Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of problem formulation on LNG process optimization

The power consumption of a single mixed-refrigerant process (PRICO®) for natural gas liquefaction was minimized using four different constraint formulations to handle the trade-off between investment and operating costs. Aspen HYSYS® was used for process simulation, while a sequential quadratic programming algorithm (NLPQLP) was used for optimization. The results confirm that optimal utilization of the heat exchanger area is only obtained with a constraint based on a maximum heat exchanger conductance (UA). The minimum temperature difference constraint commonly used in process design gives a significant energy penalty as it is incapable of accounting for the distribution of driving forces with respect to temperature, the nonlinearity of the composite curves and the trade-off between driving forces and cooling load. The results also indicate that the maximum UA constraint leads to increased complexity of the optimization problem, and that the success rate of the optimization method used therefore is reduced. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3598–3610, 2016
The Disease Modification Conundrum in Parkinson’s Disease: Failures and Hopes

In the last half-century, Parkinson’s disease (PD) has played a historical role in demonstrating our ability to translate preclinical scientific advances in pathology and pharmacology into highly effective clinical therapies. Yet, as highly efficacious symptomatic treatments were successfully developed and adopted in clinical practice, PD remained a progressive disease without a cure. In contrast with the success story of symptomatic therapies, the lack of translation of disease-modifying interventions effective in preclinical models into clinical success has continued to accumulate failures in the past two decades. The ability to stop, prevent or mitigate progression in PD remains the “holy grail” in PD science at the present time. The large number of high-quality disease modification clinical trials in the past two decades with its lessons learned, as well as the growing knowledge of PD molecular pathology should enable us to have a deeper understanding of the reasons for past failures and what we need to do to reach better outcomes. Periodic reviews and mini-reviews of the unsolved disease modification conundrum in PD are important, considering how this field is rapidly evolving along with our views and understanding of the possible explanations.
Periodontal Inflamed Surface Area Is Associated With Increased Gestational Blood Pressure and Uric Acid Levels Among Pregnant Women From Rural North China

Background Periodontal disease has been associated with gestational complications and both conditions have a high prevalence in rural populations from developing regions. A cross-sectional study was carried out to explore the relationship between periodontal inflamed surface area (PISA), blood pressure (BP), and, serum uric acid levels (UA) in a group of rural North Chinese pregnant women in the third trimester of pregnancy. Methods Three hundred and thirty-five rural women aged 20–34 years, with normal body mass index (BMI) were examined in a cross-sectional study during their third trimester of gestation. Exclusion criteria were history of pregnancy complications, multiple pregnancy, smoking habits, diabetes, hypertension or any known infectious disease. Socio-demographic variables, including age and socioeconomic status (SES), systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings, serum UA levels, and PISA values were recorded. A structural equation model was implemented with two constructed latent variables including “Dem” (comprising of age and SES category to represent unobserved demographic variables) and, “BP” (comprising of SBP and DBP to account for measurement error and lack of multiple BP readings). The model accounted for co-variance of BP and UA, and implemented simultaneous regressions for BP and UA as outcomes, upon Dem and PISA values as exogenous variables. Results The median PISA score was 1,081.7 (IQR = 835.01), reflecting high levels of periodontal inflammation in the sample. SEM showed a significant association of PISA with BP (estimate = 0.011, 95% CI = 0.009–0.012 p < 0.001) and UA (estimate = 0.001, 95% CI = 0.001–0.001, p < 0.001). Conclusion Higher PISA values were significantly associated with higher blood pressure and uric acid levels among rural pregnant women in a cross-sectional sample from a center in North China after accounting for a latent demographic construct derived from age and SES.
Optic Nerve Ultrasound Evaluation in Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) is a disease with a heterogeneity of possible causes, which needs to be quickly diagnosed. Ocular ultrasonography could be considered a useful tool to diagnose this condition in a fast and non-invasive way. In fact, Karl Ossoinig had already proposed this diagnostic tool in the 1970s for the evaluation of intracranial pressure changes under several pathological conditions, including idiopathic intracranial hypertension. The aim of this review is to analyze scientific articles published in the last 30 years concerning the use of ocular ultrasonography to assess optic nerve indices in patients with idiopathic intracranial hypertension. Specifically, 15 published articles found in PubMed database were included and analyzed in the present review. Our conclusion suggests that ocular ultrasonography is a reliable diagnostic technique to be utilized in all the cases of suspected raised intracranial pressure. To obtain the best possible accuracy and precision in the least invasive way, standardized A-scan seems to be the best choice.
Hearing Loss and Cognition: What We Know and Where We Need to Go

Although a causal association remains to be determined, epidemiologic evidence suggests an association between hearing loss and increased risk of dementia. If we determine the association is causal, opportunity for targeted intervention for hearing loss may play a fundamental role in dementia prevention. In this discussion, we summarize current research on the association between hearing loss and dementia and review potential casual mechanisms behind the association (e.g., sensory-deprivation hypothesis, information-degradation hypothesis, common cause). We emphasize key areas of research which might best inform our investigation of this potential casual association. These selected research priorities include examination of the causal mechanism, measurement of co-existing hearing loss and cognitive impairment and determination of any bias in testing, potential for managing hearing loss for prevention of dementia and cognitive decline, or the potential to reduce dementia-related symptoms through the management of hearing loss. Addressing these research gaps and how results are then translated for clinical use may prove paramount for dementia prevention, management, and overall health of older adults.
Overview of Cannabis including Kampo Medicine and Therapy for Treatment of Dementia: A Review

Cannabis sativa L. is an annual herb oldest cultivated plants as a source of fiber since about 5000 B.C. On the other hand, the cannabis flower and seed are listed in Shennong’s classic Materia Medica approximately 2000 years ago. The formulas prescribed with cannabis in Kampo medicine have been summarized. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the major neurological and psychiatric cannabinoids, and develop to drugs. It becomes evident that the therapeutic CBD and/or THC are the important candidate of anti-dementia drugs having different mechanism for Alzheimer’s patients. Two receptors and endocannabinoids are also discussed for underlying mechanism of action. In order to promote the breeding of cannabis plant containing higher concentration of target cannabinoid the biosynthetic enzymes were isolated, cloning and the tertiary structure of THCA synthase determined by x-ray analysis resulting in the possibility of molecular breeding for cannabinoids.
The Reconnection of Rough Sleepers within the UK: An Evaluation

The increased strategic emphasis on reconnection has largely occurred in the absence of robust evidence regarding the impacts on rough sleepers, however. This study aimed to begin to redress this gap in evidence, by documenting the rationale underpinning the utilisation of reconnection, examining the ways it is articulated ‘on the ground’, and assessing its impact on rough sleepers. Both ‘indigenous’ and migrant rough sleepers are affected by reconnection, but this study restricted focus to the former, that is, British nationals reconnected within the UK. ‘Reconnection’, defined in policy terms as “the process by which people sleeping rough, who have a connection to another area where they can access accommodation and/or social, family and support networks, are supported to return to this area in a planned way”
Systematic Review and Meta-analysis: Association of Aspirin With Incidence of Hepatocellular Carcinoma

Aim: To explore the relationship between the use of aspirin and the incidence of hepatocellular carcinoma (HCC). Methods: MEDLINE, EMBASE, Web of Science and Cochrane CENTRAL databases were searched systematically from the earliest available date to 13 March 2020. The primary outcome was incidence of HCC, and the secondary outcomes were recurrence and mortality of HCC. The results were expressed as the Hazard Ratio (HR) and 95% confidence interval (CI). Based on the heterogeneity evaluated with the I 2 statistic, a meta-analysis was performed using either a random- or fixed-effects model. Results: A total of sixteen articles (2781100 participants) were included. There was lower incidence of HCC in aspirin users than those in non-aspirin users (HR, 0.56; 95% CI, 0.46-0.69; p < 0.001). Subgroup analysis further showed that the incidence of liver cancer in patients with alcoholic cirrhosis (HR, 0.14; 95% CI, 0.09-0.22; p < 0.001) and virus hepatitis (HR, 0.68; 95% CI, 0.62-0.74; p < 0.001) who use aspirin was lower than that of patients who do not use aspirin. In addition, aspirin was found to associate with decreased risk of HCC mortality (HR, 0.71; 95% CI, 0.65-0.78; p < 0.001), not HCC recurrence (HR, 0.52; 95% CI, 0.15-1.76; p = 0.291). Conclusions: Aspirin use is significantly associated with the low incidence rate of liver cancer.
The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration

Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.
Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation

The mutant proinsulin syndrome is a monogenic cause of diabetes mellitus due to toxic misfolding of insulin’s biosynthetic precursor. Also designated mutant INS-gene induced diabetes of the young (MIDY), this syndrome defines molecular determinants of foldability in the endoplasmic reticulum (ER) of β-cells. Here, we describe a peptide model of a key proinsulin folding intermediate and variants containing representative clinical mutations; the latter perturb invariant core sites in native proinsulin (LeuB15→Pro, LeuA16→Pro, and PheB24→Ser). The studies exploited a 49-residue single-chain synthetic precursor (designated DesDi), previously shown to optimize in vitro efficiency of disulfide pairing. Parent and variant peptides contain a single disulfide bridge (cystine B19-A20) to provide a model of proinsulin’s first oxidative folding intermediate. The peptides were characterized by circular dichroism and redox stability in relation to effects of the mutations on (a) in vitro foldability of the corresponding insulin analogs and (b) ER stress induced in cell culture on expression of the corresponding variant proinsulins. Striking correlations were observed between peptide biophysical properties, degree of ER stress and age of diabetes onset (neonatal or adolescent). Our findings suggest that age of onset reflects the extent to which nascent structure is destabilized in proinsulin’s putative folding nucleus. We envisage that such peptide models will enable high-resolution structural studies of key folding determinants and in turn permit molecular dissection of phenotype-genotype relationships in this monogenic diabetes syndrome. Our companion study (next article in this issue) employs two-dimensional heteronuclear NMR spectroscopy to define site-specific perturbations in the variant peptides.
Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells

The strong invasive and metastatic abilities of oral squamous cell carcinoma (OSCC) cells in the early stage are the main reason for its poor prognosis. The early diagnosis and treatment of OSCC may reduce the metastasis rate and improve the survival rate. The aim of this study was to explore candidate biomarkers related to the prognosis and progression of OSCC. We performed weighted gene coexpression network analysis to identify key modules and genes associated with OSCC and intersected the differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA)-OSCC and GSE30784 datasets. Next, we performed survival analysis and immunohistochemistry to screen and validate the hub gene insulin-like growth factor 2 (IGF2) mRNA binding protein 2 IGF2BP2. We also used TCGA pan-cancer data to verify that IGF2BP2 was expressed at high levels in a variety of cancers and was related to a poor prognosis in patients. Furthermore, we divided patients with OSCC into high and low expression groups based on the median expression level of IGF2BP2. Gene set enrichment analysis (GSEA) showed that IGF2BP2 led to a poor prognosis in OSCC by affecting cancer-related (epithelial-mesenchymal transition, glycolysis, cell cycle, etc.) and immune-related biological functions and pathways. Single-sample GSEA (ssGSEA), CIBERSORT, and xCell algorithms helped reveal that high IGF2BP2 expression was accompanied by a significant reduction in the immune score, stromal score, and microenvironment score and a decrease in the number of infiltrating CD8+ T cells in OSCC. In addition, silencing IGF2BP2 suppressed the proliferation, migration, and invasion of OSCC cells. In general, IGF2BP2 is a potential biomarker for the progression, immunotherapy response, and prognosis of OSCC.
Two Compact Cas9 Ortholog-Based Cytosine Base Editors Expand the DNA Targeting Scope and Applications In Vitro and In Vivo

CRISPR/Cas9-based base editing tools enable precise genomic installation and hold great promise for gene therapy, whereas the big size of Cas9 nucleases and its reliability on specific protospacer adjacent motif (PAM) sequences as well as target site preferences restrict the extensive applications of base editing tools. Here, we generate two cytosine base editors (CBEs) by fusing cytidine deaminases with two compact codon-optimized Cas9 orthologs from Streptococcus_gordonii_str. _Challis_substr. _CH1 (ancSgo-BE4) and Streptococcus_thermophilus_LMG_18311 (ancSth1a-BE4), which are much smaller than Streptococcus pyogenes (SpCas9) and recognize NNAAAG and NHGYRAA PAM sequences, respectively. Both CBEs display high activity, high fidelity, a different editing window, and low by-products for cytosine base editing with minimal DNA and RNA off-targeting activities in mammalian cells. Moreover, both editors show comparable or higher editing efficiencies than two engineered SpCas9 variant (SpCas9-NG and SpRY)-based CBEs in our tested target sites, which perfectly match the PAM sequences for ancSgo-BE4 or ancSth1a-BE4. In addition, we successfully generate two mouse models harboring clinically relevant mutations at the Ar gene via ancSgo-BE4 and ancSth1a-BE4, which display androgen insensitivity syndrome and/or developmental lethality in founder mice. Thus, the two novel CBEs broaden the base editing tool kits with expanded targeting scope and window for efficient gene modification and applications, respectively.
Incidence of and Risk Factors for Paradoxical Psoriasis or Psoriasiform Lesions in Inflammatory Bowel Disease Patients Receiving Anti-TNF Therapy: Systematic Review With Meta-Analysis

Background Paradoxical psoriasis or psoriasiform lesions induced by anti-tumor necrosis factor (anti-TNF) therapies receive increasing attention worldwide. However, no comprehensive meta-analysis investigating the incidence estimates and risk factors for anti-TNF-induced psoriasis is currently available. We aimed to precisely quantify its incidence as well as risk factors in patients with inflammatory bowel disease (IBD). Methods This study was registered on PROSPERO database under review registration number CRD42021233695. The electronic databases PubMed, EMBASE, and the Cochrane library were comprehensively searched for observational studies published as full-length papers in English and reporting the incidence and/or predictors for psoriasis or psoriasiform lesions in IBD patients. A random-effects meta-analysis was performed to calculate the pooled incidence. Pooled odds ratio (OR) and 95% confidence interval for potential predictors were combined using a fixed-effects or random-effects model. Results In total, 30 articles comprising 24,547 IBD patients treated by anti-TNF were finally included. The overall pooled incidence of psoriasis and/or psoriasiform lesions following anti-TNF therapy was 6.0% (5.0–7.0%; I 2 = 93.9%), with 6.9% (5.1–8.7%; I 2 = 92.4%) for psoriasiform lesions and 4.6% (3.6–5.6%; I 2 = 93.9%) for psoriasis. Multivariable meta-regression analysis indicated regions and populations that significantly contributed to the heterogeneity. A statistically higher risk for psoriasis or psoriasiform lesions during anti-TNF therapy was observed in female patients (OR 1.46, 1.23–1.73), those who are at a younger age at anti-TNF initiation (OR 1.03, 1.00–1.05), smokers (OR 1.97, 1.56–2.48), ileocolonic Crohn’s disease patients (OR 1.48, 1.03–2.13), and those who are using adalimumab or certolizumab (vs. infliximab) (OR: 1.48 and 2.87 respectively). Conclusions The incidence of psoriasis or psoriasiform lesions was not uncommon in IBD patients following anti-TNF therapy. Female, younger age, smoker, ileocolonic Crohn’s disease, and the types of anti-TNF were significantly associated with such risk. These findings may help gastroenterologists to make more individualized decisions and understand the mechanisms of this paradoxical phenomenon. Systematic Review Registration https://www.crd. york.ac. uk/PROSPERO/display_record. php? RecordID=233695, identifier CRD42021233695.
Transarterial Chemoembolization Combined With Lenvatinib Plus PD-1 Inhibitor for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study

Purpose To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE-L-P) versus TACE combined with lenvatinib (TACE-L) for patients with advanced hepatocellular carcinoma (HCC). Materials and Methods Data of advanced HCC patients treated with TACE-L-P (TACE-L-P group) or TACE-L (TACE-L group) from January 2019 to December 2020 were prospectively collected and retrospectively analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were determined. Results A total of 81 patients were included in this study. Among them, 41 received TACE-L-P and 40 received TACE-L. The patients in TACE-L-P group had prolonged OS (median, 16.9 vs. 12.1 months, P=0.009), longer PFS (median, 7.3 vs. 4.0 months, P=0.002) and higher objective response rate (56.1% vs. 32.5%, P=0.033) and disease control rate (85.4% vs. 62.5%, P=0.019) than those in TACE-L group. Multivariate analyses revealed that the treatment option of TACE-L, main portal vein invasion and extrahepatic metastasis were the independent risk factors for OS, while TACE-L and extrahepatic metastasis were the independent risk factors for PFS. In subgroup analyses, a superior survival benefit was achieved with TACE-L-P in patients with extrahepatic metastasis or tumor number >3 but not in those with main portal vein invasion. The incidence and severity of AEs in TACE-L-P group were comparable to those in TACE-L group (any grade, 92.7% vs. 95.0%, P=1.000; grade 3, 36.6% vs. 32.5%, P=0.699). Conclusion TACE-L-P significantly improved survival over TACE-L with an acceptable safety profile in advanced HCC patients, especially those with extrahepatic metastasis or tumor number >3 but without main portal vein invasion.
What Can Make the Difference Between Chronotypes in Sleep Duration? Testing the Similarity of Their Homeostatic Processes

The two-process conceptualization of sleep-wake regulation suggests that the biological underpinnings of the differences between morning and evening types in sleep timing and duration might be related to either the circadian process or the homeostatic process or both. The purpose of this report was to test whether morning and evening types might have similar homeostatic processes to achieve such ultimate goal of homeostatic sleep regulation as taking an adequate amount of sleep on free days. Weekend and weekday rise- and bedtimes reported for 50 paired samples of morning and evening types were averaged and simulated with a model of sleep-wake regulation. In morning and evening types of the same age, the homeostatic components of the sleep-wake regulation were found to be identical. Therefore, the difference in the circadian process between chronotypes of similar age can account for the observed differences between them in sleep timing and duration on weekdays and weekends. It was also demonstrated that the model-based simulations might have practical implications for informing an individual about the extent of unrecoverable reduction of his/her sleep on weekdays.