bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal mortality and video assessment of resuscitation in four district hospitals in Pemba, Tanzania
Authors: Holm-Hansen Charlotte Carina , Lund Stine , Skytte Tine Bruhn , Molenaar Jil , Steensgaard Christina Nadia , Mohd Ulfat Amour , Mzee Said , Ali Said Mouhammed , Kjærgaard Jesper , Greisen Gorm , Sorensen Jette Led , Poulsen Anja 
Published: September 2023

AbstractBackgroundWe aimed to assess risk factors for neonatal mortality, quality of neonatal resuscitation (NR) on videos and identify potential areas for improvement.MethodsThis prospective cohort study included women in childbirth and their newborns at four district hospitals in Pemba, Tanzania. Videos were analysed for quality-of-care. Questionnaires on quality-of-care indicators were answered by health workers (HW) and women. Risk factors for neonatal mortality were analysed in a binomial logistic regression model.Results1440 newborns were enrolled. 34 newborns died within the neonatal period (23.6 per 1000 live births). Ninety neonatal resuscitations were performed, 20 cases on video. Positive pressure ventilation (PPV) was inadequate in 15 cases (75%). Half (10/20) did not have PPV initiated within the first minute, and in one case (5.0%), no PPV was performed. PPV was not sustained in 16/20 (80%) newborns. Of the 20 videos analysed, death occurred in 10 newborns: 8 after resuscitation attempts and two within the first 24 h. Most of HW 49/56 (87.5%) had received training in NR.ConclusionsVideo analysis of NR revealed significant deviations from guidelines despite 87.5% of HW being trained in NR. Videos provided direct evidence of gaps in the quality of care and areas for future education, particularly effective PPV.ImpactNeonatal mortality in Pemba is 23.6 per 1000 livebirths, with more than 90% occurring in the first 24 h of life.Video assessment of neonatal resuscitation revealed deviations from guidelines and can add to understanding challenges and aid intervention design.The present study using video assessment of neonatal resuscitation is the first one performed at secondary-level hospitals where many of the world’s births are conducted.Almost 90% of the health workers had received training in neonatal resuscitation, and the paper can aid intervention design by understanding the actual challenges in neonatal resuscitation.
Polygenic risk scores of lithium response and treatment resistance in major depressive disorder
Authors: Xiong Ying , Karlsson Robert , Song Jie , Kowalec Kaarina , Rück Christian , Sigström Robert , Jonsson Lina , Clements Caitlin C. , Andersson Evelyn , Boberg Julia , Lewis Cathryn M. , Sullivan Patrick F. , Landén Mikael , Lu Yi 
Published: September 2023

AbstractTreatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within ~4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10–1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.
Psychological interventions for the prevention of depression relapse: systematic review and network meta-analysis
Authors: Zhou Yurong , Zhao Defeng , Zhu Xiaotong , Liu Lu , Meng Ming , Shao Xiaojun , Zhu Xueyan , Xiang Jing , He Jiali , Zhao Yimeng , Yuan Yuman , Gao Rui , Jiang Lin , Zhu Gang 
Published: September 2023

AbstractDepression is highly prevalent and easily relapses. Psychological interventions are effective for the prevention of depression relapse. This systematic review and network meta-analysis aimed to compare the efficacy at the same follow-up time points of psychological interventions in depression. We searched PubMed, Embase, and PsycINFO via OVID, and the Cochrane Library published up to December 12, 2021, and PubMed up to July 1, 2022. The primary outcome was depression relapse, considering the same time points that were extracted on survival curves or relapse curves. The study protocol was registered with PROSPERO, CRD42022343327. A total of 2,871 patients were included from 25 RCTs. Mindfulness-based cognitive therapy (MBCT) was significantly better than placebo at the 3 months, the 6 months, and the 9 months at follow-up. Cognitive behavioral therapy (CBT) was significantly better than treatment as usual at the 3 months, the 9 months, the 12 months, and the 15 months at follow-up. CBT was significantly better than placebo at the 21 months and the 24 months at follow-up. Behavioral activation therapy was significantly better than placebo at the 21 months and the 24 months at follow-up. Interpersonal psychotherapy was significantly better than placebo at the 24-month follow-up. All psychological interventions included in the study were significantly better than supportive counseling most of the time. The results were robust in various sensitivity and subgroup analyses. In conclusion, MBCT had a continuous effect in preventing relapse of depression. CBT had the longest but not continuous effect in preventing relapse of depression. The effects of behavioral activation therapy and interpersonal therapy for the prevention of depression appeared late. All psychological interventions included in the study were more effective than supportive counseling. More evidence is needed from large comparative trials that provide long-term follow-up data.
Synthesis of a covalent organic framework with hetero-environmental pores and its medicine co-delivery application
Authors: Ji Wenyan , Zhang Pai , Feng Guangyuan , Cheng Yuan-Zhe , Wang Tian-Xiong , Yuan Daqiang , Cha Ruitao , Ding Xuesong , Lei Shengbin , Han Bao-Hang 
Published: September 2023

AbstractThe topology type and the functionalization of pores play an important role in regulating the performance of covalent organic frameworks. Herein, we designed and synthesized the covalent organic framework with hetero-environmental pores using predesigned asymmetrical dialdehyde monomer. According to the results of structural characterization, crystallinity investigation, and theoretical calculation, the hetero-environmental pores of the obtained framework are regarded as the alternant arrangement. The distinctive hetero pore structure leads the designed material to show more advantages as compared with control materials in loading both hydrophobic and hydrophilic antibiotics for wound healing. This dual-antibiotic strategy can expand the antibacterial range as compared with the single antibiotic one, and reduce the generation of drug resistance. In summary, this strategy for designing covalent organic frameworks with hetero-environmental pores can extend the structural variety and provide a pathway for improving the practical application performance of these materials.
Defining the condensate landscape of fusion oncoproteins
Authors: Tripathi Swarnendu , Shirnekhi Hazheen K. , Gorman Scott D. , Chandra Bappaditya , Baggett David W. , Park Cheon-Gil , Somjee Ramiz , Lang Benjamin , Hosseini Seyed Mohammad Hadi , Pioso Brittany J. , Li Yongsheng , Iacobucci Ilaria , Gao Qingsong , Edmonson Michael N. , Rice Stephen V. , Zhou Xin , Bollinger John , Mitrea Diana M. , White Michael R. , McGrail Daniel J. , Jarosz Daniel F. , Yi S. Stephen , Babu M. Madan , Mullighan Charles G. , Zhang Jinghui , Sahni Nidhi , Kriwacki Richard W. 
Published: September 2023

AbstractFusion oncoproteins (FOs) arise from chromosomal translocations in ~17% of cancers and are often oncogenic drivers. Although some FOs can promote oncogenesis by undergoing liquid-liquid phase separation (LLPS) to form aberrant biomolecular condensates, the generality of this phenomenon is unknown. We explored this question by testing 166 FOs in HeLa cells and found that 58% formed condensates. The condensate-forming FOs displayed physicochemical features distinct from those of condensate-negative FOs and segregated into distinct feature-based groups that aligned with their sub-cellular localization and biological function. Using Machine Learning, we developed a predictor of FO condensation behavior, and discovered that 67% of ~3000 additional FOs likely form condensates, with 35% of those predicted to function by altering gene expression. 47% of the predicted condensate-negative FOs were associated with cell signaling functions, suggesting a functional dichotomy between condensate-positive and -negative FOs. Our Datasets and reagents are rich resources to interrogate FO condensation in the future.
Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner
Authors: Luis Tiago C. , Barkas Nikolaos , Carrelha Joana , Giustacchini Alice , Mazzi Stefania , Norfo Ruggiero , Wu Bishan , Aliouat Affaf , Guerrero Jose A. , Rodriguez-Meira Alba , Bouriez-Jones Tiphaine , Macaulay Iain C. , Jasztal Maria , Zhu Guangheng , Ni Heyu , Robson Matthew J. , Blakely Randy D. , Mead Adam J. , Nerlov Claus , Ghevaert Cedric , Jacobsen Sten Eirik W. 
Published: September 2023

AbstractHematopoietic stem cells (HSCs) residing in specialized niches in the bone marrow are responsible for the balanced output of multiple short-lived blood cell lineages in steady-state and in response to different challenges. However, feedback mechanisms by which HSCs, through their niches, sense acute losses of specific blood cell lineages remain to be established. While all HSCs replenish platelets, previous studies have shown that a large fraction of HSCs are molecularly primed for the megakaryocyte-platelet lineage and are rapidly recruited into proliferation upon platelet depletion. Platelets normally turnover in an activation-dependent manner, herein mimicked by antibodies inducing platelet activation and depletion. Antibody-mediated platelet activation upregulates expression of Interleukin-1 (IL-1) in platelets, and in bone marrow extracellular fluid in vivo. Genetic experiments demonstrate that rather than IL-1 directly activating HSCs, activation of bone marrow Lepr+ perivascular niche cells expressing IL-1 receptor is critical for the optimal activation of quiescent HSCs upon platelet activation and depletion. These findings identify a feedback mechanism by which activation-induced depletion of a mature blood cell lineage leads to a niche-dependent activation of HSCs to reinstate its homeostasis.
NLRP6 potentiates PI3K/AKT signalling by promoting autophagic degradation of p85α to drive tumorigenesis
Authors: Zhi Feng , Li Bowen , Zhang Chuanxia , Xia Fan , Wang Rong , Xie Weihong , Cai Sihui , Zhang Dawei , Kong Ren , Hu Yiqiao , Yang Yilin , Peng Ya , Cui Jun 
Published: September 2023

AbstractThe PI3K/AKT pathway plays an essential role in tumour development. NOD-like receptors (NLRs) regulate innate immunity and are implicated in cancer, but whether they are involved in PI3K/AKT pathway regulation is poorly understood. Here, we report that NLRP6 potentiates the PI3K/AKT pathway by binding and destabilizing p85α, the regulatory subunit of PI3K. Mechanistically, NLRP6 recruits the E3 ligase RBX1 to p85α and ubiquitinates lysine 256 on p85α, which is recognized by the autophagy cargo receptor OPTN, causing selective autophagic degradation of p85α and subsequent activation of the PI3K/AKT pathway by reducing PTEN stability. We further show that loss of NLRP6 suppresses cell proliferation, colony formation, cell migration, and tumour growth in glioblastoma cells in vitro and in vivo. Disruption of the NLRP6/p85α interaction using the Pep9 peptide inhibits the PI3K/AKT pathway and generates potent antitumour effects. Collectively, our results suggest that NLRP6 promotes p85α degradation via selective autophagy to drive tumorigenesis, and the interaction between NLRP6 and p85α can be a promising therapeutic target for tumour treatment.
An amide to thioamide substitution improves the permeability and bioavailability of macrocyclic peptides
Authors: Ghosh Pritha , Raj Nishant , Verma Hitesh , Patel Monika , Chakraborti Sohini , Khatri Bhavesh , Doreswamy Chandrashekar M. , Anandakumar S. R. , Seekallu Srinivas , Dinesh M. B. , Jadhav Gajanan , Yadav Prem Narayan , Chatterjee Jayanta 
Published: September 2023

AbstractSolvent shielding of the amide hydrogen bond donor (NH groups) through chemical modification or conformational control has been successfully utilized to impart membrane permeability to macrocyclic peptides. We demonstrate that passive membrane permeability can also be conferred by masking the amide hydrogen bond acceptor (>C = O) through a thioamide substitution (>C = S). The membrane permeability is a consequence of the lower desolvation penalty of the macrocycle resulting from a concerted effect of conformational restriction, local desolvation of the thioamide bond, and solvent shielding of the amide NH groups. The enhanced permeability and metabolic stability on thioamidation improve the bioavailability of a macrocyclic peptide composed of hydrophobic amino acids when administered through the oral route in rats. Thioamidation of a bioactive macrocyclic peptide composed of polar amino acids results in analogs with longer duration of action in rats when delivered subcutaneously. These results highlight the potential of O to S substitution as a stable backbone modification in improving the pharmacological properties of peptide macrocycles.
Computational remodeling of an enzyme conformational landscape for altered substrate selectivity
Authors: St-Jacques Antony D. , Rodriguez Joshua M. , Eason Matthew G. , Foster Scott M. , Khan Safwat T. , Damry Adam M. , Goto Natalie K. , Thompson Michael C. , Chica Roberto A. 
Published: September 2023

AbstractStructural plasticity of enzymes dictates their function. Yet, our ability to rationally remodel enzyme conformational landscapes to tailor catalytic properties remains limited. Here, we report a computational procedure for tuning conformational landscapes that is based on multistate design of hinge-mediated domain motions. Using this method, we redesign the conformational landscape of a natural aminotransferase to preferentially stabilize a less populated but reactive conformation and thereby increase catalytic efficiency with a non-native substrate, resulting in altered substrate selectivity. Steady-state kinetics of designed variants reveals activity increases with the non-native substrate of approximately 100-fold and selectivity switches of up to 1900-fold. Structural analyses by room-temperature X-ray crystallography and multitemperature nuclear magnetic resonance spectroscopy confirm that conformational equilibria favor the target conformation. Our computational approach opens the door to targeted alterations of conformational states and equilibria, which should facilitate the design of biocatalysts with customized activity and selectivity.
The neglected role of abandoned cropland in supporting both food security and climate change mitigation
Authors: Zheng Qiming , Ha Tim , Prishchepov Alexander V. , Zeng Yiwen , Yin He , Koh Lian Pin 
Published: September 2023

AbstractDespite the looming land scarcity for agriculture, cropland abandonment is widespread globally. Abandoned cropland can be reused to support food security and climate change mitigation. Here, we investigate the potentials and trade-offs of using global abandoned cropland for recultivation and restoring forests by natural regrowth, with spatially-explicit modelling and scenario analysis. We identify 101 Mha of abandoned cropland between 1992 and 2020, with a capability of concurrently delivering 29 to 363 Peta-calories yr-1 of food production potential and 290 to 1,066 MtCO2 yr-1 of net climate change mitigation potential, depending on land-use suitability and land allocation strategies. We also show that applying spatial prioritization is key to maximizing the achievable potentials of abandoned cropland and demonstrate other possible approaches to further increase these potentials. Our findings offer timely insights into the potentials of abandoned cropland and can inform sustainable land management to buttress food security and climate goals.
Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex
Authors: Yuan Ling , Han Yaoyao , Zhao Jiazheng , Zhang Yixiao , Sun Yadong 
Published: September 2023

AbstractRemoval of introns from transfer RNA precursors (pre-tRNAs) occurs in all living organisms. This is a vital phase in the maturation and functionality of tRNA. Here we present a 3.2 Å-resolution cryo-EM structure of an active human tRNA splicing endonuclease complex bound to an intron-containing pre-tRNA. TSEN54, along with the unique regions of TSEN34 and TSEN2, cooperatively recognizes the mature body of pre-tRNA and guides the anticodon-intron stem to the correct position for splicing. We capture the moment when the endonucleases are poised for cleavage, illuminating the molecular mechanism for both 3′ and 5′ cleavage reactions. Two insertion loops from TSEN54 and TSEN2 cover the 3′ and 5′ splice sites, respectively, trapping the scissile phosphate in the center of the catalytic triad of residues. Our findings reveal the molecular mechanism for eukaryotic pre-tRNA recognition and cleavage, as well as the evolutionary relationship between archaeal and eukaryotic TSENs.
Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane
Authors: Park Si Hoon , Han Juhyun , Jeong Byung-Cheon , Song Ju Han , Jang Se Hwan , Jeong Hyeongseop , Kim Bong Heon , Ko Young-Gyu , Park Zee-Yong , Lee Kyung Eun , Hyun Jaekyung , Song Hyun Kyu 
Published: September 2023

AbstractDefects in plasma membrane repair can lead to muscle and heart diseases in humans. Tripartite motif-containing protein (TRIM)72 (mitsugumin 53; MG53) has been determined to rapidly nucleate vesicles at the site of membrane damage, but the underlying molecular mechanisms remain poorly understood. Here we present the structure of Mus musculus TRIM72, a complete model of a TRIM E3 ubiquitin ligase. We demonstrated that the interaction between TRIM72 and phosphatidylserine-enriched membranes is necessary for its oligomeric assembly and ubiquitination activity. Using cryogenic electron tomography and subtomogram averaging, we elucidated a higher-order model of TRIM72 assembly on the phospholipid bilayer. Combining structural and biochemical techniques, we developed a working molecular model of TRIM72, providing insights into the regulation of RING-type E3 ligases through the cooperation of multiple domains in higher-order assemblies. Our findings establish a fundamental basis for the study of TRIM E3 ligases and have therapeutic implications for diseases associated with membrane repair.
A synthetic data set to benchmark anti-money laundering methods
Authors: Jensen Rasmus Ingemann Tuffveson , Ferwerda Joras , Jørgensen Kristian Sand , Jensen Erik Rathje , Borg Martin , Krogh Morten Persson , Jensen Jonas Brunholm , Iosifidis Alexandros 
Published: September 2023

AbstractBank transactions are highly confidential. As a result, there are no real public data sets that can be used to investigate and compare anti-money laundering (AML) methods in banks. This severely limits research on important AML problems such as efficiency, effectiveness, class imbalance, concept drift, and interpretability. To address the issue, we present SynthAML: a synthetic data set to benchmark statistical and machine learning methods for AML. The data set builds on real data from Spar Nord, a systemically important Danish bank, and contains 20,000 AML alerts and over 16 million transactions. Experimental results indicate that performance on SynthAML can be transferred to the real world. As use cases, we present and discuss open problems in the AML literature.
A novel signature for predicting prognosis and immune landscape in cutaneous melanoma based on anoikis-related long non-coding RNAs
Authors: Zhang Miao , Zuo Yuzhi , Guo Jian , Yang Lushan , Wang Yizhi , Tan Meiyun , Guo Xing 
Published: September 2023

AbstractAnoikis is a unique form of apoptosis associated with vascularization and distant metastasis in cancer. Eliminating anoikis resistance in tumor cells could be a promising target for improving the prognosis of terminal cancer patients. However, current studies have not elaborated on the prognosis effect of anoikis-related long non-coding RNAs (lncRNAs) in cutaneous melanoma. Pre-processed data, including RNA sequences and clinical information, were retrieved from TCGA and GTEx databases. After a series of statistical analyses, anoikis-related lncRNAs with prognostic significance were identified, and a unique risk signature was constructed. Risk scores were further analyzed in relation to the tumor microenvironment, tumor immune dysfunction and exclusion, immune checkpoint genes, and RNA methylation genes. The indicators were also used to predict the potentially sensitive anti-cancer drugs. An anoikis-related lncRNAs risk signature consisting of LINC01711, POLH-AS1, MIR205HG, and LINC02416 was successfully established in cutaneous melanoma. Overall survival and progression-free survival of patients were strongly linked with the risk score, independently of other clinical factors. The low-risk group exhibited a more beneficial immunological profile, was less affected by RNA methylation, and was more sensitive to the majority of anti-cancer drugs, all of which indicated a better prognostic outcome. The 4 hub lncRNAs may be fundamental to studying the mechanism of anoikis in cutaneous melanoma and provide personalized therapy for salvaging drug resistance.