Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitamin D binding protein is required to utilize skin-generated vitamin D

Significance The primary source of vitamin D in man is production in the skin following exposure to sunlight or artificially produced ultraviolet (UV) light. Despite the importance of this source, the mechanisms surrounding the transport of cutaneous vitamin D into the circulation have not been clearly defined. We have examined the vitamin D response to UVB in mutant mice lacking vitamin D binding protein (DBP). We have shown that in the absence of DBP, UVB does not correct vitamin D deficiency. Further, injection of small amounts of recombinant DBP to DBP−/− mice restores the response to vitamin D produced in skin. These results demonstrate a requirement for DBP in the utilization of vitamin D produced in the epidermis by UV light. Vitamin D is produced in the skin following exposure to sunlight. Ultraviolet (UV) B (UVB, 280–310 nm) results in isomerization of 7-dehydrocholesterol to previtamin D that spontaneously isomerizes to vitamin D. This pool of skin-derived vitamin D is the major source of vitamin D for animals. However, the mechanisms by which it becomes available remain undefined. It has been assumed that cutaneous vitamin D is transported into the circulation by vitamin D binding protein (DBP), but experimental evidence is lacking. To determine whether cutaneous vitamin D is transported by DBP, we utilized DBP−/− mice that were made vitamin D-deficient. These animals lack measurable 25(OH)D in blood and are hypocalcemic. As controls, DBP+/+ animals were vitamin D depleted and made equally hypocalcemic. UV irradiation of DBP+/+ animals restored serum calcium and serum 25(OH)D while the same treatment of DBP−/− animals failed to show either a serum calcium or 25(OH)D response despite having normal vitamin D production in skin. Intravenous injection of small amounts of recombinant DBP to the vitamin D-deficient DBP−/− mice restored the response to UV light. These results demonstrate a requirement for DBP to utilize cutaneously produced vitamin D.
Minimizing and managing treatment-associated complications in patients with chronic lymphocytic leukemia

ABSTRACT Introduction: During recent years, therapy in chronic lymphocytic leukemia (CLL) has changed dramatically. The introduction of small molecule inhibitors has shown remarkable clinical efficacy in both previously untreated and relapsed CLL patients. However, these therapies are associated with an increased risk of specific adverse events. Selection of the best therapeutic approach for patients with CLL should be based on an assessment of general condition, comorbidities, and most importantly, the individual risk of serious side effects. Areas covered: The review presents available data about the occurrence, prophylaxis and management of the most common and clinically most relevant adverse events associated with novel therapy in CLL. Expert opinion: The incorporation of novel drugs, such as B-cell receptor inhibitors and venetoclax, a selective inhibitor of B-cell lymphoma, influences the CLL management paradigm. An individualized approach to CLL is now possible with targeted therapies. The appropriate and optimal use of current therapies requires a precise understanding of their mechanisms of action, efficacy and adverse effect profiles. A fuller understanding of the prophylaxis and management of specific adverse events stemming from CLL therapy could minimize its associated morbidity and mortality. Next-generation agents with improved efficacy and better safety profiles will further advance outcomes for patients with CLL.
Fidelity of prespacer capture and processing is governed by the PAM-mediated interactions of Cas1-2 adaptation complex in CRISPR-Cas type I-E system

Prokaryotes deploy CRISPR-Cas–based RNA-guided adaptive immunity to fend off mobile genetic elements such as phages and plasmids. During CRISPR adaptation, which is the first stage of CRISPR immunity, the Cas1-2 integrase complex captures invader-derived prespacer DNA and specifically integrates it at the leader-repeat junction as spacers. For this integration, several variants of CRISPR-Cas systems use Cas4 as an indispensable nuclease for selectively processing the protospacer adjacent motif (PAM) containing prespacers to a defined length. Surprisingly, however, a few CRISPR-Cas systems, such as type I-E, are bereft of Cas4. Despite the absence of Cas4, how the prespacers show impeccable conservation for length and PAM selection in type I-E remains intriguing. Here, using in vivo and in vitro integration assays, deep sequencing, and exonuclease footprinting, we show that Cas1-2/I-E—via the type I-E–specific extended C-terminal tail of Cas1—displays intrinsic affinity for PAM containing prespacers of variable length in Escherichia coli. Although Cas1-2/I-E does not prune the prespacers, its binding protects the prespacer boundaries from exonuclease action. This ensures the pruning of exposed ends by exonucleases to aptly sized substrates for integration into the CRISPR locus. In summary, our work reveals that in a few CRISPR-Cas variants, such as type I-E, the specificity of PAM selection resides with Cas1-2, whereas the prespacer processing is co-opted by cellular non-Cas exonucleases, thereby offsetting the need for Cas4.
Prediction of major torso organs in low-contrast micro-CT images of mice using a two-stage deeply supervised fully convolutional network

Delineation of major torso organs is a key step of mouse micro-CT image analysis. This task is challenging due to low soft tissue contrast and high image noise, therefore anatomical prior knowledge is needed for accurate prediction of organ regions. In this work, we develop a deeply supervised fully convolutional network which uses the organ anatomy prior learned from independently acquired contrast-enhanced micro-CT images to assist the segmentation of non-enhanced images. The network is designed with a two-stage workflow which firstly predicts the rough regions of multiple organs and then refines the accuracy of each organ in local regions. The network is trained and evaluated with 40 mouse micro-CT images. The volumetric prediction accuracy (Dice score) varies from 0.57 for the spleen to 0.95 for the heart. Compared to a conventional atlas registration method, our method dramatically improves the Dice of the abdominal organs by 18%–26%. Moreover, the incorporation of anatomical prior leads to more accurate results for small-sized low-contrast organs (e.g. the spleen and kidneys). We also find that the localized stage of the network has better accuracy than the global stage, indicating that localized single organ prediction is more accurate than global multiple organ prediction. With this work, the accuracy and efficiency of mouse micro-CT image analysis are greatly improved and the need for using contrast agent and high x-ray dose is potentially reduced.
Prevalence of apical periodontitis and its association with previous root canal treatment, root canal filling length and type of coronal restoration - a cross-sectional study.

AIM To analyze the prevalence of periapical lesions and their association with previous root canal treatment, root canal filling length, and type of coronal restoration using in vivo cone-beam computed tomographic (CBCT) assessment. METHODOLOGY A global sample of 20,836 teeth, with a combined total of 27,046 roots, from 1160 patients, was analyzed via CBCT assessment in 8 health centres. Each tooth was evaluated by one out of five examiners after having performed a defined calibration procedure on the basis of 319 teeth. Intra and inter-rater reliability tests were performed. Each tooth was classified according the tooth number, presence/absence of periapical lesions, presence/absence of previous root canal treatment, length of root canal filling (short, good or overfilling), and type of coronal restoration. The z-test for proportions was used to analyze differences between tooth subgroups and an odds ratio was determined in order to analyze the association between treatment status and periapical lesions. A p < 0.05 was considered significant. RESULTS At a tooth level, the overall prevalence of periapical lesions in the sample was 10.4%. Maxillary teeth were associated with a significantly larger percentage of lesions (13.1%), while maxillary first molars had the greater proportion of lesions (21.2%). The prevalence of periapical lesions was significantly larger in root filled teeth (55.5%), short root canal fillings (72.7%), and in teeth restored with crowns (46.1%). At a root level, the mesio-buccal roots of both maxillary first molars had a tendency for a larger percentage of periapical lesions. CONCLUSION History of root canal treatment, root canal filling length, and type of coronal restoration influenced the presence of periapical lesions. Molars were more commonly associated with periapical lesions on root filled teeth, particularly those with short root fillings and those with crowns.
Changes in the elimination and resurgence of alcohol-maintained behavior in rats and the effects of naltrexone.

Resurgence may be a mechanism of relapse in alcohol use disorder patients upon discharge from treatment as part of an abuse-treatment-relapse cycle. Adjunctive pharmacotherapies may be a means to facilitate behavioral treatments and block resurgence. Experiments were conducted using a model of alcohol self-administration to assess the repeatability of the elimination and resurgence of alcohol-maintained behavior and the effects of naltrexone. Experiments had three phases. In Phase 1, behavior was maintained by oral alcohol under a fixed-ratio schedule. In Phase 2, behavior was extinguished via condensed milk delivery under a differential-reinforcement-of-other-behavior (DRO) schedule. In Phase 3, the DRO schedule was eliminated. In Experiment 1, this 3-phase cycle was replicated 4 times. Across replications, response rates and dose of alcohol consumed did not differ in Phase 1, alcohol-maintained behavior was eliminated more rapidly in Phase 2, and the resurgence effect was generally stable in Phase 3. In Experiment 2, naltrexone was administered in Phase 2, Phase 3, or both Phases 2 and 3, to separate groups of rats. Naltrexone facilitated the elimination of alcohol-maintained behavior in Phase 2 and, the resurgence of alcohol-maintained behavior was reduced only for those rats that received naltrexone in both phases. Together, these experiments demonstrate that the resurgence of alcohol-maintained behavior is replicable within-subjects and, further, resurgence of alcohol-maintained behavior may be a useful model to evaluate pharmacological interventions to facilitate behavioral treatments and reduce the likelihood of relapse. Results with naltrexone support the use of medication-assisted therapy approaches to reduce relapse risk in patients. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Prioritised self-referential processing is modulated by emotional arousal

Stimuli related to the self are processed more efficiently in a variety of cognitive tasks. Recent studies have shown that this self-referential processing bias is modulated by emotion. However, a clear understanding of how emotional valence and arousal affect self-referential processing is still lacking. With a label–shape matching task, Experiment 1 measured a self-prioritisation effect in four different mood states. The results revealed stronger self-prioritisation effects in moods with higher arousal levels and a reliable correlation between the self-prioritisation effect and the arousal level reported by the participants; however, the effect of emotional valence was not statistically reliable. Experiment 2 further showed that alerting cues, known to raise arousal level, effectively increased the self-prioritisation effect in the same label–shape matching task. Experiment 3 clarified that alerting cues do not affect reward processing in a similar label–shape matching task, suggesting that arousal may selectively modulate self-referential processing. These observations provide clear evidence that emotional arousal modulates self-referential processing.
The Reproducibility of the Jaw Index in the Measurement of Healthy Newborns

Objective: Establish the reliability of the jaw index to objectify the relationship between the maxilla and mandible in healthy newborns. Design: Cohort study. Setting: Tertiary setting. Patients: A total of 52 healthy newborns were included to detect an inter and intraclass correlation coefficient (ICC) of 0.8 with a 95% confidence interval (95% CI) of width 0.3. Inclusion criteria were children born full term without respiratory or feeding problems, and without congenital malformations or facial deformities due to birth trauma. Uncooperative patients were excluded. Interventions: The jaw index, a measuring tool for objectifying micrognathia in children suspected of having Robin sequence, was used. An ICC of greater than 0.8 was considered clinically relevant. Main Outcome Measure(s): Primary outcomes are the reliability of the jaw index expressed as interclass correlation coefficient and ICC. Secondary outcomes are the mean jaw index and mean length of the mandible, maxilla, and the alveolar overjet. Results: An interclass correlation coefficient of 0.74 (95% CI: 0.49-0.86) and an ICC of 0.81 (95% CI: 0.66-0.89) were found. The mandible had an average length of 162.6 mm (standard deviation [SD] 11.1), the maxilla 168.7 mm (SD 9.4), the alveolar overjet 2.0 mm (SD 0.60), and the mean jaw index was 2.1 (SD 0.64). Conclusion: The jaw index is a consistent instrument between different observers as well as for one observer measuring consecutively in the same child, to objectify the size of the lower jaw compared to that of the upper jaw in healthy newborns.
Individualised tailored assessment of therapeutic alternatives for HCC patients within the Milan criteria

We read with interest the leading article by Gerbes et al 1 published in Gut. This roundtable meeting article proposed that hepatocellular carcinoma (HCC) staging linked to first-line treatment indication can help clinicians guide patients through treatment decision-making process, patients and researchers need reliable ways to stage disease and predict prognosis. Controversies always exist during multidisciplinary team (MDT) decision-making for HCC patients within the Milan criteria (MC) due to the lack of evidence-based studies of composite multiparametric evaluations among the three potential curative therapies: liver transplantation (LT), liver resection (LR) and local ablation (LA). 2–4 Herein, we retrospectively evaluated the efficacy of LT, LR and LA for HCC patients within the MC and explored an individualised assessment prediction model to assist with MDT decision-making. Institutional ethics committees approved the retrospective analyses of consecutive HCC patients admitted to two medical centres of Nankai University (Tianjin, China) between November 2011 and March 2016. A total of 283 HCC patients within the MC were finally enrolled and classified into LT (n=100), LR (n=89) and LA (n=94) groups based on the first-line treatments. Under the three treatment groups, subgroups were divided according to …
Making cell culture more physiological: a call for more a comprehensive assessment of racial disparities in endothelial cell culture studies.

In the United States, cardiovascular diseases (CVDs) are the leading cause of death and disproportionately affect ethnic and racial minority populations. Black individuals are more likely to develop advanced CVD and microvascular complications resulting in end-organ damage. Endothelial cell dysfunction leads to micro- and macro-vascular dysfunction and is predictive of the development of CVD. Black vs white racial disparities in in vivo and in vitro studies of endothelial cell function are well-documented. However, race-related disparities in maternal lifestyle may be a major unconsidered factor in racial differences in endothelial cell culture studies. Further, rates of hypertensive disorders of pregnancy are higher in black versus white women. These pregnancy complications may result in placental dysfunction, including excess production of inflammatory and anti-angiogenic molecules that impair endothelial function. Therefore, studies that include other ethnic and racial minorities are needed, in addition to a more thorough characterization of endothelial cell donors and targeted cell culture studies (e.g., genotyping) to generate information that can be translated into effective preventive or treatment strategies for ethnic/racial disparities in CVD.
Intercalation of small molecules into DNA in chromatin is primarily controlled by superhelical constraint

The restricted access of regulatory factors to their binding sites on DNA wrapped around the nucleosomes is generally interpreted in terms of molecular shielding exerted by nucleosomal structure and internucleosomal interactions. Binding of proteins to DNA often includes intercalation of hydrophobic amino acids into the DNA. To assess the role of constrained superhelicity in limiting these interactions, we studied the binding of small molecule intercalators to chromatin in close to native conditions by laser scanning cytometry. We demonstrate that the nucleosome-constrained superhelical configuration of DNA is the main barrier to intercalation. As a result, intercalating compounds are virtually excluded from the nucleosome-occupied regions of the chromatin. Binding of intercalators to extranucleosomal regions is limited to a smaller degree, in line with the existence of net supercoiling in the regions comprising linker and nucleosome free DNA. Its relaxation by inducing as few as a single nick per ~50 kb increases intercalation in the entire chromatin loop, demonstrating the possibility for long-distance effects of regulatory potential.
The Efficacy of a Resilience Intervention Among Diverse, At-Risk, College Athletes: A Mixed-Methods Study

BACKGROUND: Adverse childhood experiences (ACEs) have been associated with psychological and physiological disease, and risky health behaviors. A person’s ability to be resilient may protect them from these negative health outcomes, as resilience has been associated with increased emotional awareness, coping, belonging, and greater likelihood of good health and well-being. AIMS: The purpose of this pilot study was to assess the efficacy of a strengths-based resilience intervention to improve access to internal and external resources that effect perceptions of stress, resilience, emotional awareness, and belonging among student-athletes. METHODS: A mixed-methods design was used to examine variables of interest between intervention and control groups. A sample of 56 college athletes completed surveys and engaged in expressive writing during a 5-week resilience intervention. RESULTS: Self-report data indicated that student-athletes in the intervention group improved decision making, lowered perceived stress, and increased resilience compared with controls. Of note, participants with ACEs showed greater increments of positive change in emotional awareness scales than participants without ACEs. Descriptions of emotion management, authentic connections, and increased ability to request support from others were identified in the qualitative data. CONCLUSIONS: A strengths-based course designed to increase resilience—offered as academic and athletic stress is mounting—provided a unique opportunity to promote student-athlete success. Participants gained skills key to victory on and off the field, including health-promoting behaviors, a sense of belonging, persistence, and the ability to negotiate external resources.
Experimental investigations and statistical modeling of cutting force and torque in rotary ultrasonic bone drilling of human cadaver bone

Cutting force and torque are important factors in the success of the bone drilling process. In the recent past, many attempts have been made to reduce the cutting force and torque in the bone drilling process. In this work, drilling on human cadaver bones has been performed using rotary ultrasonic bone drilling process to investigate the effect of drilling parameters on cutting force and torque. The experimental work was carried on a recently developed rotary ultrasonic bone drilling machine for surgical operations. The experimental work was performed in two phases. The first phase includes a comparative study between rotary ultrasonic bone drilling and conventional surgical bone drilling, to study the influence of various drilling parameters (rotational speed, drill diameter, and drilling tool feed rate) on the cutting force and torque. The results revealed that the cutting force and torque produced during drilling operations in rotary ultrasonic bone drilling were lesser (30%–40%) than conventional surgical bone drilling. In the second phase, response surface methodology was used to perform the statistical modeling of cutting force and torque in rotary ultrasonic bone drilling process. Analysis of variance was performed at a confidence interval of 95% to analyze the significant contribution (p < 0.05) of process parameters (drilling speed, feed rate, drill diameter, and abrasive particle size) on the responses (cutting force and torque). The confirmatory experiments were performed to validate the developed statistical models. It was found that both cutting force and torque decrease with increase in drilling speed and increases with the increasing drill diameter, feed rate, and abrasive particle size.
Cross-Cultural and Cross-Organizational Evidence for an Evolved Hazing Motivation

We report the first cross-cultural and cross-organizational evidence for an evolved hazing motivation. Using experiments performed in the United States, Japan, and among members of a hazing and a nonhazing organization, we demonstrate an invariant set of core hazing predictors. In particular, we show that the perception of near-term group benefits, which would have been ancestrally exploitable by new group members, substantially increases desired hazing severity in all samples. Results are discussed in light of human organizational psychology and the difficulty of reliably suppressing hazing behavior.
The impact of sample processing on inflammatory markers in serum: Lessons learned

Abstract Objectives: To investigate the effect of sample handling on inflammatory cytokines in serum and highlight challenges with using samples pre-collected from biobanks for biomarker research. Methods: Cytokine concentrations (IL-1β, IL-2, IL-6, IL-8, IL-10, TNFα, and IFNγ) were measured in serum samples of 205 patients with bipoldar disorder (BD) from the Mayo Clinic Bipolar Disorder Biobank and 205 non-psychiatric controls from the Mayo Clinic Biobank. As cytokine concentrations varied by recruitment site, post-hoc models were used to test the effect of clinical variables and pre-processing time on cytokines. To evaluate the effect of pre-processing time experimentally, cytokines were assayed in serum and plasma from 6 healthy volunteers processed at different time points. Results: Cytokine levels were significantly higher in the BD group. However, both cytokine levels and pre-processing times differed by recruitment site, and post-hoc analyses revealed that pre-processing time was significantly associated with several cytokines. An experiment using samples from healthy volunteers confirmed that concentrations for most cytokines increased with longer pre-processing times. Conclusions: Delays in processing influence cytokine concentrations in blood samples. Given the increasing use of biobanks in research, this study highlights the need to carefully evaluate sample collection and handling methods when designing biomarker studies.