathuru Anil , Hossain Mamdud , Muthukrishnan Ramkumar , Balogun Yakubu , Pancholi Ketan , Hussain Tanvir , Lokachari Siddharth , Horri Bahman Amini , Bankhead Mark
Published: June 2024

Thermochemical water splitting stands out as the most efficient techniques to produce hydrogen through electrolysis at a high temperature, relying on a series of chemical reactions within a loop. However, achieving a durable thermochemical cycle system poses a significant challenge, particularly in manufacturing suitable coating materials for reaction vessels and pipes capable of enduring highly corrosive conditions created by high‐temperature molten salts. The review summarizes thermally sprayed coatings (deposited on structural materials) that can withstand thermochemical cycle corrosive environments, geared towards nuclear thermochemical copper–chlorine (CuCl) cycles. An assessment was conducted to explore material composition and selection (structure–property relations), single and multi‐layer coating manufacturing, as well as corrosion environment and testing methods. The aim was to identify the critical areas for research and development in utilizing the feedstock materials and thermal spray coating techniques for applications in molten salt thermochemical applications, as well as use lessons learnt from other application areas (e.g., nuclear reaction vessels, boilers, waste incinerators, and aero engine gas‐turbine) where other types of molten salt and temperature are expected. Assessment indicated that very limited sets of coating‐substrate system with metallic interlayer is likely to survive high temperature corrosive environment for extended period of testing. However, within the known means and methods, as well as application of advanced thermal spray manufacturing processes could be a way forward to have sustainable coating‐substrate assembly with extended lifetime. Spraying multi‐layered coating (nano‐structured or micro‐structured powder materials) along with the application of modern suspension or solution based thermal spray techniques are considered to result in dense microstructures with improved resistance to high temperature thermochemical environment.
A geomorphic perspective on discharge–area relationships
Authors: Kadu Akshay , Biswal Basudev
Published: June 2024

It is well‐documented that the discharge‐area power‐law scaling exponent (θ) can be much lower than 1 during peak flow periods. A physical explanation for this phenomenon is generally given with the help of the channel network width function, which represents pure surface flow (PSF). When PSF ceases to dominate, θ is expected to increase due to the increasing contribution of mixed surface sub‐surface flow (MSSF) and approach 1. However, to our knowledge, no study thus far has conducted a systematic investigation of the variation of θ. In this study, we use a channel network morphology‐based routing model that considers both PSF and MSSF to investigate the variation of θ across the streamflow spectrum. The model captures the increasing trend of θ quite well during recession periods, attributable to the growing dominance of MSSF. We also demonstrate that the analysis of the discharge‐area scaling is further complicated by several factors, including spatio‐temporal variation of rainfall. The uniqueness of the model is that it suggests θ to assume values much greater than 1 because the flow in smaller basins decreases at a higher rate during late recession periods. Demonstrating this effect using observed data is difficult since obtaining sufficiently long recession curves is practically challenging. However, the predicted trend of θ is well supported by observed data when we perform percentile‐based discharge‐area scaling analysis. Our results thus indicate the possibility that a basin is not merely a sum of its hillslopes, with far‐reaching consequences for modelling hydrological and ecological phenomena.
EPB tunnelling at the Silvertown Tunnel Project in London
Authors: Conrads Alena , Hooi Lim Oon , Thomas Ivor
Published: June 2024

The Silvertown Tunnel is a new twin‐bore road tunnel under the River Thames in the east of London that increases the river crossing capacity in this area and provides enough clearance for the zero‐emission double‐decker buses. It is being delivered by Riverlinx CJV on behalf on Transport for London (TfL). The overall project consists of tunnel approach ramps at both portals, cut and cover tunnels, and two 1.1 km‐long bored tunnel sections as well as highway connections including a new footbridge and service buildings for operating the tunnel from either end. In this article, the approach and challenges of mechanised tunnelling including the river crossing in a high‐density area, with a large‐diameter earth pressure balance (EPB) machine in mixed‐face conditions, are presented. The Tunnel Bori selection based on the geological and geotechnical information is evaluated and compared to the experience during execution of tunnelling. In detail, the actual EPB drive is evaluated by considering the face pressure support, predicted surface settlements and planned cutterhead maintenance.
Long‐term teduglutide associated with improved response in pediatric short bowel syndrome‐associated intestinal failure
Authors: Wales Paul W. , Hill Susan , Robinson Ian , Raphael Bram P. , Matthews Cheney , Cohran Valeria , Carter Beth , Venick Robert , Kocoshis Samuel
Published: June 2024

Objectives

Patients with short bowel syndrome‐associated intestinal failure (SBS‐IF) require long‐term parenteral nutrition and/or intravenous fluids (PN/IV) to maintain fluid or nutritional balance. We report the long‐term safety, efficacy, and predictors of response in pediatric patients with SBS‐IF receiving teduglutide over 96 weeks.

Methods

This was a pooled, post hoc analysis of two open‐label, long‐term extension (LTE) studies (NCT02949362 and NCT02954458) in children with SBS‐IF. Endpoints included treatment‐emergent adverse events (TEAEs) and clinical response (≥20% reduction in PN/IV volume from baseline). A multivariable linear regression identified predictors of teduglutide response; the dependent variable was mean change in PN/IV volume at each visit over 96 weeks.

Results

Overall, 85 patients were analyzed; 78 patients received teduglutide in the parent and/or LTE studies (any teduglutide [TED] group), while seven patients did not receive teduglutide in either the parent or LTE studies. Most TEAEs were moderate or severe in intensity in both groups. By week 96, 82.1% of patients from the any TED group achieved a clinical response, with a mean fluid decrease of 30.1 mL/kg/day and an energy decrease of 21.6 kcal/kg/day. Colon‐in‐continuity, non‐White race, older age at baseline, longer duration of teduglutide exposure, and increasing length of remaining small intestine were significantly associated with a reduction in mean PN/IV volume requirements.

Conclusions

In pediatric patients with SBS‐IF, teduglutide treatment resulted in long‐term reductions in PN/IV requirements. The degree of PN/IV volume reduction depended on the duration of teduglutide exposure, underlying bowel anatomy, and demographics.
Assessment of risk factors for adverse events in analgosedation for pediatric endoscopy: A 10‐year retrospective analysis
Authors: Schneck Emmanuel , Knittel Fabienne , Markmann Melanie , Balzer Felix , Rubarth Kerstin , Zajonz Thomas , Schreiner Anna‐Lena , Hecker Andreas , Naehrlich Lutz , Koch Christian , Laffolie Jan de , Sander Michael
Published: June 2024

Objectives

Data regarding the occurrence of complications specifically during pediatric anesthesia for endoscopic procedures is limited. By evaluating such data, factors could be identified to assure proper staffing and preparation to minimize adverse events and improve patient safety during flexible endoscopy.

Methods

This retrospective cohort study included children undergoing anesthesia for gastroscopy, colonoscopy, bronchoscopy, or combined endoscopic procedures over 10‐year period. The primary study aim was to evaluate the incidence of complications and identify risk factors for adverse events.

Results

Overall, 2064 endoscopic procedures including 1356 gastroscopies (65.7%), 93 colonoscopies (4.5%), 235 bronchoscopies (11.4%), and 380 combined procedures (18.4%) were performed. Of the 1613 patients, 151 (7.3%) patients exhibited an adverse event, with respiratory complications being the most common (65 [3.1%]). Combination of gastrointestinal endoscopies did not lead to an increased adverse event rate (gastroscopy: 5.5%, colonoscopy: 3.2%). Diagnostic endoscopy as compared to interventional had a lower rate. If bronchoscopy was performed, the rate was similar to that of bronchoscopy alone (19.5% vs. 20.4%). Age < 5.8 years or body weight less than 20 kg, bronchoscopy, American Society of Anesthesiologists status ≥ 2 or pre‐existing anesthesia‐relevant diseases, and urgency of the procedure were independent risk factors for adverse events. For each risk factor, the risk for events increased 2.1‐fold [1.8–2.4].

Conclusions

This study identifies multiple factors that increase the rate of adverse events associated anesthesia‐based endoscopy. Combined gastrointestinal procedures did not increase the risk for adverse events while combination of bronchoscopy to gastrointestinal endoscopy showed a similar risk as bronchoscopy alone.
Behavioural tendencies of the last British–Irish Ice Sheet revealed by data–model comparison
Authors: Ely Jeremy C. , Clark Chris D. , Bradley Sarah L. , Gregoire Lauren , Gandy Niall , Gasson Ed , Veness Remy L.J. , Archer Rosie
Published: June 2024

Integrating ice‐sheet models with empirical data pertaining to palaeo‐ice sheets promotes advances in the models used in sea‐level predictions and can improve our understanding of past ice‐sheet behaviour. The large number of empirical constraints on the last British–Irish Ice Sheet make it ideal for model–data comparison experiments. Here, we present an ensemble of 600 model simulations, which are compared with data on former ice‐flow extent, flow geometry and deglaciation timing. Simulations which poorly recreate data were ruled out, allowing us to examine the remaining physically realistic simulations which capture the ice sheets' behavioural tendencies. Our results led to a novel reconstruction of behaviour in the data‐poor region of the North Sea, insights into the ice stream, potential ice‐shelf and readvance dynamics, and the potential locations of peripheral ice caps. We also propose that the asynchronous behaviour of the British–Irish Ice Sheet is a consequence of the geography of the British Isles and the merging and splitting of different bodies of ice through saddle merger and collapse. Furthermore, persistent model–data mismatches highlight the need for model development, especially regarding the physics of ice–ocean interactions. Thus, this work highlights the power of integrating models and data, a long‐held aim of palaeoglaciology.
Check dams in the Yellow River basin: Sediment reduction efficiency and future development
Authors: Haidong Gao , Mengdie Wang , Xinjing Hao
Published: June 2024

Human activities are the main reasons for reducing sediment transport in the Yellow River, with thousands of check dams playing a crucial role. Quantifying the sediment reduction efficiency and analyzing the future development of check dams can help ecological construction and management in the Yellow River basin. This study developed a calculation method for sediment reduction by check dams and calculated the annual sediment reduction, and further estimated the sediment reduction efficiency at different periods. In addition, this study also analyzed the construction intensity and proposed construction strategies of check dams in the Yellow River basin. The results show that from 1952 to 2011, the cumulative sediment reduction of check dams in the middle reaches of the Yellow River was 8056 million tons, the annual sediment reduction varied from 0 to 403 million tons, with a multiyear average of 134 million tons. Among the major tributaries in the middle reaches of the Yellow River, the sediment reduction efficiency of check dams ranged from 0.51% to 76.88% due to the ecological management of slopes and the loss of sediment retention capacity by small‐ and medium‐sized check dams, the sediment reduction efficiency from 1980 to 1999 was higher than from 2000 to 2011. Following the analysis of the suitability of check dam construction, we calculated the potential and intensity of check dam construction in the Yellow River basin. The intensity of check dam construction exceeded 50% in the TDG‐LM region (Toudaoguai hydrological station to Longmen hydrological station) in the middle reaches of the Yellow River. We analyzed the siltation situation of large‐sized check dams and proposed strategies for the construction and management of check dams.
Prick “filter bubbles” by enhancing consumers' novelty‐seeking: The role of personalized recommendations of unmentionable products
Authors: Lv Linxiang , Kang Khloe Qi , Liu Guanrong (Gus)
Published: June 2024

Personalized recommendation algorithms inadvertently foster “filter bubbles,” wherein consumers are predominantly exposed to information that aligns with their existing preferences, limiting their exposure to novel items. This phenomenon raises ethical concerns regarding consumer well‐being, as it potentially compromises the quality of consumption decisions by reinforcing a homogeneity of information. Introducing novelty into recommendation systems is a viable strategy to counteract this issue, as the predominance of homogeneous information plays a crucial role in the formation of filter bubbles. However, there is a notable gap in the literature regarding self‐directed strategies for consumers to break through these filter bubbles. Grounded in social identification theory and utilizing a series of experimental studies, our research employs a range of analytical techniques, including ANOVA, mediation, and moderated‐mediation analysis. Our findings suggest that personalized recommendations of unmentionable products, defined as products eliciting disgust, offense, or anger due to delicacy, ethics, or fear, (vs. ordinary products) can increase consumers' novelty‐seeking by enhancing their motivation to change their implicit social labels given by intelligent recommendation systems. Nonetheless, we observe that this drive for novelty‐seeking diminishes during social‐focused recommendations because this recommendation is based on the behaviors of others in consumers' social networks rather than their actions.
Lipopolysaccharide released from gut activates pyroptosis of macrophages via Caspase 11‐Gasdermin D pathway in systemic lupus erythematosus
Authors: Xin Yue , Gao Changxing , Wang Lai , Liu Qianmei , Lu Qianjin
Published: June 2024

Noncanonical pyroptosis is triggered by Caspase 4/5/11, which cleaves Gasdermin D (GSDMD), leading to cell lysis. While GSDMD has been studied previously in systemic lupus erythematosus (SLE), the role of pyroptosis in SLE pathogenesis remains unclear and contentious, with limited understanding of Caspase 11‐mediated pyroptosis in this condition. In this study, we explored the level of Caspase 11‐mediated pyroptosis in SLE, identifying both the upstream pathways and the interaction between pyroptosis and adaptive immune responses. We observed increased Caspase 5/11 and GSDMD‐dependent pyroptosis in the macrophages/monocytes of both lupus patients and mice. We identified serum lipopolysaccharide (LPS), released from the gut due to a compromised gut barrier, as the signal that triggers Caspase 11 activation in MRL/lpr mice. We further discovered that pyroptotic macrophages promote the differentiation of mature B cells independently of T cells. Additionally, inhibiting Caspase 11 and preventing LPS leakage proved effective in improving lupus symptoms in MRL/lpr mice. These findings suggest that elevated serum LPS, resulting from a damaged gut barrier, induces Caspase 11/GSDMD‐mediated pyroptosis, which in turn promotes B cell differentiation and enhances autoimmune responses in SLE. Thus, targeting Caspase 11 could be a viable therapeutic strategy for SLE.
CircMALAT1 promotes cancer stem‐like properties and chemoresistance via regulating Musashi‐2/c‐Myc axis in esophageal squamous cell carcinoma
Authors: Zhao Zitong , Deng Yingni , Han Jing , Ma Liying , Zhu Yumeng , Zhang Hua , He Zhixu , Song Yongmei
Published: June 2024

The primary challenge in treating esophageal squamous cell carcinoma (ESCC) is resistance to chemotherapy. Cancer stem cell (CSC) is the root cause of tumor drug resistance. Therefore, targeting CSCs has been considered promising therapeutic strategy for tumor treatment. Here, we report that circMALAT1 was significantly upregulated in ESCC CSC‐like cells and primary tumors from ESCC patients. Clinically, there was a positive correlation between circMALAT1 expression and ESCC stage and lymph node metastasis, as well as poor prognosis for ESCC patients. In vitro and in vivo functional studies revealed that circMALAT1 promoted CSC‐like cells expansion, tumor growth, lung metastasis and drug resistance of ESCC. Mechanistically, circMALAT1 directly interacted with CSC‐functional protein Musashi RNA Binding Protein 2 (MSI2). CircMALAT1 inhibited MSI2 ubiquitination by preventing it from interacting with β‐transducin repeat containing protein (BTRC) E3 ubiquitin ligase. Also, circMALAT1 knockdown inhibited the expression of MSI2‐regulating CSC‐markers c‐Myc in ESCC. Collectively, circMALAT1 modulated the ubiquitination and degradation of the MSI2 protein signaling with ESCC CSCs and accelerated malignant progression of ESCC. CircMALAT1 has the potential to serve as a biomarker for drug resistance and as a target for therapy in CSCs within ESCC.