Fusion-driven Spindle Cell Rhabdomyosarcomas of Bone and Soft Tissue: A Clinicopathologic and Molecular Genetic Study of 25 Cases.

The evolving classification of rhabdomyosarcoma (RMS) now includes spindle cell RMS (SRMS). Bone/soft tissue SRMS often harbor TFCP2, or less often MEIS1 rearrangements. We studied 25 fusion-driven SRMS involving bone (n = 19) and soft tissue (n = 6). Osseous SRMS occurred in 13 women and 6 men (median age: 41 years) and involved the pelvis (5), sacrum (2), spine (4), maxilla (4), mandible (1), skull (1), and femur (2). Follow-up (median: 5 months) demonstrated local recurrence in 2/16 and distant metastases in 8/17 patients (median time to metastasis: 1 month). Eight patients died of disease; 9 were alive with disease. Soft tissue SRMS occurred in 4 men and 2 women (median: 50 years). Follow-up (median: 10 months) revealed distant metastasis at diagnosis (1), alive with unresected tumor (1), and no evidence of disease (4). Next-generation sequencing demonstrated FUS::TFCP2 (12), EWSR1::TFCP2 (3) and MEIS1::NCOA2 (2); FISH identified EWSR1 (2) rearrangements. Most TFCP2-rearranged SRMS (13/17) showed spindled/epithelioid morphology, rarely with rhabdomyoblasts. The bone tumors were diffusely desmin and MyoD1 positive with limited myogenin; 10/13 were ALK -positive and 6/15 were keratin positive. Soft tissue SRMS harbored EWSR1::TFCP2, MEIS1::NCOA2, ZFP64::NCOA2, MEIS1::FOXO1, TCF12::VGLL3 and DCTN1::ALK, and displayed spindled/epithelioid, leiomyomatous, and myxofibrosarcoma-like morphologies. Immunohistochemistry (IHC) was positive for MyoD1 (6/6), focal desmin (5/6), myogenin (3/6), and keratin (1/6). We conclude that TFCP2-rearranged SRMS of bone and soft tissue show consistent morphologic and IHC features, likely representing a distinct subset of RMS. Non-TFCP2 fusion-positive SRMS could represent a single RMS subset, multiple subtypes of RMS, or "fusion-defined" sarcomas with rhabdomyoblastic differentiation.

Escalation from intra-aortic balloon pump to axillary impella 5.5 support: Staged removal of the femoral access.

Background: With the growing population of advanced heart failure, the use of Impella 5.5 has been increasing. Here, we report an effective strategy of removing the intra-aortic balloon pump (IABP) in the setting of escalation of support to Impella 5.5.Results: From January 1, 2022 to June 30, 2022, a total of 6 patients have undergone IABP removal during Impella 5.5 insertion. The IABP was subsequently removed over the long wire with manual compression on the femoral artery to control bleeding. An 8 or 9 Fr short sheath is inserted over the wire. Staged hemostasis was successfully performed in 4 patients, and the remaining two patients required escalation of support to veno-arterial membrane oxygenation as EC-PELLA utilizing the femoral arterial sheath.Conclusion: This does not only achieve secured hemostasis but also enables a smooth transition to further escalate support such as extracorporeal membrane oxygenation support, if necessary.

Paradigms about the COVID-19 pandemic: knowledge, attitudes and practices from medical students.

BACKGROUND: As the disease caused by the novel coronavirus has spread globally, there has been significant economic instability in the healthcare systems. This reality was especially accentuated in Ecuador where, the shortage of healthcare workers combined with cultural and macroeconomic factors has led Ecuador to face the most aggressive outbreak in Latin America. In this context, the participation of final-year medical students on the front line is indispensable. Appropriate training on COVID-19 is an urgent requirement that universities and health systems must guarantee. We aimed to describe the knowledge, attitudes, and practices of Ecuadorian final-year medical students that could potentially guide the design of better medical education curricula regarding COVID-19. METHODS: This was a cross-sectional 33-item online survey conducted between April 6 to April 2020 assessing the knowledge, attitudes, and practices toward the diagnosis, treatment, prevention, and prognosis toward COVID-19 in Ecuadorian final-year medical students. It was sent by email, Facebook, and WhatsApp. RESULTS: A total of 309 students responded to the survey. Out of which 88% of students scored high (≥ 70% correct) for knowledge of the disease. The majority of students were pessimistic about possible government actions, which is reflected in the negative attitude towards the control of COVID-19 and volunteering during the outbreak in Ecuador (77%, and 58% of the students, respectively). Moreover, 91% of students said they did not have adequate protective equipment. The latter finding was significantly associated with negative attitudes. CONCLUSIONS: Although a large number of students displayed negative attitudes, the non-depreciable percentage of students who were willing to volunteer and the coexisting high level of knowledge displayed by students, suggests that Ecuador has a capable upcoming workforce that could benefit from an opportunity to strengthen, improve and advance their training in preparation for COVID-19. Not having personal protective equipment was significantly associated to negative attitudes. Providing the necessary tools and creating a national curriculum may be one of the most effective ways to ensure all students are trained, whilst simultaneously focusing on the students' most pressing concerns. With this additional training, negative attitudes will improve and students will be better qualified.

ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation.

The interplay between transcription factors and epigenetic writers like the DNA methyltransferases (DNMTs), and the role of this interplay in gene expression, is being increasingly appreciated. ZBTB24, a poorly characterized zinc-finger protein, or the de novo methyltransferase DNMT3B, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting an underlying mechanistic link. Chromatin immunoprecipitation coupled with loss-of-function approaches in model systems revealed common loci bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns required for normal cellular function. We identify a ZBTB24 DNA binding motif, which is contained within the promoters of most of its transcriptional targets, including CDCA7, AXIN2, and OSTC. Direct binding of ZBTB24 at the promoters of these genes targets them for transcriptional activation. ZBTB24 binding at the promoters of RNF169 and CAMKMT, however, targets them for transcriptional repression. The involvement of ZBTB24 targets in diverse cellular programs, including the VDR/RXR and interferon regulatory pathways, suggest that ZBTB24's role as a transcriptional regulator is not restricted to immune cells.

Enhanced production of triacylglycerols and polyunsaturated fatty acids in novel acid-tolerant mutants of the green microalga Chlorella saccharophila.

In this study, the microalga Chlorella saccharophila was subjected to ultraviolet (UV) mutagenesis, and mutant screening was conducted based on acidity tolerance to generate mutants with increased triacylglycerol (TAG) and polyunsaturated fatty acid (PUFA) contents. Two improved mutant strains (M1 and M5) were generated. M1 and M5 accumulated 27.2% and 27.4% more TAG, respectively, and showed stronger fluorescence intensity than the wild-type (WT) strain when the cells of these mutants were stained with the lipophilic Nile Red stain. In the M1 mutant, 50.5% of the fatty acid methyl esters (FAMEs) were saturated (C16:0 and C18:0) and 25.27% were monounsaturated (C18:1) fatty acids which are suitable for biofuels production. In the M5 mutant, 65.19% of the total FAMEs were nutritional PUFAs (C16:2, C18:2, and C18:3), while these FAMEs were not detected in the WT. These results demonstrated that UV mutagenesis coupled to an acid pH screening strategy represents a valuable and fast platform to generate mutants of C. saccharophila with improved TAG and PUFA contents for biofuels and nutraceutical applications, respectively.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma.

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04-0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05-0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only (p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.

Clinical Validation of Tagmentation-Based Genome Sequencing for Germline Disorders.

Genome sequencing (GS) is a powerful clinical tool used for the comprehensive diagnosis of germline disorders. GS library preparation typically involves mechanical DNA fragmentation, end repair, and bead-based library size selection followed by adapter ligation, which can require a large amount of input genomic DNA. Tagmentation using bead-linked transposomes can simplify the library preparation process and reduce the DNA input requirement. Here we describe the clinical validation of tagmentation-based PCR-free GS as a clinical test for rare germline disorders. Compared with the Genome-in-a-Bottle Consortium benchmark variant sets, GS had a recall >99.7% and a precision of 99.8% for single nucleotide variants and small insertion-deletions. GS also exhibited 100% sensitivity for clinically reported sequence variants and the copy number variants examined. Furthermore, GS detected mitochondrial sequence variants above 5% heteroplasmy and showed reliable detection of disease-relevant repeat expansions and SMN1 homozygous loss. Our results indicate that while lowering DNA input requirements and reducing library preparation time, GS enables uniform coverage across the genome as well as robust detection of various types of genetic alterations. With the advantage of comprehensive profiling of multiple types of genetic alterations, GS is positioned as an ideal first-tier diagnostic test for germline disorders.

Severe Chagas disease in Ecuador: a countrywide geodemographic epidemiological analysis from 2011 to 2021.

Background: Chagas disease is a neglected and often forgotten tropical disease caused by the Trypanosoma cruzi. This parasite can be transmitted through the direct contact of human skin with feces and urine of the triatomine insect. According to the World Health Organization (WHO), an estimated 6-7 million people are infected worldwide, killing at least 14,000 every year. The disease has been reported in 20 of the 24 provinces of Ecuador, with El Oro, Guayas, and Loja being the most affected. Methodology: We analyzed the morbidity and mortality rates of severe Chagas disease in Ecuador on a nationwide, population-based level. Hospitalization cases and deaths were also examined based on altitude, including low (< 2,500 m) and high (> 2,500 m) altitudes, according to the International Society. Data was retrieved from the National Institute of Statistics and Census hospital admissions and in-hospital mortality databases from 2011 to 2021. Results: A total of 118 patients have been hospitalized in Ecuador since 2011 due to Chagas disease. The overall in-hospital mortality rate was 69.4% (N = 82). Men have a higher incidence rate (4.8/1,000,000) than women, although women have a significantly higher mortality rate than men (6.9/1,000,000). Conclusion: Chagas disease is a severe parasitic condition that primarily affects rural and poorer areas of Ecuador. Men are more likely to be infected due to differences in work and sociocultural activities. Using average elevation data, we conducted a geodemographic analysis to assess incidence rates by altitude. Our findings indicate that the disease is more common at low and moderate altitudes, but recent increases in cases at higher altitudes suggest that environmental changes, such as global warming, could be driving the proliferation of disease-carrying vectors in previously unaffected areas.

Job Satisfaction and Self-Perceptions Among Ecuadorian Medical Doctors During Their Compulsory Rural Community Social Service: A Countrywide Cross-Sectional Analysis.

INTRODUCTION: Job satisfaction has been shown to have important effects at the organizational level. In various corners of the world, physicians are obliged to perform a period of social service, generally at the first level of care in rural or remote areas. OBJECTIVE: To describe the level of job satisfaction and perceptions of Ecuadorian rural physicians regarding compulsory social service. METHODOLOGY: A descriptive, cross-sectional study was conducted based on a self-administered online questionnaire from February to March 2022, in Ecuadorian rural physicians who were performing their compulsory social service. Participants were invited through official outreach groups. A total of 247 surveys were included in this study. We assessed job satisfaction by means of the S20/23 job satisfaction questionnaire and compared these results with sociodemographic variables and job characteristics of the participants. We performed the reliability test (Cronbach's alpha) to find the validity of the S20/23 questionnaire in physicians performing compulsory social service. RESULTS: The majority of participants were women (61.0%), and overall job satisfaction was 4.1/7.0 pts. "indifferent." The only satisfaction factor in which a predominance of dissatisfaction was found related to benefits/remuneration (43.3%). Participants' perceptions of wrong academic guidance during training, insufficient induction, and negative experiences during work were related to higher levels of dissatisfaction (P < .05). CONCLUSION: The level of job satisfaction of Ecuadorian rural physicians during their compulsory social service was low and graduates indicated a neutral attitude toward job satisfaction in general. Negative perceptions with respect to training and expectation formation prior to and during the mandatory social service generated greater dissatisfaction. The Ministry of Health of Ecuador, as an organizational entity, should implement improvements to increase the job satisfaction of recently graduated physicians, given the implications that this experience may have for their professional future.

Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study.

BACKGROUND: Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women. METHODS: This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay). Eligible women were aged 30-64 years, sexually active, did not have a history of cervical cancer or treatment for cervical precancer or a hysterectomy, and were not planning to move outside of the study area. Women were screened with HPV DNA testing and cytology. HPV-positive women were referred to colposcopy using a standardised protocol, including biopsy collection of observed lesions, endocervical sampling for transformation zone (TZ) type 3, and treatment as needed. Women with initial normal colposcopy or no high-grade cervical lesions on histology (less than cervical intraepithelial neoplasia [CIN] grade 2) were recalled after 18 months for another HPV test to complete disease ascertainment; HPV-positive women were referred for a second colposcopy with biopsy and treatment as needed. Diagnostic accuracy of colposcopy was assessed by considering a positive test result when the colposcopic impression at the initial colposcopy was positive minor, positive major, or suspected cancer, and was considered negative otherwise. The main study outcome was histologically confirmed CIN3+ (defined as grade 3 or worse) detected at the initial visit or 18-month visit. FINDINGS: Between Dec 12, 2012, and Dec 3, 2021, 42 502 women were recruited, and 5985 (14·1%) tested positive for HPV. 4499 participants with complete disease ascertainment and follow-up were included in the analysis, with a median age of 40·6 years (IQR 34·7-49·9). CIN3+ was detected in 669 (14·9%) of 4499 women at the initial visit or 18-month visit (3530 [78·5%] negative or CIN1, 300 [6·7%] CIN2, 616 [13·7%] CIN3, and 53 [1·2%] cancers). Sensitivity was 91·2% (95% CI 88·9-93·2) for CIN3+, whereas specificity was 50·1% (48·5-51·8) for less than CIN2 and 47·1% (45·5-48·7) for less than CIN3. Sensitivity for CIN3+ significantly decreased in older women (93·5% [95% CI 91·3-95·3] in those aged 30-49 years vs 77·6% [68·6-85·0] in those aged 50-65 years; p<0·0001), whereas specificity for less than CIN2 significantly increased (45·7% [43·8-47·6] vs 61·8% [58·7-64·8]; p<0·0001). Sensitivity for CIN3+ was also significantly lower in women with negative cytology than in those with abnormal cytology (p<0·0001). INTERPRETATION: Colposcopy is accurate for CIN3+ detection in HPV-positive women. These results reflect ESTAMPA efforts in an 18-month follow-up strategy to maximise disease detection with an internationally validated clinical management protocol and regular training, including quality improvement practices. We showed that colposcopy can be optimised with proper standardisation to be used as triage in HPV-positive women. FUNDING: WHO; Pan American Health Organization; Union for International Cancer Control; National Cancer Institute (NCI); NCI Center for Global Health; National Agency for the Promotion of Research, Technological Development, and Innovation; NCI of Argentina and Colombia; Caja Costarricense de Seguro Social; National Council for Science and Technology of Paraguay; International Agency for Research on Cancer; and all local collaborative institutions.

Quercetin-3-methyl ether suppresses proliferation of mouse epidermal JB6 P+ cells by targeting ERKs.

Chemoprevention has been acknowledged as an important and practical strategy for the management of skin cancer. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer-promoting activity. We identified this compound by in silico virtual screening of the Traditional Chinese Medicine Database using extracellular signal-regulated kinase 2 (ERK2) as the target protein. Here, we showed that quercetin-3-methyl ether inhibited proliferation of mouse skin epidermal JB6 P+ cells in a dose- and time-dependent manner by inducing cell cycle G(2)-M phase accumulation. It also suppressed 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic cell transformation in a dose-dependent manner. Its inhibitory effect was greater than quercetin. The activation of activator protein-1 was dose-dependently suppressed by quercetin-3-methyl ether treatment. Western blot and kinase assay data revealed that quercetin-3-methyl ether inhibited ERKs kinase activity and attenuated phosphorylation of ERKs. Pull-down assays revealed that quercetin-3-methyl ether directly binds with ERKs. Furthermore, a loss-of-function ERK2 mutation inhibited the effectiveness of the quercetin-3-methyl ether. Overall, these results indicated that quercetin-3-methyl ether exerts potent chemopreventive activity by targeting ERKs.

Identification of dynamical hinge points of the L1 ligase molecular switch.

The L1 ligase is an in vitro selected ribozyme that uses a noncanonically base-paired ligation site to catalyze regioselectively and regiospecifically the 5' to 3' phosphodiester bond ligation, a reaction relevant to origin of life hypotheses that invoke an RNA world scenario. The L1 ligase crystal structure revealed two different conformational states that were proposed to represent the active and inactive forms. It remains an open question as to what degree these two conformers persist as stable conformational intermediates in solution, and along what pathway are they able to interconvert. To explore these questions, we have performed a series of molecular dynamics simulations in explicit solvent of the inactive-active conformational switch in L1 ligase. Four simulations were performed departing from both conformers in both the reactant and product states, in addition to a simulation where local unfolding in the active state was induced. From these simulations, along with crystallographic data, a set of four virtual torsion angles that span two evolutionarily conserved and restricted regions were identified as dynamical hinge points in the conformational switch transition. The ligation site visits three distinct states characterized by hydrogen bond patterns that are correlated with the formation of specific contacts that may promote catalysis. The insights gained from these simulations contribute to a more detailed understanding of the coupled catalytic/conformational switch mechanism of L1 ligase that may facilitate the design and engineering of new catalytic riboswitches.

Trypanosoma cruzi: seroprevalence detected in the blood bank of the Instituto Nacional de Pediatría, Mexico City, in the period 2004 through 2009.

BACKGROUND: The second most common mode of Trypanosoma cruzi or Chagas disease transmission is via therapeutic blood transfusion. In Mexico, control of T. cruzi is still in its initial phase; in fact, there are only 14 studies published covering 10 states on T. cruzi seroprevalence in donated blood in Mexico. Here we present the results of 5 years of trypanosomiasis screening in the blood bank of the Instituto Nacional de Pediatría. STUDY DESIGN AND METHODS: Samples from all blood donated in the period from 2004 to 2009 were analyzed. We screened for T. cruzi using an enzyme-linked immunosorbent assay technique. Seropositive samples were then processed using the polymerase chain reaction (PCR) to detect a nuclear gene segment. RESULTS: A total of 37,333 samples were analyzed and a 0.17% (64 samples) T. cruzi seroprevalence was found. Donors were mostly from Mexico State and Mexico City, which is considered nonendemic for T. cruzi area. Of 64 seropositive samples, only two tested positive by PCR (3.12%), which amplified a 189-bp product from nuclear gene from the parasite. CONCLUSION: Although the seroprevalence of T. cruzi infection was low, this surveillance program prevented the infection of more than 100 children because each unit of blood provides 2.6 to 3.5 blood products. The majority of the donors were from Mexico State and Mexico City, which is a nonendemic area. The serodetection of T. cruzi in this region is evidence that is necessary to increase our understanding of its distribution in the Mexico City and surrounding places.

Coronary Intravascular Lithotripsy.

Coronary artery calcification is strongly associated with adverse cardiac events and can impede the success of percutaneous coronary intervention (PCI) due to challenges with delivery of equipment and expansion of stents. Current treatment modalities for mitigation of coronary calcification have limitations and inherent risk of complications. Coronary intravascular lithotripsy (IVL) is a novel technique to modify coronary artery calcification via acoustic pressure waves. IVL utilizes an easy-to-use device, which does not require a steep learning curve. Prospective studies have shown this technique to be safe and effective and can be used to adequately modify calcified coronary stenoses in preparation for PCI and stent deployment and optimization. IVL has unique features that can be used alone or as an adjunctive therapy to other available calcium modification tools. As compared to the currently established modalities of calcium modification, IVL has the potential to facilitate successful PCI with fewer serious procedural complications. In this review article, we discuss the importance of coronary artery calcification, the role of IVL, its mechanism, the current clinical data behind its use and future directions. Overall, coronary IVL is a promising technology for the treatment of severely calcified coronary stenoses, with a need for, long-term clinical outcome data of IVL-facilitated PCI.

Parallelization of Nullspace Algorithm for the computation of metabolic pathways.

Elementary mode analysis is a useful metabolic pathway analysis tool in understanding and analyzing cellular metabolism, since elementary modes can represent metabolic pathways with unique and minimal sets of enzyme-catalyzed reactions of a metabolic network under steady state conditions. However, computation of the elementary modes of a genome- scale metabolic network with 100-1000 reactions is very expensive and sometimes not feasible with the commonly used serial Nullspace Algorithm. In this work, we develop a distributed memory parallelization of the Nullspace Algorithm to handle efficiently the computation of the elementary modes of a large metabolic network. We give an implementation in C++ language with the support of MPI library functions for the parallel communication. Our proposed algorithm is accompanied with an analysis of the complexity and identification of major bottlenecks during computation of all possible pathways of a large metabolic network. The algorithm includes methods to achieve load balancing among the compute-nodes and specific communication patterns to reduce the communication overhead and improve efficiency.

Higher Playing Times Accumulated Across Entire Games and Prior to Intense Passages Reduce the Peak Demands Reached by Elite, Junior, Male Basketball Players.

The aim of this study was to analyze the effects of different factors on the external peak demands (PD) encountered by elite, junior, male basketball players in games, including the (1) total playing time during games and (2) playing time accumulated directly prior to each PD episode. Workload variables included the PD for total distance, distance covered in different intensity zones, accelerations >2 m·s-2 (ACC), decelerations <-2 m·s-2 (DEC), and PlayerLoad. PD were calculated across different sample durations for each variable. Linear mixed models were used to identify differences in PD between groups based on playing times. PD for total distance (5-min window), high-speed running (>18 km·h-1) distance (2-min window), and ACC (30-s, 45-s, 1-min, 2-min, and 5-min windows) were significantly (p < .05) higher for players who completed lower total playing times (16.6 ± 2.4 min) than players who completed higher total playing times (25.0 ± 3.4 min). The PD for total distance (30-s, 45-s, 1-min, and 2-min windows), high-speed running distance (30-s and 5-min windows), and PlayerLoad (1-min and 2-min windows) were significantly (p < .05) higher for players who accumulated lower playing times before each PD episode than players who accumulated higher playing times before each PD episode. Players who undertake less playing time overall and prior to each PD episode can reach higher peak external loads aggregated across varied time windows. These findings can inform tactical coaching decisions during games for high external loads to be accomplished during important passages of play.

Peak Match Demands in Young Basketball Players: Approach and Applications.

BACKGROUND: The aim of this study is to describe the peak match demands and compare them with average demands in basketball players, from an external load point of view, using different time windows. Another objective is to determine whether there are differences between positions and to provide an approach for practical applications. METHODS: During this observational study, each player wore a micro technology device. We collected data from 12 male basketball players (mean ± SD: age 17.56 ± 0.67 years, height 196.17 ± 6.71 cm, body mass 90.83 ± 11.16 kg) during eight games. We analyzed intervals for different time windows using rolling averages (ROLL) to determine the peak match demands for Player Load. A separate one-way analysis of variance (ANOVA) was used to identify statistically significant differences between playing positions across different intense periods. RESULTS: Separate one-way ANOVAs revealed statistically significant differences between 1 min, 5 min, 10 min, and full game periods for Player Load, F (3,168) = 231.80, ηp2 = 0.76, large, p < 0.001. It is worth noting that guards produced a statistically significantly higher Player Load in 5 min (p < 0.01, ηp2 = -0.69, moderate), 10 min (p < 0.001, ηp2 = -0.90, moderate), and full game (p < 0.001, ηp2 = -0.96, moderate) periods than forwards. CONCLUSIONS: The main finding is that there are significant differences between the most intense moments of a game and the average demands. This means that understanding game demands using averages drastically underestimates the peak demands of the game. This approach helps coaches and fitness coaches to prepare athletes for the most demanding periods of the game and present potential practical applications that could be implemented during training and rehabilitation sessions.

Coverage profile correction of shallow-depth circulating cell-free DNA sequencing via multidistance learning.

Shallow-depth whole-genome sequencing (WGS) of circulating cell-free DNA (ccfDNA) is a popular approach for non-invasive genomic screening assays, including liquid biopsy for early detection of invasive tumors as well as non-invasive prenatal screening (NIPS) for common fetal trisomies. In contrast to nuclear DNA WGS, ccfDNA WGS exhibits extensive inter- and intra- sample coverage variability that is not fully explained by typical sources of variation in WGS, such as GC content. This variability may inflate false positive and false negative screening rates of copy-number alterations and aneuploidy, particularly if these features are present at a relatively low proportion of total sequenced content. Herein, we propose an empirically-driven coverage correction strategy that leverages prior annotation information in a multi-distance learning context to improve within-sample coverage profile correction. Specifically, we train a weighted k-nearest neighbors-style method on non-pregnant female donor ccfDNA WGS samples, and apply it to NIPS samples to evaluate coverage profile variability reduction. We additionally characterize improvement in the discrimination of positive fetal trisomy cases relative to normal controls, and compare our results against a more traditional regression-based approach to profile coverage correction based on GC content and mappability. Under cross-validation, performance measures indicated benefit to combining the two feature sets relative to either in isolation. We also observed substantial improvement in coverage profile variability reduction in leave-out clinical NIPS samples, with variability reduced by 26.5-53.5% relative to the standard regression-based method as quantified by median absolute deviation. Finally, we observed improvement discrimination for screening positive trisomy cases reducing ccfDNA WGS coverage variability while additionally improving NIPS trisomy screening assay performance. Overall, our results indicate that machine learning approaches can substantially improve ccfDNA WGS coverage profile correction and downstream analyses.

Organic Thin-Film Transistors as Gas Sensors: A Review.

Organic thin-film transistors (OTFTs) are miniaturized devices based upon the electronic responses of organic semiconductors. In comparison to their conventional inorganic counterparts, organic semiconductors are cheaper, can undergo reversible doping processes and may have electronic properties chiefly modulated by molecular engineering approaches. More recently, OTFTs have been designed as gas sensor devices, displaying remarkable performance for the detection of important target analytes, such as ammonia, nitrogen dioxide, hydrogen sulfide and volatile organic compounds (VOCs). The present manuscript provides a comprehensive review on the working principle of OTFTs for gas sensing, with concise descriptions of devices' architectures and parameter extraction based upon a constant charge carrier mobility model. Then, it moves on with methods of device fabrication and physicochemical descriptions of the main organic semiconductors recently applied to gas sensors (i.e., since 2015 but emphasizing even more recent results). Finally, it describes the achievements of OTFTs in the detection of important gas pollutants alongside an outlook toward the future of this exciting technology.

Sustainably reducing device utilization and device-related infections with DeCATHlons, device alternatives, and decision support.

Engagement of frontline staff, along with senior leadership, in competition-style healthcare-associated infection reduction efforts, combined with electronic clinical decision support tools, appeared to reduce antibiotic regimen initiations for urinary tract infections (P = .01). Mean monthly standardized infection and device utilization ratios also decreased (P < .003 and P < .0001, respectively).