Miracle-dz/UniFAR-FTUs huggingface dataset:
Prime Editing Guide RNA Design Automation Using PINE-CONE

CRISPR-based technologies are paramount in genome engineering and synthetic biology. Prime editing (PE) is a technology capable of installing genomic edits without double-stranded DNA breaks (DSBs) or donor DNA. Prime editing guide RNAs (pegRNAs) simultaneously encode both guide and edit template sequences. They are more design intensive than CRISPR single guide RNAs (sgRNAs). As such, application of PE technology is hindered by the limited throughput of manual pegRNA design. To that end, we designed a software tool, Prime Induced Nucleotide Engineering Creator of New Edits (PINE-CONE), that enables high-throughput automated design of pegRNAs and prime editing strategies. PINE-CONE translates edit coordinates and sequences into pegRNA designs, accessory guides, and oligonucleotides for facile cloning workflows. To demonstrate PINE-CONE’s utility in studying disease-relevant genotypes, we rapidly design a library of pegRNAs targeting Alzheimer’s Disease single nucleotide polymorphisms (SNPs). Overall, PINE-CONE will accelerate the application of PEs in synthetic biology and biomedical research.
Gas Cell Infrared and Attenuated Total Reflection Infrared Spectroscopic Studies for Organic–Inorganic Interactions in Adsorption of Fulvic Acid on the Goethite Surface Generating Carbon Dioxide

The generation of carbon dioxide (CO2) from Nordic fulvic acid (FA) solution in the presence of goethite (α-FeOOH) was observed in FA–goethite interaction experiments at 25–80 ℃. CO2 generation processes observed by gas cell infrared (IR) spectroscopy indicated two steps: the zeroth order slower CO2 generation from FA solution commonly occurring in the heating experiments of the FA in the presence and absence of goethite (activation energy: 16–19 kJ mol–1), and the first order faster CO2 generation from FA solution with goethite (activation energy: 14 kJ mol–1). This CO2 generation from FA is possibly related to redox reactions between FA and goethite. In situ attenuated total reflection infrared (ATR-IR) spectroscopic measurements indicated rapid increases with time in IR bands due to COOH and COO– of FA on the goethite surface. These are considered to be due to adsorption of FA on the goethite surface possibly driven by electrostatic attraction between the positively charged goethite surface and negatively charged deprotonated carboxylates (COO–) in FA. Changes in concentration of the FA adsorbed on the goethite surface were well reproduced by the second order reaction model giving an activation energy around 13 kJ mol–1. This process was faster than the CO2 generation and was not its rate-determining step. The CO2 generation from FA solution with goethite is faster than the experimental thermal decoloration of stable structures of Nordic FA in our previous report possibly due to partial degradations of redox-sensitive labile structures in FA. Graphical Abstract
Lumbar Disc Herniation and Preoperative Modic Changes: A Prospective Analysis of the Clinical Outcomes After Microdiscectomy

Study design: Prospective comparative cohort study. Objectives: The study aims to elucidate the relationship between Modic endplate changes and clinical outcomes after a lumbar microdiscectomy. Methods: Consecutive patients undergoing microdiscectomy for lumbar disc herniation (LDH) were prospectively studied. Pre-operative clinical and radiological parameters were recorded. The pain was assessed by Numeric pain rating scale (NPRS), and functional assessment by Oswestry Disability Index (ODI). Minimal clinically important difference (MCID) in outcome was calculated for both the groups. Complications related to surgery were studied. Follow-up was done at 6 weeks, 3 months, 6 months and 1 year. Mac Nab criteria were used to assess patient satisfaction at 1 year. Results: Out of 309 patients, 86 had Modic changes, and 223 had no Modic changes. Both groups had similar back pain (p-value: 0.07) and functional scores (p-value: 0.85) pre-operatively. Postoperatively patients with Modic changes had poorer back pain and ODI scores in the third month, sixth month and 1 year (p-value: 0.001). However, MCID between the groups were not significant (p-value: 0.18 for back pain and 0.58 for ODI scores). Mac Nab criteria at 1 year were worse in Modic patients (p-value: 0.001). No difference was noted among Modic types in the pre-operative and postoperative pain and functional outcomes. Four patients in Modic group (4.7%) and one patient in the non-Modic group (0.5%) developed postoperative discitis (p-value: 0.009). Conclusions: Preoperative Modic changes in lumbar disc herniation is associated with less favorable back pain, functional scores and patient satisfaction in patients undergoing microdiscectomy.
Adhesion Properties of Thin Film Multilayers: Comparison of Nanoindentation and Four-Point-Bending Techniques

In this study, we investigated the adhesion strength of SiO2/SiN/TiW/Cu film stacks on silicon by the use of cross-sectional nanoindentation (CSN) technique. The delamination occurred along the SiN/TiW interface as determined by means of SEM and EDX analysis. The critical energy release rate was determined as a quantitative measure of the adhesion strength by application of analytical models as well as Finite Element Method (FEM). Comparative measurements on samples of the same layer composition using the well-established four-point bending (4PB) technique were performed to validate the results of the CSN measurements. FEM was performed to calculate the loading conditions and stress distribution in the samples. The calculations also allowed separating the contribution of plastic and elastic energy in the metallization layers during delamination testing and thereby estimating the value of the interfacial adhesion energy. The experimental results show the good applicability of both the 4PB and CSN method for determining quantitative values of the fracture toughness of thin-film interfaces found in microelectronic components and indicate a good agreement between the two methods.
A new ΔR value for the southern North Sea and its application in coastal research

Abstract Accelerator mass spectrometry (AMS) radiocarbon (14C) dating of Cerastoderma edule (Linnaeus 1767) and Mytilus edulis (Linnaeus 1758) shells sampled in AD 1889 near the island of Wangerooge gave a new local correction factor ΔR of −85 ± 17 14C years for the Wadden Sea area. The value is considerably higher than the available scattered data from the North Sea, which were obtained from pre-bomb growth rings of living Arctica islandica (Linnaeus 1767). This can be explained by the incorporation of 14C-depleted terrestrial carbon into the shell material which compensates the intensified exchange of CO2 between atmosphere and shallow coastal water, e.g. by tidal currents. Additionally, two examples of application of the new ΔR value in coastal research give deeper insights into the dynamics of bivalve shell preservation in the Wadden Sea and the need for further research to clarify the Holocene reintroduction of Mya arenaria (Linnaeus 1758) into European waters.
Protein Extraction from Spirulina platensis by Using Ultrasound Assisted Extraction: Effect of Solvent Types and Extraction Time

Protein is a substantial nutrition that essentially required by human. Spirulina platensis (Spp), well known as protein source could be a significant source to be used for many industrial applications. This study was investigated the effectiveness of ultrasound assisted extraction (UAE) method for protein extraction from Spp at various composition of solvent mixture and extraction time. Ethanol and mixture of methanol-ethanol were used as solvent. Extraction was conducted by varying ratios of solvent to biomass at 10:1, 12.5:1, and 15:1 (v/w), and extraction time (20, 35, and 50 min). Optimum protein recovery from dry Spp was 42.55 ± 0.43% obtained by using 20 ml of the mixture of methanol and ethanol at 50 min of extraction time. This study also conducted that mixture of methanol and ethanol was a better solvent on improving the ultrasound assisted extraction, as indicated by high protein recovery with less amount of solvent volume used.
Seasonal variability in the diet and feeding ecology of black-and-white ruffed lemurs (Varecia variegata) in Ranomafana National Park, southeastern Madagascar.

OBJECTIVES We characterized the diet and foraging ecology of the black-and-white ruffed lemur (Varecia variegata), a specialized frugivore, and investigated behavioral strategies exhibited in response to seasonal changes in resource availability. MATERIALS AND METHODS Behavioral data were collected from the same two adjacent communities across 29 months during two observation periods (2007-2008; 2017-2018) in Mangevo, a primary rainforest habitat in southeastern Madagascar. To analyze feeding in the context of energy maximization versus time minimization strategies, we used nonparametric tests to compare plant part constituents, dietary diversity, activity budgets, and canopy strata use between fruit-abundant versus fruit-lean seasons. RESULTS Individuals dedicated ~30% of their time to feeding year-round, mostly in the middle canopy (11-20 m). Animals fed primarily on fruits (74% of diet), but frugivory decreased and folivory increased markedly during fruit-lean seasons. Abundant season dietary diversity (98 taxa, H' = 0.71-1.37) was greater than lean season diversity (70 taxa, H' = 0.56-1.06), which coincided with less traveling, more resting, and higher canopy use-though interannual variation was observed. CONCLUSIONS Herein, we describe behavioral and dietary patterns that are concordant with a time minimizing behavioral strategy. Black-and-white ruffed lemur diets comprised lower taxonomic diversity, fewer fruits, and more leaves during fruit-lean months. Further, shifts toward less travel, more resting, and greater use of higher canopy levels during this time were most likely for thermoregulatory benefits.
Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer

Prostate cancer is one of the deadliest cancers in men. RNA-binding proteins play a critical role in human cancers; however, whether they have a significant effect on the prognosis of prostate cancer has yet to be elucidated. In the present study, we performed a comprehensive analysis of RNA sequencing and clinical data from the Cancer Genome Atlas dataset and obtained differentially expressed RNA-binding proteins between prostate cancer and benign tissues. We constructed a protein-protein interaction network and Cox regression analyses were conducted to identify prognostic hub RNA-binding proteins. SNRPA1 was associated with the highest risk of poor prognosis and was therefore selected for further analysis. SNRPA1 expression was positively correlated with Gleason score and pathological TNM stage in prostate cancer patients. Furthermore, the expression profile of SNRPA1 was validated using the Oncomine, Human Protein Atlas, and Cancer Cell Line Encyclopedia databases. Meanwhile, the prognostic profile of SNRPA1 was successfully verified in GSE70769. Additionally, the results of molecular experiments revealed the proliferative role of SNRPA1 in prostate cancer cells. In summary, our findings evidenced a relationship between RNA-binding proteins and prostate cancer and indicated the prognostic significance of SNRPA1 in prostate cancer.
Standardized pathology report for breast cancer

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of ‘standard data elements,’ ‘conditional data elements,’ and a biomarker report form. The ‘standard data elements’ consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the ‘conditional data elements. ’ In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.
Impact of accreditation on documentation and staff perception in the ophthalmology department of an Indian medical college

Purpose: National Accreditation Board for Hospitals and Healthcare Providers operates the health-care accreditation program in India. Research on impact of accreditation on eye-care centers is scarce. This article was conceptualized to scientifically evaluate the changes in documentation brought about by accreditation and its effects on staff in the Ophthalmology Department of an Indian Medical College. Methods: This was conducted as a quasi-experimental study in four steps. First, a point-based evaluation of case sheets in both pre-accreditation and postaccreditation phase, along with statistical analysis of the results, was done. Step two involved analysis of quality indicators and patient safety indices in successive years from inception of data to post-accreditation phase. Step three comprised a survey of staff employing a validated tool, and finally, face-to-face semistructured interviews with designated authorities, including finance departmental head, completed the study. Results: A statistically significant difference was seen in scores achieved by the pre and postaccreditation case sheets, with the postphase case sheets achieving 15% increased scores over the prephase case sheets. Quality indicator indices displayed improvements post-accreditation. There was an accompanying increase in quantity of documentation. Financial data analysis showed increased expenditure for accreditation under multiple heads. Staff believed that accreditation led to increased workload but did not express decreased satisfaction and felt that accreditation was eventually beneficial. However, staff believed rewards for improving quality can be enhanced. Conclusion: Accreditation increases quality and quantity of documentation, and staff workload. Increased financial costs also ensue.Staff believe that accreditation improves quality, is beneficial, but desire enhanced rewards.
Development of a microencapsulated probiotic delivery system for New Zealand black-footed abalone (Haliotis iris)

Abstract Conventional methods of probiotics delivery to farmed aquatic animals are not efficient due to loss of probiotic’s viability before the probiotics can reach their site of action. This study aims to develop a microencapsulated probiotic delivery system for black-footed abalone (Haliotis iris). An emulsion technique was used to encapsulate probiotic bacteria within chitosan-coated alginate microparticles (CALG). The efficacy of CALG microparticles in delivering probiotics to abalone was assessed using ex vivo and in vivo experiments. Microparticles (113 ± 4 µm) with encapsulation efficiency of more than 75% were developed using an internal gelation formulation approach. The ex vivo release experiments revealed the lack of probiotic discharge in the first 6 h of incubating CALG in seawater followed by a slight bacterial release within the next 20 h. The exposure of CALG microparticles to simulated gastric and intestinal media showed a significantly higher release of encapsulated bacteria in the simulated intestinal medium. The results of feeding trial revealed that the number of probiotic bacteria in probiotic-fed abalone was significantly higher than the one in the control animals. The results suggest that CALG microparticles can be used as a controlled release system for delivering viable probiotic bacteria to the gastrointestinal tract of abalone. Graphical Abstract
Frequency of interruptions to prolonged sitting and postprandial metabolic responses in young, obese, Chinese men

ABSTRACT This study aimed to examine the effects of 3-min light-intensity walking every 30 min (3-min) and 6-min light-intensity walking every 60 min (6-min) compared with prolonged sitting (SIT) on the postprandial metabolic responses in young, centrally obese, Chinese men. Twenty-one Chinese men with central obesity (age, 23 ± 4 years; body mass index, 29.8 ± 3.2 kg·m−2; waist circumference, 98.7 ± 7.1 cm; mean ± SD) underwent three 6-h experiments with a 7-day washout period, SIT, 3-min, and 6-min, in randomized order. Compared with SIT, neither walking condition showed differences in total and net incremental area under the curve (tAUC and iAUC, respectively) for glucose, insulin, nor non-esterified fatty acids. The tAUC and iAUC for triglycerides for the SIT condition (10.8 [9.3, 12.2] and 4.4 [3.7, 5.1] mmol·h·L−1, respectively; mean [95% confidence interval]) was higher than 3-min (10.4 [9.0, 11.8] and 3.8 [3.3, 4.3] mmol·h·L−1, respectively, both Ps <0.05) and 6-min (9.6 [8.1, 11.0] and 3.5 [2.9, 4.2] mmol·h·L−1, respectively, both Ps <0.01) conditions. Interrupting prolonged sitting regardless of frequency-reduced postprandial triglycerides. A higher volume of physical activity may be required to obtain greater glycaemic benefits in young Chinese men with central obesity.
Influence of Mn and Ni on Austenite Stabilization during a High Temperature Q&P Treatment

The aim of this work was to study the influence of quenching and partitioning temperatures combined with various levels of Mn and Ni contents on the austenite stabilization along the quenching and partitioning (Q&P) cycle. Three steels with 2 wt. %, 4 wt. % and 6 wt. % manganese and one steel with 2 wt. % nickel content were investigated. Phase transformation temperatures and critical cooling rates were obtained experimentally using dilatometer for each alloy. Q&P cycles with different quenching and partitioning temperatures were also done in dilatometer, thus, allowing monitoring of the expansion/contraction during the whole Q&P cycle. Microstructure characterization was performed by means of a Scanning Electron Microscope and X-Ray Diffraction to measure retained austenite content. It was found that, strongly depending on the Q&P conditions, austenite stabilization or decomposition occurs during partitioning and final cooling. In case of high partitioning temperature cycles, austenite reverse transformation was observed. Certain cycles resulted in a very effective austenite stabilization and interesting microstructure.
Progress in Green Polymer Composites from Lignin for Multifunctional Applications: A Review

Rising environmental concerns and depletion of petro-chemical resources has resulted in an increased interest in biorenewable polymer-based environmentally friendly materials. Among biorenewable polymers, lignin is the second most abundant and fascinating natural polymer next to cellulose. Lignin is one of the three major components found in the cell walls of natural lignocellulosic materials. Lignin is widely available as a major byproduct of a number of industries involved in retrieving the polysaccharide components of plants for industrial applications, such as in paper making, ethanol production from biomass, etc. The impressive properties of lignin, such as its high abundance, low weight, environmentally friendliness and its antioxidant, antimicrobial, and biodegradable nature, along with its CO2 neutrality and reinforcing capability, make it an ideal candidate for the development of novel polymer composite materials. Considerable efforts are now being made to effectively utilize waste lignin as one .
School Social Workers as Nepantleras in Equity Work for Immigrant Students: A Conceptual Exploration

This article investigates the critical role school social workers play in promoting equity and advocating for immigrant students in K–12 settings. We explore and conceptualize the notion of nepantlera from the work of Gloria Anzaldúa and draw from qualitative data to show how school social workers function as nepantleras in service and advocacy roles for immigrant students. We further argue that the school settings in which these services take place should be understood as borderlands. Throughout the article, we explore the following questions: What is a paradigm for school social worker practice with immigrant students that is informed by the concept of nepantlera? How do we begin to consider such a paradigm in a way that honors the complexity of Anzaldúa’s work? While pursuing these questions we present qualitative data from a national sample of school workers. We offer implications for a nepantlera-informed paradigm in school social work practice.
Functional Limitations, Social Integration, and Daily Activities in Late Life.

OBJECTIVES Disability in late life has been associated with increases in receiving care and loss of autonomy. The Disablement Process Model suggests that physical impairments lead to functional limitations that contribute to disabilities in managing household, job or other demands. Yet, we know surprisingly little about how functional limitations are related to activities throughout the day among community-dwelling adults, or the possible moderating role of social integration on these associations. METHODS Community-dwelling adults (N = 313) aged 65+ completed a baseline interview assessing their functional limitations, social ties, and background characteristics. Over 5 to 6 days, they answered questions about daily activities and encounters with social partners every 3 hours on handheld Android devices. RESULTS Multilevel logistic models revealed that functional limitations are associated with increased likelihood of activities associated with poor health (e.g., TV watching, medical appointments), and reduced likelihood of social activities, or physical activities, chores, or leaving the home. Most moderation analyses were not significant; family and friends did not mitigate associations between functional limitations and daily activities, with the exception of medical appointments. Individuals with functional limitations were more likely to attend medical appointments when with their social partners than when alone. DISCUSSION This study provided modest indication that functional limitations in community-dwelling older adults are associated with patterns of activity that may lead to further limitations, disability or loss of autonomy. Findings warrant longitudinal follow-up to establish subsequent patterns of decline or stability.
Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced‐stage, classical Hodgkin lymphoma: A prespecified subgroup analysis of high‐risk patients from the ECHELON‐1 study

Approximately one‐third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high‐risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4–7, enrolled in the ECHELON‐1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first‐line therapy after a median follow‐up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4–7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537–0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4–7 (HR, 0.588; 95% CI, 0.386–0.894; p = 0.012). The most common adverse events (AEs) in A + AVD‐treated versus ABVD‐treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4–7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high‐risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON‐1 shows a favorable benefit‐risk balance in high‐risk patients.