Takshan/R1 huggingface dataset:
Why people use herbal medicine: insights from a focus-group study in Germany.

BACKGROUND: The use of herbal medicine, as one element of complementary and alternative medicine, is increasing worldwide. Little is known about the reasons for and factors associated with its use. This study derives insights for the use of herbal medicine in Germany regarding the usage aims, role played by the type of illness, reasons for preferred usage and sources of information. METHODS: Using a qualitative methodological approach, six focus groups (n = 46) were conducted. Two groups with young, middle-aged and elderly participants, respectively. After audiotaping and verbatim transcription, the data were analysed with a qualitative content analysis. RESULTS: We found that treating illnesses was the most frequently discussed aim for using herbal medicine over all age groups. Preventing illnesses and promoting health were less frequently mentioned overall, but were important for elderly people. Discussions on herbal medicine were associated with either mild/moderate diseases or using herbal medicine as a starting treatment before applying conventional medicine. In this context, participants emphasized the limits of herbal medicine for severe illnesses. Dissatisfaction with conventional treatment, past good experiences, positive aspects associated with herbal medicine, as well as family traditions were the most commonly-mentioned reasons why herbal medicine was preferred as treatment. Concerning information sources, independent reading and family traditions were found to be equally or even more important than consulting medicinal experts. CONCLUSIONS: Although herbal medicine is used mostly for treating mild to moderate illnesses and participants were aware of its limits, the combination of self-medication, non-expert consultation and missing risk awareness of herbal medicine is potentially harmful. This is particularly relevant for elderly users as, even though they appeared to be more aware of health-related issues, they generally use more medicine compared to younger ones. In light of our finding that dissatisfaction with conventional medicine was the most important reason for a preferred use of herbal medicine, government bodies, doctors, and pharmaceutical companies need to be aware of this problem and should aim to establish a certain level of awareness among users concerning this issue.
Measurement properties of the Dutch Unité Rhumatologique des Affections de la Main and its ability to measure change due to Dupuytren's disease progression compared with the Michigan Hand outcomes Questionnaire.

Data of a prospective longitudinal cohort study including 233 Dupuytren's patients was used to determine: (1) whether the Unité Rhumatologique des Affections de la Main scale and Michigan Hand outcomes Questionnaire can detect change in hand function due to Dupuytren's disease progression and to compare their abilities; (2) the concurrent validity, reliability, responsiveness and interpretability of the Dutch Unité Rhumatologique des Affections de la Main. The Unité Rhumatologique des Affections de la Main and Michigan Hand outcomes Questionnaire had comparable measurement properties, and were both able to distinguish participants with disease progression from those without progression (resp. U = 1252.5, p = 0.008, and U = 1086.0, p < 0.001), but only at a group level. Individual cases of progression could not be detected using these outcome measures, as indicated by the fact that the smallest detectable change was larger than the minimal important change, and area under the receiver operating curve (AUC) values of 0.75 for Michigan Hand outcomes Questionnaire and 0.67 for Unité Rhumatologique des Affections de la Main. LEVEL OF EVIDENCE: II.
Identification of new loci involved in the host susceptibility to Salmonella Typhimurium in collaborative cross mice.

BACKGROUND: Salmonella is a Gram-negative bacterium causing a wide range of clinical syndromes ranging from typhoid fever to diarrheic disease. Non-typhoidal Salmonella (NTS) serovars infect humans and animals, causing important health burden in the world. Susceptibility to salmonellosis varies between individuals under the control of host genes, as demonstrated by the identification of over 20 genetic loci in various mouse crosses. We have investigated the host response to S. Typhimurium infection in 35 Collaborative Cross (CC) strains, a genetic population which involves wild-derived strains that had not been previously assessed. RESULTS: One hundred and forty-eight mice from 35 CC strains were challenged intravenously with 1000 colony-forming units (CFUs) of S. Typhimurium. Bacterial load was measured in spleen and liver at day 4 post-infection. CC strains differed significantly (P < 0.0001) in spleen and liver bacterial loads, while sex and age had no effect. Two significant quantitative trait loci (QTLs) on chromosomes 8 and 10 and one suggestive QTL on chromosome 1 were found for spleen bacterial load, while two suggestive QTLs on chromosomes 6 and 17 were found for liver bacterial load. These QTLs are caused by distinct allelic patterns, principally involving alleles originating from the wild-derived founders. Using sequence variations between the eight CC founder strains combined with database mining for expression in target organs and known immune phenotypes, we were able to refine the QTLs intervals and establish a list of the most promising candidate genes. Furthermore, we identified one strain, CC042/GeniUnc (CC042), as highly susceptible to S. Typhimurium infection. CONCLUSIONS: By exploring a broader genetic variation, the Collaborative Cross population has revealed novel loci of resistance to Salmonella Typhimurium. It also led to the identification of CC042 as an extremely susceptible strain.
Recurrent Loss of APOBEC3H Activity during Primate Evolution.

Genes in the APOBEC3 family encode cytidine deaminases that provide a barrier against viral infection and retrotransposition. Of all the APOBEC3 genes in humans, APOBEC3H (A3H) is the most polymorphic: some genes encode stable and active A3H proteins, while others are unstable and poorly antiviral. Such variation in human A3H affects interactions with the lentiviral antagonist Vif, which counteracts A3H via proteasomal degradation. In order to broaden our understanding of A3H-Vif interactions, as well as its evolution in Old World monkeys, we characterized A3H variation within four African green monkey (AGM) subspecies. We found that A3H is highly polymorphic in AGMs and has lost antiviral activity in multiple Old World monkeys. This loss of function was partially related to protein expression levels but was also influenced by amino acid mutations in the N terminus. Moreover, we demonstrate that the evolution of A3H in the primate lineages leading to AGMs was not driven by Vif. Our work suggests that the activity of A3H is evolutionarily dynamic and may have a negative effect on host fitness, resulting in its recurrent loss in primates. IMPORTANCE Adaptation of viruses to their hosts is critical for viral transmission between different species. Previous studies had identified changes in a protein from the APOBEC3 family that influenced the species specificity of simian immunodeficiency viruses (SIVs) in African green monkeys. We studied the evolution of a related protein in the same system, APOBEC3H, which has experienced a loss of function in humans. This evolutionary approach revealed that recurrent loss of APOBEC3H activity has taken place during primate evolution, suggesting that APOBEC3H places a fitness cost on hosts. The variability of APOBEC3H activity between different primates highlights the differential selective pressures on the APOBEC3 gene family.
Structure-based prediction of protein- peptide binding regions using Random Forest.

Motivation: Protein-peptide interactions are one of the most important biological interactions and play crucial role in many diseases including cancer. Therefore, knowledge of these interactions provides invaluable insights into all cellular processes, functional mechanisms, and drug discovery. Protein-peptide interactions can be analyzed by studying the structures of protein-peptide complexes. However, only a small portion has known complex structures and experimental determination of protein-peptide interaction is costly and inefficient. Thus, predicting peptide-binding sites computationally will be useful to improve efficiency and cost effectiveness of experimental studies. Here, we established a machine learning method called SPRINT-Str (Structure-based prediction of protein-Peptide Residue-level Interaction) to use structural information for predicting protein-peptide binding residues. These predicted binding residues are then employed to infer the peptide-binding site by a clustering algorithm. Results: SPRINT-Str achieves robust and consistent results for prediction of protein-peptide binding regions in terms of residues and sites. Matthews' Correlation Coefficient (MCC) for 10-fold cross validation and independent test set are 0.27 and 0.293, respectively, as well as 0.775 and 0.782, respectively for area under the curve. The prediction outperforms other state-of-the-art methods, including our previously developed sequence-based method. A further spatial neighbor clustering of predicted binding residues leads to prediction of binding sites at 20-116% higher coverage than the next best method at all precision levels in the test set. The application of SPRINT-Str to protein binding with DNA, RNA and carbohydrate confirms the method's capability of separating peptide-binding sites from other functional sites. More importantly, similar performance in prediction of binding residues and sites is obtained when experimentally determined structures are replaced by unbound structures or quality model structures built from homologs, indicating its wide applicability. Availability and implementation: http://sparks-lab.org/server/SPRINT-Str. Contact: yangyd25@mail.sysu.edu.cn. Supplementary information: Supplementary data are available at Bioinformatics online.
SPOT-ligand 2: improving structure-based virtual screening by binding-homology search on an expanded structural template library.

Motivation: The high cost of drug discovery motivates the development of accurate virtual screening tools. Binding-homology, which takes advantage of known protein-ligand binding pairs, has emerged as a powerful discrimination technique. In order to exploit all available binding data, modelled structures of ligand-binding sequences may be used to create an expanded structural binding template library. Results: SPOT-Ligand 2 has demonstrated significantly improved screening performance over its previous version by expanding the template library 15 times over the previous one. It also performed better than or similar to other binding-homology approaches on the DUD and DUD-E benchmarks. Availability and Implementation: The server is available online at http://sparks-lab.org . Contacts: yaoqi.zhou@griffith.edu.au or yuedong.yang@griffith.edu.au. Supplementary information: Supplementary data are available at Bioinformatics online.
Landscape of Genomic Alterations in Pituitary Adenomas.

Purpose: Pituitary adenomas are the second most common primary brain tumor, yet their genetic profiles are incompletely understood. Experimental Design: We performed whole-exome sequencing of 42 pituitary macroadenomas and matched normal DNA. These adenomas included hormonally active and inactive tumors, ones with typical or atypical histology, and ones that were primary or recurrent. Results: We identified mutations, insertions/deletions, and copy-number alterations. Nearly one-third of samples (29%) had chromosome arm-level copy-number alterations across large fractions of the genome. Despite such widespread genomic disruption, these tumors had few focal events, which is unusual among highly disrupted cancers. The other 71% of tumors formed a distinct molecular class, with somatic copy number alterations involving less than 6% of the genome. Among the highly disrupted group, 75% were functional adenomas or atypical null-cell adenomas, whereas 87% of the less-disrupted group were nonfunctional adenomas. We confirmed this association between functional subtype and disruption in a validation dataset of 87 pituitary adenomas. Analysis of previously published expression data from an additional 50 adenomas showed that arm-level alterations significantly impacted transcript levels, and that the disrupted samples were characterized by expression changes associated with poor outcome in other cancers. Arm-level losses of chromosomes 1, 2, 11, and 18 were significantly recurrent. No significantly recurrent mutations were identified, suggesting no genes are altered by exonic mutations across large fractions of pituitary macroadenomas. Conclusions: These data indicate that sporadic pituitary adenomas have distinct copy-number profiles that associate with hormonal and histologic subtypes and influence gene expression. Clin Cancer Res; 23(7); 1841-51. ©2016 AACR.
Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: precision medicine analysis of 203 pediatric brain tumors.

BACKGROUND: Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice are not yet well established. METHODS: Profile is an institution-wide prospective clinical research initiative that uses targeted sequencing to identify targetable alterations in tumors. OncoPanel, a multiplexed targeted exome-sequencing platform that includes 300 cancer-causing genes, was used to assess single nucleotide variants and rearrangements/indels. Alterations were annotated (Tiers 1-4) based on clinical significance, with Tier 1 alterations having well-established clinical utility. OncoCopy, a clinical genome-wide array comparative genomic hybridization (aCGH) assay, was also performed to evaluate copy number alterations and better define rearrangement breakpoints. RESULTS: Cancer genomes of 203 pediatric brain tumors were profiled across histological subtypes, including 117 samples analyzed by OncoPanel, 146 by OncoCopy, and 60 tumors subjected to both methodologies. OncoPanel revealed clinically relevant alterations in 56% of patients (44 cancer mutations and 20 rearrangements), including BRAF alterations that directed the use of targeted inhibitors. Rearrangements in MYB-QKI, MYBL1, BRAF, and FGFR1 were also detected. Furthermore, while copy number profiles differed across histologies, the combined use of OncoPanel and OncoCopy identified subgroup-specific alterations in 89% (17/19) of medulloblastomas. CONCLUSION: The combination of OncoPanel and OncoCopy multiplex genomic assays can identify critical diagnostic, prognostic, and treatment-relevant alterations and represents an effective precision medicine approach for clinical evaluation of pediatric brain tumors.
Tactile acuity testing at the neck: A comparison of methods.

BACKGROUND: Interest in measurement of tactile acuity in musculoskeletal practice has emerged following its link to functional reorganization of the somatosensory cortex in ongoing pain states. Several tactile acuity measurement methods have been described but have not been thoroughly investigated in the cervical region. OBJECTIVE: This study examined reliability, concurrent validity and responsiveness of four tests of tactile acuity-Two-point discrimination, Point-to-point, Graphesthesia, and Localisation tests-at the cervical region. METHOD: Forty-two healthy participants were included. In Part 1 (n = 22), participants' tactile acuity was assessed at two time points, 30 min apart, to determine the test-retest reliability and concurrent validity of each of the tests. In Part 2 (n = 20), participants received five daily tactile training sessions, delivered via a vibro-tactile device. Tactile acuity was assessed pre- and post-training to examine responsiveness of each test. RESULTS: Two-point discrimination demonstrated excellent test-retest reliability (ICC = 0.85, SEM = 3.7 mm), Point-to-point and Localisation tests demonstrated good reliability (ICC = 0.60, SEM = 2.8 mm; ICC = 0.60, SEM = 8.8%), and Graphesthesia demonstrated fair reliability (ICC = 0.48, SEM = 1.9/20). There was no significant correlation among measures. Only Graphesthesia failed to show responsiveness to change following training. CONCLUSION: The reliability of Two-point discrimination appears superior to other examined tests of tactile acuity, however measurement variability should be considered. Two-point discrimination, Point-to-point, and Localisation tests appear responsive to change, although testing in clinical samples is needed. The lack of concurrent validity among tests suggests that they cannot be used interchangeably.
Modular organisation of inducer recognition and allostery in the tetracycline repressor.

UNLABELLED: Induction of the tetracycline repressor (TetR) results from antibiotic-dependent changes in the relative positioning of the DNA-binding domains within the promoter-associated repressor dimer, but the key determinants of this allosteric effect remain poorly characterised. Intriguingly, previous mutational analyses of the tetracycline-interacting site revealed a lack of correlation between residual affinity and induction propensity, suggesting that some of the residues in contact with the antibiotic primarily act in ligand recognition and retention, whereas others are required to transmit the allosteric signal. Here, we provide a structural basis for these observations via crystallographic analysis of the point mutants N82A, H100A, T103A and E147A in complex with the inducer 5a,6-anhydrotetracycline. In conjunction with the available functional data, the four structures demonstrate that a trigger-like movement of the region between helices α6 and α7 towards and into the binding site plays a decisive role in the intramolecular communication process. In sharp contrast, residues lining the binding cavity proper have little or no influence on the allosteric mechanism as such. This nearly complete physical separation of ligand recognition and allostery will have allowed diverging TetR-like repressors to bind novel effectors while the existing induction mechanism remained intact. Consequently, the modularity described here may have been a key factor in the evolutionary success of the widespread and highly diversified repressor class. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 5FKK, 5FKL, 5FKM, 5FKN and 5FKO.
Crystal structure of raptor adenovirus 1 fibre head and role of the beta-hairpin in siadenovirus fibre head domains.

BACKGROUND: Most adenoviruses recognize their host cells via an interaction of their fibre head domains with a primary receptor. The structural framework of adenovirus fibre heads is conserved between the different adenovirus genera for which crystal structures have been determined (Mastadenovirus, Aviadenovirus, Atadenovirus and Siadenovirus), but genus-specific differences have also been observed. The only known siadenovirus fibre head structure, that of turkey adenovirus 3 (TAdV-3), revealed a twisted beta-sandwich resembling the reovirus fibre head architecture more than that of other adenovirus fibre heads, plus a unique beta-hairpin embracing a neighbouring monomer. The TAdV-3 fibre head was shown to bind sialyllactose. METHODS: Raptor adenovirus 1 (RAdV-1) fibre head was expressed, crystallized and its structure was solved and refined at 1.5 Å resolution. The structure could be solved by molecular replacement using the TAdV-3 fibre head structure as a search model, despite them sharing a sequence identity of only 19 %. Versions of both the RAdV-1 and TAdV-3 fibre heads with their beta-hairpin arm deleted were prepared and their stabilities were compared with the non-mutated proteins by a thermal unfolding assay. RESULTS: The structure of the RAdV-1 fibre head contains the same twisted ABCJ-GHID beta-sandwich and beta-hairpin arm as the TAdV-3 fibre head. However, while the predicted electro-potential surface charge of the TAdV-3 fibre head is mainly positive, the RAdV-1 fibre head shows positively and negatively charged patches and does not appear to bind sialyllactose. Deletion of the beta-hairpin arm does not affect the structure of the raptor adenovirus 1 fibre head and only affects the stability of the RAdV-1 and TAdV-3 fibre heads slightly. CONCLUSIONS: The high-resolution structure of RAdV-1 fibre head is the second known structure of a siadenovirus fibre head domain. The structure shows that the siadenovirus fibre head structure is conserved, but differences in the predicted surface charge suggest that RAdV-1 uses a different natural receptor for cell attachment than TAdV-3. Deletion of the beta-hairpin arm shows little impact on the structure and stability of the siadenovirus fibre heads.
Dual Hg-Rb magneto-optical trap.

We present a two-species laser cooling apparatus capable of simultaneously collecting Rb and Hg atomic gases into a magneto-optical trap (MOT). The atomic sources, laser system, and vacuum set-up are described. While there is a loss of Rb atoms in the MOT due to photoionization by the Hg cooling laser, we show that it does not prevent simultaneous trapping of Rb and Hg. We also demonstrate interspecies collision-induced losses in the <sup>87</sup>Rb-<sup>202</sup>Hg system.
Characterization of clinical signs in the human interactome.

MOTIVATION: Many diseases are related by shared associated molecules and pathways, exhibiting comorbidities and common phenotypes, an indication of the continuous nature of the human pathological landscape. Although it is continuous, this landscape is always partitioned into discrete diseases when studied at the molecular level. Clinical signs are also important phenotypic descriptors that can reveal the molecular mechanisms that underlie pathological states, but have seldom been the subject of systemic research. Here, we quantify the modular nature of the clinical signs associated with genetic diseases in the human interactome. RESULTS: We found that clinical signs are reflected as modules at the molecular network level, to at least to the same extent as diseases. They can thus serve as a valid complementary partition of the human pathological landscape, with implications for etiology research, diagnosis and treatment. CONTACT: monica.chagoyen@cnb.csic.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.