bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Analysis of Distal Pancreatectomy for Pancreatic Body and/or Tail Cancer Involving the Portal Vein
Authors: Yamamoto Yusuke , Sugiura Teiichi , Okamura Yukiyasu , Ito Takaaki , Ashida Ryo , Ohgi Katsuhisa , Aramaki Takeshi , Notsu Akifumi , Uesaka Katsuhiko 
Published: July 2022

Objectives
To the best of our knowledge, the prognostic impact of distal pancreatectomy (DP) for pancreatic body and/or tail cancer involving portal vein (PV) has not been analyzed.

Methods
A total of 155 patients with pancreatic body and/or tail cancer who were eligible candidates for resection between 2002 and 2017 were analyzed.

Results
Twenty-seven patients had PV contact ≤180°. Fifteen patients underwent preoperative treatment; finally, 132 patients underwent DP, and 21 underwent DP with celiac axis resection. The overall survival (OS) of the PV contact group (n = 27, median survival time [MST], 25.6 months) was worse than the non-PV contact group (n = 128; MST, 58.4 months; P = 0.002); however, it was better than the unresectable group (MST, 14.2 months; P = 0.011). The OS of the PV contact with preoperative chemotherapy group (MST, not available) was comparable to the non-PV contact group and better than the PV contact without preoperative chemotherapy group (MST, 13.4 months; P = 0.017). The multivariate analysis identified PV contact (P = 0.046) as one of the independent prognostic factors of OS.

Conclusions
Pancreatic body and/or tail cancer contact with PV ≤180° should be considered borderline resectable because of poor survival.
Racial/Ethnic Variation in White Matter Hyperintensity Progression in the ACCORDION MIND Study
Authors: Herman Alison L. , de Havenon Adam , Falcone Guido J. , Prabhakaran Shyam , Sheth Kevin N. 
Published: July 2022

Background:
White matter hyperintensities (WMHs) are linked to cognitive decline and stroke. We investigate the impact of race on WMH progression in the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORDION MIND) trial.

Materials and Methods:
The primary outcome is WMH progression in milliliters, evaluated by fitting linear regression to WMH volume on the month 80 magnetic resonance imaging (MRI) and including the WMH volume on the baseline MRI. The primary predictor is patient race, with the exclusion of patients defined as “other” race. We also derived predicted probabilities of our outcome for systolic blood pressure (SBP) levels.

Results:
We included 276 patients who completed the baseline and month 80 MRI, of which 207 (75%) were White, 48 (17%) Black, and 21 (8%) Hispanic. During follow-up, the mean number of SBP, low-density lipoprotein (LDL), and A1c measurements per patient was 21, 8, and 15. The median (IQR) WMH progression was 1.5 mL (0.5 to 3.9) for Black patients, 1.0 mL (0.4 to 4.0) for Hispanics, and 1.3 mL (0.5 to 2.7) for Whites (Kruskal-Wallis test, P=0.59). In the multivariate regression model, Black, compared with White, patients had significantly more WMH progression (β Coefficient 1.26, 95% confidence interval 0.45 to 2.06, P=0.002). Hispanic, compared with White, patients neither have significantly different WMH progression (P=0.392), nor was there a difference when comparing Hispanic to Black patients (P=0.162). The predicted WMH progression was significantly higher for Black compared with White patients across a mean SBP of 117 to 139 mm Hg.

Conclusions:
Black diabetic patients in Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORDION MIND) have a higher risk of WMH progression than White patients across a normal range of SBP.
Impact of Prophylactic Corticosteroid Use on In-hospital Mortality and Respiratory Failure After Esophagectomy for Esophageal Cancer
Authors: Hirano Yuki , Konishi Takaaki , Kaneko Hidehiro , Itoh Hidetaka , Matsuda Satoru , Kawakubo Hirofumi , Uda Kazuaki , Matsui Hiroki , Fushimi Kiyohide , Daiko Hiroyuki , Itano Osamu , Yasunaga Hideo , Kitagawa Yuko 
Published: July 2022

Objective:
To assess the effect of preoperative prophylactic corticosteroid use on short-term outcomes after oncologic esophagectomy.

Background:
Previous studies have shown that prophylactic corticosteroid use may decrease the risk of respiratory failure following esophagectomy by attenuating the perioperative systemic inflammation response. However, its effectiveness has been controversial, and its impact on mortality remains unknown.

Methods:
Data of patients who underwent oncologic esophagectomy between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting, propensity score matching, and instrumental variable analyses were performed to investigate the associations between prophylactic corticosteroid use and short-term outcomes, such as in-hospital mortality and respiratory failure, adjusting for potential confounders.

Results:
Among 35,501 eligible patients, prophylactic corticosteroids were used in 22,620 (63.7%) patients. In-hospital mortality, respiratory failure, and severe respiratory failure occurred in 924 (2.6%), 5440 (15.3%), and 2861 (8.1%) patients, respectively. In stabilized inverse probability of treatment weighting analyses, corticosteroids were significantly associated with decreased in-hospital mortality [odds ratio (OR)=0.80; 95% confidence interval (CI): 0.69–0.93], respiratory failure (OR=0.84; 95% CI: 0.79–0.90), and severe respiratory failure (OR=0.87; 95% CI: 0.80–0.95). Corticosteroids were also associated with decreased postoperative length of stay and total hospitalization costs. The proportion of anastomotic leakage did not differ with the use of Propensity score matching and instrumental variable analysis demonstrated similar results.

Conclusions:
Prophylactic corticosteroid use in oncologic esophagectomy was associated with lower in-hospital mortality as well as decreased respiratory failure and severe respiratory failure, suggesting a potential benefit for preoperative corticosteroid use in esophagectomy.
The diagnostic accuracy of prehysterectomy curettage in determining tumor type and grade in patients with endometrial cancer
Authors: Mhmed Ali Rihan 
Published: July 2022

Objectives:
This study aims to evaluate the reliability of endometrial curettage in determining tumor grade and type in patients of endometrial cancer, and to study correlations between histologic and clinical findings.

Methods:
A retrospective cohort study was conducted between January 2014 and December 2020 at obstetrics and gynecology university hospital. A total of 75 cases of endometrial curettage with total hysterectomy using H&E stains were studied. Inter-rater reliability test was done.

Results:
The most common category in this study was endometrioid carcinoma in the sixth decade with second grade and first stage. Sensitivity was 93%. Positive predictive value was 93%.

Conclusion:
Endometrial curettage is a reliable investigation in evaluating endometrial cancer. Determining tumor grade and type are possible on the initial report of endometrial curettage thus, using it for therapeutic management for patients of endometrial cancer.
Hospital admissions and mortality for acute exacerbations of COPD during the COVID-19 pandemic: a nationwide study in France
Authors: Poucineau Jonas , Delory Tristan , Lapidus Nathanael , Hejblum Gilles , Chouaïd Christos , Cœur Sophie Le , Khlat Myriam 
Published: July 2022

AbstractBackgroundA global reduction in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) was observed during the first months of the COVID-19 pandemic. Large-scale studies covering the entire pandemic period are lacking. We investigated hospitalizations for AECOPD and the associated in-hospital mortality at the national level in France during the first two years of the pandemic.MethodsWe used the French National Hospital Database to analyse the time trends in (1) monthly incidences of hospitalizations for AECOPD, considering intensive care unit (ICU) admission and COVID-19 diagnoses, and (2) the related in-hospital mortality, from January 2016 to November 2021. Pandemic years were compared with the pre-pandemic years using Poisson regressions.ResultsThe database included 565,890 hospitalizations for AECOPD during the study period. The median age at admission was 74 years (interquartile range 65–83), and 37% of the stays concerned women. We found: (1) a dramatic and sustainable decline in hospitalizations for AECOPD over the pandemic period (from 8,899 to 6,032 monthly admissions, relative risk (RR) 0.65, 95% confidence interval (CI) 0.65–0.66), and (2) a concomitant increase in in-hospital mortality for AECOPD stays (from 6.2% to 7.6% per month, RR 1.24, 95% CI 1.21-1.27). The proportion of stays yielding ICU admission was similar in the pre-pandemic and pandemic years, 21.5% and 21.3%, respectively. In-hospital mortality increased to a greater extent for stays without ICU admission (RR 1.39, 95% CI 1.35–1.43) than for those with ICU admission (RR 1.09, 95% CI 1.05–1.13). Since January 2020, only 1.5% of stays were associated with a diagnosis of COVID-19, and their mortality rate was nearly 3-times higher than those without COVID-19 (RR 2.66, 95% CI 2.41–2.93).ConclusionThe decline in admissions for AECOPD during the pandemic could be attributed to a decrease in the incidence of exacerbations for COPD patients and/or to a possible shift from hospital to community care. The rise in in-hospital mortality is partially explained by COVID-19, and could be related to restricted access to ICUs for some patients and/or to greater proportions of severe cases among the patients hospitalized during the pandemic.
Individual Variation in Risky Decisions Is Related to Age and Gender but not to Mental Health Symptoms
Authors: Talwar Anahita , Cormack Francesca , Huys Quentin J. M. , Roiser Jonathan P. 
Published: July 2022

AbstractRisky decisions involve choosing between options where the outcomes are uncertain. Cognitive tasks such as the CANTAB Cambridge Gamble Task (CGT) have revealed that patients with depression make more conservative decisions, but the mechanisms of choice evaluation underlying such decisions, and how they lead to the observed differences in depression, remain unknown. To test this, we used a computational modelling approach in a broad general-population sample (N = 753) who performed the CANTAB CGT and completed questionnaires assessing symptoms of mental illness, including depression. We fit five different computational models to the data, including two novel ones, and found that a novel model that uses an inverse power function in the loss domain (contrary to standard Prospect Theory accounts), and is influenced by the probabilities but not the magnitudes of different outcomes, captures the characteristics of our dataset very well. Surprisingly, model parameters were not significantly associated with any mental health questionnaire scores, including depression scales; but they were related to demographic variables, particularly age, with stronger associations than typical model-agnostic task measures. This study showcases a new methodology to analyse data from CANTAB CGT, describes a noteworthy null finding with respect to mental health symptoms, and demonstrates the added precision that a computational approach can offer.
SMALL MOLECULE CLPP AGONISTS INDUCE SENESCENCE AND ALTER TRAIL-MEDIATED APOPTOTIC RESPONSE OF TRIPLE-NEGATIVE BREAST CANCER CELLS
Authors: Aponte-Collazo Lucas J. , Fennell Emily M. J. , East Michael P. , Gilbert Thomas S. K. , Graves Paul R. , Ashamalla Hani , Iwanowicz Edwin J. , Greer Yoshimi Endo , Lipkowitz Stanley , Graves Lee M. 
Published: July 2022

AbstractImipridones are a novel class of anticancer drugs with promising antiproliferative effects in several cancer cell types, including breast cancer. Recent studies identified the mitochondrial ATP-dependent caseinolytic peptidase P (ClpP) as the target for imipridones and related analogs. Despite these findings, the specific processes by which ClpP activators inhibit cancer cell growth remain poorly understood. Here we report that two structurally distinct ClpP activators, ONC201 and TR-57, promote senescence in SUM159 and MDA-MB-231 triple-negative breast cancer (TNBC) cell lines. Induction of senescence was measured through β-galactosidase assays and confirmed by the increase of H2A.X phosphorylation, hypophosphorylation of retinoblastoma protein (Rb), upregulation of multiple interleukin mRNAs and other markers. The level of senescence induced by these compounds was equivalent to that observed with the CDK4/6 inhibitor and positive control abemaciclib. To confirm the crucial role of ClpP activation in senescence induction, we generated ClpP null TNBC cell lines using CRISPR interference (CRISPRi). Neither ONC201 nor TR-57 induced senescence in the ClpP null models. Incubation of WT cells with ClpP activators led to a reduction in the levels of apoptosis-related proteins like XIAP, SMAC/DIABLO, Survivin, DR4 and DR5, which correlated with the lack of apoptosis observed in these cells. Interestingly, treatment with TR-57 strongly reduced apoptosis induced by staurosporine but increased sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To investigate the enhanced effects of TRAIL, we examined the expression of Wee1 in senescent cells and found that both TR-57 and abemaciclib down-regulated Wee1. Addition of a Wee1 inhibitor partially sensitized cells to TRAIL suggesting the importance of Wee1 in this process. In summary, we show that ClpP activators induce senescence in a ClpP-dependent manner and that combined treatment of ClpP activators with TRAIL provides an effective approach to eliminate malignant senescent cells in vitro.HIGHLIGHTSTreatment of TNBC cells with ClpP activators induces senescence in vitroInduction of senescence is ClpP dependentActivation of ClpP leads to changes in mRNA levels of senescence associated cytokinesSenescent TNBC cells are sensitized to TRAIL mediated apoptosis
Nationwide genomic biobank in Mexico unravels demographic history and complex trait architecture from 6,057 individuals
Authors: Sohail Mashaal , Chong Amanda Y. , Quinto-Cortes Consuelo D. , Palma-Martínez María J. , Ragsdale Aaron , Medina-Muñoz Santiago G. , Barberena-Jonas Carmina , Delgado-Sánchez Guadalupe , Cruz-Hervert Luis Pablo , Ferreyra-Reyes Leticia , Ferreira-Guerrero Elizabeth , Mongua-Rodríguez Norma , Jimenez-Kaufmann Andrés , Moreno-Macías Hortensia , Aguilar-Salinas Carlos A. , Auckland Kathryn , Cortés Adrián , Acuña-Alonzo Víctor , Ioannidis Alexander G. , Gignoux Christopher R. , Wojcik Genevieve L. , Fernández-Valverde Selene L. , Hill Adrian V.S. , Tusié-Luna María Teresa , Mentzer Alexander J. , Novembre John , García-García Lourdes , Moreno-Estrada Andrés 
Published: July 2022

AbstractLatin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories as well as complex trait architectures remain hidden due to the lack of Big Data. To fill this gap, the Mexican Biobank project genotyped 1.8 million markers in 6,057 individuals from 32 states and 898 sampling localities across Mexico with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Through a suite of state-of-the-art methods for ancestry deconvolution and inference of identity-by-descent (IBD) segments, we inferred detailed ancestral histories for the last 200 generations in different Mesoamerican regions, unraveling native and colonial/post-colonial demographic dynamics. We observed large variations in runs of homozygosity (ROH) among genomic regions with different ancestral origins reflecting their demographic histories, which also affect the distribution of rare deleterious variants across Mexico. We analyzed a range of biomedical complex traits and identified significant genetic and environmental factors explaining their variation, such as ROH found to be significant predictors for trait variation in BMI and triglycerides.
A New In-Silico Approach for PROTAC Design and Quantitative Rationalization of PROTAC mediated Ternary Complex Formation
Authors: Ben Geoffrey A S , Kulkarni Nagaraj M , Agrawal Deepak , Vetrivel Rajappan , Gurram Kishan 
Published: July 2022

AbstractProteolysis-Targeting Chimeric Molecules (PROTAC) is a rapidly emerging technology for drug target protein degradation and drugging undruggable drug targets. There is a growing literature on in-silico approaches to the complex problem of PROTAC design, specifically the advantages of AI/ in-silico methods in the PROTAC Design Make Test Analyze (DMTA) cycle. Our work presented here aims to contribute to the growing literature of in-silico approaches to PROTAC design by incorporating and demonstrating incremental advancement over previously published methods. We use AI based generative methods for PRTOAC design and Molecular Dynamics to evaluate the stability of the ternary complex formed and ability of the PROTAC to hold the target protein and E3 ligase together stably. To quantify the performance of the PROTAC candidate, we also estimate computationally the PROTAC performance metrics routinely measured by the experimentalists in PROTAC assays. We use highly accurate absolute binding free energy calculations used traditionally in protein-ligand space for the PROTAC system. We calculate (Gibbs free energy change) ΔG for binary complex formation and ternary complex formation mediated by the PROTAC using Free Energy Perturbation - Thermodynamics Integration (FEP-TI) method which is benchmarked in literature with a root mean square error of 0.8 kcal/mol. We calculate ΔG for ternary and binary complexes and estimate whether ΔG for ternary is lower than the ΔG estimated for binary complexes. When the ΔG for ternary is lower than the binary it is inferred that ternary complexation is favoured over binary. Therefore, through these methods we can theoretical estimate ΔG measured by experimentalists in PROTAC assays such as Isothermal titration calorimetry (ITC) and Surface plasmon resonance (SPR) which capture the ΔG for ternary and binary complex formation mediated by the PROTAC. This method will help reduce time as well as costs of the PROTAC DMTA cycle and will accelerate early stage PROTAC drug discovery. As an illustrative application of our in-silico PROTAC design approach, we chose the target Fibroblast growth factor receptor 1(FGFR-1) which is a target approved drug for colorectal cancer. We report the findings and conclude with future research directions.
Computational Enhanced Hi-C data reveals the function of structural geometry in genomic regulation
Authors: He Yueying , Xue Yue , Wang Jingyao , Huang Yupeng , Liu Lu , Huang Yanyi , Gao Yi Qin 
Published: July 2022

AbstractHigh-throughput chromosome conformation capture (Hi-C) technique profiles the genomic structure in a genome-wide fashion. The reproducibility and consistency of Hi-C data are essential in characterizing dynamics of genomic structures. We developed a diffusion-based method, CTG (Hi-C To Geometry), to deal with the technical bias induced by insufficient sampling in sequencing and obtain reliable gemeotric information of the chromatin. CTG properly quantifies dubiously weak or even undetected interactions and produces a consistent and reproducible framework for the 3D genomic structure. CTG allows for a reliable genome-wide insight on the alteration of genomic structures under different cellular conditions and reveals correlations between genomic-proximal genes at both transcriptional and translational levels. Cell-specific correspondence between gene-gene and corresponding protein-protein physical interactions, as well as that with the transcription correlation reveals the coordinated inter-molecular structural and regulatory information passage in the central dogma.
Trim28 plays an indispensable role in maintaining functions and transcriptional integrity of hematopoietic stem cells
Authors: Silvestri Giovannino , Rathinam Chozha Vendan 
Published: July 2022

AbstractHematopoiesis is a complex process that is regulated at multiple levels and through both intrinsic and extrinsic regulators. Trim28 is a multidomain protein that functions as a transcription factor and E3 ubiquitin ligase. Recent studies have established the pivotal roles of Trim28 in a variety of pathophysiologic processes including inflammation, autoimmune disorders, viral pathogenesis, cancer, tumor microenvironment and epithelial-to- mesenchymal transition. However, importance of Trim28 in early hematopoiesis, particularly in the maintenance and functions of hematopoietic stem and progenitor cells (HSPCs), remains largely unknown. In the present study, we identified Trim28 as a critical regulator of self-renewal, quiescence, and functions of hematopoietic stem cells (HSC). Conditional ablation of Trim28 in HSCs leads to perinatal lethality, due to pancytopenia within the hematopoietic lineage. Loss of Trim28 in HSCs affects their differentiation into myeloid-, erythroid-, and lymphoid- lineages. Trim28 deletion leads to altered frequencies and absolute numbers of HSCs, Multipotent Progenitors (MPPs) and lineage committed progenitors in the bone marrow (BM). Primary- and secondary- BM transplantation studies identified an indispensable and a cell-intrinsic role for Trim28 in HSCs. Mechanistic studies identified hyperproliferation of HSPCs and deregulated expression of cell cycle regulators in HSPCs. Strikingly, gene expression studies demonstrated that Trim28 deficiency impairs the transcriptional landscape and transcription factors signatures of HSPCs. In essence, these studies highlight a previously unknown role for Trim28 in the maintenance, functions, and multi-lineage differentiation of HSPCs.
Neuronal glutamate transporters control reciprocal inhibition and gain modulation in D1 medium spiny neurons
Authors: Petroccione Maurice A. , D’Brant Lianna Y. , Affinnih Nurat , Wehrle Patrick H. , Todd Gabrielle C. , Zahid Shergil , Chesbro Haley E. , Tschang Ian L. , Scimemi Annalisa 
Published: July 2022

AbstractUnderstanding the function of glutamate transporters has broad implications for explaining how neurons integrate information and relay it through complex neuronal circuits. Most of what is currently known about glutamate transporters, specifically their ability to maintain glutamate homeostasis and limit glutamate diffusion away from the synaptic cleft, is based on studies of glial glutamate transporters. By contrast, little is known about the functional implications of neuronal glutamate transporters. The neuronal glutamate transporter EAAC1 is widely expressed throughout the brain, particularly in the striatum, the primary input nucleus of the basal ganglia, a region implicated with movement execution and reward. Here, we show that EAAC1 limits synaptic excitation onto a population of striatal medium spiny neurons identified for their expression of D1 dopamine receptors (D1-MSNs). In these cells, EAAC1 also contributes to strengthen lateral inhibition from other D1-MSNs. Together, these effects contribute to reduce the gain of the input-output relationship and increase the offset at increasing levels of synaptic inhibition in D1-MSNs. By reducing the sensitivity and dynamic range of action potential firing in D1-MSNs, EAAC1 limits the propensity of mice to rapidly switch between behaviors associated with different reward probabilities.