bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five-year visual outcome of treatment for retinopathy of prematurity in infants weighing less than 500 g at birth: A multicenter cohort study from J-CREST
Authors: Tomioka Mizuki , Murakami Tomoya , Okamoto Fumiki , Kinoshita Takamasa , Shinomiya Kayo , Nishi Tomo , Jujo Tatsuya , Obata Shumpei , Tsukitome Hideyuki , Ogura Shuntaro , Ueda Kaori , Ishii Ryota , Oshika Tetsuro 
Published: December 2023

Purpose:
To investigate the 5-year treatment outcomes of retinopathy of prematurity (ROP) in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor (VEGF) therapies.

Methods:
A multicenter retrospective study comprised 24 eyes of 13 patients treated for type 1 ROP, followed for 5 years. Initial treatment was laser and anti-VEGF in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, ROP characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent (SE), and astigmatism at 5 years post-treatment.

Results:
Median BCVA was 0.15 logMAR (IQR, 0.0–0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median SE was -2.37 (IQR, -6.1–-0.1); 75% had myopia (≤ -0.5 D), and 25% had high myopia (≤ -6.0 D). Median astigmatism was 1.25 (IQR, 0.9–3.0); 46% had ≥1.5 D. Anti-VEGF treated eyes showed less myopia (p<0.009), with no BCVA or astigmatism difference (p=0.997, p=0.271) compared to laser-treated eyes.

Conclusion:
One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of 20/20 or better) 5 years post-ROP treatment. Refractive errors were common. Anti-VEGF therapy may be superior to laser therapy in terms of myopic refractive error.
Resilience of Patients With Brain Tumor While Awaiting Surgery
Authors: Maneekrong Supawadee , Tankumpuan Thitipong , Danaidutsadeekul Suporn , Siwanuwatn Rungsak 
Published: December 2023

ABSTRACTBACKGROUND:Resilience is the ability of patients to adapt effectively when given a diagnosis of an illness. While awaiting brain tumor surgery, patients often experience uncertainty from brain tumor–related symptoms resulting in inducing depressive symptoms, having physical disability, and reducing quality of life. Resilience studies have been widely conducted in the postoperative phase with a limited knowledge on the preoperative phase. This study aimed to identify predictors of resilience while awaiting brain tumor surgery.METHODS:This cross-sectional predictive study includes 100 participants 18 years and older, with diagnosis of brain tumors, and waiting for brain tumor surgery at the outpatient department of 1 tertiary hospital in Bangkok between August 2022 and February 2023. Multiple linear regression was used to examine the predictors of resilience.RESULTS:Most of the sample (77%) were female with a mean age of 52.71 (13.17) years. The most common type of brain tumor was meningioma (38%). The median waiting time since brain tumor diagnosis until the date of preadmission for operation was 18 (3-1464) days. Symptom severity, social support, and treatment plan were able to explain 37.3% of the variance of resilience in patients awaiting brain tumor surgery (F= 19.077,P< .01,R2= 0.373, adjustedR2= 0.354).CONCLUSION:Resilience is an important skill for patients with brain tumor to manage uncertainty events that occur in their lives. The preoperation phase needs to assess both physical and mental tumor-related symptoms, and include caregivers as part of the care, to promote resilience skill for patients awaiting brain tumor surgery.
Effect of Azilsartan on clinical blood pressure reduction compared to other angiotensin receptor blockers: a systematic review and meta-analysis
Authors: Khan Qaisar Ali , Sharma Shalini , Mulk Ittehad ul , Li David , Belay Naod F. , Afzal Muhammad , Farrukh Ameer Mustafa , Asad Muhammad , Baqi Abdul , Semakieh Bader 
Published: December 2023

Background:
Hypertension has significantly contributed to morbidity and mortality, necessitating effective management. Angiotensin receptor blockers (ARBs) have emerged as a cornerstone in hypertension treatment. Azilsartan, a relatively recent addition to the ARB family, offers unique characteristics, including prodrug activation. This systematic review and meta-analysis aimed to evaluate Azilsartan’s role in reducing clinical blood pressure compared to other ARBs and determine the most effective dosage.

Methods:
Following PRISMA guidelines, a comprehensive literature search was conducted in Medline, Web of Science, Cochrane Library, and clinicaltrials.gov. Eligible studies included adult hypertensive patients receiving Azilsartan compared to other ARBs, with clinical systolic blood pressure (SBP) and diastolic blood pressure (DBP) outcomes. Data extraction and quality assessment were performed, and statistical analysis employed comprehensive meta-analysis (CMA) software.

Results:
Eleven randomized controlled trials encompassing 18 studies involving 6024 patients were included. Azilsartan demonstrated significant reductions in clinical SBP (mean difference=−2.85 mmHg) and DBP (mean difference=−2.095 mmHg) compared to other ARBs. Higher doses of Azilsartan showed greater efficacy, with 80 mg exhibiting the most substantial reduction in SBP. The analysis emphasized the need for more studies investigating lower Azilsartan doses (10 and 20 mg).

Conclusion:
This systematic review and meta-analysis underscore Azilsartan’s effectiveness in reducing SBP and DBP. Dose-dependent effects emphasize the importance of optimal dosing when prescribing Azilsartan. These findings provide valuable insights for clinicians in managing hypertension effectively and call for further research, primarily focusing on lower Azilsartan doses and a more diverse patient population.
Specific Pathology Features Enrich Selection of Endometrial Carcinomas for POLE Testing
Authors: Keyhanian Kianoosh , Han Lucy , Howitt Brooke E. , Longacre Teri 
Published: December 2023

Identification of ultramutated/POLE-mutated endometrial carcinomas (POLE
M ECs) has important implications given its association with better prognosis. However, POLE mutation testing is not widely available. Our objective was to evaluate POLE
M ECs versus POLE wild-type (POLE
WT) ECs, within a cohort of consultation cases with features suggestive of an ultramutated phenotype. Consultation cases of EC that had undergone POLE hotspot mutation testing over a 3.5-year period were included. Tumor morphology and immunohistochemistry were reviewed for both groups. Chi-square test and t test were used for statistical analysis. Of 25 consultation cases, 12 harbored a POLE mutation (48%) and 13 were wild-type (52%). Patients with POLE
M ECs were younger (59 vs. 71.3 y; P=0.01). Ambiguous histomorphology (5/12 vs. 1/13; P=0.04) and the presence of more than rare bizarre nuclei (8/12 vs. 2/12; P=0.01) differed significantly between POLE
M and POLE
WT ECs, respectively. In the POLE
M group, one case (1/12) demonstrated PMS2 loss, and one (1/12) showed subclonal MLH1/PMS2 loss. Among POLE
WT ECs, 3/13 (23%) showed MLH1/PMS2 loss. p53 was subclonally overexpressed in 4/10 POLE
M and 1/13 POLE
WT cases (P=0.06). Mutant p53 patterns were seen in 1/10 POLE
M versus 6/13 of POLE
WT ECs, respectively (P=0.06). Within our cohort, the specificity of ambiguous histomorphology, bizarre nuclei, subclonal biomarker expression, and marked tumor-infiltrating lymphocytes for POLE
M EC was 83%, 80%, 80%, and 71%, respectively. Where universal POLE testing is not available, these data suggest that morphologic screening (particularly ambiguous histomorphology and the presence of more than rare bizarre nuclei) can be useful for selective enrichment of ECs for POLE testing.
‘Shaking the Ladder’ reveals how analytic choices can influence associations in nutrition epidemiology: beef intake and coronary heart disease as a case study
Authors: Vorland Colby J. , O’Connor Lauren E. , Henschel Beate , Huo Cuiqiong , Shikany James M. , Serrano Carlos A. , Henschel Robert , Dickinson Stephanie L. , Ejima Keisuke , Bidulescu Aurelian , Allison David B. , Brown Andrew W. 
Published: December 2023

AbstractBackgroundMany analytic decisions are made when analyzing an observational dataset, such as how to define an exposure or which covariates to include and how to configure them. Modelling the distribution of results for many analytic decisions may illuminate how instrumental decisions are on conclusions in nutrition epidemiology.ObjectiveWe explored how associations between self-reported dietary intake and a health outcome depend on different analytical decisions, using self-reported beef intake from a food frequency questionnaire and incident coronary heart disease as a case study.DesignWe used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and various selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes. We designed three model sets: in the first and second sets (self-reported beef intake modeled as continuous and quintile-defined, respectively), we randomly sampled 1,000,000 model specifications informed by choices used in the published literature, all sharing a consistent covariate base set. The third model set directly emulated existing covariate combinations.ResultsFew models (<1%) were statistically significant at p<0.05. More hazard ratio (HR) point estimates were >1 when beef was polychotomized via quintiles (95% of models) vs. continuous intake (79% of models). When covariates related to race or multivitamin use were included in models, HRs tended to be shifted towards the null with similar confidence interval widths compared to when they were not included. Models emulating existing published associations were all above HR of 1.ConclusionsWe quantitatively illustrated the impact that analytical decisions can have on HR distribution of nutrition-related exposure/outcome associations. For our case study, exposure configuration resulted in substantially different HR distributions, with inclusion or exclusion of some covariates being associated with higher or lower HRs.This project was registered at OSF:https://doi.org/10.17605/OSF.IO/UE457
Comparative analysis of HPV-Human Protein Interaction Networks in Oropharyngeal and Oral Squamous cell carcinomas
Authors: Riaz Arsalan , Khan Faisal F. 
Published: December 2023

AbstractOral Squamous Cell Carcinoma (OSCC) accounts for more than 90% of reported head and neck cancers which is the sixth leading cancer worldwide. Oropharyngeal squamous cell carcinoma (OPSCC) cases, a closely located but a different sub-type of head and neck cancer, are also rising worldwide specifically among young individuals with risk factors including viral infection, smoking and alcohol. HPV infection specifically the subtype HPV16 is a significant risk factor in the initiation and progression of OPSCC, but has not been reported to play a role in OSCC. This study sets out to decipher mechanistic differences at the molecular level by comparing the viral-human protein-protein interaction (PPI) networks both in oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). We found that the unbiased HPV16-Human network consisted of 479 nodes, including 7 HPV16 proteins and 472 human proteins. Enrichment analysis revealed significant involvement of the identified human proteins in ubiquitination, protein degradation, and cancer-related pathways. A subset of 37 genes showed differential expression in HPV-positive OPSCC and OSCC, with TP53 over-expressed and ENDOD1 under-expressed in both cancers. Six genes (NUTM1, MYC, SCN9A, COL27A1, ITGB4, and GNB2) exhibited distinct changes in HPV-positive OPSCC compared to the other groups, where NUTM1 was the most over-expressed in OPSCC HPV+. The identified genes and pathways could serve as potential targets for precision medicine and therapeutic interventions in HPV-associated cancers. Further investigations are required to validate their clinical implication inin vitroandin vivomodels.
Therapeutic validation of MMR-associated genetic modifiers in a humanex vivomodel of Huntington’s disease
Authors: Ferguson Ross , Goold Robert , Coupland Lucy , Flower Michael , Tabrizi Sarah J 
Published: December 2023

ABSTRACTThe pathological huntingtin (HTT) trinucleotide repeat underlying Huntington’s disease (HD) continues to expand throughout life. Repeat length correlates both with earlier age at onset (AaO) and faster progression, making slowing its expansion an attractive therapeutic approach. Genome-wide association studies have identified candidate variants associated with altered AaO and progression, with many found in DNA mismatch repair (MMR) associated genes.We examine whether lowering expression of these genes affects the rate of somatic expansion in humanex vivomodels using HD iPSCs and HD iPSC-derived striatal neurons. We have generated a stable CRISPR interference HD iPSC line in which we can specifically and efficiently lower gene expression from a donor carrying over 125 CAG repeats.Lowering expression of each member of the MMR complexes MutS (MSH2, MSH3 & MSH6), MutL (MLH1, PMS1, PMS2 & MLH3) and LIG1 resulted in characteristic MMR deficiencies. Reduced MSH2, MSH3 and MLH1 slowed repeat expansion to the largest degree, while lowering either PMS1, PMS2 and MLH3 slowed it to a lesser degree. These effects were recapitulated in iPSC derived striatal cultures where MutL factor expression was lowered.Here, reducing the expression of MMR factors by CRISPRi to levels typically reached by current therapeutics effectively slows the pathogenic expansion of the HTT CAG repeat tract. We highlight members of the MutL family as potential therapeutic targets to slow repeat expansion with the aim to delay onset and progression of HD, and potentially other repeat expansion disorders exhibiting somatic instability.GRAPHICAL ABSTRACT
Cue-Invariant Geometric Structure of the Population Codes in Macaque V1 and V2
Authors: Massot Corentin , Zhang Xiaoqi , Wang Zitong , Rockwell Harold , Papandreou George , Yuille Alan , Lee Tai-Sing 
Published: December 2023

AbstractWe investigated the cue-invariant representation of visual patterns associated with surface boundaries in V1 and V2. We found that individual neurons exhibited a modest degree of tuning invariance in their responses to these patterns. This tuning invariance is stronger in V1 than in V2. At a population activity level, we studied the performance of a decoder trained with one cue in decoding patterns defined in another cue. We found that cue-transfer decoding is greatly enhanced when a geometric transform is first performed to align the population activities across cues. With this geometric transform, transfer decoding can be successful even when the tuning invariance of the individual neurons are destroyed by shuffling and when the neurons are from distinct populations. These findings suggest that abstract representation of these boundary-related patterns in V1 and V2 might be primarily encoded in the geometric structures of the population codes, rather than the cue-invariant tuning properties of the individual neurons.
Ras Activation by Hydrostatic Pressure is Enhanced by GAP and GEFin vitro
Authors: Matsuda Teruhiko , Chang Minki , Furukawa Katsuko , Ushida Takashi , Uyeda Taro Q.P. 
Published: December 2023

AbstractHydrostatic pressure (HP) is a necessary stimulus for cell differentiation and growth in cultured chondrocytes. Assuming that Ras activation is involved in HP-induced reactions, if cellular Ras activity is increased by HP, Ras itself, Raf, Ras regulators including GTPase activating proteins (GAP) and guanine nucleotide exchange factors (GEF), then the upstream receptor and/or interactions between them should have HP sensitivity. Based on this hypothesis, we first attempted to examine whether Ras is activated by HP, and in the affirmative, identify which factors displayed HP sensitivity using anin vitrosystem to measure Ras activity. Thisin vitrosystem included mRaichu, a FRET-based Ras activity probe, to which two-point mutations were introduced to reduce Ras-independent signals. This improved Raichu was used to investigate the HP sensitivity of two components, the GAP domain (GAPd) derived from p120GAP and the GEF domain (GEFd) derived from hSOS-1. It was found that HP weakly activated Ras activity in the absence of GAPd and GEFd, presumably by facilitating GDP dissociation from Ras. A low concentration of GAPd enhanced HP-induced Ras activation by 16.3% whereas high concentrations of GAPd removed HP sensitivity, suggesting that HP partially dissociates GAPd from the GAPd-Ras-GDP complex and reduces the fraction of inactive Ras. Moreover, a broad concentration range of GEFd also enhanced HP-induced Ras activation. Given that HP also increased Ras activity under a condition mimicking cellular Ras activity, we propose that Ras activation is involved in the differentiation and growth stimulation of chondrocytes by HP.Statement of SignificanceThe Ras-cycle has been implicated in the regulation of growth and differentiation of eukaryotic cells. Here, we investigated the relationship between hydrostatic pressure (HP) and components of the Ras-cycle: Ras-Raf, the GAP domain, and the GEF domain. Generally, HP tends to weaken protein-protein and protein-ligand interactions, but in this study, a seemingly positive response was observed: HP-induced Ras activation. Additionally, this response was enhanced by the GEF domain and the GAP domain. Thus, given the multiple cellular functions of Ras and the responses of the Ras-cycle to HP, this study will help clarify the molecular mechanism by which HP modulates cellular functions, particularly in chondrocytes, which are subjected to repetitive HP stimuliin vivo.
Inhibition of the melanocortin-3 receptor (MC3R) causes generalized sensitization to anorectic agents
Authors: Dahir Naima S. , Gui Yijun , Wu Yanan , Sweeney Patrick R. , Williams Savannah Y. , Gimenez Luis E. , Sawyer Tomi K. , Joy Stephen T. , Mapp Anna K. , Cone Roger D. 
Published: December 2023

AbstractThe melanocortin-3 receptor (MC3R) acts presynaptically to regulate GABA release from agouti-related protein (AgRP) nerve terminals and thus may be a negative regulator of multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of MC3R in regulating the response to various anorexigenic agents. Our findings reveal that genetic deletion or pharmacological inhibition of MC3R improves the dose responsiveness to Glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to other agents, including the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor, leptin, demonstrated that increased sensitivity to anorectic agents is a generalized result of MC3R antagonism. Enhanced neuronal activation in multiple nuclei, including ARH, VMH, and DMH, was observed using Fos immunohistochemistry following low-dose liraglutide in MC3R knockout mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits regulating multiple aspects of feeding behavior. The enhanced anorectic response inMc3r-/-mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1R analogs, suggesting that MC3R antagonists may have value in enhancing the dose-response range of obesity therapeutics.
Axon guidance genes are regulated by TDP-43 and RGNEF through the rate of long-intron processing
Authors: Abbassi Yasmine , Cappelli Sara , Spagnolo Eugenio , Gennari Alice , Visani Giulia , Barattucci Simone , Paron Francesca , Stuani Cristiana , Droppelmann Cristian A. , Strong Michael J. , Buratti Emanuele 
Published: December 2023

AbstractRho guanine nucleotide exchange factor (RGNEF) is a guanine nucleotide exchange factor (GEF) mainly involved in regulating the activity of Rho-family GTPases. Previous work has shown that RGNEF inclusions in the spinal motor neurons of ALS patients co-localise with TDP-43, the major RNA binding protein aggregating in the brain and spinal cord of ALS patients. To further characterise their relationship, we have compared the transcriptomic profiles of neuronal-like cells depleted of TDP-43 and RGNEF and show that these two factors predominantly act in an antagonistic manner when regulating the expression of axon guidance genes. From a mechanistic point of view, our experiments show that the effect of these factors on the processivity of long introns can explain their mode of action. Our findings highlight that neurodegenerative processes at the RNA level can often represent the result of combinatorial interactions between different RNA binding factors, leading to a better understanding of pathogenic mechanisms occurring in patients where more than one specific protein may be aggregating in their neurons.
Noninvasive Injectable Optical Nanosensor-Hydrogel Hybrids Detect Doxorubicin in Living Mice
Authors: Cohen Zachary , Alpert Dave J. , Weisel Adam C. , Roach Arantxa , Rahman Syeda , Gaikwad Pooja V. , Nicoll Steven B. , Williams Ryan M. 
Published: December 2023

AbstractWhile the tissue-transparent fluorescence of single-walled carbon nanotubes (SWCNTs) imparts substantial potential for use in non-invasive biosensors, development of non-invasive systems is yet to be realized. Here, we investigated the functionality of a SWCNT-based nanosensor in several injectable SWCNT-hydrogel systems, ultimately finding SWCNT encapsulation in a sulfonated methylcellulose hydrogel optimal for detection of ions, small molecules, and proteins. We found that the hydrogel system and nanosensor signal were stable for several weeks in live mice. We then found that this system successfully detects local injections of the chemotherapeutic agent doxorubicin in mice. We anticipate future studies to adapt this device for detection of other analytes in animals and, ultimately, patients.
Characterization of thePristionchus pacificus“epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2
Authors: Brown Audrey , Meiborg Adriaan B. , Franz-Wachtel Mirita , Macek Boris , Gordon Spencer , Rog Ofer , Weadick Cameron J , Werner Michael S. 
Published: December 2023

AbstractComparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation – or lack thereof – of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematodePristionchus pacificushas emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the “epigenetic toolkit” available toP. pacificusas a resource for future functional work on plasticity, and as a comparison withC. elegansto investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function betweenC. elegansandP. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing inP. pacificus.We described the deletion/pseudogenization of the PRC2 genesmes-2andmes-6and concluded that both were lost in the last common ancestor ofP. pacificusand a related speciesP. arcanus.Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes inP. pacificusto enable reverse-genetic experiments related to plasticity, and in doing so have described the first loss of PRC2 in a multicellular organism.