bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Implementation Playbook: study protocol for the development and feasibility evaluation of a digital tool for effective implementation of evidence-based innovations
Authors: Barwick Melanie , Brown Jacquie , Petricca Kadia , Stevens Bonnie , Powell Byron J. , Jaouich Alexia , Shakespeare Jill , Seto Emily 
Published: March 2023

AbstractBackgroundEvidence-based innovations can improve health outcomes, but only if successfully implemented. Implementation can be complex, highly susceptible to failure, costly and resource intensive. Internationally, there is an urgent need to improve the implementation of effective innovations. Successful implementation is best guided by implementation science, but organizations lack implementation know-how and have difficulty applying it. Implementation support is typically shared in static, non-interactive, overly academic guides and is rarely evaluated. In-person implementation facilitation is often soft-funded, costly, and scarce. This study seeks to improve effective implementation by (1) developing a first-in-kind digital tool to guide pragmatic, empirically based and self-directed implementation planning in real-time; and (2) exploring the tool’s feasibility in six health organizations implementing different innovations.MethodsIdeation emerged from a paper-based resource, The Implementation Game©, and a revision called The Implementation Roadmap©; both integrate core implementation components from evidence, models and frameworks to guide structured, explicit, and pragmatic planning. Prior funding also generated user personas and high-level product requirements. This study will design, develop, and evaluate the feasibility of a digital tool called The Implementation Playbook©. In Phase 1, user-centred design and usability testing will inform tool content, visual interface, and functions to produce a minimum viable product. Phase 2 will explore the Playbook’s feasibility in six purposefully selected health organizations sampled for maximum variation. Organizations will use the Playbook for up to 24 months to implement an innovation of their choosing. Mixed methods will gather: (i) field notes from implementation team check-in meetings; (ii) interviews with implementation teams about their experience using the tool; (iii) user free-form content entered into the tool as teams work through implementation planning; (iv) Organizational Readiness for Implementing Change questionnaire; (v) System Usability Scale; and (vi) tool metrics on how users progressed through activities and the time required to do so.DiscussionEffective implementation of evidence-based innovations is essential for optimal health. We seek to develop a prototype digital tool and demonstrate its feasibility and usefulness across organizations implementing different innovations. This technology could fill a significant need globally, be highly scalable, and potentially valid for diverse organizations implementing various innovations.
MANIFEST: Pelabresib in Combination With Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Myelofibrosis
Authors: Mascarenhas John , Kremyanskaya Marina , Patriarca Andrea , Palandri Francesca , Devos Timothy , Passamonti Francesco , Rampal Raajit K. , Mead Adam J. , Hobbs Gabriella , Scandura Joseph M. , Talpaz Moshe , Granacher Nikki , Somervaille Tim C. P. , Hoffman Ronald , Wondergem Marielle J. , Salama Mohamed E. , Colak Gozde , Cui Jike , Kiladjian Jean-Jacques , Vannucchi Alessandro M. , Verstovsek Srdan , Curto-García Natalia , Harrison Claire , Gupta Vikas 
Published: March 2023

PURPOSE Standard therapy for myelofibrosis comprises Janus kinase inhibitors (JAKis), yet spleen response rates of 30%-40%, high discontinuation rates, and a lack of disease modification highlight an unmet need. Pelabresib (CPI-0610) is an investigational, selective oral bromodomain and extraterminal domain inhibitor (BETi). METHODS MANIFEST (ClinicalTrails.gov identifier: NCT02158858 ), a global, open-label, nonrandomized, multicohort, phase II study, includes a cohort of JAKi-naïve patients with myelofibrosis treated with pelabresib and ruxolitinib. The primary end point is a spleen volume reduction of ≥ 35% (SVR35) at 24 weeks. RESULTS Eighty-four patients received ≥ 1 dose of pelabresib and ruxolitinib. The median age was 68 (range, 37-85) years; 24% of patients were intermediate-1 risk, 61% were intermediate-2 risk, and 16% were high risk as per the Dynamic International Prognostic Scoring System; 66% (55 of 84) of patients had a hemoglobin level of < 10 g/dL at baseline. At 24 weeks, 68% (57 of 84) achieved SVR35, and 56% (46 of 82) achieved a total symptom score reduction of ≥ 50% (TSS50). Additional benefits at week 24 included 36% (29 of 84) of patients with improved hemoglobin levels (mean, 1.3 g/dL; median, 0.8 g/dL), 28% (16 of 57) with ≥ 1 grade improvement in fibrosis, and 29.5% (13 of 44) with > 25% reduction in JAK2V617F-mutant allele fraction, which was associated with SVR35 response ( P = .018, Fisher's exact test). At 48 weeks, 60% (47 of 79) of patients had SVR35 response. Grade 3 or 4 toxicities seen in ≥ 10% patients were thrombocytopenia (12%) and anemia (35%), leading to treatment discontinuation in three patients. 95% (80 of 84) of the study participants continued combination therapy beyond 24 weeks. CONCLUSION The rational combination of the BETi pelabresib and ruxolitinib in JAKi-naïve patients with myelofibrosis was well tolerated and showed durable improvements in spleen and symptom burden, with associated biomarker findings of potential disease-modifying activity.
Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease
Authors: Cobleigh Melody A. , Vogel Charles L. , Tripathy Debu , Robert Nicholas J. , Scholl Susy , Fehrenbacher Louis , Wolter Janet M. , Paton Virginia , Shak Steven , Lieberman Gracie , Slamon Dennis J. 
Published: March 2023

PURPOSE Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease. PATIENTS AND METHODS Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals. RESULTS Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events. CONCLUSION Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.
Higher-order shock wave structures and phase plane analysis in multicomponent dusty plasma
Authors: Kaur Rajneet , Slathia Geetika , Saini N. S. 
Published: March 2023

Abstract
In this investigation, dust acoustic (DA) shocks and dressed shocks formed due to the contribution of higher-order effects in a non-Maxwellian plasma have been examined. The reductive perturbation method is employed to derive the nonlinear Burgers and Burgers-type inhomogeneous equations with the contribution of higher-order effects of nonlinearity and dissipation. The properties of dust acoustic shocks and higher order (dressed shocks) are examined from the solutions of these nonlinear equations under the effect of various plasma parameters. Furthermore, the travelling wave analysis is used to obtain the dynamical system for the Burgers equation using bifurcation theory. The characteristic properties of DA periodic waves have also been analysed under the influence of various plasma parameters.
Evaluation of Stress Response in Middle-Aged Male Diabetic Hypertensive Patients
Authors: Alloqi Tahirbegolli Iliriana , Tahirbegolli Bernard , Şen Selçuk , Sayın Betül , Kaşkal Mert , Üresin Ali Yağız 
Published: March 2023

Abstract

Context
Stress triggers a cascade of reactions that alter the organism's dynamic steady state. There is a scarcity of interventional studies that show cortisol variability upon stress over time in groups of patients with chronic noncommunicable diseases and comorbidities.

Objective
We aimed to examine salivary cortisol changes in the cognitive stress response of patients with hypertension and diabetes mellitus (HT&DM) and patients with hypertension (HT) and to determine differences between them.

Methods
The study was conducted using a stress test of solving an arithmetic task in 62 patients with HT&DM and HT who were being treated in the outpatient clinic of the Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital.

Results
There was no statistically significant difference between the HT&DM and HT groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values (P = .331 and P = .058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, P &lt; .0001], SBP [F (2.185, 60) = 12.080, P &lt; .0001], DBP [F (2.793, 60) = 6.043, P = .001], and heart rate [F (2.073, 60) = 13.259, P &lt; .0001] were statistically significant for the main effect (time), while the effect of the group × time interaction factor was statistically not significant (P = .773; P = .751; P = .713 and P = .506, respectively).

Conclusion
The arithmetic problem-solving task used with the HT&DM and HT patients was useful as an acute stress test in the laboratory environment. There was no statistically significant difference for group × time interaction factor between the HT&DM and HT groups; however, the salivary cortisol and BP values increased significantly after acute stress within each group.
Ribosome biogenesis and function in development and disease
Authors: Ni Chunyang , Buszczak Michael 
Published: March 2023

ABSTRACT
Although differential transcription drives the development of multicellular organisms, the ultimate readout of a protein-coding gene is ribosome-dependent mRNA translation. Ribosomes were once thought of as uniform molecular machines, but emerging evidence indicates that the complexity and diversity of ribosome biogenesis and function should be given a fresh look in the context of development. This Review begins with a discussion of different developmental disorders that have been linked with perturbations in ribosome production and function. We then highlight recent studies that reveal how different cells and tissues exhibit variable levels of ribosome production and protein synthesis, and how changes in protein synthesis capacity can influence specific cell fate decisions. We finish by touching upon ribosome heterogeneity in stress responses and development. These discussions highlight the importance of considering both ribosome levels and functional specialization in the context of development and disease.
Low-Level Laser Therapy Facilitates Postcontraction Recovery with Ischemic Preconditioning
Authors: CHEN YI-CHING , LIN YEN-TING , HU CHIA-LING , HWANG ING-SHIOU 
Published: March 2023

ABSTRACT

Purpose
Despite early development of muscle fatigue, ischemic preconditioning is gaining popularity for strength training combined with low-load resistance exercise. This study investigated the effect of low-level laser (LLL) on postcontraction recovery with ischemic preconditioning.

Methods
Forty healthy adults (22.9 ± 3.5 yr) were allocated into sham (11 men, 9 women) and LLL (11 men, 9 women) groups. With ischemic preconditioning, they were trained with three bouts of intermittent wrist extension of 40% maximal voluntary contraction (MVC). During the recovery period, the LLL group received LLL (wavelength of 808 nm, 60 J) on the working muscle, whereas the sham group received no sham therapy. MVC, force fluctuations, and discharge variables of motor units (MU) for a trapezoidal contraction were compared between groups at baseline (T0), postcontraction (T1), and after-recovery (T2).

Results
At T2, the LLL group exhibited a higher normalized MVC (T2/T0; 86.22% ± 12.59%) than that of the sham group (71.70% ± 13.56%; P = 0.001). The LLL group had smaller normalized force fluctuations (LLL, 94.76% ± 21.95%; sham, 121.37% ± 29.02%; P = 0.002) with greater normalized electromyography amplitude (LLL, 94.33% ± 14.69%; sham, 73.57% ± 14.94%; P < 0.001) during trapezoidal contraction. In the LLL group, the smaller force fluctuations were associated with lower coefficients of variation of interspike intervals of MUs (LLL, 0.202 ± 0.053; sham, 0.208 ± 0.048; P = 0.004) with higher recruitment thresholds (LLL, 11.61 ± 12.68 %MVC; sham, 10.27 ± 12.73 %MVC; P = 0.003).

Conclusions
LLL expedites postcontraction recovery with ischemic preconditioning, manifesting as superior force generation capacity and force precision control for activation of MU with a higher recruitment threshold and lower discharge variability.
Reliability and Usefulness of the SKILLCOURT as a Computerized Agility and Motor–Cognitive Testing Tool
Authors: FRIEBE DAVID , HÜLSDÜNKER THORBEN , GIESCHE FLORIAN , BANZER WINFRIED , PFAB FLORIAN , HASER CHRISTIAN , VOGT LUTZ 
Published: March 2023

ABSTRACT

Introduction
Agility and cognitive skills are essential in sports. However, standardized agility assessment tools often lack a reactive component, and cognitive assessments are performed using computer-based or paper-pencil tests. The SKILLCOURT is a newly developed testing and training device allowing agility and cognitive assessments in a more ecologically valid setting. This study evaluated the reliability and sensitivity to changes in performance (usefulness) of the SKILLCOURT technology.

Methods
In a test–retest (7 d, 3 months) design, 27 healthy adults (♀ = 12; age, 24.9 ± 3.3 yr) performed three trials of agility (Star Run, Random Star Run) and motor–cognitive tests (1-back, 2-back, executive function). Absolute and relative intersession and intrasession reliability was determined using the intraclass coefficient (ICC) and coefficient of variation (CV). A repeated-measures ANOVA was applied to identify potential learning effects between trials and test sessions. The smallest worthwhile change and typical error (TE) were calculated to investigate the intrasession and intersession usefulness of the tests.

Results
Agility tests revealed good relative and absolute intersession (ICC, 83–0.89; CV, 2.7%–4.1%) and intrasession (ICC, 7–0.84; CV, 2.4%–5.5%) reliability accompanied by adequate usefulness from test day 3 onward. Motor–cognitive tests showed good relative intersession reliability (ICC, 0.7–0.77) with marginal CV values (4.8%–8.6%). Adequate intrasession reliability and usefulness can be assumed from test day 2 (1-back test, executive function test) and day 3 (2-back test) onward. For all tests, learning effects were observed within and compared with test day 1.

Conclusions
The SKILLCOURT is a reliable diagnostic tool for assessing reactive agility and motor–cognitive performance. Because of learning effects, sufficient familiarization with the tests is required when used for diagnostic purposes.
Evaluation of patient profiles, treatment paradigms and clinical efficacy, and safety outcomes in adult patients with vitamin D deficiency or insufficiency in India: A multicenter, prospective, non-interventional study
Authors: Tiwaskar Mangesh , Soratia Zubair , Karmakar Arnab , Patil Neelkanth , Bhardwaj Vikas , Sharma Rakesh , Majid Sarfaraz , Rao Akhila , Ranjit SDI 
Published: March 2023

Background: Nationwide studies assessing sociodemographic factors associated with poor vitamin D status and efficacy-safety of vitamin D supplementation in Indian clinical practice are limited. Methods: In this multicenter, prospective, non-interventional study, patients with vitamin D deficiency (25[OH]D <20 ng/mL)/insufficiency (25[OH]D 21-29 ng/mL) were enrolled at 9 sites across India and prescribed vitamin D supplements per routine practice. Primary endpoints were patient profiles associated with vitamin D deficiency/insufficiency and change in visual analog scale (VAS) scores for clinical signs/symptoms from baseline to weeks 4 and 8. Key secondary endpoints were prescription pattern of vitamin D supplements and incidence of adverse drug reactions (ADRs)/serious ADRs. Change in systolic/diastolic blood pressure (SBP/DBP [hypertensive patients]) and glycated hemoglobin (HbA1c [diabetic patients]) were assessed from baseline to weeks 8 and 12, respectively. Paired t test was used to assess statistical significance, except for patient profile association, where analysis of variance model was used. Results: Of 201 enrolled patients (mean [standard deviation] age: 43.4 [14.52] years), 61.7% were women. Most demographic and anthropometric factors, except for current sunscreen use (p=0.0297) and socioeconomic status (p=0.0222), were not significantly associated with vitamin D deficiency/insufficiency. Upper-lower class had significantly higher odds (p=0.033) for vitamin D deficiency versus insufficiency versus lower class. Most of the patients were prescribed 60000 IU/week orally. VAS scores for bone and lower back pain, bone loss, low bone mineral density, and muscle pain were significantly reduced at weeks 4 and 8 (p<0.001). SBP/DBP of hypertensive patients and HbA1c of diabetic patients were also significantly decreased (p<0.05). No ADRs/serious ADRs were observed. Conclusion: Sunscreen use and socioeconomic status were significantly associated with vitamin D deficiency/insufficiency. Vitamin D supplementation improved clinical symptoms, HbA1c levels (diabetic patients), and SBP/DBP (hypertensive patients), without any adverse safety outcomes. Nevertheless, studies with long-term follow-up and larger sample sizes are warranted.
Case Report: A Rare Case of Eosinophilic Ureteritis in a Woman with Reccuring Bilateral Ureteric Strictures causing Hydroureteronephrosis
Authors: Matondang Sahat Basana Romanti Ezer , Imam Adistra , Darmawan Guntur , Achmadsyah Armand , Hilmy Ibrahim Abubakar , Harsanto Andrian , Sumardi Rochani 
Published: March 2023

Introduction: Eosinophilic ureteritis is a very rare etiology of ureteric obstruction that leads to hydroureteronephrosis. We have only so far discovered a few case reports discussing eosinophilic ureteritis and the exact cause of this condition is poorly understood. Clinical findings: we report a very interesting case of a 71-year-old patient presenting with general weakness and oliguria, computed tomography (CT) scan found bilateral hydroureteronephrosis caused by recurring ureteric strictures. Diagnosis, interventions, and outcomes: ureterorenoscopy (URS) to extract a specimen for biopsy and laser fulguration to relieve ureteral strictures was performed. Double-J (DJ) stents were inserted both in the left and right ureters to overcome the ureteric strictures. Microscopy of the excised specimen revealed dominant eosinophilic infiltration. Therefore, diagnosis of eosinophilic ureteritis was made. In addition to stenting, Meropenem and Mirabegron was given to the patient. After a week of observation, the patient made a full recovery with no signs of initial symptoms. Conclusion: It is important to consider eosinophilic ureteritis in the differential diagnosis of any ureteric stricture because it is a highly uncommon entity with variable clinical characteristics. The gold standard procedure, which should be utilized to make the diagnosis, is a histological examination.
Amodiaquine drug pressure selects nonsynonymous mutations in pantothenate kinase 1, diacylglycerol kinase, and phosphatidylinositol-4 kinase in Plasmodium berghei ANKA
Authors: Chepngetich Jean , Muriithi Brenda , Gachie Beatrice , Thiong'o Kevin , Jepkorir Mercy , Gathirwa Jeremiah , Kimani Francis , Mwitari Peter , Kiboi Daniel 
Published: March 2023

Background: Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of malaria treatment in Africa. Studies have shown that PQ, AQ, and LM resistance may arise independently of predicted modes of action. Protein kinases have emerged as mediators of drug action and efficacy in malaria parasites; however, the link between top druggable Plasmodium kinases with LM, PQ, and AQ resistance remains unclear. Using LM, PQ, or AQ-resistant Plasmodium berghei parasites, we have evaluated the association of choline kinase (CK), pantothenate kinase 1 (PANK1), diacylglycerol kinase (DAGK), and phosphatidylinositol-4 kinase (PI4Kβ), and calcium-dependent protein kinase 1 (CDPK1) with LM, PQ, and AQ resistance in Plasmodium berghei ANKA. Methods: We used in silico bioinformatics tools to identify ligand-binding motifs, active sites, and sequence conservation across the different parasites. We then used PCR and sequencing analysis to probe for single nucleotide polymorphisms (SNPs) within the predicted functional motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1. Using qPCR analysis, we finally measured the mRNA amount of PANK1, DAGK, and PI4Kβ at trophozoites and schizonts stages. Results: We reveal sequence conservation and unique ligand-binding motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1 across malaria species. DAGK, PANK1, and PI4Kβ possessed nonsynonymous mutations; surprisingly, the mutations only occurred in the AQr parasites. PANK1 acquired Asn394His, while DAGK contained K270R and K292R mutations. PI4Kβ had Asp366Asn, Ser1367Arg, Tyr1394Asn and Asp1423Asn. We show downregulation of PANK1, DAGK, and PI4Kβ in the trophozoites but upregulation at the schizonts stages in the AQr parasites. Conclusions: The selective acquisition of the mutations and the differential gene expression in AQ-resistant parasites may signify proteins under AQ pressure. The role of the mutations in the resistant parasites and the impact on drug responses require further investigations in malaria parasites.