bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a nurse-led sexual rehabilitation intervention for women with gynaecological cancers receiving radiotherapy: results of a randomised trial
Authors: Suvaal Isabelle , Hummel Susanna B. , Mens Jan-Willem M. , Tuijnman-Raasveld Charlotte C. , Tsonaka Roula , Velema Laura A. , Westerveld Henrike , Cnossen Jeltsje S. , Snyers An , Jürgenliemk-Schulz Ina M. , Lutgens Ludy C. H. W. , Beukema Jannet C. , Haverkort Marie A. D. , Nowee Marlies E. , Nout Remi A. , de Kroon Cor D. , van den Hout Wilbert B. , Creutzberg Carien L. , van Doorn Helena C. , ter Kuile Moniek M. 
Published: July 2024

Abstract
Background
The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers.

Methods
Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time.

Results
In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly.

Discussion
Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment.

Clinical trial registration
NCT03611517.
DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance
Authors: Cyll Karolina , Skaaheim Haug Erik , Pradhan Manohar , Vlatkovic Ljiljana , Carlsen Birgitte , Löffeler Sven , Kildal Wanja , Skogstad Karin , Hauge Torkelsen Frida , Syvertsen Rolf Anders , Askautrud Hanne A. , Liestøl Knut , Kleppe Andreas , Danielsen Håvard E. 
Published: July 2024

Abstract
Background
Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients.

Methods
We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint.

Results
The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (p < 0.0001) and 1.94 (p < 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025; p = 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01; p = 0.027).

Conclusions
DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol.
Selective PI3Kδ inhibitor TYM-3-98 suppresses AKT/mTOR/SREBP1-mediated lipogenesis and promotes ferroptosis in KRAS-mutant colorectal cancer
Authors: Zheng Ya-nan , Lou Si-yue , Lu Jun , Zheng Fan-li , Tang Yong-mei , Zhang En-jun , Cui Sun-liang , Zhao Hua-jun 
Published: July 2024

AbstractColorectal cancer (CRC) is one of the most common tumors of the digestive system worldwide. KRAS mutations limit the use of anti-EGFR antibodies in combination with chemotherapy for the treatment of CRC. Therefore, novel targeted therapies are needed to overcome the KRAS-induced oncogenesis. Recent evidence suggests that inhibition of PI3K led to ferroptosis, a nonapoptotic cell death closely related to KRAS-mutant cells. Here, we showed that a selective PI3Kδ inhibitor TYM-3–98 can suppress the AKT/mTOR signaling and activate the ferroptosis pathway in KRAS-mutant CRC cells in a concentration-dependent manner. This was evidenced by the lipid peroxidation, iron accumulation, and depletion of GSH. Moreover, the overexpression of the sterol regulatory element-binding protein 1 (SREBP1), a downstream transcription factor regulating lipid metabolism, conferred CRC cells greater resistance to ferroptosis induced by TYM-3–98. In addition, the effect of TYM-3–98 was confirmed in a xenograft mouse model, which demonstrated significant tumor suppression without obvious hepatoxicity or renal toxicity. Taken together, our work demonstrated that the induction of ferroptosis contributed to the PI3Kδ inhibitor-induced cell death via the suppression of AKT/mTOR/SREBP1-mediated lipogenesis, thus displaying a promising therapeutic effect of TYM-3–98 in CRC treatment.
Generation of functional neurons from adult human mucosal olfactory ensheathing glia by direct lineage conversion
Authors: Portela-Lomba María , Simón Diana , Callejo-Móstoles Marta , de la Fuente Gemma , Fernández de Sevilla David , García-Escudero Vega , Moreno-Flores M. Teresa , Sierra Javier 
Published: July 2024

AbstractA recent approach to promote central nervous system (CNS) regeneration after injury or disease is direct conversion of somatic cells to neurons. This is achieved by transduction of viral vectors that express neurogenic transcription factors. In this work we propose adult human mucosal olfactory ensheathing glia (hmOEG) as a candidate for direct reprogramming to neurons due to its accessibility and to its well-characterized neuroregenerative capacity. After induction of hmOEG with the single neurogenic transcription factor NEUROD1, the cells under study exhibited morphological and immunolabeling neuronal features, fired action potentials and expressed glutamatergic and GABAergic markers. In addition, after engraftment of transduced hmOEG cells in the mouse hippocampus, these cells showed specific neuronal labeling. Thereby, if we add to the neuroregenerative capacity of hmOEG cultures the conversion to neurons of a fraction of their population through reprogramming techniques, the engraftment of hmOEG and hmOEG-induced neurons could be a procedure to enhance neural repair after central nervous system injury.
A mitochondrial checkpoint to NF-κB signaling
Authors: Guilbaud Emma , Galluzzi Lorenzo 
Published: July 2024

AbstractMitochondrial dysfunction can elicit multiple inflammatory pathways, especially when apoptotic caspases are inhibited. Such an inflammatory program is negatively regulated by the autophagic disposal of permeabilized mitochondria. Recent data demonstrate that the ubiquitination of mitochondrial proteins is essential for NEMO-driven NF-kB activation downstream of mitochondrial permeabilization.
Plac8-ERK pathway modulation of monocyte function in sepsis
Authors: Zhang Teng , Fu Jing-nan , Chen Gui-bing , Zhang Xiu 
Published: July 2024

AbstractSepsis, a life-threatening condition caused by infection, is characterized by the dysregulation of immune responses and activation of monocytes. Plac8, a protein, has been implicated in various inflammatory conditions. This study aimed to investigate the effect of Plac8 upregulation on monocyte proliferation and activation in sepsis patients. Peripheral blood samples were collected from healthy individuals and sepsis patients. Monocytes were stimulated with lipopolysaccharide (LPS) to create an in vitro sepsis model, while a murine sepsis model was established using cecal ligation and puncture (CLP). The levels of monocyte markers, proliferation index (PI), and pro-inflammatory cytokines were assessed using flow cytometry and qPCR, respectively. Plac8 and phosphorylated ERK protein levels were determined by western blot, and TNF-α, IL-6, and IL-10 levels were quantified using ELISA. The CCK-8 assay was used to evaluate PBMC proliferation and activation. The results showed that Plac8 was highly expressed in sepsis models, promoting the survival, proliferation, and activation of monocytes. Plac8 upregulation activated the ERK pathway, leading to increased phosphorylation of ERK protein and elevated levels of CD14, CD16, TNF-α, IL-6, Plac8, and IL-10. In sepsis mice, Plac8 overexpression similarly activated the ERK pathway and promoted the survival, proliferation, and activation of monocytes. In conclusion, the upregulation of Plac8 enhances the activation of the ERK pathway and promotes monocyte proliferation and activation in sepsis patients.
Anti-CCL2 therapy reduces oxygen toxicity to the immature lung
Authors: Shahzad Tayyab , Dong Ying , Behnke Nina K. , Brandner Julia , Hilgendorff Anne , Chao Cho-Ming , Behnke Judith , Bellusci Saverio , Ehrhardt Harald 
Published: July 2024

AbstractOxygen toxicity constitutes a key contributor to bronchopulmonary dysplasia (BPD). Critical step in the pathogenesis of BPD is the inflammatory response in the immature lung with the release of pro-inflammatory cytokines and the influx of innate immune cells. Identification of efficient therapies to alleviate the inflammatory response remains an unmet research priority. First, we studied macrophage and neutrophil profiles in tracheal aspirates of n = 103 preterm infants <29 weeks´ gestation requiring mechanical ventilation. While no differences were present at birth, a higher fraction of macrophages, the predominance of the CD14+CD16+ subtype on day 5 of life was associated with moderate/severe BPD. Newborn CCL-2−/− mice insufficient in pulmonary macrophage recruitment had a reduced influx of neutrophils, lower apoptosis induction in the pulmonary tissue and better-preserved lung morphometry with higher counts of type II cells, mesenchymal stem cells and vascular endothelial cells when exposed to hyperoxia for 7 days. To study the benefit of a targeted approach to prevent the pulmonary influx of macrophages, wildtype mice were repeatedly treated with CCL-2 blocking antibodies while exposed to hyperoxia for 7 days. Congruent with the results in CCL-2−/− animals, the therapeutic intervention reduced the pulmonary inflammatory response, attenuated cell death in the lung tissue and better-preserved lung morphometry. Overall, our preclinical and clinical datasets document the predominant role of macrophage recruitment to the pathogenesis of BPD and establish the abrogation of CCL-2 function as novel approach to protect the immature lung from hyperoxic injury.
Reversible two-way tuning of thermal conductivity in an end-linked star-shaped thermoset
Authors: Hartquist Chase M. , Li Buxuan , Zhang James H. , Yu Zhaohan , Lv Guangxin , Shin Jungwoo , Boriskina Svetlana V. , Chen Gang , Zhao Xuanhe , Lin Shaoting 
Published: July 2024

AbstractPolymeric thermal switches that can reversibly tune and significantly enhance their thermal conductivities are desirable for diverse applications in electronics, aerospace, automotives, and medicine; however, they are rarely achieved. Here, we report a polymer-based thermal switch consisting of an end-linked star-shaped thermoset with two independent thermal conductivity tuning mechanisms—strain and temperature modulation—that rapidly, reversibly, and cyclically modulate thermal conductivity. The end-linked star-shaped thermoset exhibits a strain-modulated thermal conductivity enhancement up to 11.5 at a fixed temperature of 60 °C (increasing from 0.15 to 2.1 W m−1 K−1). Additionally, it demonstrates a temperature-modulated thermal conductivity tuning ratio up to 2.3 at a fixed stretch of 2.5 (increasing from 0.17 to 0.39 W m−1 K−1). When combined, these two effects collectively enable the end-linked star-shaped thermoset to achieve a thermal conductivity tuning ratio up to 14.2. Moreover, the end-linked star-shaped thermoset demonstrates reversible tuning for over 1000 cycles. The reversible two-way tuning of thermal conductivity is attributed to the synergy of aligned amorphous chains, oriented crystalline domains, and increased crystallinity by elastically deforming the end-linked star-shaped thermoset.
Dynamics of polarization-tuned mirror symmetry breaking in a rotationally symmetric system
Authors: Zhang Yu , Li Zhibin , Che Zhen , Zhang Wang , Zhang Yusen , Lin Ziqi , Lv Zhan , Wu Chunling , Han Longwei , Tang Jieyuan , Zhu Wenguo , Xiao Yi , Zheng Huadan , Zhong Yongchun , Chen Zhe , Yu Jianhui 
Published: July 2024

AbstractLateral momentum conservation is typically kept in a non-absorptive rotationally symmetric system through mirror symmetry via Noether’s theorem when illuminated by a homogeneous light wave. Therefore, it is still very challenging to break the mirror symmetry and generate a lateral optical force (LOF) in the rotationally symmetric system. Here, we report a general dynamic action in the SO(2) rotationally symmetric system, originating from the polarization-tuned mirror symmetry breaking (MSB) of the light scattering. We demonstrate theoretically and experimentally that MSB can be generally applied to the SO(2) rotationally symmetric system and tuned sinusoidally by polarization orientation, leading to a highly tunable and highly efficient LOF (9.22 pN/mW/μm−2) perpendicular to the propagation direction. The proposed MSB mechanism and LOF not only complete the sets of MSB of light-matter interaction and non-conservative force only using a plane wave but also provide extra polarization manipulation freedom.
Barbed arrow-like structure membrane with ultra-high rectification coefficient enables ultra-fast, highly-sensitive lateral-flow assay of cTnI
Authors: Li Juanhua , Liu Yiren , Wu Tianyu , Xiao Zihan , Du Jianhang , Liang Hongrui , Zhou Cuiping , Zhou Jianhua 
Published: July 2024

AbstractAcute myocardial infarction (AMI) has become a public health disease threatening public life safety due to its high mortality. The lateral-flow assay (LFA) of a typical cardiac biomarker, troponin I (cTnI), is essential for the timely warnings of AMI. However, it is a challenge to achieve an ultra-fast and highly-sensitive assay for cTnI (hs-cTnI) using current LFA, due to the limited performance of chromatographic membranes. Here, we propose a barbed arrow-like structure membrane (BAS Mem), which enables the unidirectional, fast flow and low-residual of liquid. The liquid is rectified through the forces generated by the sidewalls of the barbed arrow-like grooves. The rectification coefficient of liquid flow on BAS Mem is 14.5 (highest to date). Using BAS Mem to replace the conventional chromatographic membrane, we prepare batches of lateral-flow strips and achieve LFA of cTnI within 240 s, with a limit of detection of 1.97 ng mL−1. The lateral-flow strips exhibit a specificity of 100%, a sensitivity of 93.3% in detecting 25 samples of suspected AMI patients. The lateral-flow strips show great performance in providing reliable results for clinical diagnosis, with the potential to provide early warnings for AMI.
KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2
Authors: Bi Shilei , Huang Lijun , Chen Yongjie , Hu Zhenhua , Li Shanze , Wang Yifan , Huang Baoying , Zhang Lizi , Huang Yuanyuan , Dai Beibei , Du Lili , Tu Zhaowei , Wang Yijing , Xu Dan , Xu Xiaotong , Sun Wen , Kzhyshkowska Julia , Wang Haibin , Chen Dunjin , Wang Fengchao , Zhang Shuang 
Published: July 2024

AbstractAbnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.
Climatic pacing of extreme Nile floods during the North African Humid Period
Authors: Blanchet Cécile L. , Ramisch Arne , Tjallingii Rik , Ionita Monica , Laruelle Louison , Bagge Meike , Klemann Volker , Brauer Achim 
Published: July 2024

AbstractUnderstanding how large river systems will respond to an invigorated hydrological cycle as simulated under higher global temperatures is a pressing issue. Insights can be gained from studying past wetter-than-present intervals, such as the North African Humid Period during the early Holocene Epoch (~11–6 thousand years ago). Here we present a 1,500-year-long annually laminated (varved) offshore sediment record that tracks the seasonal discharge of the Nile River during the North African Humid Period. The record reveals mobilization of large amounts of sediments during strong summer floods that may have rendered the Nile valley uninhabitable. More frequent and rapid transitions between extremely strong and weak floods between 9.2 and 8.6 thousand years ago indicate highly instable fluvial dynamics. Climate simulations suggest flood variability was paced by El Niño/Southern Oscillation on interannual timescales, while multi-decadal oscillatory modes drove changes in extreme flood events. These pacemakers have also been identified in the Nile flow records from the Common Era, which implies their stationarity under contrasting hydroclimatic conditions.
Narrative cave art in Indonesia by 51,200 years ago
Authors: Oktaviana Adhi Agus , Joannes-Boyau Renaud , Hakim Budianto , Burhan Basran , Sardi Ratno , Adhityatama Shinatria , Hamrullah  , Sumantri Iwan , Tang M. , Lebe Rustan , Ilyas Imran , Abbas Abdullah , Jusdi Andi , Mahardian Dewangga Eka , Noerwidi Sofwan , Ririmasse Marlon N. R. , Mahmud Irfan , Duli Akin , Aksa Laode M. , McGahan David , Setiawan Pindi , Brumm Adam , Aubert Maxime 
Published: July 2024

AbstractPrevious dating research indicated that the Indonesian island of Sulawesi is host to some of the oldest known rock art1–3. That work was based on solution uranium-series (U-series) analysis of calcite deposits overlying rock art in the limestone caves of Maros-Pangkep, South Sulawesi1–3. Here we use a novel application of this approach—laser-ablation U-series imaging—to re-date some of the earliest cave art in this karst area and to determine the age of stylistically similar motifs at other Maros-Pangkep sites. This method provides enhanced spatial accuracy, resulting in older minimum ages for previously dated art. We show that a hunting scene from Leang Bulu’ Sipong 4, which was originally dated using the previous approach to a minimum of 43,900 thousand years ago (ka)3, has a minimum age of 50.2 ± 2.2 ka, and so is at least 4,040 years older than thought. Using the imaging approach, we also assign a minimum age of 53.5 ± 2.3 ka to a newly described cave art scene at Leang Karampuang. Painted at least 51,200 years ago, this narrative composition, which depicts human-like figures interacting with a pig, is now the earliest known surviving example of representational art, and visual storytelling, in the world3. Our findings show that figurative portrayals of anthropomorphic figures and animals have a deeper origin in the history of modern human (Homo sapiens) image-making than recognized to date, as does their representation in composed scenes.
Adenosine signalling to astrocytes coordinates brain metabolism and function
Authors: Theparambil Shefeeq M. , Kopach Olga , Braga Alice , Nizari Shereen , Hosford Patrick S. , Sagi-Kiss Virag , Hadjihambi Anna , Konstantinou Christos , Esteras Noemi , Gutierrez Del Arroyo Ana , Ackland Gareth L. , Teschemacher Anja G. , Dale Nicholas , Eckle Tobias , Andrikopoulos Petros , Rusakov Dmitri A. , Kasparov Sergey , Gourine Alexander V. 
Published: July 2024

AbstractBrain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply1,2. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism3,4, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood5,6. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3′,5′-monophosphate–protein kinase A signalling pathway, leading to rapid activation of astrocyte glucose metabolism and the release of lactate, which supplements the extracellular pool of readily available energy substrates. Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes showed that adenosine-mediated metabolic signalling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply. Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory and disrupted sleep. These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.