Miracle-dz/UniFAR-FTUs huggingface dataset:
The Origin of Carbonate Veins Within the Sedimentary Cover and Igneous Rocks of the Cocos Ridge: Results From IODP Hole U1414A

Carbonate veins in the igneous basement and in the lithified sedimentary cover of the Cocos Ridge at International Ocean Discovery Program (IODP) Hole 344‐U1414A reveal the hydrologic system and fluid‐rock interactions. IODP Hole 344‐U1414A was drilled on the northern flank of the Cocos Ridge and is situated 1 km seaward from the Middle America Trench offshore Costa Rica. Isotopic and elemental compositions were analyzed to constrain the fluid source of the carbonate veins and to reveal the thermal history of Hole 344‐U1414A. The formation temperatures (oxygen isotope thermometer) of the carbonate veins in the lithified sedimentary rocks range from 70 to 92 °C and in the basalt from 32 to 82 °C. 87Sr/86Sr ratios of the veins in the altered Cocos Ridge basalt range between 0.707307 and 0.708729. The higher ratios are similar to seawater strontium ratios in the Neogene. 87Sr/86Sr ratios lower 0.7084 indicate exchange of Sr with the igneous host rock. The calcite veins hosted by the sedimentary rocks are showing more primitive 87Sr/86Sr ratios <0.706396. The isotopic compositions indicate seawater, modified into a hydrothermal fluid by subsequent heating, as the main fluid source. Low‐temperature alteration and the presence of a high‐temperature fluid resulted in different carbonate precipitates forming up to several cm thick veins. The geochemical data combined with age data of the sedimentary rocks suggest intraplate seamount volcanism in the area between the Galapagos hot spot and the Cocos Island as an additional heating source, after the formation of the Cocos Ridge at the Galapagos hot spot.
Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

To the Editor: Sandborn et al. (May 4 issue)1 raise two important issues that deserve attention. First, when patients with moderate-to-severe ulcerative colitis show no improvement in response to treatment with mesalamine or a dosage of glucocorticoids lower than 25 mg per day, guidelines indicate that the daily dosage of glucocorticoids may be increased to 0.75 to 1.0 mg per kilogram of body weight,2 a level at which there is a higher rate of remission. However, Sandborn et al. reported a remission rate of only 16.6 to 18.5% in the tofacitinib group, a result that is disappointing. Another weakness of this study is that glucocorticoid withdrawal was not considered as an end point. Second, it is noteworthy that activation of the Janus kinase–signal transducers and activators of transcription 3 (JAK–STAT3) cascade in intestinal epithelial cells and some subsets of T cells is essential in maintaining intestinal homeostasis and promoting mucosal healing in several murine models of colitis.3,4 Paradoxically, persistent inhibition of the JAK–STAT3 pathway by tofacitinib could thus have had deleterious effects in the gut.
A Variational Model for Data Fitting on Manifolds by Minimizing the Acceleration of a Bézier Curve

We derive a variational model to fit a composite Bezier curve to a set of data points on a Riemannian manifold. The resulting curve is obtained in such a way that its mean squared acceleration is minimal in addition to remaining close the data points. We approximate the acceleration by discretizing the squared second order derivative along the curve. We derive a closed-form, numerically stable and efficient algorithm to compute the gradient of a Bezier curve on manifolds with respect to its control points, expressed as a concatenation of so-called adjoint Jacobi fields. Several examples illustrate the capabilites and validity of this approach both for interpolation and approximation. The examples also illustrate that the approach outperforms previous works tackling this problem.
Hispanic ethnicity as a moderator of the effects of aerobic and resistance exercise in survivors of breast cancer

Metabolic syndrome (MSY) is associated with an increased risk of cardiovascular disease, type 2 diabetes, and recurrence in breast cancer survivors (BCS). MSY is 1.5 times more common in Hispanic women compared with non‐Hispanic women. Although exercise mitigates MSY in BCS, to the best of the authors’ knowledge, few studies to date have focused on minorities. This secondary analysis examined ethnicity as a moderator of the effects of a 16‐week aerobic and resistance exercise intervention on MSY, sarcopenic obesity, and serum biomarkers in BCS.
Cefuroxime-induced anaphylaxis with prominent central nervous system manifestations: A case report

Cefuroxime is a second-generation cephalosporin antibiotic that causes immediate hypersensitivity reactions, ranging from mild urticaria to severe anaphylactic shock. Anaphylactic reactions typically involve multiple systems, most notably, the skin and the respiratory and cardiovascular systems. Here, we report the unusual case of a patient who presented with oral cefuroxime-induced anaphylaxis with prominent neurologic manifestations. To identify the drug responsible for the anaphylaxis, we performed skin tests. Based on positive skin-prick test results, the diagnosis of cefuroxime-induced anaphylaxis was confirmed. Therefore, we suggest that clinicians should consider the possibility of a drug-induced anaphylactic reaction when neurologic but not cutaneous symptoms are present. The skin-prick test is a safe and useful diagnostic tool to confirm this kind of immediate drug hypersensitivity.
Beyond Selection: The Use of Situational Judgement Tests in the Teaching and Assessment of Professionalism.

PROBLEM Professionalism is a critical attribute of medical graduates. Its measurement is challenging. The authors sought to assess final-year medical students' knowledge of appropriate professional behavior across a broad range of workplace situations. APPROACH Situational judgement tests (SJTs) are used widely in applicant selection to assess judgement or decision making in work-related settings as well as attributes such as empathy, integrity, and resilience. In 2014, the authors developed three 40-item SJTs with scenarios relevant to interns (first-year junior doctors) and delivered the tests to final-year medical students to assess aspects of professionalism. As preparation, students discussed SJT-style scenarios; after the tests they completed an evaluation. The authors applied the Angoff method for the standard-setting process, delivered electronic individualized feedback reports to students post test, and provided remediation for students failing to meet the cut score. OUTCOMES Evaluation revealed that the tests positively affected students' learning and that students accepted them as an assessment tool. Validity and reliability were acceptable. Implementation costs were initially high but will be recouped over time. NEXT STEPS Recent improvements include changes to pass requirements, question revision based on reliability testing, and provision of detailed item-level feedback. Work is currently under way to expand the item bank and to introduce tests earlier in the course. Future research will explore correlation of SJT performance with other measures of professionalism and focus on the impact of SJTs on professionalism and interns' ability to deal with challenging workplace situations.
The empirical characteristics of human pattern vision defy theoretically-driven expectations

Contrast is the most fundamental property of images. Consequently, any comprehensive model of biological vision must incorporate this attribute and provide a veritable description of its impact on visual perception. Current theoretical and computational models predict that vision should modify its characteristics at low contrast: for example, it should become broader (more lowpass) to protect from noise, as often demonstrated by individual neurons. We find that the opposite is true for human discrimination of elementary image elements: vision becomes sharper, not broader, as contrast approaches threshold levels. Furthermore, it suffers from increased internal variability at low contrast and it transitions from a surprisingly linear regime at high contrast to a markedly nonlinear processing mode in the low-contrast range. These characteristics are hard-wired in that they happen on a single trial without memory or expectation. Overall, the empirical results urge caution when attempting to interpret human vision from the standpoint of optimality and related theoretical constructs. Direct measurements of this phenomenon indicate that the actual constraints derive from intrinsic architectural features, such as the co-existence of complex-cell-like and simple-cell-like components. Small circuits built around these elements can indeed account for the empirical results, but do not appear to operate in a manner that conforms to optimality even approximately. More generally, our results provide a compelling demonstration of how far we still are from securing an adequate computational account of the most basic operations carried out by human vision.
The regulation of hydroxysteroid 17β-dehydrogenase type 1 and 2 gene expression in breast cancer cell lines by estradiol, dihydrotestosterone, microRNAs, and genes related to breast cancer

Aim. To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2. Materials. Breast cancer cell lines ZR-75-1, MCF7, T47D, SK-BR-3, and the immortalized epithelial cell line MCF10A were used. Cells were treated either with estradiol or dihydrotestosterone for 6, 24, 48 hours, or 7 days or treated with miRNAs or siRNAs predicted to influence HSD17B expression Results and discussion. Estradiol treatment decreased HSD17B1 expression and had a time-dependent effect on HSD17B2 expression. This effect was lost in estrogen receptor-α down-regulated or negative cell lines. Dihydrotestosterone treatment increased HSD17B2 expression, with limited effect on HSD17B1 expression. No effect was seen in cells without AR or in combination with the AR inhibitor hydroxyflutamide. The miRNA-17 up-regulated HSD17B1, while miRNA-210 and miRNA-7-5p had up- and down-regulatory effect and miRNA-1304-3p reduced HSD17B1 expression. The miRNA-204-5p, 498, 205-3p and 579-3p reduced HSD17B2 expression. Downregulation of CX3CL1, EPHB6, and TP63 increased HSD17B1 and HSD17B2 expression, while GREB1 downregulation suppressed HSD17B1 and promoted HSD17B2 expression. Conclusion. We show that HSD17B1 and HSD17B2 are controlled by estradiol, dihydrotestosterone, and miRNAs, as well as modulated by several breast cancer-related genes, which could have future clinical applications.
The combination of metformin and 2‐deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease

The pathogenic mechanism of autosomal dominant polycystic kidney disease (ADPKD) is unclear. Similar to tumour cells, polycystic kidney cells are primarily dependent on aerobic glycolysis for ATP production. Compared with rodents, miniature pigs are more similar to humans. This study is the first time to investigate the effects of the combination of metformin and 2‐deoxyglucose (2DG) in a pig model of chronic progressive ADPKD.
SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency.

CONTEXT Multiple autosomal recessive genes have been etiologically linked to primary adrenal insufficiency (PAI). Recently, sphingosine-1-phosphate lyase 1 (SGPL1) gene mutations were recognized as a cause of steroid-resistant nephrotic syndrome type 14 (NPHS14), a sphingolipidosis with multisystemic manifestations, including PAI. OBJECTIVE To check if SGPL1 mutations are involved in the pathogenesis of PAI in patients who do not exhibit nephrotic syndrome. METHODS Sequencing of the SGPL1 gene in 21 patients with familial glucocorticoid disease or triple A syndrome. RESULTS We identified two missense SGPL1 variants in four patients, two of whom were first cousins. We describe in detail the proband, a boy born to Saudi Arabian consanguineous parents with a homozygous c.665G>A, p.R222Q SGPL1 variant. The patient presented with hypoglycemia and seizures at age 2 years and was ultimately diagnosed with PAI (isolated glucocorticoid deficiency). Brain MRI showed abnormalities in the basal ganglia consistent with a degenerative process albeit the patient had no neurologic symptoms. CONCLUSIONS New genetic causes of PAI continue to be identified. We suggest that screening for SGPL1 mutations should not be reserved only for patients with nephrotic syndrome but may also include patients with PAI who lack other clinical manifestations of NPHS14 because, in certain cases, kidney disease and accompanying features might develop. Timely diagnosis of this specific sphingolipidosis while the kidneys still function normally can lead to prompt initiation of therapy and improve outcome.
A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(−)) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnOSM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnOSM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution.
Deep learning for predicting in‐hospital mortality among heart disease patients based on echocardiography

Heart disease (HD) is the leading cause of global death; there are several mortality prediction models of HD for identifying critically‐ill patients and for guiding decision making. The existing models, however, cannot be used during initial treatment or screening. This study aimed to derive and validate an echocardiography‐based mortality prediction model for HD using deep learning (DL).
Longitudinal Data Analyses Using Linear Mixed Models in SPSS: Concepts, Procedures and Illustrations

Although different methods are available for the analyses of longitudinal data, analyses based on generalized linear models (GLM) are criticized as violating the assumption of independence of observations. Alternatively, linear mixed models (LMM) are commonly used to understand changes in human behavior over time. In this paper, the basic concepts surrounding LMM (or hierarchical linear models) are outlined. Although SPSS is a statistical analyses package commonly used by researchers, documentation on LMM procedures in SPSS is not thorough or user friendly. With reference to this limitation, the related procedures for performing analyses based on LMM in SPSS are described. To demonstrate the application of LMM analyses in SPSS, findings based on six waves of data collected in the Project P.A. T.H. S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong are presented.
Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition

Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut–brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.
Assessing the relation of the coded nursing care and nursing intensity data: Towards the exploitation of clinical data for administrative use and the design of nursing workload

Patient-care data from the electronic health record systems are increasingly in demand for re-use in administration and resource planning. Nursing documentation with coded concepts is expected to produce more reliable data, fulfilling better requirements for re-use. The aim was to ascertain what kind of relation exist between coded nursing diagnoses, nursing interventions, and nursing intensity and to discuss the possibilities for re-using nursing data for workload design. We analysed the retrospective nursing records of 794 patients documented by the Finnish Care Classification and nursing intensity data assessed by the Oulu Patient Classification over a 15-day period in nine inpatient units at a university hospital. Using the generalised linear mixed model, the clear relationship between the number of coded nursing notes and nursing intensity levels were ascertained. The number of coded nursing notes increases when the nursing intensity increases. The outcomes construct a good basis for continuing elaboration of electronic health record data re-use.
Understanding the economic impact of leishmaniasis on households in endemic countries: a systematic review

ABSTRACT Introduction: Leishmaniasis is a poverty-related disease that causes a significant socioeconomic burden to affected households. Visceral leishmaniasis is fatal if untreated, yet illness costs may lead to delays in accessing care. Skin manifestations of leishmaniasis cause a psychological burden and even longer treatment trajectories. The objective of this review is to evaluate illness costs associated with leishmaniasis across different settings (Asia, Africa, and Latin America) and the consequences to households. Areas covered: Through a systematic review of cost-of-illness studies, we documented the distribution of costs, the health-seeking behavior, and the consequences of leishmaniasis. We discuss the value of cost-of-illness studies for leishmaniasis. Expert commentary: Despite the free provision of diagnostics and treatment in the public health care sector, out-of-pocket payments remain substantial. There has been progress in addressing the economic burden of leishmaniasis, particularly through the elimination initiative in the Indian subcontinent. Though the illness cost is decreasing due to shorter treatment regimens and better access to care, the situation remains challenging in Africa. Improvement of control tools is critical. There is a need to update cost estimates to inform policy-making and ensure sustainable solutions to reduce financial barriers to leishmaniasis care, especially in pursuing universal health coverage.
Prediction of folding mechanisms for Ig‐like beta sandwich proteins based on inter‐residue average distance statistics methods

To understand the folding mechanism of a protein is one of the goals in bioinformatics study. Nowadays, it is enigmatic and difficult to extract folding information from amino acid sequence using standard bioinformatics techniques or even experimental protocols which can be time consuming. To overcome these problems, we aim to extract the initial folding unit for titin protein (Ig and fnIII domains) by means of inter‐residue average distance statistics, Average Distance Map (ADM) and contact frequency analysis (F‐value). TI I27 and TNfn3 domains are used to represent the Ig‐domain and fnIII‐domain, respectively. Beta‐strands 2, 3, 5, and 6 are significant for the initial folding processes of TI I27. The central strands of TNfn3 were predicted as a primary folding segment. Known 3D structure and unknown 3D structure domains were investigated by structure or non‐structure based multiple sequence alignment, respectively, to learn the conserved hydrophobic residues and predicted compact region relevant to evolution. Our results show good correspondence to experimental data, phi‐value and protection factor from H‐D exchange experiments. The significance of conserved hydrophobic residues near F‐value peaks for structural stability using hydrophobic packing is confirmed. Our prediction methods once again could extract a folding mechanism only knowing the amino acid sequence.
Discovery and Characterization of Recurrent, Targetable ALK Fusions in Leiomyosarcoma

Soft-tissue sarcomas such as leiomyosarcoma pose a clinical challenge because systemic treatment options show only modest therapeutic benefit. Discovery and validation of targetable vulnerabilities is essential. To discover putative kinase fusions, we analyzed existing transcriptomic data from leiomyosarcoma clinical samples. Potentially oncogenic ALK rearrangements were confirmed by application of multiple RNA-sequencing fusion detection algorithms and FISH. We functionally validated the oncogenic potential and targetability of discovered kinase fusions through biochemical, cell-based (Ba/F3, NIH3T3, and murine smooth muscle cell) and in vivo tumor modeling approaches. We identified ALK rearrangements in 9 of 377 (2.4%) patients with leiomyosarcoma, including a novel KANK2-ALK fusion and a recurrent ACTG2-ALK fusion. Functional characterization of the novel ALK fusion, KANK2-ALK, demonstrates it is a dominant oncogene in Ba/F3 or NIH3T3 model systems, and has tumorigenic potential when introduced into smooth muscle cells. Oral monotherapy with targeted ALK kinase inhibitor lorlatinib significantly inhibits tumor growth and prolongs survival in a murine model of KANK2-ALK leiomyosarcoma. These results provide the first functional validation of a targetable oncogenic kinase fusion as a driver in a subset of leiomyosarcomas. Overall, these findings suggest that some soft-tissue sarcomas may harbor previously unknown kinase gene translocations, and their discovery may propel new therapeutic strategies in this treatment-refractory cancer. Implications: A subset of leiomyosarcomas harbor previously unrecognized oncogenic ALK fusions that are highly responsive to ALK inhibitors and thus these data emphasize the importance of detailed genomic investigations of leiomyosarcoma tumors.