bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the osmosensitive transcription factor NFAT5 in corneal edema resorption after injury
Authors: Hadrian Karina , Musial Gwen , Schönberg Alfrun , Georgiev Tihomir , Küper Christoph , Bock Felix , Jantsch Jonathan , Cursiefen Claus , Eming Sabine A. , Hos Deniz 
Published: March 2023

AbstractThe osmosensitive transcription factor nuclear factor of activated T cells 5 (NFAT5; or tonicity-responsive enhancer binding protein; TonEBP) plays a key role in macrophage-driven regulation of cutaneous salt and water balance. In the immune-privileged and transparent cornea, disturbances in fluid balance and pathological edema result in corneal transparency loss, which is one of the main causes of blindness worldwide. The role of NFAT5 in the cornea has not yet been investigated. We analyzed the expression and function of NFAT5 in naive corneas and in an established mouse model of perforating corneal injury (PCI), which causes acute corneal edema and transparency loss. In uninjured corneas, NFAT5 was mainly expressed in corneal fibroblasts. In contrast, after PCI, NFAT5 expression was highly upregulated in recruited corneal macrophages. NFAT5 deficiency did not alter corneal thickness in steady state; however, loss of NFAT5 led to accelerated resorption of corneal edema after PCI. Mechanistically, we found that myeloid cell-derived NFAT5 is crucial for controlling corneal edema, as edema resorption after PCI was significantly enhanced in mice with conditional loss of NFAT5 in the myeloid cell lineage, presumably due to increased pinocytosis of corneal macrophages. Collectively, we uncovered a suppressive role for NFAT5 in corneal edema resorption, thereby identifying a novel therapeutic target to combat edema-induced corneal blindness.
The impact of obesity and overweight on response to internet-delivered cognitive behavioural therapy for adults with chronic health conditions
Authors: Heriseanu Andreea I. , Karin Eyal , Walker Jennie , Scott Amelia J. , Bisby Madelyne A. , Gandy Milena , Dudeney Joanne , Fisher Alana , Titov Nickolai , Dear Blake F. 
Published: March 2023

AbstractBackgroundThere is growing evidence that internet-delivered cognitive behavioural therapy (iCBT) can improve functioning and reduce psychological distress in people with chronic health conditions. Obesity frequently co-occurs with chronic health conditions, yet its impact on response to psychological interventions in this population is not known. The current study examined associations between BMI and clinical outcomes (depression, anxiety, disability, and satisfaction with life) following a transdiagnostic iCBT program targeting adjustment to chronic illness.MethodsParticipants from a large randomised controlled trial, who provided information on height and weight, were included (N = 234; mean age= 48.32, SD = 13.80; mean BMI = 30.43, SD = 8.30, range 16.18–67.52; 86.8% female). The influence of baseline BMI range on treatment outcomes at post-treatment and 3-month follow-up was examined using generalized estimating equations. We also examined changes in BMI and in participants’ perceived impact of weight on their health.ResultsImprovement in all outcomes occurred across BMI ranges; additionally, persons with obesity or overweight generally experienced greater symptom reductions than those within a healthy weight range. A greater proportion of participants with obesity achieved clinically significant change on key outcomes (e.g., depression: 32% [95% CI: 25%, 39%]) than participants with a healthy weight (21% [95% CI: 15%, 26%]) or overweight (24% [95% CI: 18%, 29%],p = 0.016). There were no significant changes in BMI from pre-treatment to 3-month follow-up, however there were significant reductions on the self-rated impact of weight on health.ConclusionsPersons with chronic health conditions and with obesity or overweight benefit at least as much as those with a healthy BMI from iCBT programs targeting psychological adjustment to chronic illness, even without changes in BMI. iCBT programs may be an important component in the self-management of this population, and may address barriers implicated in health behaviour change.
Label-free superior contrast with c-band ultra-violet extinction microscopy
Authors: Ströhl Florian , Wolfson Deanna L. , Opstad Ida S. , Hansen Daniel H. , Mao Hong , Ahluwalia Balpreet S. 
Published: March 2023

AbstractIn 1934, Frits Zernike demonstrated that it is possible to exploit the sample’s refractive index to obtain superior contrast images of biological cells. The refractive index contrast of a cell surrounded by media yields a change in the phase and intensity of the transmitted light wave. This change can be due to either scattering or absorption caused by the sample. Most cells are transparent at visible wavelengths, which means the imaginary component of their complex refractive index, also known as extinction coefficient k, is close to zero. Here, we explore the use of c-band ultra-violet (UVC) light for high-contrast high-resolution label-free microscopy, as k is naturally substantially higher in the UVC than at visible wavelengths. Using differential phase contrast illumination and associated processing, we achieve a 7- to 300-fold improvement in contrast compared to visible-wavelength and UVA differential interference contrast microscopy or holotomography, and quantify the extinction coefficient distribution within liver sinusoidal endothelial cells. With a resolution down to 215 nm, we are, for the first time in a far-field label-free method, able to image individual fenestrations within their sieve plates which normally requires electron or fluorescence superresolution microscopy. UVC illumination also matches the excitation peak of intrinsically fluorescent proteins and amino acids and thus allows us to utilize autofluorescence as an independent imaging modality on the same setup.
Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study
Authors: Kirenga Bruce J. , Mugenyi Levicatus , Sánchez-Rico Marina , Kyobe Henry , Muttamba Winters , Mugume Raymond , Mwesigwa Eliya , Kalimo Ezra , Nyombi Vicky , Segawa Ivan , Namakula Loryndah Olive , Sekibira Rogers , Kabweru Wilberforce , Byanyima Rosemary , Aanyu Hellen , Byakika-Kibwika Pauline , Mwebesa Henry G. , Hoertel Nicolas , Bazeyo William 
Published: March 2023

AbstractPrior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.
Nicotine dependence and insula subregions: functional connectivity and cue-induced activation
Authors: Ghahremani Dara G. , Pochon Jean-Baptiste F. , Diaz Maylen Perez , Tyndale Rachel F. , Dean Andy C. , London Edythe D. 
Published: March 2023

AbstractNicotine dependence is a major predictor of relapse in people with Tobacco Use Disorder (TUD). Accordingly, therapies that reduce nicotine dependence may promote sustained abstinence from smoking. The insular cortex has been identified as a promising target in brain-based therapies for TUD, and has three major sub-regions (ventral anterior, dorsal anterior, and posterior) that serve distinct functional networks. How these subregions and associated networks contribute to nicotine dependence is not well understood, and therefore was the focus of this study. Sixty individuals (28 women; 18–45 years old), who smoked cigarettes daily, rated their level of nicotine dependence (on the Fagerström Test for Nicotine Dependence) and, after abstaining from smoking overnight (~12 h), underwent functional magnetic resonance imaging (fMRI) in a resting state. A subset of these participants (N = 48) also completing a cue-induced craving task during fMRI. Correlations between nicotine dependence and resting-state functional connectivity (RSFC) and cue-induced activation of the major insular sub-regions were evaluated. Nicotine dependence was negatively correlated with connectivity of the left and right dorsal, and left ventral anterior insula with regions within the superior parietal lobule (SPL), including the left precuneus. No relationship between posterior insula connectivity and nicotine dependence was found. Cue-induced activation in the left dorsal anterior insula was positively associated with nicotine dependence and negatively associated with RSFC of the same region with SPL, suggesting that craving-related responsivity in this subregion was greater among participants who were more dependent. These results may inform therapeutic approaches, such as brain stimulation, which may elicit differential clinical outcomes (e.g., dependence, craving) depending on the insular subnetwork that is targeted.
Multi-omics analysis identifies RFX7 targets involved in tumor suppression and neuronal processes
Authors: Schwab Katjana , Coronel Luis , Riege Konstantin , Sacramento Erika K. , Rahnis Norman , Häckes David , Cirri Emilio , Groth Marco , Hoffmann Steve , Fischer Martin 
Published: March 2023

AbstractRecurrently mutated in lymphoid neoplasms, the transcription factor RFX7 is emerging as a tumor suppressor. Previous reports suggested that RFX7 may also have a role in neurological and metabolic disorders. We recently reported that RFX7 responds to p53 signaling and cellular stress. Furthermore, we found RFX7 target genes to be dysregulated in numerous cancer types also beyond the hematological system. However, our understanding of RFX7’s target gene network and its role in health and disease remains limited. Here, we generated RFX7 knock-out cells and employed a multi-omics approach integrating transcriptome, cistrome, and proteome data to obtain a more comprehensive picture of RFX7 targets. We identify novel target genes linked to RFX7’s tumor suppressor function and underscoring its potential role in neurological disorders. Importantly, our data reveal RFX7 as a mechanistic link that enables the activation of these genes in response to p53 signaling.
The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency
Authors: Athanasouli Paraskevi , Balli Martina , De Jaime-Soguero Anchel , Boel Annekatrien , Papanikolaou Sofia , van der Veer Bernard K. , Janiszewski Adrian , Vanhessche Tijs , Francis Annick , El Laithy Youssef , Nigro Antonio Lo , Aulicino Francesco , Koh Kian Peng , Pasque Vincent , Cosma Maria Pia , Verfaillie Catherine , Zwijsen An , Heindryckx Björn , Nikolaou Christoforos , Lluis Frederic 
Published: March 2023

AbstractEarly during preimplantation development and in heterogeneous mouse embryonic stem cells (mESC) culture, pluripotent cells are specified towards either the primed epiblast or the primitive endoderm (PE) lineage. Canonical Wnt signaling is crucial for safeguarding naive pluripotency and embryo implantation, yet the role and relevance of canonical Wnt inhibition during early mammalian development remains unknown. Here, we demonstrate that transcriptional repression exerted by Wnt/TCF7L1 promotes PE differentiation of mESCs and in preimplantation inner cell mass. Time-series RNA sequencing and promoter occupancy data reveal that TCF7L1 binds and represses genes encoding essential naive pluripotency factors and indispensable regulators of the formative pluripotency program, including Otx2 and Lef1. Consequently, TCF7L1 promotes pluripotency exit and suppresses epiblast lineage formation, thereby driving cells into PE specification. Conversely, TCF7L1 is required for PE specification as deletion of Tcf7l1 abrogates PE differentiation without restraining epiblast priming. Taken together, our study underscores the importance of transcriptional Wnt inhibition in regulating lineage specification in ESCs and preimplantation embryo development as well as identifies TCF7L1 as key regulator of this process.
Identifying tumour microenvironment-related signature that correlates with prognosis and immunotherapy response in breast cancer
Authors: Zhao Hongying , Yin Xiangzhe , Wang Lixia , Liu Kailai , Liu Wangyang , Bo Lin , Wang Li 
Published: March 2023

AbstractTumor microenvironment (TME) plays important roles in prognosis and immune evasion. However, the relationship between TME-related genes and clinical prognosis, immune cell infiltration, and immunotherapy response in breast cancer (BRCA) remains unclear. This study described the TME pattern to construct a TME-related prognosis signature, including risk factors PXDNL, LINC02038 and protective factors SLC27A2, KLRB1, IGHV1-12 and IGKV1OR2-108, as an independent prognostic factor for BRCA. We found that the prognosis signature was negatively correlated with the survival time of BRCA patients, infiltration of immune cells and the expression of immune checkpoints, while positively correlated with tumor mutation burden and adverse treatment effects of immunotherapy. Upregulation of PXDNL and LINC02038 and downregulation of SLC27A2, KLRB1, IGHV1-12 and IGKV1OR2-108 in high-risk score group synergistically contribute to immunosuppressive microenvironment which characterized by immunosuppressive neutrophils, impaired cytotoxic T lymphocytes migration and natural killer cell cytotoxicity. In summary, we identified a TME-related prognostic signature in BRCA, which was connected with immune cell infiltration, immune checkpoints, immunotherapy response and could be developed for immunotherapy targets.
A new class A beta-lactamase gene blaCAE-1 coexists with blaAFM-1 in a novel untypable plasmid in Comamonas aquatica
Authors: Li Ying , Fang Chengju , Wang Xu , Liu Qian , Qiu Yichuan , Dai Xiaoyi , Zhang Luhua 
Published: March 2023

AbstractAntimicrobial resistance, especially carbapenem resistance, poses a serious threat to global public health. Here, a carbapenem-resistant Comamonasaquatica isolate SCLZS63 was recovered from hospital sewage. Whole-genome sequencing showed that SCLZS63 has a 4,048,791-bp circular chromosome and three plasmids. The carbapenemase gene blaAFM-1 is located on the 143,067-bp untypable plasmid p1_SCLZS63, which is a novel type of plasmid with two multidrug-resistant (MDR) regions. Notably, a novel class A serine β-lactamase gene, blaCAE-1, coexists with blaAFM-1 in the mosaic MDR2 region. Cloning assay showed that CAE-1 confers resistance to ampicillin, piperacillin, cefazolin, cefuroxime, and ceftriaxone, and elevates the MIC of ampicillin-sulbactam two-fold in Escherichia coli DH5α, suggesting that CAE-1 functions as a broad-spectrum β-lactamase. Amino acid sequences analysis suggested that blaCAE-1 may originate from Comamonadaceae. The blaAFM-1 in p1_SCLZS63 is located in a conserved structure of ISCR29-ΔgroL-blaAFM-1-ble-ΔtrpF-ΔISCR27-msrB-msrA-yfcG-corA. Comprehensive analysis of the blaAFM-bearing sequences revealed important roles of ISCR29 and ΔISCR27 in the mobilization and truncation of the core module of blaAFM alleles, respectively. The diverse passenger contents of class 1 integrons flanking the blaAFM core module make the complexity of genetic contexts for blaAFM. In conclusion, this study reveals that Comamonas may act as an important reservoir for antibiotics-resistance genes and plasmids in the environment. Continuous monitoring for the environmental emergence of antimicrobial-resistant bacteria is needed to control the spread of antimicrobial resistance.
Depression, anxiety and post-traumatic stress during the 2022 Russo-Ukrainian war, a comparison between populations in Poland, Ukraine, and Taiwan
Authors: Chudzicka-Czupała Agata , Hapon Nadiya , Chiang Soon-Kiat , Żywiołek-Szeja Marta , Karamushka Liudmyla , Lee Charlotte T. , Grabowski Damian , Paliga Mateusz , Rosenblat Joshua D. , Ho Roger , McIntyre Roger S. , Chen Yi-Lung 
Published: March 2023

AbstractUkraine has been embroiled in an increasing war since February 2022. In addition to Ukrainians, the Russo-Ukraine war has affected Poles due to the refugee crisis and the Taiwanese, who are facing a potential crisis with China. We examined the mental health status and associated factors in Ukraine, Poland, and Taiwan. The data will be used for future reference as the war is still ongoing. From March 8 to April 26, 2022, we conducted an online survey using snowball sampling techniques in Ukraine, Poland, and Taiwan. Depression, anxiety, and stress were measured using the Depression, Anxiety, and Stress (DASS)-21 item scale; post-traumatic stress symptoms by the Impact of Event Scale-Revised (IES-R) and coping strategies by the Coping Orientation to Problems Experienced Inventory (Brief-COPE). We used multivariate linear regression to identify factors significantly associated with DASS-21 and IES-R scores. There were 1626 participants (Poland: 1053; Ukraine: 385; Taiwan: 188) in this study. Ukrainian participants reported significantly higher DASS-21 (p < 0.001) and IES-R (p < 0.01) scores than Poles and Taiwanese. Although Taiwanese participants were not directly involved in the war, their mean IES-R scores (40.37 ± 16.86) were only slightly lower than Ukrainian participants (41.36 ± 14.94). Taiwanese reported significantly higher avoidance scores (1.60 ± 0.47) than the Polish (0.87 ± 0.53) and Ukrainian (0.91 ± 0.5) participants (p < 0.001). More than half of the Taiwanese (54.3%) and Polish (80.3%) participants were distressed by the war scenes in the media. More than half (52.5%) of the Ukrainian participants would not seek psychological help despite a significantly higher prevalence of psychological distress. Multivariate linear regression analyses found that female gender, Ukrainian and Polish citizenship, household size, self-rating health status, past psychiatric history, and avoidance coping were significantly associated with higher DASS-21 and IES-R scores after adjustment of other variables (p < 0.05). We have identified mental health sequelae in Ukrainian, Poles, and Taiwanese with the ongoing Russo-Ukraine war. Risk factors associated with developing depression, anxiety, stress, and post-traumatic stress symptoms include female gender, self-rating health status, past psychiatric history, and avoidance coping. Early resolution of the conflict, online mental health interventions, delivery of psychotropic medications, and distraction techniques may help to improve the mental health of people who stay inside and outside Ukraine.
Increased probability of hot and dry weather extremes during the growing season threatens global crop yields
Authors: Heino Matias , Kinnunen Pekka , Anderson Weston , Ray Deepak K. , Puma Michael J. , Varis Olli , Siebert Stefan , Kummu Matti 
Published: March 2023

AbstractAlthough extreme weather events recur periodically everywhere, the impacts of their simultaneous occurrence on crop yields are globally unknown. In this study, we estimate the impacts of combined hot and dry extremes as well as cold and wet extremes on maize, rice, soybean, and wheat yields using gridded weather data and reported crop yield data at the global scale for 1980–2009. Our results show that co-occurring extremely hot and dry events have globally consistent negative effects on the yields of all inspected crop types. Extremely cold and wet conditions were observed to reduce crop yields globally too, although to a lesser extent and the impacts being more uncertain and inconsistent. Critically, we found that over the study period, the probability of co-occurring extreme hot and dry events during the growing season increased across all inspected crop types; wheat showing the largest, up to a six-fold, increase. Hence, our study highlights the potentially detrimental impacts that increasing climate variability can have on global food production.
Learning curve for open surgical repair of acute type A aortic dissection
Authors: Hou Bo-Cheng , Huang Yu-Tung , Hsiao Fu-Chih , Wu Chien-Chia , Cheng Yu-Ting , Liu Kuo-Sheng , Chang Shang-Hung , Chu Pao-Hsien , Chou An-Hsun , Chen Shao-Wei 
Published: March 2023

AbstractThere is scarce evidence about the surgeon learning curve of acute type A aortic dissection surgery and whether the optimal procedure number exists when training a cardiovascular surgeon. A total of 704 patients with acute type A aortic dissection surgery performed by 17 junior surgeons who can identify their first career surgery from January 1, 2005, to December 31, 2018, are included. The surgeon experience volume is defined as the cumulative number of acute type A aortic dissection surgery of the surgeon since January 1, 2005. The primary outcome was in-hospital mortality. The possibility of non-linearity and cutoffs for surgeon experience volume level was explored using a restricted cubic spline model. The results revealed that more surgeon experience volume is significantly correlated to a lower in-hospital mortality rate (r = − 0.58, P = 0.010). The RCS model shows for an operator who reaches 25 cumulative volumes of acute type A aortic dissection surgery, the average in-hospital mortality rate of the patients can be below 10%. Furthermore, the longer duration from the 1st to 25th operations of the surgeon is significantly correlated to a higher average in-hospital mortality rate of the patients (r = 0.61, p = 0.045). Acute type A aortic dissection surgery has a prominent learning curve in terms of improving clinical outcomes. The findings suggest fostering high-volume surgeons at high-volume hospitals can achieve optimal clinical outcomes.