Miracle-dz/UniFAR-FTUs huggingface dataset:
Routine surveillance for symptomatic toxicities with real‐time clinician reporting in Danish breast cancer patients—Organization and design of the first national, cluster randomized trial using the Patient‐Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO‐CTCAE)

The Patient‐Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO‐CTCAE) was developed by the National Cancer Institute to capture patient self‐reports of symptomatic toxicities during cancer treatment. The aim of this short communication is to describe the design of a national study, which examine the effect of using patients’ electronic PRO‐CTCAE reporting with real‐time feedback to clinicians on treatment events for breast cancer patients receiving adjuvant chemotherapy. The study's end‐points are defined as dose reduction, hospitalization, and febrile neutropenia. This is the first report on the impact of PRO‐CTCAE in a national breast cancer population during chemotherapy treatment.
Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation

Genetic testing for BRCA1, a DNA repair protein, can identify carriers of pathogenic variants associated with a substantially increased risk for breast and ovarian cancers. However, an association with increased risk is unclear for a large fraction of BRCA1 variants present in the human population. Most of these variants of uncertain clinical significance lead to amino acid changes in the BRCA1 protein. Functional assays are valuable tools to assess the potential pathogenicity of these variants. Here, we systematically probed the effects of substitutions in the C terminus of BRCA1: the N- and C-terminal borders of its tandem BRCT domain, the BRCT-[N-C] linker region, and the α1 and α′1 helices in BRCT-[N] and -[C]. Using a validated transcriptional assay based on a fusion of the GAL4 DNA-binding domain to the BRCA1 C terminus (amino acids 1396–1863), we assessed the functional impact of 99 missense variants of BRCA1. We include the data obtained for these 99 missense variants in a joint analysis to generate the likelihood of pathogenicity for 347 missense variants in BRCA1 using VarCall, a Bayesian integrative statistical model. The results from this analysis increase our understanding of BRCA1 regions less tolerant to changes, identify functional borders of structural domains, and predict the likelihood of pathogenicity for 98% of all BRCA1 missense variants in this region recorded in the population. This knowledge will be critical for improving risk assessment and clinical treatment of carriers of BRCA1 variants.
Occupational exposures and chronic obstructive pulmonary disease: incontrovertible evidence for causality?

addition and of great pathogenetic concern, a hereditary (i.e., gene-determined) component is believed to contribute importantly to the clinical occurrence of each condition. However, the culprit genes, so far at least, have eluded identification. Thousands of patients with heart disease, cancer, and chronic obstructive pulmonary disease, along with suitable numbers of healthy control subjects, have had genome-wide association studies, and more and more people are having genomic analyses; yet all that has turned up are some low-risk genetic variants that both alone and in combination fall far short of accounting for the putative hereditary link with the disease. Much of importance seems to be missing. Useful offshoots of pharmacogenomics, how variations in the human genome affect the response to medications, are beginning to show up in everyday medicine. The Food and Drug Administration now requires genetic information in the labeling of warfarin, clopidogrel, and several other commonly used drugs. Moreover, tumor biomarkers are being increasingly used to optimize choice of chemotherapeutic regimens in various malignancies, including non–small-cell cancer of the lung (7). Detection of cancers bearing the gene encoding mutated epidermal growth factor receptor or the EML/ALK4 translocation and treatment with specifically addressed chemotherapeutic agents has led to significantly prolonged therapeutic responses, which do not occur in patients without the biomarker. Recent observations suggest that some of the individualized clinical advantages resulting from the detection of tell-tale biomarkers and treatment with tailored agents might be lost or attenuated (8); it turns out that renal cell cancers, and probably other malignancies, contain multiple markers or mutations that may not show up in a single biopsy specimen, thereby confusing the personalized “genomics landscape. ” (Sometimes people equate genetic testing with genomic analysis, but the two are very different. Separate tests are now available to determine if a person carries one of the more than 1,000 known genes linked to human diseases, nearly all of which are infrequent and seldom encountered in medical practice, and which for the most part were not discovered by genomic analysis.) The enormously complicated and high-priced steps leading to full realization of the seemingly vast clinical potential inherent in the human genome were cataloged in the 2007 Health and Human Services document already cited (3). The summary account of the recent NHLBI-sponsored conference, “New Frontiers in Personalized Medicine: Cardiovascular Research and Clinical Care,” added a few more charges (9). Both reports stress that implementation stretches considerably beyond simply learning more than we know now about how and which genes regulate human disease; neither proffered a timetable nor budget.
The Number, Organization, and Size of Polymorphic Membrane Protein Coding Sequences as well as the Most Conserved Pmp Protein Differ within and across Chlamydia Species

Variation is a central trait of the polymorphic membrane protein (Pmp) family. The number of pmp coding sequences differs between Chlamydia species, but it is unknown whether the number of pmp coding sequences is constant within a Chlamydia species. The level of conservation of the Pmp proteins has previously only been determined for Chlamydia trachomatis. As different Pmp proteins might be indispensible for the pathogenesis of different Chlamydia species, this study investigated the conservation of Pmp proteins both within and across C. trachomatis,C. pneumoniae,C. abortus, and C. psittaci. The pmp coding sequences were annotated in 16 C. trachomatis, 6 C. pneumoniae, 2 C. abortus, and 16 C. psittaci genomes. The number and organization of polymorphic membrane coding sequences differed within and across the analyzed Chlamydia species. The length of coding sequences of pmpA,pmpB, and pmpH was conserved among all analyzed genomes, while the length of pmpE/F and pmpG, and remarkably also of the subtype pmpD, differed among the analyzed genomes. PmpD, PmpA, PmpH, and PmpA were the most conserved Pmp in C. trachomatis,C. pneumoniae,C. abortus, and C. psittaci, respectively. PmpB was the most conserved Pmp across the 4 analyzed Chlamydia species.
Hyperglycemia-associated Alzheimer’s-like symptoms and other behavioral effects attenuated by Plumeria obtusa L. Extract in alloxan-induced diabetic rats

Diabetes mellitus is a chronic metabolic complaint with numerous short- and long-term complications that harm a person’s physical and psychological health. Plumeria obtusa L. is a traditional medicine used in the treatment of diabetes to reduce complications related to behavior. Plumeria is a genus with antipsychotic activities. The objective of this study was to examine the effects of a methanolic extract of Plumeria obtusa L. in the attenuation of diabetes, on symptoms of Alzheimer disease, and on other associated behavioral aspects. A single dose of alloxan was administered to an experimental group of rats to induce development of diabetes (150 mg/kg, intraperitoneal) and the rats were then administered selected doses of methanolic extract of Plumeria obtusa L. (Po.Cr) or glibenclamide (0.6 mg/kg) for 45 consecutive days. Behavioral effects were evaluated using three validated assays of anxiety-related behavior: the open field test, the light and dark test, and the elevated plus maze. Anti-depressant effects of Plumeria obtusa L. were evaluated using the forced swim test (FST) and memory and learning were assessed using the Morris water maze (MWM) task. Po.Cr was also evaluated for phytochemicals using total phenolic content (TPC), total flavonoid content (TFC), and high-performance liquid chromatography assays, and antioxidant capability was assessed through assays of DPPH radical scavenging, total oxidation capacity, and total reducing capacity. In the alloxan-induced model of diabetes, the administration of Po.Cr and glibenclamide for 45 days produced a marked decrease (p < 0.001) in hyperglycemia compared to control animals. Po.Cr treatment also resulted in improvement in indicators, such as body weight and lipid profile (p < 0.05), as well as restoration of normal levels of alanine transaminase (ALT) (p < 0.001), a biomarker of liver function. Diabetic rats presented more Alzheimer-like symptoms, with greater impairment of memory and learning, and increased anxiety and depression compared to non-diabetic normal rats, whereas treated diabetic rats showed significant improvements in memory and behavioral outcomes. These results demonstrate that Po.Cr reversed alloxan-induced hyperglycemia and ameliorated Alzheimer-related behavioral changes, which supports additional study and assessment of conventional use of the plant to treat diabetes and associated behavioral complications.
Low cost video endoscopes with simplified integration

The availability of miniature imagers enables endoscopic systems with simplified integration. Here, the optical elements together with the imager are located at the distal end of these so called video endoscopes. The overall system can be flexible since no relaying optics is required in order to image the object at a remote position. Compared to conventional flexible systems based on light guiding fiber bundles, higher spatial resolutions can be achieved due to the ever decreasing pixel size in CMOS imager fabrication technology. We propose system designs and prototypes for f/4, 3mm outer diameter endoscopes with 70° and 110° field of view using a CMOS imager with 650x650 pixels of 2. 8μm pitch. The systems are based on a simplified and rugged integration using a single polymer lens made by injection molding, a GRIN lens and a dispensed lens made of UV curing material allowing for high performance paired with low fabrication cost allowing for the usage as a disposable unit. Additionally, a side view system angled at 30° is presented based on a tilting reflection prism requiring minimum construction space allowing for an outer diameter of 3mm.
Impact of yoga based mind-body intervention on systemic inflammatory markers and co-morbid depression in active Rheumatoid arthritis patients: A randomized controlled trial.

BACKGROUND Recovery of patients with rheumatoid arthritis (RA) depends on several physical and psychological factors, besides pharmacological treatment. Co-morbid depression adversely affects the outcome in RA. Usual medical therapies have a limited scope and fail to cure the psychological component of the disease. With advanced therapeutic options, achieving a state of remission has become the treatment goal, yoga based mind body intervention (MBI) may provide a holistic approach in its treatment dimension. Hence, MBIs are the need of hour as majority of diseases have a psychosomatic component. OBJECTIVE To explore the effect of Yoga based MBI on disease specific inflammatory markers and depression severity in active RA patients on routine disease modifying anti-rheumatic drugs (DMARDs) therapy. METHODS A total of 72 RA patients were randomized into 2 groups: yoga group (yoga with DMARDs) and control group (DMARDs only). Blood samples were collected pre and post intervention for primary outcome measurements of systemic biomarkers. Disease activity score 28, erythrocyte sedimentation rate (DAS28ESR) and health assessment questionnaire disability index (HAQ-DI) were used to assess disease activity and functional status respectively at pre and post intervention time-points. Secondary outcome, depression severity, was assessed by Beck Depression Inventory II scale (BDI-II) at 2 weekly intervals during 8 weeks of the study interventional plan. RESULTS After 8 weeks of yoga based MBI, there was significant decrease in the severity of RA as seen by reduction in levels of various systemic inflammatory markers as well as in DAS28ESR (p-value <0.0001; effect size = 0.210) and HAQ-DI (p-value 0.001; effect size = 0.159). Also, yoga group experienced a statistically significant time dependent step-wise decline in depression symptoms over the period of 8 weeks as compared to control group (p-value <0.0001; effect size = 0.5). Regression analysis showed greater reduction in the scores of BDI-II with DAS28ESR (R2 = 0.426; p < 0.0001) and HAQ-DI (R2 = 0.236; p = 0.003) in yoga group. CONCLUSIONS Yoga, a mind body intervention re-established immunological tolerance by aiding remission at molecular and cellular level along with significant reduction in depression. Thus in this severe autoimmune inflammatory arthritis with a major psychosomatic component, yoga can be used as a complementary/adjunct therapy.
Transient hippocampal CA1 lesions in humans impair pattern separation performance

Day‐to‐day life involves the perception of events that resemble one another. For the sufficient encoding and retrieval of similar information, the hippocampus provides two essential computational processes. Pattern separation refers to the differentiation of overlapping memory representations, whereas pattern completion reactivates memories based on noisy or degraded input. Evidence from human and rodent studies suggest that pattern separation specifically relies on neuronal ensemble activity in hippocampal subnetworks in the dentate gyrus and CA3. Although a role for CA1 in pattern separation has been shown in animal models, its contribution in the human hippocampus remains elusive. In order to elucidate the contribution of CA1 neurons to pattern separation, we examined 14 patients with an acute transient global amnesia (TGA), a rare self‐limiting dysfunction of the hippocampal system showing specific lesions to CA1. Patients' pattern separation performance was tested during the acute amnestic phase and follow‐up using an established mnemonic similarity test. Patients in the acute phase showed a profound deficit in pattern separation (p < .05) as well as recognition memory (p < .001) that recovered during follow‐up. Specifically, patients tested in a later stage of the amnesia were less impaired in pattern separation than in recognition memory. Considering the time dependency of lesion‐associated hippocampal deficits in early and late acute stages of the TGA, we showed that the pattern separation function recovered significantly earlier than recognition memory. Our results provide causal evidence that hippocampal CA1 neurons are critical to pattern separation performance in humans.
Synthesis, structure and antiproliferative and optical activities of two new biphenyl-derived Schiff bases.

Two novel Schiff bases derived from indole and biphenyl have been designed and synthesized, namely 3-((E)-{(E)-[1-(biphenyl-4-yl)ethylidene]hydrazinylidene}methyl)-1-methyl-1H-indole (3-BEHMI) acetonitrile monosolvate, C24H21N3·CH3CN, and 3-((E)-{(E)-[1-(biphenyl-4-yl)ethylidene]hydrazinylidene}methyl)-1-methyl-1H-indole (3-BEHEI) acetonitrile monosolvate, C24H21N3·CH3CN. Their structures were characterized by elemental analysis, quadrupole time-of-flight MS, NMR and UV-Vis spectroscopy. The single-crystal packing structure of 3-BEHMI is largely dominated by C-H. π interactions and weak van der Waals interactions. The in vitro cytotoxicity of the two title compounds have been evaluated against two tumour cell lines (A549 human lung cancer and 4T1 mouse breast cancer) and two normal cell lines (MRC-5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that 3-BEHEI exhibits a slightly weaker antiproliferative capability (IC50 = ∼50 µM) than the previously reported similar Schiff base 3-BEHI (IC50 = ∼20 µM). This is in line with docking results. 3-BEHMI demonstrates a weak cytotoxic activity, with IC50 values around 110 µM, which disagrees with its docking results. Overall, the tested compounds manifest relevant cytotoxicities on the selected cancer cell lines and normal cell lines. The UV-Vis and fluorescence spectra were recorded and reproduced through the TD-DFT method with four types of hybrid density functionals, including B3LYP, M062X, PBE1PBE and WB97XD.
The effects of a multidisciplinary high‐throughput skin clinic on healthcare costs of organ transplant recipients

A long‐term complication among organ transplant recipients (OTRs) is skin malignancies which are associated with level and duration of immunosuppressive treatment, sun exposure and age. Dermatological surveillance is recommended for OTRs at high risk of skin malignancies, but evidence is lacking on the benefits of such services.
Physical activity and quality of life in people living with HIV

ABSTRACT As life expectancy in people living with HIV (PWH) has increased, the focus of management has shifted to preventing and treating chronic illnesses. Regular physical activity (PA) has been shown to reduce the impact of HIV on both physical and mental health. Our objectives were to assess the PA levels of PWH compared to HIV negative controls; investigate factors associated with PA; and determine the effect of PA levels on quality of life and mental well-being. We recruited 110 PWH and 110 HIV negative controls in this cross-sectional, single-centre study. Physical activity, quality of life and mental well-being were assessed using the rapid assessment of physical activity tool, EQ-5D-5L Questionnaire, and the Warwick-Edinburgh Mental Well-being Score. Binary logistic regression and multiple linear regression were used to identify factors associated with PA levels and mental well-being scores respectively. PWH were less likely to meet the WHO-recommended PA requirements compared to controls (50.0% vs. 64.5%; p = 0.041) and had significantly lower mental wellbeing and quality of life scores. Additionally, in PWH higher PA levels were associated with improved self-rated quality of life scores (p = 0.027). Our results suggest that targeted exercise programmes could have a beneficial effect on health status in PWH.
Short Sequence Classification Through Discriminable Linear Dynamical System

Linear dynamical system (LDS) offers a convenient way to reveal the unobservable structure behind the data. This makes it useful for data representation and explanatory analysis. An immediate limitation with this model is that most training algorithms train a model to best approximate a sequential instance. They do not consider its class or label which indicates the dissimilarity/similarity to other instances. As a result, LDS’s trained in this way are inclined to be indistinguishable over classes, resulting in a poor performance in the model-based classification. In this paper, after revisiting this limitation, we propose to promote the diversity between the two models of different classes. The diversity, measured by determinantal point process (DPP) on LDS’s, is utilized to remedy the greedy behavior of the electromagnetic algorithm. The training goal is a model that balances the goodness of fit and being distinguishable over classes. Experiments on synthetic data confirm its effectiveness in generating discriminative systems under supervisory information. The classification on short time-span data sets confirms that the models generated by our approach could generalize well to unseen data.
Mediators of Lifestyle Behaviour Changes in Obese Pregnant Women. Secondary Analyses from the DALI Lifestyle Randomised Controlled Trial

A better understanding of what drives behaviour change in obese pregnant overweight women is needed to improve the effectiveness of lifestyle interventions in this group at risk for gestational diabetes (GDM). Therefore, we assessed which factors mediated behaviour change in the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) Lifestyle Study. A total of 436 women, with pre-pregnancy body mass index ≥29 kg/m2, ≤19 + 6 weeks of gestation and without GDM, were randomised for counselling based on motivational interviewing (MI) on healthy eating and physical activity, healthy eating alone, physical activity alone, or to a usual care group. Lifestyle was measured at baseline, and at 24–28 and 35–37 weeks of gestation. Outcome expectancy, risk perception, task self-efficacy and social support were measured at those same time points and considered as possible mediators of intervention effects on lifestyle. All three interventions resulted in increased positive outcome expectancy for GDM reduction, perceived risk to the baby and increased task self-efficacy. The latter mediated intervention effects on physical activity and reduced sugared drink consumption. In conclusion, our MI intervention was successful in increasing task self-efficacy, which was related to improved health behaviours.
Individualized acromegaly treatment: Is stereotactic radiation therapy changing the paradigm?

COPYRIGHT © 2022 Liu and Fleseriu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Opinion PUBLISHED 15 December 2022 DOI 10.3389/fendo.2022. 1034576
Corrigendum: mlplasmids: a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species

There was an error in the Funding information section in the published article. The Funding information section should include the following sentence: ‘This study was supported by the Joint Programming Initiative in Antimicrobial Resistance (JPIAMR Third call, STARCS, JPIAMR2016-AC16/00039 to SA, RJLW). ’ The author apologizes for any inconvenience caused.