Takshan/R1 huggingface dataset:
Consensus on hypotonia via Delphi process.

OBJECTIVES: To generate consensus on the assessment of hypotonia in the pediatric population, more specifically with respect to the clinical characteristics and first line tests and methods to be used to assess these characteristics. METHODS: Consensus methodology was used. A sample of experts was recruited based on specific inclusion criteria. A two-round Delphi process was conducted electronically, which was based on a prior literature appraisal and survey amongst a cohort of clinicians. An a priori threshold margin error of 70 ± 5 % was pre-determined, with Cronbach's α measuring the level of internal consistency. RESULTS: The 2-round iteration was useful in establishing consensus on clinical characteristics and tests /methods in the assessment of low muscle tone in the pediatric population (2-5 y age band). Twenty-four clinical characteristics, organized into 11 clusters were determined as relevant for inclusion. For each characteristic, one test (as a first line assessment method) had been identified with consensus after two rounds. Additionally, consensus on the importance of collateral sources was determined. The ranking order of importance of characteristics however revealed variations. CONCLUSIONS: The results of this study have displayed that Delphi, if executed with available guidelines, may be a useful technique in moving towards consensus on issues that may be contentious and have assisted in providing initial data to move towards consensus on the assessment of hypotonia in children.
Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. PATIENTS AND METHODS: This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. RESULTS: Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. CONCLUSIONS: In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.
'Toning' up hypotonia assessment: A proposal and critique.

BACKGROUND: Clinical assessment of hypotonia is challenging due to the subjective nature of the initial clinical evaluation. This poses dilemmas for practitioners in gaining accuracy, given that the presentation of hypotonia can be either a non-threatening or malevolent sign. The research question posed was how clinical assessment can be improved, given the current contentions expressed in the scientific literature. OBJECTIVES: This paper describes the development and critique of a clinical algorithm to aid the assessment of hypotonia. METHODS: An initial exploratory sequential phase, consisting of a systematic review, a survey amongst clinicians and a Delphi process, assisted in the development of the algorithm, which is presented within the framework of the International Classification of Functioning, Disability and Health. The ensuing critique followed a qualitative emergent-systematic focus group design with a purposive sample of 59 clinicians. Data were analysed using semantical content analysis and are presented thematically with analytical considerations. RESULTS: This study culminated in the development of an evidence-based clinical algorithm for practice. The qualitative critique of the algorithm considered aspects such as inadequacies, misconceptions and omissions; strengths; clinical use; resource implications; and recommendations. CONCLUSIONS: The first prototype and critique of a clinical algorithm to assist the clinical assessment of hypotonia in children has been described. Barriers highlighted include aspects related to knowledge gaps of clinicians, issues around user-friendliness and formatting concerns. Strengths identified by the critique included aspects related to the evidence-based nature of the criteria within the algorithm, the suitability of the algorithm in being merged or extending current practice, the potential of the algorithm in aiding more accurate decision-making, the suitability of the algorithm across age groups and the logical flow. These findings provide a starting point towards ascertaining the clinical utility of the algorithm as an essential step towards evidence-based praxis.
Validation of a Survival Score for Patients Receiving Radiosurgery or Fractionated Stereotactic Radiotherapy for 1 to 3 Brain Metastases.

BACKGROUND/AIM: We developed a scoring system to predict 1-year survival after radiosurgery for 1-3 brain metastases. This study aimed to validate this system. PATIENTS AND METHODS: Seventy-six new patients were included in this validation study. Like in the original scoring-system, three factors (age, performance status, extra-cranial metastases) were used. For each factor, 1-year survival rates in % were divided by 10, and the three scoring-points were added for each patient. RESULTS: Patient's scores were 10, 11, 13, 14, 16 or 17 points with 1-year survival rates ranging between 31% and 80%. Two groups, 10-14 and 16-17 points were formed. In the 14-16 points group, 1-year survival was 47% (versus 33% in the preceding study, p=0.060). In the 16-17 points group, 1-year survival rates were 75% versus 77% (p=0.79). CONCLUSION: In the more favorable group, the scoring-system was very reproducible. In the less favorable group, the difference was larger, but also not signficant.
Under-reported dosimetry errors due to interplay effects during VMAT dose delivery in extreme hypofractionated stereotactic radiotherapy.

Unzureichend untersuchte Dosimetriefehler aufgrund von Interplay-Effekten bei VMAT-Bestrahlung einer extrem hypofraktionierten stereotaktischen Strahlentherapie. BACKGROUND AND PURPOSE: Radiotherapy of extracranial metastases changed from normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using VMAT beam techniques. Random interaction between tumour motion and dynamically changing beam parameters might result in underdosage of the CTV even for an appropriately dimensioned ITV (interplay effect). This study presents a clinical scenario of extreme hypofractionated stereotactic treatment and analyses the impact of interplay effects on CTV dose coverage. METHODS: For a thoracic/abdominal phantom with an integrated high-resolution detector array placed on a 4D motion platform, dual-arc treatment plans with homogenous target coverage were created using a common VMAT technique and delivered in a single fraction. CTV underdosage through interplay effects was investigated by comparing dose measurements with and without tumour motion during plan delivery. RESULTS: Our study agrees with previous works that pointed out insignificant interplay effects on target coverage for very regular tumour motion patterns like simple sinusoidal motion. However, we identified and illustrated scenarios that are likely to result in a clinically relevant CTV underdosage. For tumour motion with abnormal variability, target coverage quantified by the CTV area receiving more than 98% of the prescribed dose decreased to 78% compared to 100% at static dose measurement. CONCLUSION: This study is further proof of considerable influence of interplay effects on VMAT dose delivery in stereotactic radiotherapy. For selected conditions of an exemplary scenario, interplay effects and related motion-induced target underdosage primarily occurred in tumour motion pattern with increased motion variability and VMAT plan delivery using complex MLC dose modulation.
Stereotactic Body Radiotherapy (SBRT) for liver metastasis - clinical outcomes from the international multi-institutional RSSearch® Patient Registry.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver metastases treated with SBRT from a multi-center, international patient registry. METHODS: Patients with liver metastases treated with SBRT were identified in the RSSearch® Patient Registry. Patient, tumor and treatment characteristics associated with treatment outcomes were assessed. Dose fractionations were normalized to BED10. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test. RESULTS: The study included 427 patients with 568 liver metastases from 25 academic and community-based centers. Median age was 67 years (31-91 years). Colorectal adenocarcinoma (CRC) was the most common primary cancer. 73% of patients received prior chemotherapy. Median tumor volume was 40 cm3 (1.6-877 cm3), median SBRT dose was 45 Gy (12-60 Gy) delivered in a median of 3 fractions [1-5]. At a median follow-up of 14 months (1-91 months) the median overall survival (OS) was 22 months. Median OS was greater for patients with CRC (27 mo), breast (21 mo) and gynecological (25 mo) metastases compared to lung (10 mo), other gastro-intestinal (GI) (18 mo) and pancreatic (6 mo) primaries (p < 0.0001). Smaller tumor volumes (< 40 cm3) correlated with improved OS (25 months vs 15 months p = 0.0014). BED10 ≥ 100 Gy was also associated with improved OS (27 months vs 15 months p < 0.0001). Local control (LC) was evaluable in 430 liver metastases from 324 patients. Two-year LC rates was better for BED10 ≥ 100 Gy (77.2% vs 59.6%) and the median LC was better for tumors < 40 cm3 (52 vs 39 months). There was no difference in LC based on histology of the primary tumor. CONCLUSIONS: In a large, multi-institutional series of patients with liver metastasis treated with SBRT, reasonable LC and OS was observed. OS and LC depended on dose and tumor volume, while OS varied by primary tumor. Future prospective trials on the role of SBRT for liver metastasis from different primaries in the setting of multidisciplinary management including systemic therapy, is warranted. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01885299 .
Automated chart review utilizing natural language processing algorithm for asthma predictive index.

BACKGROUND: Thus far, no algorithms have been developed to automatically extract patients who meet Asthma Predictive Index (API) criteria from the Electronic health records (EHR) yet. Our objective is to develop and validate a natural language processing (NLP) algorithm to identify patients that meet API criteria. METHODS: This is a cross-sectional study nested in a birth cohort study in Olmsted County, MN. Asthma status ascertained by manual chart review based on API criteria served as gold standard. NLP-API was developed on a training cohort (n = 87) and validated on a test cohort (n = 427). Criterion validity was measured by sensitivity, specificity, positive predictive value and negative predictive value of the NLP algorithm against manual chart review for asthma status. Construct validity was determined by associations of asthma status defined by NLP-API with known risk factors for asthma. RESULTS: Among the eligible 427 subjects of the test cohort, 48% were males and 74% were White. Median age was 5.3 years (interquartile range 3.6-6.8). 35 (8%) had a history of asthma by NLP-API vs. 36 (8%) by abstractor with 31 by both approaches. NLP-API predicted asthma status with sensitivity 86%, specificity 98%, positive predictive value 88%, negative predictive value 98%. Asthma status by both NLP and manual chart review were significantly associated with the known asthma risk factors, such as history of allergic rhinitis, eczema, family history of asthma, and maternal history of smoking during pregnancy (p value < 0.05). Maternal smoking [odds ratio: 4.4, 95% confidence interval 1.8-10.7] was associated with asthma status determined by NLP-API and abstractor, and the effect sizes were similar between the reviews with 4.4 vs 4.2 respectively. CONCLUSION: NLP-API was able to ascertain asthma status in children mining from EHR and has a potential to enhance asthma care and research through population management and large-scale studies when identifying children who meet API criteria.
Efficacy of a marine bacterial nuclease against biofilm forming microorganisms isolated from chronic rhinosinusitis.

BACKGROUND: The persistent colonization of paranasal sinus mucosa by microbial biofilms is a major factor in the pathogenesis of chronic rhinosinusitis (CRS). Control of microorganisms within biofilms is hampered by the presence of viscous extracellular polymers of host or microbial origin, including nucleic acids. The aim of this study was to investigate the role of extracellular DNA in biofilm formation by bacteria associated with CRS. METHODS/PRINCIPAL FINDINGS: Obstructive mucin was collected from patients during functional endoscopic sinus surgery. Examination of the mucous by transmission electron microscopy revealed an acellular matrix punctuated occasionally with host cells in varying states of degradation. Bacteria were observed in biofilms on mucosal biopsies, and between two and six different species were isolated from each of 20 different patient samples. In total, 16 different bacterial genera were isolated, of which the most commonly identified organisms were coagulase-negative staphylococci, Staphylococcus aureus and α-haemolytic streptococci. Twenty-four fresh clinical isolates were selected for investigation of biofilm formation in vitro using a microplate model system. Biofilms formed by 14 strains, including all 9 extracellular nuclease-producing bacteria, were significantly disrupted by treatment with a novel bacterial deoxyribonuclease, NucB, isolated from a marine strain of Bacillus licheniformis. Extracellular biofilm matrix was observed in untreated samples but not in those treated with NucB and extracellular DNA was purified from in vitro biofilms. CONCLUSION/SIGNIFICANCE: Our data demonstrate that bacteria associated with CRS form robust biofilms which can be reduced by treatment with matrix-degrading enzymes such as NucB. The dispersal of bacterial biofilms with NucB may offer an additional therapeutic target for CRS sufferers.
Genome-Wide Screens Reveal New Gene Products That Influence Genetic Competence in Streptococcus mutans.

A network of genes and at least two peptide signaling molecules tightly control when Streptococcus mutans becomes competent to take up DNA from its environment. Widespread changes in the expression of genes occur when S. mutans is presented with competence signal peptides in vitro, including the increased production of the alternative sigma factor, ComX, which activates late competence genes. Still, the way that gene products that are regulated by competence peptides influence DNA uptake and cellular physiology are not well understood. Here, we developed and employed comprehensive transposon mutagenesis of the S. mutans genome, with a screen to identify mutants that aberrantly expressed comX, coupled with transposon sequencing (Tn-seq) to gain a more thorough understanding of the factors modulating comX expression and progression to the competent state. The screens effectively identified genes known to affect competence, e.g., comR, comS, comD, comE, cipB, clpX, rcrR, and ciaH, but disclosed an additional 20 genes that were not previously competence associated. The competence phenotypes of mutants were characterized, including by fluorescence microscopy to determine at which stage the mutants were impaired for comX activation. Among the novel genes studied were those implicated in cell division, the sensing of cell envelope stress, cell envelope biogenesis, and RNA stability. Our results provide a platform for determining the specific chemical and physical cues that are required for genetic competence in S. mutans, while highlighting the effectiveness of using Tn-seq in S. mutans to discover and study novel biological processes. IMPORTANCEStreptococcus mutans acquires DNA from its environment by becoming genetically competent, a physiologic state triggered by cell-cell communication using secreted peptides. Competence is important for acquiring novel genetic traits and has a strong influence on the expression of virulence-associated traits of S. mutans Here, we used transposon mutagenesis and genomic technologies to identify novel genes involved in competence development. In addition to identifying genes previously known to be required for comX expression, 20 additional genes were identified and characterized. The findings create opportunities to diminish the pathogenic potential of S. mutans, while validating technologies that can rapidly advance our understanding of the physiology, biology, and genetics of S. mutans and related pathogens.
Clinimetric properties of the Nepali version of the Pain Catastrophizing Scale in individuals with chronic pain.

Background: Pain catastrophizing is an exaggerated negative cognitive response related to pain. It is commonly assessed using the Pain Catastrophizing Scale (PCS). Translation and validation of the scale in a new language would facilitate cross-cultural comparisons of the role that pain catastrophizing plays in patient function. Purpose: The aim of this study was to translate and culturally adapt the PCS into Nepali (Nepali version of PCS [PCS-NP]) and evaluate its clinimetric properties. Methods: We translated, cross-culturally adapted, and performed an exploratory factor analysis (EFA) of the PCS-NP in a sample of adults with chronic pain (N=143). We then confirmed the resulting factor model in a separate sample (N=272) and compared this model with 1-, 2-, and 3-factor models previously identified using confirmatory factor analyses (CFAs). We also computed internal consistencies, test-retest reliabilities, standard error of measurement (SEM), minimal detectable change (MDC), and limits of agreement with 95% confidence interval (LOA95%) of the PCS-NP scales. Concurrent validity with measures of depression, anxiety, and pain intensity was assessed by computing Pearson's correlation coefficients. Results: The PCS-NP was comprehensible and culturally acceptable. We extracted a two-factor solution using EFA and confirmed this model using CFAs in the second sample. Adequate fit was also found for a one-factor model and different two- and three-factor models based on prior studies. The PCS-NP scores evidenced excellent reliability and temporal stability, and demonstrated validity via moderate-to-strong associations with measures of depression, anxiety, and pain intensity. The SEM and MDC for the PCS-NP total score were 2.52 and 7.86, respectively (range of PCS scores 0-52). LOA95% was between -15.17 and +16.02 for the total PCS-NP scores. Conclusion: The PCS-NP is a valid and reliable instrument to assess pain catastrophizing in Nepalese individuals with chronic pain.
Genomic comparison of Clostridium species with the potential of utilizing red algal biomass for biobutanol production.

Background: Sustainable biofuels, which are widely considered as an attractive alternative to fossil fuels, can be generated by utilizing various biomass from the environment. Marine biomass, such as red algal biomass, is regarded as one potential renewable substrate source for biofuels conversion due to its abundance of fermentable sugars (e.g., galactose). Previous studies focused on the enhancement of biofuels production from different Clostridium species; however, there has been limited investigation into their metabolic pathways, especially on the conversion of biofuels from galactose, via whole genomic comparison and evolutionary analysis. Results: Two galactose-utilizing Clostridial strains were examined and identified as Clostridium acetobutylicum strain WA and C. beijerinckii strain WB. Via the genomic sequencing of both strains, the comparison of the whole genome together with the relevant protein prediction of 33 other Clostridium species was established to reveal a clear genome profile based upon various genomic features. Among them, five representative strains, including C. beijerinckii NCIMB14988, C. diolis DSM 15410, C. pasteurianum BC1, strain WA and WB, were further discussed to demonstrate the main differences among their respective metabolic pathways, especially in their carbohydrate metabolism. The metabolic pathways involved in the generation of biofuels and other potential products (e.g., riboflavin) were also reconstructed based on the utilization of marine biomass. Finally, a batch fermentation process was performed to verify the fermentative products from strains WA and WB using 60 g/L of galactose, which is the main hydrolysate from algal biomass. It was observed that strain WA and WB could produce up to 16.98 and 12.47 g/L of biobutanol, together with 21,560 and 10,140 mL/L biohydrogen, respectively. Conclusions: The determination of the production of various biofuels by both strains WA and WB and their genomic comparisons with other typical Clostridium species on the analysis of various metabolic pathways was presented. Through the identification of their metabolic pathways, which are involved in the conversion of galactose into various potential products, such as biobutanol, the obtained results extend the current insight into the potential capability of utilizing marine red algal biomass and provide a systematic investigation into the relationship between this genus and the generation of sustainable bioenergy.
The distribution of three candidate cold-resistant SNPs in six minorities in North China.

BACKGROUND: Heilongjiang Province located in northeast China is a multi-ethnic region with people who have lived in cold conditions for several generations. Fatty acids are important to people with cold resistance. CPT1A encodes a protein that imports long-chain fatty acids into the mitochondria for fatty-acid oxidation. FADS is an essential enzyme for the synthesis of long-chain polyunsaturated fatty acids. RESULTS: In the present study, we investigated the distributions of three cold resistance-related SNPs (rs80356779 G > A in CPT1A, rs7115739 T > G in FADS3 and rs174570 C > T in FADS2) from six populations that included 1093 individuals who have lived in Heilongjiang Province for at least three generations. The frequencies of rs174570 and rs7115739 were different in our six north minorities compared to the Chinese Dai in Xishuangbanna (CDX) in southern China. All the SNPs in Hezhen were significantly different from other five studied populations. In addition, the genetic distribution of rs174570 in Daur was significantly different from Manchu and Korea, and the frequency of rs7115739 in Ewenki was significantly different from the other populations. The results also showed that the frequencies of the three SNPs in the six minorities were different from those of Greenlandic Inuit and Siberian population. CONCLUSIONS: Our results showed the distributions of the three cold resistance-related SNPs from six populations that included 1093 individuals in northern China. Distributions of the allele frequencies for the cold resistance-related SNPs in northern China were statistically different from those in southern China. These data help to establish the DNA genome database for the six populations and fully preserve existing minority genetic information.