bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial differences in serological markers across the first year of injury in spinal cord injury: a retrospective analysis of a multi-center interventional study
Authors: Li Jia , Farrow Matthew , Ibrahim Kerollos , McTigue Dana M. , Kramer John , Tong Bobo , Jutzeler Catherine , Jones Linda , Yarar-Fisher Ceren
Published: July 2024

Study design

Secondary analysis of a randomized, multi-center, placebo-controlled study(Sygen®).

Objectives

To evaluate racial differences in serological markers in individuals with spinal cord injury(SCI) across the first year of injury.

Setting

Hospitals in North America.

Methods

Serological markers (e.g.,cell count, liver, kidney, and pancreatic function, metabolism, and muscle damage) were assessed among 316 participants (247 White, 69 Black) at admission, weeks 1, 2, 4, 8, and 52 post-injury. Linear mixed models were employed to explore the main effects of time, race (Black vs. White), and their interaction, with adjustment of covariates such as study center, polytrauma, injury (level, completeness), treatment group, and sex.

Results

A main effect of race was observed where White individuals had higher alanine transaminase, blood urea nitrogen(BUN), BUN/Creatinine ratio, sodium, and chloride, while Black individuals had higher calcium, total serum protein, and platelets. For markers with interaction effects, post-hoc comparisons showed that at week 52, White individuals had higher mature neutrophils, hematocrit, hemoglobin, mean corpuscular hemoglobin, albumin, and triglycerides, and Black individuals had higher amylase. Eosinophils, monocytes, red blood cells, aspartate aminotransferase, bilirubin, cholesterol, partial thromboplastin time, urine specific gravity, urine pH, CO2, and inorganic phosphorus did not differ between races.

Conclusions

Our results revealed racial differences in serological markers and underscores the importance of considering race as a determinant of physiological responses. Future studies are warranted to explore the causes and implications of these racial disparities to facilitate tailored clinical management and social policy changes that can improve health equity.
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

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

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

Colorectal 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

A 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

Mitochondrial 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

Sepsis, 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

Oxygen 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

Polymeric 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

Lateral 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

Acute 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

Abnormal 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

Understanding 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

Previous 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

Brain 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.
NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance
Authors: Chen Hengxing , Li Yun , Li Huafu , Chen Xiancong , Fu Huafeng , Mao Deli , Chen Wei , Lan Linxiang , Wang Chunming , Hu Kaishun , Li Jia , Zhu Chengming , Evans Ian , Cheung Eddie , Lu Daning , He Yulong , Behrens Axel , Yin Dong , Zhang Changhua
Published: July 2024

The Warburg effect is a hallmark of cancer that refers to the preference of cancer cells to metabolize glucose anaerobically rather than aerobically1,2. This results in substantial accumulation of lacate, the end product of anaerobic glycolysis, in cancer cells3. However, how cancer metabolism affects chemotherapy response and DNA repair in general remains incompletely understood. Here we report that lactate-driven lactylation of NBS1 promotes homologous recombination (HR)-mediated DNA repair. Lactylation of NBS1 at lysine 388 (K388) is essential for MRE11–RAD50–NBS1 (MRN) complex formation and the accumulation of HR repair proteins at the sites of DNA double-strand breaks. Furthermore, we identify TIP60 as the NBS1 lysine lactyltransferase and the ‘writer’ of NBS1 K388 lactylation, and HDAC3 as the NBS1 de-lactylase. High levels of NBS1 K388 lactylation predict poor patient outcome of neoadjuvant chemotherapy, and lactate reduction using either genetic depletion of lactate dehydrogenase A (LDHA) or stiripentol, a lactate dehydrogenase A inhibitor used clinically for anti-epileptic treatment, inhibited NBS1 K388 lactylation, decreased DNA repair efficacy and overcame resistance to chemotherapy. In summary, our work identifies NBS1 lactylation as a critical mechanism for genome stability that contributes to chemotherapy resistance and identifies inhibition of lactate production as a promising therapeutic cancer strategy.
Human degradation of tropical moist forests is greater than previously estimated
Authors: Bourgoin C. , Ceccherini G. , Girardello M. , Vancutsem C. , Avitabile V. , Beck P. S. A. , Beuchle R. , Blanc L. , Duveiller G. , Migliavacca M. , Vieilledent G. , Cescatti A. , Achard F.
Published: July 2024

Tropical forest degradation from selective logging, fire and edge effects is a major driver of carbon and biodiversity loss1–3, with annual rates comparable to those of deforestation4. However, its actual extent and long-term impacts remain uncertain at global tropical scale5. Here we quantify the magnitude and persistence of multiple types of degradation on forest structure by combining satellite remote sensing data on pantropical moist forest cover changes4 with estimates of canopy height and biomass from spaceborne6 light detection and ranging (LiDAR). We estimate that forest height decreases owing to selective logging and fire by 15% and 50%, respectively, with low rates of recovery even after 20 years. Agriculture and road expansion trigger a 20% to 30% reduction in canopy height and biomass at the forest edge, with persistent effects being measurable up to 1.5 km inside the forest. Edge effects encroach on 18% (approximately 206 Mha) of the remaining tropical moist forests, an area more than 200% larger than previously estimated7. Finally, degraded forests with more than 50% canopy loss are significantly more vulnerable to subsequent deforestation. Collectively, our findings call for greater efforts to prevent degradation and protect already degraded forests to meet the conservation pledges made at recent United Nations Climate Change and Biodiversity conferences.
Spike deep mutational scanning helps predict success of SARS-CoV-2 clades
Authors: Dadonaite Bernadeta , Brown Jack , McMahon Teagan E. , Farrell Ariana G. , Figgins Marlin D. , Asarnow Daniel , Stewart Cameron , Lee Jimin , Logue Jenni , Bedford Trevor , Murrell Ben , Chu Helen Y. , Veesler David , Bloom Jesse D.
Published: July 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion1 and affect other properties that contribute to viral fitness, such as ACE2 receptor binding and cell entry2,3. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning4 to measure how more than 9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully affected ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456 and 473; however, the antigenic effects of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however, many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.
Observation of the scaling dimension of fractional quantum Hall anyons
Authors: Veillon A. , Piquard C. , Glidic P. , Sato Y. , Aassime A. , Cavanna A. , Jin Y. , Gennser U. , Anthore A. , Pierre F.
Published: July 2024

Unconventional quasiparticles emerging in the fractional quantum Hall regime1,2 present the challenge of observing their exotic properties unambiguously. Although the fractional charge of quasiparticles has been demonstrated for nearly three decades3–5, the first convincing evidence of their anyonic quantum statistics has only recently been obtained6,7 and, so far, the so-called scaling dimension that determines the propagation dynamics of the quasiparticles remains elusive. In particular, although the nonlinearity of the tunnelling quasiparticle current should reveal their scaling dimension, the measurements fail to match theory, arguably because this observable is not robust to non-universal complications8–12. Here we expose the scaling dimension from the thermal noise to shot noise crossover and observe an agreement with expectations. Measurements are fitted to the predicted finite-temperature expression involving both the scaling dimension of the quasiparticles and their charge12,13, in contrast to previous charge investigations focusing on the high-bias shot-noise regime14. A systematic analysis, repeated on several constrictions and experimental conditions, consistently matches the theoretical scaling dimensions for the fractional quasiparticles emerging at filling factors ν = 1/3, 2/5 and 2/3. This establishes a central property of fractional quantum Hall anyons and demonstrates a powerful and complementary window into exotic quasiparticles.
Accelerating Formulation Design via Machine Learning: Generating a High-throughput Shampoo Formulations Dataset
Authors: Chitre Aniket , Querimit Robert C. M. , Rihm Simon D. , Karan Dogancan , Zhu Benchuan , Wang Ke , Wang Long , Hippalgaonkar Kedar , Lapkin Alexei A.
Published: July 2024

Liquid formulations are ubiquitous yet have lengthy product development cycles owing to the complex physical interactions between ingredients making it difficult to tune formulations to customer-defined property targets. Interpolative ML models can accelerate liquid formulations design but are typically trained on limited sets of ingredients and without any structural information, which limits their out-of-training predictive capacity. To address this challenge, we selected eighteen formulation ingredients covering a diverse chemical space to prepare an open experimental dataset for training ML models for rinse-off formulations development. The resulting design space has an over 50-fold increase in dimensionality compared to our previous work. Here, we present a dataset of 812 formulations, including 294 stable samples, which cover the entire design space, with phase stability, turbidity, and high-fidelity rheology measurements generated on our semi-automated, ML-driven liquid formulations workflow. Our dataset has the unique attribute of sample-specific uncertainty measurements to train predictive surrogate models.
Coronary risk factor profiles according to different age categories in premature coronary artery disease patients who have undergone percutaneous coronary intervention
Authors: Nazli Sukma Azureen , Rosman Azhari , Mohd Kasim Noor Alicezah , Al-Khateeb Alyaa , Ul-Saufie Ahmad Zia , Md Radzi Ahmad Bakhtiar , Ibrahim Khairul Shafiq , Kasim Sazzli Shahlan , Nawawi Hapizah
Published: July 2024

Many studies have investigated the coronary risk factors (CRFs) among premature coronary artery disease (PCAD) patients. However, reports on the proportion and CRFs of PCAD according to different age cut-offs for PCAD is globally under-reported. This study aimed to determine the proportion of PCAD patients and analyse the significant CRFs according to different age cut-offs among percutaneous coronary intervention (PCI)-treated patients. Patients who underwent PCI between 2007 and 2018 in two cardiology centres were included (n = 29,241) and were grouped into four age cut-off groups that defines PCAD: (A) Males/females: < 45, (B) Males: < 50; Females: < 55, (C) Males: < 55; Females: < 60 and (D) Males: < 55; Females: < 65 years old. The average proportion of PCAD was 28%; 9.2% for group (A), 21.5% for group (B), 38.6% and 41.9% for group (C) and (D), respectively. The top three CRFs of PCAD were LDL-c level, TC level and hypertension (HTN). Malay ethnicity, smoking, obesity, family history of PCAD, TC level and history of MI were the independent predictors of PCAD across all age groups. The proportion of PCAD in Malaysia is higher compared to other studies. The most significant risk factors of PCAD are LDL-c, TC levels and HTN. Early prevention, detection and management of the modifiable risk factors are highly warranted to prevent PCAD.
The vertical mobility of the first tarsometatarsal joint during demi-plié with forced turnout in ballet dancers
Authors: Ishihara Honoka , Maeda Noriaki , Komiya Makoto , Tashiro Tsubasa , Tsutsumi Shogo , Arima Satoshi , Kawai Miki , Tamura Yuki , Ikuta Yasunari , Urabe Yukio
Published: July 2024

The forced turnout has a perceived risk of development of hallux valgus (HV) in ballet dancers. We determined how the forced turnout affects the sagittal mobility of the first tarsometatarsal (TMT) joint, which is one of the pathogenic factors of HV development. Seventeen female ballet dancers (body mass index: 18.2 ± 1.8 kg/m2) were included and performed demi-plié in control, functional turnout, and forced turnout conditions. Ultrasound imaging synchronized with a three-dimensional motion analysis system was used for measuring the vertical locations of the first metatarsal and medial cuneiform (MC) to evaluate the first TMT joint mobility. Plantar displacement of MC and the first TMT joint mobility in the forced turnout were the greatest among the 3 conditions. Multiple regression analysis indicated that the greater extent of the forcing angle might increase the displacement of MC and the first TMT joint mobility. Evaluating the sagittal mobility of the first TMT joint in the forced turnout can assist in understanding the association between inappropriate techniques including the forced turnout and HV development in ballet dancers. Since the excessive mobility of the first TMT joint is a factor in HV development, the acquirement of adequate active turnout may have the potential to prevent HV development in ballet dancers.
Identification of commensal gut microbiota signatures as predictors of clinical severity and disease progression in multiple sclerosis
Authors: Montgomery Theresa L. , Wang Qin , Mirza Ali , Dwyer Deanna , Wu Qi , Dowling Catherine A. , Martens Jacob W. S. , Yang Jennifer , Krementsov Dimitry N. , Mao-Draayer Yang
Published: July 2024

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and a leading cause of neurological disability in young adults. Clinical presentation and disease course are highly heterogeneous. Typically, disease progression occurs over time and is characterized by the gradual accumulation of disability. The risk of developing MS is driven by complex interactions between genetic and environmental factors, including the gut microbiome. How the commensal gut microbiota impacts disease severity and progression over time remains unknown. In a longitudinal study, disability status and associated clinical features in 58 MS patients were tracked over 4.2 ± 0.98 years, and the baseline fecal gut microbiome was characterized via 16S amplicon sequencing. Progressor status, defined as patients with an increase in Expanded Disability Status Scale (EDSS), were correlated with features of the gut microbiome to determine candidate microbiota associated with risk of MS disease progression. We found no overt differences in microbial community diversity and overall structure between MS patients exhibiting disease progression and non-progressors. However, a total of 41 bacterial species were associated with worsening disease, including a marked depletion in Akkermansia, Lachnospiraceae, and Oscillospiraceae, with an expansion of Alloprevotella, Prevotella-9, and Rhodospirillales. Analysis of the metabolic potential of the inferred metagenome from taxa associated with progression revealed enrichment in oxidative stress-inducing aerobic respiration at the expense of microbial vitamin K2 production (linked to Akkermansia), and a depletion in SCFA metabolism (linked to Oscillospiraceae). Further, as a proof of principle, statistical modeling demonstrated that microbiota composition and clinical features were sufficient to predict disease progression. Additionally, we found that constipation, a frequent gastrointestinal comorbidity among MS patients, exhibited a divergent microbial signature compared with progressor status. These results demonstrate a proof of principle for the utility of the gut microbiome for predicting disease progression in MS in a small well-defined cohort. Further, analysis of the inferred metagenome suggested that oxidative stress, vitamin K2, and SCFAs are associated with progression, warranting future functional validation and mechanistic study.
Augmented reality navigation method based on image segmentation and sensor tracking registration technology
Authors: Zhang Xiaoying , Zhu Yonggang , Chen Lumin , Duan Peng , Zhou Meijuan
Published: July 2024

With the rapid development of modern science and technology, navigation technology provides great convenience for people's life, but the problem of inaccurate localization in complex environments has always been a challenge that navigation technology needs to be solved urgently. To address this challenge, this paper proposes an augmented reality navigation method that combines image segmentation and multi-sensor fusion tracking registration. The method optimizes the image processing process through the GA-OTSU-Canny algorithm and combines high-precision multi-sensor information in order to achieve accurate tracking of positioning and guidance in complex environments. Experimental results show that the GA-OTSU-Canny algorithm has a faster image edge segmentation rate, and the fastest start speed is only 1.8 s, and the fastest intersection selection time is 1.2 s. The navigation system combining the image segmentation and sensor tracking and registration techniques has a highly efficient performance in real-world navigation, and its building recognition rates are all above 99%. The augmented reality navigation system not only improves the navigation accuracy in high-rise and urban canyon environments, but also significantly outperforms traditional navigation solutions in terms of navigation startup time and target building recognition accuracy. In summary, this research not only provides a new framework for the theoretical integration of image processing and multi-sensor data, but also brings innovative technical solutions for the development and application of practical navigation systems.
Evaluating regression and probabilistic methods for ECG-based electrolyte prediction
Authors: von Bachmann Philipp , Gedon Daniel , Gustafsson Fredrik K. , Ribeiro Antônio H. , Lampa Erik , Gustafsson Stefan , Sundström Johan , Schön Thomas B.
Published: July 2024

Imbalances in electrolyte concentrations can have severe consequences, but accurate and accessible measurements could improve patient outcomes. The current measurement method based on blood tests is accurate but invasive and time-consuming and is often unavailable for example in remote locations or an ambulance setting. In this paper, we explore the use of deep neural networks (DNNs) for regression tasks to accurately predict continuous electrolyte concentrations from electrocardiograms (ECGs), a quick and widely adopted tool. We analyze our DNN models on a novel dataset of over 290,000 ECGs across four major electrolytes and compare their performance with traditional machine learning models. For improved understanding, we also study the full spectrum from continuous predictions to a binary classification of extreme concentration levels. Finally, we investigate probabilistic regression approaches and explore uncertainty estimates for enhanced clinical usefulness. Our results show that DNNs outperform traditional models but model performance varies significantly across different electrolytes. While discretization leads to good classification performance, it does not address the original problem of continuous concentration level prediction. Probabilistic regression has practical potential, but our uncertainty estimates are not perfectly calibrated. Our study is therefore a first step towards developing an accurate and reliable ECG-based method for electrolyte concentration level prediction—a method with high potential impact within multiple clinical scenarios.
Prediction of anastomotic insufficiency based on the mucosal microbiome prior to colorectal surgery: a proof-of-principle study
Authors: Lehr Konrad , Lange Undine Gabriele , Hipler Noam Mathias , Vilchez-Vargas Ramiro , Hoffmeister Albrecht , Feisthammel Jürgen , Buchloh Dorina , Schanze Denny , Zenker Martin , Gockel Ines , Link Alexander , Jansen-Winkeln Boris
Published: July 2024

Anastomotic leakage (AL) is a potentially life-threatening complication following colorectal cancer (CRC) resection. In this study, we aimed to unravel longitudinal changes in microbial structure before, during, and after surgery and to determine if microbial alterations may be predictive for risk assessment between sufficient anastomotic healing (AS) and AL prior surgery. We analysed the microbiota of 134 colon mucosal biopsies with 16S rRNA V1-V2 gene sequencing. Samples were collected from three location sites before, during, and after surgery, and patients received antibiotics after the initial collection and during surgery. The microbial structure showed dynamic surgery-related changes at different time points. Overall bacterial diversity and the abundance of some genera such as Faecalibacterium or Alistipes decreased over time, while the genera Enterococcus and Escherichia_Shigella increased. The distribution of taxa between AS and AL revealed significant differences in the abundance of genera such as Prevotella, Faecalibacterium and Phocaeicola. In addition to Phocaeicola, Ruminococcus2 and Blautia showed significant differences in abundance between preoperative sample types. ROC analysis of the predictive value of these genera for AL revealed an AUC of 0.802 (p = 0.0013). In summary, microbial composition was associated with postoperative outcomes, and the abundance of certain genera may be predictive of postoperative complications.
Urine metabolomics unravel the effects of short-term dietary interventions on oxidative stress and inflammation: a randomized controlled crossover trial
Authors: Singh Digar , Ham Dongwoo , Kim Seong-Ah , Kothari Damini , Park Yu Jin , Joung Hyojee , Lee Choong Hwan
Published: July 2024

Dietary biomarkers in urine remain elusive when evaluating diet-induced oxidative stress and inflammation. In our previous study, we conducted a randomized controlled crossover trial to compare the short-term (4-weeks) effects of the balanced Korean diet (BKD) with Western diets, including the 2010 dietary guidelines for Americans (2010 DGA) and typical American diet (TAD), on various metabolic indices in obese Korean adults. Building on this work, the current research focuses on the impact of these dietary interventions on oxidative stress (d-ROMs and BAP) and inflammation (CRP, TNF-α, IL-6, IL-1β, MCP-1) biomarkers in serum, and the concurrent urine metabolomes. Each dietary regimen was in silico and experimentally examined for their antioxidant levels using ABTS, DPPH, and FRAP assays, as well as total flavonoid (TFC) and total phenolic (TPC) contents. We assessed post-intervention variations in oxidative stress and inflammation biomarkers in serum, as well as the urine metabolite profiles for the participants (n = 48, average age: 41 years). Antioxidant contents and associated total antioxidant capacity (TAC) were significantly higher for the recommended diets (BKD and 2010 DGA) compared to TAD (p < 0.05). Butanol extracts from recommended diets (BKD and 2010 DGA) showed significantly higher antioxidant activity compared to TAD in ABTS (p < 0.01), DPPH, and FRAP (p < 0.05) assays. Consistent results were observed in total phenolic and flavonoid contents, mirroring their respective antioxidant activities. Following the intervention period, oxidative stress & inflammation markers in serum varied marginally, however, the urine metabolite profiles were clearly demarcated for the BKD and Western dietary groups (PC1 = 5.41%). For BKD group, the pre- and post-intervention urine metabolite profiles were clearly segregated (PLS2 = 2.93%). Compared to TAD, urine extracts from the recommended dietary group showed higher abundance of benzoic acid & phenolic derivatives (VIP > 0.7,p < 0.05). Metabolites associated with oxidative stress were observed higher in the urine samples from Western dietary groups compared to BKD. Urine metabolomics data delineated the post-intervention effects of three dietary interventions which corroborates the respective findings for their effects on metabolic indices.
Terahertz magnetic response of plasmonic metasurface resonators: origin and orientation dependence
Authors: Tesi Lorenzo , Hrtoň Martin , Bloos Dominik , Hentschel Mario , Šikola Tomáš , van Slageren Joris
Published: July 2024

The increasing miniaturization of everyday devices necessitates advancements in surface-sensitive techniques to access phenomena more effectively. Magnetic resonance methods, such as nuclear or electron paramagnetic resonance, play a crucial role due to their unique analytical capabilities. Recently, the development of a novel plasmonic metasurface resonator aimed at boosting the THz electron magnetic response in 2D materials resulted in a significant magnetic field enhancement, confirmed by both numerical simulations and experimental data. Yet, the mechanisms driving this resonance were not explored in detail. In this study, we elucidate these mechanisms using two semi-analytical models: one addressing the resonant behaviour and the other examining the orientation-dependent response, considering the anisotropy of the antennas and experimental framework. Our findings contribute to advancing magnetic spectroscopic techniques, broadening their applicability to 2D systems.