bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA
Authors: Tran Truc T , Cabrera Nicolo L , Gonzales-Luna Anne J , Carlson Travis J , Alnezary Faris , Miller William R , Sakurai Aki , Dinh An Q , Rydell Kirsten , Rios Rafael , Diaz Lorena , Hanson Blake M , Munita Jose M , Pedroza Claudia , Shelburne Samuel A , Aitken Samuel L , Garey Kevin W , Dillon Ryan , Puzniak Laura , Arias Cesar A
Published: January 2023

Background

Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA.

Methods

We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS.

Results

A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST.

Conclusions

Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.
Reducing Specimen Rejection Rates Using Concentration-Dependent Hemolysis Rejection Thresholds
Authors: Tang Nga Yeung , Mitchell Kelly R , Groboske Sarah E , Baldwin Angel D , Lenza Michael , Yeo Kiang-Teck J , van Wijk Xander M R
Published: January 2023

Background

Using middleware solutions, it is possible to implement concentration-dependent analyte-specific hemolysis rejection limits. This makes day-to-day reporting of clinical specimens more efficient and potentially lowers sample rejection rates compared to a “one-size-fits-all” approach (i.e., solely based on a single cutoff provided in the package insert).

Methods

Hemolysis interference studies were performed at multiple analyte concentrations for three frequently ordered tests. For each assay, concentration-dependent hemolysis rejection limits were designed based on the total allowable error (TAE) for the analyte as well as the clinical significance of such incurred inaccuracy at the respective concentrations. In general, the following rationale was used: if the interference exceeds 10% (or package insert cutoffs), a comment is placed on the result. If the interference exceeds the TAE, the result will not be reported. Reduction in specimen rejection rates were estimated by comparing the incurred specimen rejection rates when package inserts’ vs concentration-dependent hemolysis interference limits were applied to a data set in our institute during a three-month period.

Results

Concentration-dependent analyte-specific hemolysis rejection thresholds were designed for three commonly ordered assays that are especially susceptible to hemolysis interference. It is estimated that these novel thresholds for aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and direct bilirubin (DBIL) reduced specimen rejection rates from 9.3% to 1.3%, 31.4% to 4.8%, and 19.9% to 7.1%, respectively.

Conclusions

Concentration-dependent analyte-specific hemolysis rejection thresholds for three commonly ordered assays can reduce rejection rates without significantly compromising the quality of test results.
Metabolome of purulent materials of liver abscesses from crossbred cattle and Holstein steers fed finishing diets with or without in-feed tylosin
Authors: Amachawadi Raghavendra G , Bohney Samuel , Nagaraja T G
Published: January 2023

Liver abscesses in feedlot cattle are a polymicrobial infection with Fusobacterium necrophorum and Trueperella pyogenes as the primary and secondary etiologic agents, respectively. Cattle with liver abscesses do not exhibit clinical signs and the abscesses are detected only at slaughter. The objective was to conduct metabolomics analysis of purulent materials of liver abscesses to identify biochemicals. Liver abscesses from crossbred cattle (n = 24) and Holstein steers (n = 24), each fed high-grain finishing diet with tylosin (n = 12) or no tylosin (n = 12), were included in the study. Abscess purulent materials were analyzed by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. A total of 759 biochemicals were identified and were broadly categorized into carbohydrates, energy metabolism pathways intermediates, peptides, amino acids and their metabolites, lipids and their metabolites, nucleotides, vitamins and cofactors, xenobiotics, and partially characterized molecules. The top 50 biochemicals identified included amino acids, lipids, nucleotides, xenobiotics, peptides, and carbohydrates and their metabolites. Among the 15 amino acid metabolites in the top 50 biochemicals, four were tryptophan metabolites, indoleacrylate, indolepropionate, tryptamine, and anthranilate. The 3-phenylpropionate, a product of phenylalanine metabolism, was the predominant metabolite in purulent materials. Between the four treatment groups, a two-way ANOVA analysis identified biochemicals that exhibited significant main effects for cattle type and in-feed tylosin use and their interactions. A total of 59 and 85 biochemicals were different (P < 0.05) between the cattle type (crossbred vs. Holstein steers) and in-feed tylosin use (tylosin vs. no tylosin), respectively. Succinate, an intermediate of lactate fermentation by some bacterial species, was one of the top 30 biochemicals that differentiated the four treatment groups. A number of lysophospholipids, indicative of bacterial and host cell membrane lyses, were identified in the purulent materials. In conclusion, to our knowledge this is the first report on the metabolome of liver abscess purulent materials and several biochemicals identified were related to metabolic activities of the bacterial community, particularly F. necrophorum and T. pyogenes. Biochemicals unique to liver abscesses that appear in the blood may serve as biomarkers and be of diagnostic value to detect liver abscesses of cattle before slaughter.
Effects of supplemental Zn concentration and trace mineral source on immune function and associated biomarkers of immune status in weaned beef calves received into a feedlot
Authors: Smerchek Dathan T , Branine Mark E , McGill Jodi L , Hansen Stephanie L
Published: January 2023

Low-risk, weaned Angus-crossbred steers (n = 72; 284 ± 25 kg) were used in a 42-d receiving study. Steers were housed in pens (n = 6 steers per pen) equipped with GrowSafe bunks for determination of individual animal feed disappearance. Dietary treatments (n = 24 steers per treatment) included: 1) trace minerals (TM) from an organic source (Availa4; Zinpro Corp., Eden Prairie, MN) at 7 g·steer−1·d−1; for 42 d (ORG); 2) ORG for entire 42-d plus AvailaZn (Zn amino acid complex, Zinpro Corp., Eden Prairie, MN) to provide 1,000 mg Zn·steer−1·d−1 for first 14 d (ORG+Z); 3) inorganic TM sources to supplemented at equivalent concentration as in ORG for 42-d (ING). Cattle were weighed on day −1, 0, 14, 41, and 42. Whole blood was collected (n = 72 steers) on day 0, 14, and 42. Liver biopsies were conducted (n = 36 steers; 3 steers per pen) on day 0, 14, and 42. Flow cytometry measures were conducted using whole blood on day 1, 14, and 42 for determination of circulating frequencies of immune cell populations. There was a tendency for improved overall average daily gain (P = 0.07) where both ORG and ORG+Z were greater than ING. Final body weight did not differ (P = 0.21) and overall dry matter intake was unaffected by dietary treatment (P ≥ 0.18). However, overall gain-to-feed ratio was improved (P = 0.01) in steers supplemented organic TM (ORG and ORG+Z) compared to ING. Plasma Zn concentration did not differ at any time point during the study (P ≥ 0.20). Liver Zn concentration did not differ between treatments on day 0 or 42; however, on day 14 ING tended (P = 0.09) to be greater than ORG+Z with ORG being intermediate. Plasma Cu was unaffected by dietary treatment (P ≥ 0.34) on day 0, 14, and 42. Plasma Fe did not differ on day 0 or 42 but tended to be greater in ORG and ORG+Z compared to ING (P = 0.08) on day 14. Dietary treatment did not alter (P ≥ 0.22) liver Fe or Mn concentration at any time point. Frequency of total circulating natural killer (NK) and CD8 T cells measured on day 0, 14, and 42 did not differ (P ≥ 0.07). However, cell surface markers of activation (CD16, CD44, and CD8) on NK cells measured on day 14 did differ because of treatment (P ≤ 0.05). Results presented herein indicate TM from an organic source supplemented to steers during receiving can positively influence growth rate and feed efficiency. Regardless of source, TM supplementation affected markers of immune function but did not influence the prevalence of circulating NK and CD8 T-cell populations.
Novel Screening Tool and Considerations for Music Therapists Serving Autistic Individuals via Telehealth: Qualitative Results from a Survey of Clinicians’ Experiences
Authors: Richard Williams Nicole M , Hurt-Thaut Corene , Thaut Michael H
Published: January 2023

During the COVID-19 pandemic, music therapists transitioned services from in-person to telehealth due to health and safety concerns. Though online delivery of music therapy services for autistic individuals occurred prior to 2020, the number of North American music therapists using telehealth with autistic clients rose substantially during the pandemic. The current paper’s objective was to delineate music therapists’ perceptions regarding factors that helped or hindered autistic persons’ engagement in online music therapy sessions. In total, 192 participants completed the survey. Qualitative content analysis of an open-ended question identified seven overarching themes regarding the benefits and challenges of telehealth music therapy for autistic clients. Findings were used to create a screening tool to help music therapists evaluate autistic persons’ suitability for telehealth and meet the needs of those who can benefit from telehealth music therapy.
The Effect of Contingent Singing on Infants with Bronchopulmonary Dysplasia in the Neonatal Intensive Care Unit
Authors: Smith Amy R , Hagan Joseph , Walden Marlene , Brickley Alix , Biard Marial , Rhee Christopher , McIver Patricia , Shoemark Helen , Brand M Colleen
Published: January 2023

A significant component of care for infants with bronchopulmonary dysplasia (BPD) is providing an optimal environment for supporting neurodevelopment and growth. Interventions that support the behavioral and physiologic stability of this population may play an important role in improving overall outcomes. Contingent singing is a music intervention that allows the caregiver to tailor certain musical elements, such as rhythm and tempo, to match behavioral and physiologic cues and support the infant in achieving optimal stabilization. A randomized crossover design was used to study the effect of contingent singing on the behavioral state and physiologic measures compared to standard care practices in the neonatal intensive care unit (NICU). Data were collected on a sample of 37 infants diagnosed with BPD. There were no significant differences in the physiologic measures or behavioral states of infants in the contingent singing sessions compared to control sessions. Parents and staff reported favorable views of music therapy in the NICU, and there were no adverse responses from infants during contingent singing. Further research is needed to determine the effectiveness of this intervention on the physiologic stability of infants with BPD.
Silenced on social media: the gatekeeping functions of shadowbans in the American Twitterverse
Authors: Jaidka Kokil , Mukerjee Subhayan , Lelkes Yphtach
Published: January 2023

Algorithms play a critical role in steering online attention on social media. Many have alleged that algorithms can perpetuate bias. This study audited shadowbanning, where a user or their content is temporarily hidden on Twitter. We repeatedly tested whether a stratified random sample of American Twitter accounts (n ≈ 25,000) had been subject to various forms of shadowbans. We then identified the type of user and tweet characteristics that predict a shadowban. In general, shadowbans are rare. We found that accounts with bot-like behavior were more likely to face shadowbans, while verified accounts were less likely to be shadowbanned. The replies by Twitter accounts that posted offensive tweets and tweets about politics (from both the left and the right) were more likely to be downtiered. The findings have implications for algorithmic accountability and the design of future audit studies of social media platforms.
Dominant species play a leading role in shaping community stability in the northern Tibetan grasslands
Authors: Hou Ge , Shi Peili , Zhou Tiancai , Sun Jian , Zong Ning , Song Minghua , Zhang Xianzhou
Published: January 2023

Dominant species may strongly influence biotic conditions and interact with other species, and thus are important drivers of community dynamics and ecosystem functioning, particularly in the stressed environment of alpine grasslands. However, the effects of dominant species on the community stability of different ecosystems remain poorly understood. We examined the mechanisms underlying temporal stability (2014–2020 year) of aboveground productivity and community stability in four alpine grasslands (alpine meadow, alpine meadow steppe, alpine steppe and alpine desert steppe) of the northern Tibetan with different species composition and dominance. Our results showed that community stability was significantly higher in the alpine meadow than in the other three types of grasslands. This difference was mainly attributed to the higher compensatory effect and selection effect in the alpine meadows. Furthermore, dominant species strongly affected community stability by increasing dominant species stability and species asynchrony. However, species richness had little effect on community stability. Our findings demonstrate that dominant species, as foundation species, may play leading roles in shaping community stability in the alpine grasslands, highlighting the importance of conserving dominant species for stable ecosystem functioning in these fragile ecosystems under increasing environmental fluctuations.
Investigating paediatric sarcoma management worldwide: a study protocol
Authors: Wong William , Bandyopadhyay Soham , Zuberi Hira , Raza Muhammad R , Koko Abdullahi N , Peter Noel , Lakhoo Kokila
Published: January 2023

Introduction

Cancer is the leading cause of non-accidental death among children worldwide. The most common types of paediatric cancers include sarcomas: a group of cancers that are difficult to manage due to their heterogeneity and lack of defining features. We have designed an international multicentre cohort study to assess the management of paediatric sarcomas at tertiary healthcare centres in Nigeria, Pakistan and the UK.

Methods and Analysis

The centres will screen patient databases to identify eligible patients under the age of 18 with a clinical or histological diagnosis of sarcoma. Data will be extracted from the patient notes through an anonymized form. Patients will be recruited consecutively into the study from January 2015 to January 2021, with a minimum 12-month follow up period. The primary objectives of the study will be to determine all-cause mortality rates at 30 days, 90 days, 12 months and 3 years. Significant differences in mortality rates between countries will be determined using χ2 analysis or Fisher’s exact test. Univariate and multivariable logistic regression will be used to examine the influence of different factors and patient characteristics on outcomes.

Ethics and Dissemination

At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymized data. At other centres, participating collaborators have gained local approvals in accordance with institutional ethical regulations. Collaborators will present the data to inform decision makers about how sarcoma management may be improved. The results will be submitted for publication in a peer-reviewed journal.
A comparative study of Bianchi versus right upper transverse approach in infantile hypertrophic pyloric stenosis
Authors: Habib Murad , Raza Rafi , Ahmed Mansoor , Arif Khurrum , Chaudhary Muhammad Amjad
Published: January 2023

The objective of this study is to compare Bianchi supra umbilical curvilinear incision with a right upper transverse incision in patients presenting with infantile hypertrophic pyloric stenosis (IHPS) in terms of level of difficulty faced during the procedure, operative time, postoperative cosmesis, wound infection and wound dehiscence. A prospective comparative study was conducted at the Department of Paediatric Surgery, The Children’s Hospital, Pakistan Institute of Medical Sciences, Islamabad. The total duration of the study was 1 year from 1st March, 2020 to 28th February, 2021. The anticipated sample was minimum of 20 cases in Group A (Bianchi) and 20 cases in Group B (right upper quadrant incision), i.e. total 40 cases of IHPS. All infants up to 12 weeks admitted with the diagnosis of IHPS were added in the study. The study outcome was determined in terms of duration of surgery, wound infection and cosmetic effect after intervention with Bianchi and right upper transverse incision. Age and gender distribution was found equal when compared between study groups with male preponderance. The mean duration of surgery was 47.0 min in Group A, as compared with 32.5 min in Group B. Similarly, hospital stay was found slightly longer in Group A than Group B (5.3 versus 4.8 days, respectively). The level of difficulty while performing the surgery was slightly greater in Group A. The scar was detectable in all 20 (100.0%) patients in Group B compared with only 2 (10.0%) in Group A. Wound dehiscence was found in one (5.0%) patient in Group A, whereas none (0.0%) in Group B had it. The management of IHPS can be safely and successfully done with both Bianchi technique and right upper quadrant incision. The duration of surgery, level of difficulty while performing surgery and postoperative complications like wound infections and dehiscence were slightly more prevalent in Group A, whereas scar was significantly associated with Group B (100.0 versus 10.0%).
Detecting Interviewer Fraud Using Multilevel Models
Authors: Olbrich Lukas , Kosyakova Yuliya , Sakshaug Joseph W , Schwanhäuser Silvia
Published: January 2023

Interviewer falsification, such as the complete or partial fabrication of interview data, has been shown to substantially affect the results of survey data. In this study, we apply a method to identify falsifying face-to-face interviewers based on the development of their behavior over the survey field period. We postulate four potential falsifier types: steady low-effort falsifiers, steady high-effort falsifiers, learning falsifiers, and sudden falsifiers. Using large-scale survey data from Germany with verified falsifications, we apply multilevel models with interviewer effects on the intercept, scale, and slope of the interview sequence to test whether falsifiers can be detected based on their dynamic behavior. In addition to identifying a rather high-effort falsifier previously detected by the survey organization, the model flagged two additional suspicious interviewers exhibiting learning behavior, who were subsequently classified as deviant by the survey organization. We additionally apply the analysis approach to publicly available cross-national survey data and find multiple interviewers who show behavior consistent with the postulated falsifier types.
Ionization of inner T Tauri star discs: effects ofin situenergetic particles produced by strong magnetic reconnection events
Authors: Brunn V , Marcowith A , Sauty C , Padovani M , Rab Ch , Meskini C
Published: January 2023

Magnetic reconnection is one of the major particle acceleration processes in space and astrophysical plasmas. Low-energy supra-thermal particles emitted by magnetic reconnection are a source of ionization for circumstellar discs, influencing their chemical, thermal, and dynamical evolution. The aim of this work is to propose a first investigation to evaluate how energetic particles can propagate in the circumstellar disc of a T Tauri star and how they affect the ionization rate of the disc plasma. To that end, we have collected experimental and theoretical cross sections for the production of H+, H$_2^+$, and He+ by electrons and protons. Starting from theoretical injection spectra of protons and electrons emitted during magnetic reconnection events, we have calculated the propagated spectra in the circumstellar disc considering the relevant energy loss processes. We have considered fluxes of energetic particles with different spectral indices and different disc magnetic configurations, generated at different positions from the star considering the physical properties of the flares as deduced from the observations obtained by the Chandra Orion Ultra Deep point source catalogue. We have then computed the ionization rates for a disc whose structure has been calculated with the radiation thermo-chemical code prodimo. We find that energetic particles are potentially a very strong source of local ionization with ionization rates exceeding by several orders of magnitude the contribution due to X-rays, stellar energetic particles, and radioactivity in the inner disc.
[C ii] Haloes in ALPINE galaxies: smoking-gun of galactic outflows?
Authors: Pizzati E , Ferrara A , Pallottini A , Sommovigo L , Kohandel M , Carniani S
Published: January 2023

ALMA observations have revealed that many high-redshift galaxies are surrounded by extended (10–15 kpc) [C ii]-emitting haloes that are not predicted by even the most advanced zoom-in simulations. Using a semi-analytical model, in a previous work we suggested that such haloes are produced by starburst-driven, catastrophically cooling outflows. Here, we further improve the model and compare its predictions with data from seven star-forming ($10\lesssim \rm SFR/{\rm M}_{\odot }\, yr^{-1}\lesssim 100$) galaxies at z = 4–6, observed in the ALPINE survey. We find that (a) detected [C ii] haloes are a natural by-product of starburst-driven outflows; (b) the outflow mass loading factors are in the range 4 ≲ η ≲ 7, with higher η values for lower mass, lower star formation rate systems, and scale with stellar mass as $\eta \propto M_*^{-0.43}$, consistently with the momentum-driven hypothesis. Our model suggests that outflows are widespread phenomena in high-z galaxies. However, in low-mass systems the halo extended [C ii] emission is likely too faint to be detected with the current levels of sensitivity.
Collusion sustainability with a capacity-constrained firm
Authors: Madio Leonardo , Pignataro Aldo
Published: January 2023

We study an infinitely repeated oligopoly game in which firms compete on quantity and one of them is capacity-constrained. We show that collusion sustainability is non-monotonic in the size of the capacity-constrained firm, which has little incentive to deviate from a cartel. We also present conditions for the emergence of a partial cartel, with the capacity-constrained firm being excluded by the large firms or self-excluded. In the latter case, we show under which circumstances the small firm induces a partial conspiracy that is Pareto-dominant. Implications for cartel identification and enforcement are finally discussed.
The Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Management of Brucellosis: An Observational Cohort Study
Authors: Ghanem-Zoubi Nesrin , Kagna Olga , Dabaja-Younis Halima , Atarieh Menas , Nasrallah Elias , Kassis Imad , Keidar Zohar , Paul Mical
Published: January 2023

Background

Diagnosis of focal infection in brucellosis is important to direct optimal treatment. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) may be helpful in this aspect.

Methods

The clinical and imaging data of all patients with brucellosis, who underwent FDG PET/CT as part of the investigation in Rambam Health Care Campus, where FDG PET/CT became the recommended imaging modality for suspected focal infection in brucellosis since 2016, were analyzed retrospectively. The detection of focal infection as well as management modification before and after FDG PET/CT were recorded.

Results

FDG PET/CT was performed in 30 episodes of brucellosis occurring in 27 patients: 20 primary episodes and 10 suspected relapse episodes. The mean age of the patients was 50 ± 15.07 years. Focal disease was diagnosed in 18 of 30 (60%) episodes, of which 8 (26.6%) were diagnosed for the first time by FDG PET/CT, all of whom had spinal infection, with a concomitant additional focus in 5. Overall, multifocal disease was diagnosed in 10 of 18 (55.5%) of patients with focal disease. Management modification following FDG PET/CT was recorded in 17 of 30 (56.6%) episodes, mainly by treatment extension in spinal infection and withholding treatment in patients with suspected relapse but no evidence of active disease by FDG PET/CT.

Conclusions

FDG PET/CT was found to be helpful in the diagnosis of focal infection in brucellosis. Multifocal disease seems more prevalent than previously described. The clinical impact of adding FDG PET/CT to the diagnostic workup of brucellosis should be evaluated in future studies.
Efficacy of Telehealth for Movement-Evoked Pain in People With Chronic Achilles Tendinopathy: A Noninferiority Analysis
Authors: Post Andrew A , Rio Ebonie K , Sluka Kathleen A , Moseley G Lorimer , Bayman Emine O , Hall Mederic M , de Cesar Netto Cesar , Wilken Jason M , Danielson Jessica , Chimenti Ruth L
Published: January 2023

Objective

The purpose of this study was to compare the efficacy of physical therapy delivered via an all telehealth or hybrid format with an all in-person format on movement-evoked pain for individuals with chronic Achilles tendinopathy (AT).

Methods

Sixty-six individuals with chronic AT participated (age, 43.4 [SD = 15.4] years; 56% female; body mass index, 29.9 [SD = 7.7] kg/m2). Participants completed all in-person visits from the initiation of recruitment in September 2019 to March 16, 2020 (in-person group). From March 17 to July 15, 2020, participants completed all telehealth visits (telehealth group). From July 16, 2020, to enrollment completion in December 2020, participants could complete visits all in-person, all telehealth, or a combination of in-person and telehealth (hybrid group) based on their preference. A physical therapist provided 6 to 7 visits, including an exercise program and patient education. Noninferiority analyses of the telehealth and hybrid groups compared with the in-person group were completed for the primary outcome of movement-evoked pain during single-limb heel raises.

Results

All groups demonstrated decreases in movement-evoked pain beyond the minimal clinically important difference from baseline to 8 weeks (2 out of 10 on a numeric pain rating scale). Lower bounds of the 95% CIs for mean differences between groups did not surpass the preestablished noninferiority margin (2 out of 10) for movement-evoked pain in both the telehealth and hybrid groups (telehealth vs in-person: 0.45 [−1.1 to 2.0]; hybrid vs in-person: 0.48 [−1.0 to 1.9]).

Conclusion

Individuals with chronic AT who completed a tendon-loading program with patient education through a telehealth or hybrid format had no worse outcomes for pain than those who received the same intervention through in-person visits.

Impact

Physical therapist–directed patient care delivered via telehealth may enhance accessibility to best practice AT rehabilitation, including exercise and education. Use of telehealth technology may also provide an opportunity to prioritize patient preference for physical therapy visit format.

Lay Summary

If you are a patient with chronic AT, physical therapist–directed patient care delivered via telehealth may improve your accessibility to best practice AT rehabilitation, including exercise and education. Use of telehealth technology may also prioritize your preferences regarding the format of the physical therapy visit.
The Consequences of Direct Democracy for the Balance of Power between State and Local Governments in the United States
Authors: Uttermark Matthew J
Published: January 2023

Contemporary research in American federalism has evaluated the centralizing characteristics of several institutions within state governments—including state statutes, executive orders, and judicial decisions—and has shown that these institutions are generally associated with shifting power away from local governments toward state governments. I expand this discussion by assessing the consequences of direct democracy for the balance of power between state and local governments. In particular, I investigate whether ballot measures are associated with decentralizing power away from state governments toward local governments or rather whether these measures are associated with centralizing power in state governments. Leveraging new data across the history of direct democracy in the United States and coding 945 proposed ballot measures according to their de/centralizing impact on local governments, I find that citizen-initiated ballot measures are neither centralizing nor decentralizing, but legislature-referred ballot measures are decentralizing. I also find that regardless of whether citizens or legislators are responsible for placing measures on the ballot, voters generally provide more support for centralizing ballot measures than decentralizing ballot measures. However, voter support is conditioned on state-level partisanship and ideology.
BEAM MATCHING EVALUATION OF TWO SIMILAR LINEAR ACCELERATORS
Authors: Sistani Soroush , Babaeifar Hamidreza , Khoramian Daryoush , Arani Mahmud Naraqi , Sarvizadeh Mostafa , Kalantari Faraz , Ebrahimi Ali
Published: January 2023

To evaluate the beam-matching of two Siemens Primus medical linear accelerators (Linacs), the output factor (Sc,p), wedge factor, quality index (TPR20/10), percentage depth dose (PDD) and beam profiles were compared for 6 and 15 MV photon beams. The output factor, the PDD and the beam profile for electron beam compared for 5, 7, 8, 10 and 12 MeV electron beams. The gamma (γ) analysis of 2 mm/2% and 3 mm/3% was performed. According to the measurements, it can be said that 6 MV photon beams in all field sizes (except 4 × 4 cm2) are beam matched. For 15 MV, although the PDDs were matched in all field sizes (except 4 × 4 cm2) for both 2 mm/2% and 3 mm/3% γ criteria, beam profiles in field sizes larger than 10 × 10 cm2 for 3 mm/3% and in field sizes larger than 8 × 8 cm2 for 2 mm/2% were not matched. The electron beams in all applicator sizes (except 5 × 5 cm2 applicator) pass the acceptance γ criteria of 3 mm/3% (γ < 1). Electron beams do not fulfill beam matched in case of the acceptance γ criteria of 2 mm/2%.
H-mode dithering phase studies on ST40
Authors: Andrew Yasmin , Bland James , Buxton Peter , Dnestrovskij Alexei , Gryaznevich Mikhail , Kim Eun-jin , Romanelli Michele , Sertoli Marco , Thomas Paul , Varje Jari
Published: January 2023

The dithering H-mode phase, characterized by oscillations, is generally observed at input power values close to the L-H transition power threshold and low plasma collisionalities (low electron density and/or high plasma temperature). Measurements to characterize the dithering phase are presented for the low aspect ratio, high magnetic field tokamak, ST40. The dithering phase oscillation frequency is observed between 400 and 800 Hz and demonstrates an inverse relationship with core plasma density. Dithering phase H-modes are documented across a nonlinear, low-density power threshold operational space, with signature low- and high-density branches. The minimum power threshold for dithering H-mode access is measured at a core, line average electron density of 4.7(±0.5) × 10
19
 m
−3
, close to a predicted value of 4.1(±0.4) × 10
19
 m
−3
from multi-machine studies. ASTRA calculated values of power coupled to the ion species, at the dithering H-mode transition, exhibit a similar nonlinear dependence on density. This analysis points to the important contribution of the ion thermal channel to the L-H phase transition. The low-frequency plasma density and D-alpha dithers appear to be accompanied by sudden bursts of magnetohydrodynamic (MHD) activity. A simple model is tested to demonstrate a possible scenario of self-regulation among turbulence, zonal flows, pressure (density) gradient and MHD activities.

This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.
Characteristics of constrained turbulent transport in flux-driven toroidal plasmas
Authors: Kishimoto Y. , Imadera K. , Ishizawa A. , Wang W. , Li J. Q.
Published: January 2023

We study the dynamics of turbulence transport subject to a constraint on the profile formation and relaxation, dominated by the ion temperature gradient modes, within the framework of adiabatic electron response using a flux-driven global gyro-kinetic toroidal code, GKNET. We observe exponentially constrained profiles, with two different scale lengths, that are spatially constant in each region in higher input power regimes. The profiles are smoothly connected in the knee region located at

1

/

2
−
2

/

3

of the minor radius, outside which the gradient is steepened and shows a weak confinement improvement. Based on the probability density function analysis of heat flux eddies, the power law demonstrates a dependence on the eddy size
S
, as

P
∼

S

−
α

, which distinguishes events into diffusive and non-diffusive parts including the validation of quasi-linear hypotheses. Radially localized avalanches and global bursts, which exhibit different spatial scales, play central roles in giving rise to constrained profiles on an equal footing. It is also found that the

E
×
B

shear layers
are initiated by the global bursts, which evolve downward on a slow time scale across the knee region and play a role in adjusting the profile by increasing the gradient.

This article is part of a discussion meeting issue ‘H-mode transition and pedestal studies in fusion plasmas’.
Turbulence and
E
×
B
flow correlations across the L-H transition in DIII-D deuterium and hydrogen plasmas
Authors: Schmitz Lothar
Published: January 2023

The isotope dependence of the low- to high confinement-mode (L- to H-mode) transition power threshold
P
LH
presents significant challenges for the initial (non-nuclear) hydrogen operations phase of the international thermonuclear experimental reactor (ITER). Here, we examine the isotope dependence of turbulence and

E 

× 

B

flow correlation properties in the L-mode edge plasma, leading up to the L-H transition. At marginal auxiliary power (near
P
LH
), turbulence is initially suppressed periodically during limit cycle oscillations (LCO) that precede the transition to sustained H-mode confinement. We present evidence that the long-range (toroidal) correlation of the

E 

× 

B

edge plasma flow across the LCO phase is much weaker in hydrogen than in deuterium in the DIII-D tokamak, congruent with the higher threshold power
P
LH
required to access LCO and H-mode in hydrogen. Concomitantly, the time required to initially quench edge turbulence via localized edge

E 

× 

B

flow shear is significantly longer in hydrogen (1–1.5 ms) than in deuterium (approx. 100 µs). No toroidal long-range correlation of the turbulence amplitude is observed, in agreement with expectations based on the relatively short poloidal turbulence correlation length. Radial edge turbulence and flow correlation lengths are longer in deuterium than in hydrogen plasmas as one would expect from ‘naïve’ gyro-Bohm isotope transport scaling, despite the substantially higher thermal flux across the last closed flux surface in hydrogen before the L-H transition.

This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.
An overview of dynamical methods for studying transitions between states in sheared plasma flows
Authors: Teaca Bogdan , Pringle Christopher C. T. , Smith Oliver J. , McMillan Ben F.
Published: January 2023

The self-organization of structures in a tokamak plasma as it undergoes an

H

-mode transition shows properties similar to simpler shear flow configurations. We will describe recent dynamical studies of plasma shear flows, including the idea of tracking the edge of chaos that separates two bistable states, computing the nonlinear minimal seed that can lead to turbulence, finding the attractor solution on the edge and seeing how starting from this solution we can understand the stability of relative period orbits that permeate the turbulent basin of attraction. We present a modus operandi developed for these simple configurations that can be adapted to understand the

H

-mode transition.

This article is part of a discussion meeting issue ‘H-mode transition and pedestal studies in fusion plasmas’.
Bifurcation behaviour of resonant magnetic perturbation control of edge localized modes in tokamaks: nonlinear simulation results
Authors: Thyagaraja Anantanarayanan , Sen Abhijit , Chandra Debasis
Published: January 2023

In this article, some novel results of two fluid nonlinear simulations on the control of edge localized modes (ELMs) in tokamaks by resonant magnetic perturbations (RMPs) are presented. Many experiments around the world have demonstrated that RMPs are effective in possibly mitigating or even completely suppressing strong (type I) ELMs that would seriously degrade confinement and could cause other heat-flux problems in both present (e.g. JET) and planned future tokamaks (ITER). Our simulations demonstrate that non-axisymmetric RMPs with toroidal mode numbers

n
=
2
,
3
,
4

and suitable field-strengths (kAturns) at the plasma wall imply significant bifurcations in their ability to mitigate or even suppress type-I ELMs, qualitatively similar to RMP effects on ELMs reported in experiments.

This article is part of a discussion meeting issue ‘H-mode transition and pedestal studies in fusion plasmas’.
Genetic Divergence Analysis among Sesame (Sesamum IndicumL.) Accessions in Middle Awash, Ethiopia
Authors: Gimbichu Mesay Tadesse , Gurmu Gudeta Nepir , Ayana Negash Geleta
Published: January 2023

This research was conducted to assess genetic distance, extent, and pattern of diversity among sesame accessions. A total of 64 sesame Accessions were evaluated in an 8 x 8 lattice design with two replications in 2021 at Werer Agricultural Research Center. Analysis of variance revealed that there was a statistically significant difference among the accessions for all traits except for 50% days to emergence and the number of seeds per pod. Principal components analysis showed the first five PCAs viz. PC1 (21.9%), PC2 (11.00%), PC3 (15.6%), PC4 (18.3%), and PC5 (9.5) with a total contribution of 76.3% variation. The dendrogram was constructed using the Unweighted Pair-group Method with Arithmetic Means to separate Accessions into five distinct clusters. Sesame accessions with high seed yield and high mean values for other desirable traits were grouped into Cluster I Cluster V. Cluster IV and Cluster V had the highest inter-cluster distance. Accession in Cluster V (Acc.241297) could be crossed with other clusters to come up with promising segregation for further improvement programs.
Design and fabrication of a low-cost microfluidic cartridge with integrated pressure-driven check valve for molecular diagnostics platforms
Authors: Downen R. Scott , Dong Quan , Chen Julius Lee , Li Zhenyu
Published: January 2023

This paper describes the design, fabrication, and preliminary testing of a low-cost, easy to manufacture microfluidics cartridge capable of fluid storage and manipulation through a custom pressure-driven check valve. Cartridge components are fabricated using a desktop CNC and laser cutter, the check valve is fabricated using PDMS in a custom acrylic mold, and the components are assembled using a thermal diffusion welder. Following assembly, preliminary testing of the cartridge, including fluid manipulation and use for molecular diagnostics, was performed. To pull a sample into the lysing chamber, a vacuum over 1.4PSI was required. No opening of the valve to the reaction chamber was observed. Moving fluid across the custom valve from the lysing chamber to the reaction chamber then required a vacuum over 4.5PSI. Finally, a proof-of-concept demonstration of one potential application was performed using a custom benchtop LAMP system for molecular diagnostic testing. The low-cost nature of the design, ease of manufacturing, fluid storage and manipulation demonstrated make this design ideal for research and high-volume testing in low resource environments.

Abstract Figure

Graphical abstract

Custom cartridge is fabricated using a combination of a) benchtop laser cutter and b) benchtop micromilling machine. c) Components are then assembled with a 0.22µm micron filter and custom plug-style check valve. d) The cartridge assembly is then bonded using a thermal diffusion bonder. e) By pulling a vacuum through the first air trap, a sample can be pulled into the pre-filled lysing chamber. f) Pulling a vacuum through the second air trap, the lysed sample can then be pulled into the pre-filled reaction chamber. g) For a proof of concept, the filled cartridge was then tested in a custom benchtop Loop Mediated Isothermal System. Following a heating cycle, reaction fluoresce can be monitored. h) An S-Curve observed through the custom LAMP system, thus demonstrating feasibility of the cartridge for use with molecular diagnostic platforms.
Analysis of the genome-scale metabolic model ofBacillus subtilisto design novel in-silico strategies for native and recombinant L-asparaginase overproduction
Authors: Barge Nisha Sanjay , Sahoo Ansuman , Dasu Veeranki Venkata
Published: January 2023

L-asparaginase is an enzyme with widescale use in the food and medicine industry. It is used as a chemotherapeutic drug in the treatment of acute lymphoblastic leukemia. Limitations of side effects associated with commercially available L-asparaginase necessitate the search for alternative sources.Bacillus subtilisis an emerging host for the production of chemicals and therapeutic products. This study deals with L-asparaginase production inBacillus subtilisusing systems metabolic engineering approach. System biology offers a detailed understanding of organism metabolism at the network level unlike the conventional molecular approach of metabolic engineering allowing one to study the effects of metabolite production on growth. Metabolism ofBacillus subtilisis studied using genome-scale metabolic model iYO844 which consists of relationships between the genes and proteins present inBacillus subtilis. Also, the model contains information about all the metabolic reactions and pathways allowing convenient metabolic engineering methods. Computational methods like flux balance analysis, flux variability analysis, robustness analysis, etc. are carried out to study the metabolic capabilities ofBacillus subtilis. The model predicted a specific growth rate of 0.6242 h-1, which was comparable to the experimental value. Further, the model is used to simulate recombinant L-asparaginase production generating a maximum production rate of 0.4028 mmol gDW-1h-1. Flux scanning based on enforced objective flux and OptKnock design strategies are used for strain development ofBacillus subtilisfor higher production of both native and recombinant L-asparaginase.
An engineered ACE2 decoy broadly neutralizes Omicron subvariants and shows therapeutic effect in SARS-CoV-2-infected cynomolgus macaques
Authors: Urano Emiko , Itoh Yumi , Suzuki Tatsuya , Sasaki Takanori , Kishikawa Jun-ichi , Akamatsu Kanako , Higuchi Yusuke , Sakai Yusuke , Okamura Tomotaka , Mitoma Shuya , Sugihara Fuminori , Takada Akira , Kimura Mari , Hirose Mika , Sasaki Tadahiro , Koketsu Ritsuko , Tsuji Shunya , Yanagida Shota , Shioda Tatsuo , Hara Eiji , Matoba Satoaki , Matsuura Yoshiharu , Kanda Yasunari , Arase Hisashi , Okada Masato , Takagi Junichi , Kato Takayuki , Hoshino Atsushi , Yasutomi Yasuhiro , Saito Akatsuki , Okamoto Toru
Published: January 2023

The Omicron variant continuously evolves under the humoral immune pressure obtained by vaccination and SARS-CoV-2 infection and the resultant Omicron subvariants exhibit further immune evasion and antibody escape. Engineered ACE2 decoy composed of high-affinity ACE2 and IgG1 Fc domain is an alternative modality to neutralize SARS-CoV-2 and we previously reported its broad spectrum and therapeutic potential in rodent models. Here, we show that engineered ACE2 decoy retains the neutralization activity against Omicron subvariants including the currently emerging XBB and BQ.1 which completely evade antibodies in clinical use. The culture of SARS-CoV-2 under suboptimal concentration of neutralizing drugs generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against engineered ACE2 decoy. As the efficient drug delivery to respiratory tract infection of SARS-CoV-2, inhalation of aerosolized decoy treated mice infected with SARS-CoV-2 at a 20-fold lower dose than the intravenous administration. Finally, engineered ACE2 decoy exhibited the therapeutic efficacy for COVID-19 in cynomolgus macaques. Collectively, these results indicate that engineered ACE2 decoy is the promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation can be considered as a non-invasive approach to enhance efficacy in the treatment of COVID-19.
Femtomolar-level PCR-free quantification of microRNA cancer biomarkers in serum
Authors: Kanavarioti Anastassia
Published: January 2023

We developed a technology to measure microRNA (miRNA) copies in serum and tested it on a commercially available combined human serum (H6914 from Sigma-Aldrich). Copies of miR-15b and miR-16, believed to be constant among healthy and diseased individuals, were measured and agreed with the ones reported by Mitchell PS et al. (2008). Cancer biomarkers let7-b, miR-21, miR-141 and miR-375 varied 3,000 to 6,000 copies per 1 microLiter H6914 (5-10 femtomolar (fM)). Detection and quantification of oligos and miRNAs at such low concentration was shown earlier. It is accomplished by repurposing the commercial MinION nanopore platform to conduct single-molecule voltage-driven ion-channel measurements, employing osmium-tagged oligo probes, and using a publicly available algorithm. These miRNAs were quantified in the serum of healthy individuals or cancer patients using novel optimized probes and a detailed protocol that delivers miRNA copies with better than 85% confidence across all concentrations. A linear correlation, the same with healthy and cancer serum samples, is observed between miR-15b copies and RNA concentration in serum. The assay’s simplicity, readiness, sensitivity, and precision advocate for its use as a Laboratory Developed Test (LDT) for disease-screening based on miRNA dysregulation.