bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of an Algorithm for Autonomous, Closed-Loop Neuromodulation During Motor Rehabilitation
Authors: Epperson Joseph D. , Meyers Eric C. , Pruitt David T. , Wright Joel M. , Hudson Rachael A. , Adehunoluwa Emmanuel A. , Nguyen-Duong Y-Nhy , Rennaker Robert L. , Hays Seth A. , Kilgard Michael P. 
Published: May 2024

Background Recent evidence demonstrates that manually triggered vagus nerve stimulation (VNS) combined with rehabilitation leads to increased recovery of upper limb motor function after stroke. This approach is premised on studies demonstrating that the timing of stimulation relative to movements is a key determinant in the effectiveness of this approach. Objective The overall goal of the study was to identify an algorithm that could be used to automatically trigger VNS on the best movements during rehabilitative exercises while maintaining a desired interval between stimulations to reduce the burden of manual stimulation triggering. Methods To develop the algorithm, we analyzed movement data collected from patients with a history of neurological injury. We applied 3 different algorithms to the signal, analyzed their triggering choices, and then validated the best algorithm by comparing triggering choices to those selected by a therapist delivering VNS therapy. Results The dynamic algorithm triggered above the 95th percentile of maximum movement at a rate of 5.09 (interquartile range [IQR] = 0.74) triggers per minute. The periodic algorithm produces stimulation at set intervals but low movement selectivity (34.05%, IQR = 7.47), while the static threshold algorithm produces long interstimulus intervals (27.16 ± 2.01 seconds) with selectivity of 64.49% (IQR = 25.38). On average, the dynamic algorithm selects movements that are 54 ± 3% larger than therapist-selected movements. Conclusions This study shows that a dynamic algorithm is an effective strategy to trigger VNS during the best movements at a reliable triggering rate.
Collaborative Study of Thresholds for Mutagens: Adaptive Responses in the Micronucleus Test and Gene Induction by Mutagenic Treatments
Authors: Sutou Shizuyo , Koeda Akiko , Komatsu Kana , Shiragiku Toshiyuki , Seki Hiroshi , Kudo Toshiyuki ,   The Collaborative Study Group of Thresholds for Mutagens
Published: May 2024

Background We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint. Methods The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells. Results When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45 A and P21, were induced in a dose- and time-dependent manner. Conclusion Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.
The relationships among trait mindfulness, obsessive passion, and emotions in high school sport managers
Authors: Lee Ye Hoon , Cho Heetae 
Published: May 2024

Purpose Mindfulness emerges as a possible means to alleviate obsessive passion. Nevertheless, its application in sport leadership context remains understudied, despite the significant levels of stress and turnover that are common in this profession. This study aims to investigate the relationships among trait mindfulness, obsessive passion, and specific positive (e.g., happiness), neutral (e.g., calmness), and negative (e.g., anger) emotions in high school sport managers. Method In total, 358 high school sport managers ( Mage = 48.47, SD = 8.93) working in 46 states in the United States completed the online questionnaires measuring the proposed variables. Descriptive statistics, correlation analysis, confirmatory factor analysis, and structural equation modeling were utilized to examine the hypotheses. Result The results showed that trait mindfulness negatively predicted obsessive passion. Additionally, obsessive passion negatively predicted the feelings of happiness and calmness, while it positively predicted anger. The mediation analysis revealed that obsessive passion fully mediated the relationships between trait mindfulness and the three types of emotion. Conclusion These findings are significant because they demonstrate the buffering role of trait mindfulness in obsessive passion. Furthermore, the study provides meaningful insights into sport managers’ emotional experiences, particularly by empirically examining the effect of obsessive passion on different emotions.
Novel use of structural equation modeling to examine the development of a framework of patient-centered two-way referral systems for building digital subjective well-being healthcare: A cross-sectional survey in Central China
Authors: Wen Xintong , Song Qingyuan , OuYang Shuang , Yao Zhiwei , Luo Ying 
Published: May 2024

Background Digital health technologies are progressively assuming significant roles in aspects encompassing in-hospital management, patient-centered design, and tiered referral systems. Nevertheless, current studies do not involve exploration into the potential value and mechanisms of digital health in a patient-centered context. This study aimed to explore the development of a framework of comprehensive, evidence-based digital health technologies for the construction of welfare-oriented healthcare. Methods From March to June 2023, a cross-sectional online study was performed, involving 335 respondents with prior referral experiences hailing from the Central China region. Data on welfare-oriented healthcare factors (clinical pathway management, medical structure configuration, healthcare service accessibility, two-way referrals) underwent factor analysis in advance, and correlation between these factors and their association with two-way referrals was evaluated by testing for direct and indirect (mediating) effects. Results Firstly, there existed a significant positive correlation between integrative medical indicators and welfare-centered healthcare ( β = 0.02–0.16, p < 0.05). Furthermore, two-way referral had an direct association with integrative medical parameters and the welfare healthcare service system ( β = 0.15–0.31, p < 0.05), but exerted a partial mediatory function in the welfare healthcare service system ( β = 0.005–0.021, α < 0.05). Two-way referrals partially mediate the integrated medical indicators, mainly through direct effects, while also providing complementary support. Clinical pathways, medical structure, and accessibility are closely linked to welfare healthcare and significantly influence healthcare quality. Thus, improving these factors should be prioritized. Conclusion This study proposes a method combining integrated evaluation indicators with pathway mechanism design. This pathway mechanism design includes key steps such as patient registration, information extraction, hospital allocation or referral, diagnosis and treatment, rehabilitation plan monitoring, service feedback, and demand resolution. This design aims to change patients’ intentions in seeking healthcare, thereby increasing their acceptance of bidirectional referrals, and ultimately enhancing the effectiveness and realization of welfare healthcare.
Quality Improvement and Patient Safety Education in Postgraduate Training Program—A Survey of Residents in Saudi Arabia
Authors: Al-Najmi Yahya , Assiri Mousa , Aynusah Muntasir , Alqasmi Ibrahim 
Published: May 2024

OBJECTIVE To review the senior resident health trainee's perceived status and need for quality improvement and patient safety (QIPS) education in the residency training program of Saudi Arabia. METHODS Residents of medical, dentistry, and pharmacy education were surveyed in 2023 by using pretested 10 QIPS questions. The median and interquartile range (IQR) of the score was correlated to gender, branch, and level of residency training. RESULTS We surveyed 202 senior residents. Males were 131 (64.9%). Residents of medical (126, 62.4%), dentistry (39, 19.3%), and pharmacy (37, 18.3%). The median score of responses to the QIPS survey was 7.0 (IQR 4.0, 11.6). The median score of residents of dentistry, medicine, and pharmacy were 10 (IQR 7.0, 12.5), 6.75 (IQR 4.0, 12.0), and 5.0 (IQR 2.5, 8.0) respectively, and was significantly different (Kruskal Wallis (KW) chi-square = 19.8, P = .001). The exposure to the QIPS project was significantly and positively associated with a high QIPS score (MW U P = .02). The variations in the score by gender (Mann Whitney P = .148) and the level of residency (KW P = .86) were not statistically significant. Three-fourths of participants feel the need for formal training about QIPS. Nearly half of the participants were not happy with the current method of QIPS training methodology. More than 40% of participants were not sure about questions about opportunities and mentorship of QIPS projects. One-third were involved in QIPS projects. CONCLUSIONS Although senior residents were interested in QIPS, they were dissatisfied with current methods and opportunities to execute supervised QIPS projects. Residents of dentistry and those having performed QIPS projects had higher QPIS knowledge and satisfaction with training.
The Outcomes of Isolated Tibiocalcaneal Arthrodesis: A Systematic Review
Authors: Cossins Charlotte , George Ben , Talia Adrian J. , Loizou Constantinos , Kendal Adrian 
Published: May 2024

Background: Tibiocalcaneal arthrodesis (TCA) can be achieved by internal fixation (intramedullary nail or plate), external fixation, or a combination. Evidence for the optimal approach is limited. This systematic review examines the outcomes of these different approaches to guide surgical management. Methods: A MEDLINE and Oxford SOLO search was performed using “tibiocalcaneal,” “ankle,” “fusion OR arthrodesis.” The primary outcome was union. Secondary outcomes included rates of postoperative complications, weightbearing status, rates of revision surgery, and PROMs. We included any studies with follow-up greater than 6 months that contained our primary outcome and at least 1 secondary outcome. Results: The initial search yielded 164 articles, of which 9 studies totaling 53 cases met the criteria. The majority of articles were excluded because they were nonsurgical studies, or were not about isolated TCA but were for tibiotalocalcaneal arthrodesis, more complex reconstructions (eg, Charcot), case reports, and/or did not include the predetermined outcome measures. TCA union rate was 86.2% following external fixation, 82.4% for intramedullary nail fixation, and 83.3% for plate fixation. One patient underwent a hybrid of external and internal fixation, and the outcome was nonunion. The rate of complications following TCA was 69.8%. Conclusion: There is limited evidence on the best operative approach for isolated tibiocalcaneal arthrodesis. Both external and internal fixation methods had comparable union rates. External fixation had frequent complications and a more challenging postoperative protocol. Novel techniques such as 3D-printed cages and talus replacement may become a promising alternative but require further investigation.
Patients’ Preferences Regarding Modes of Systemic Psoriasis Treatment – A Qualitative Study
Authors: Zaino Mallory , Parks Emily , McNeil Jasmine , Feldman Steven 
Published: May 2024

Background Treatment with pathogenesis-directed biologics and oral systemic drugs have made complete clearance of psoriasis a realistic expectation for many patients with psoriasis. Patients’ preferences among these treatments varies. Objective To understand factors impacting psoriasis patients’preferences for injection vs oral medication. Methods Psoriasis patients who receive systemic psoriasis treatment were asked to participate in a semi-structured interview. Sample size was based on achieving saturation with equal number of patients preferring oral vs injectable medications to ensure equal representation of both groups. Qualitative analysis was performed to interpret the results. Results Twenty-two patients participated in the study, 12 males and 10 females. Ten patients were receiving oral medication (apremilast or methotrexate) and 12 patients were receiving injectables (guselkumab, adalimumab, risankizumab, secukinumab, ixekizumab, or tildrakizumab) due to self-reported preference. Five themes resulted from the analysis: patients receiving injectables more frequently discussed the positive impact of the medication on quality of life compared to patients on oral medication; fear of side effects, particularly fear of immunosuppression, is associated with injection medications; avoidance of needles drives patients away from injection medication and towards oral systemic medication; patients prioritize convenience when selecting systemic therapy, though the definition of convenience is subject to perception; and patients value the medication recommendation of the physician, regardless of the route of administration. Conclusion Improving medication adherence and disease outcomes through individualized treatment plans, with an emphasis on patients’ preferences using a shared decision-making approach, may be helpful.
Open Approach for Repair of Tibial PCL Avulsion
Authors: Newcomb Nicholas , Curtis William , Kurnik Christopher , Wharton Matthew , Treme Gehron , Shultz Christopher 
Published: May 2024

Background: Tibial avulsion of the posterior cruciate ligament (PCL) often requires operative fixation, which frequently results in successful outcomes if identified acutely. Open or arthroscopic techniques are most commonly used. Indications: Primary surgical indications for open fixation include acute tibial avulsion of the PCL. Secondary indications include grade 2 to grade 3 posterior drawer test and radiographic posterior subluxation of the tibia. Ideally, the joint space and articular cartilage should be well preserved. Technique Description: In the simplified approach initially described by Burks and Schaffer, the patient is placed prone, and an inverted L-shaped incision is made over the posteromedial corner of the knee. A plane is developed between the medial head of the gastrocnemius and the semimembranosus down to the knee joint capsule. The gastrocnemius is retracted laterally to protect neurovascular structures and a vertical capsulotomy is performed. The tibial attachment of the PCL is reduced and held with K (Kirschner) wires and then fixated with screw and washer. Results: Six months post operation, our patient achieved full active and passive range of motion with a stable posterior drawer test. He returned to work without difficulty. Multiple studies have shown success with open PCL fixation and decreased rates of arthrofibrosis when compared with arthroscopic approach. In this case, the patient did not develop arthrofibrosis. Discussion/Conclusion: PCL tibial avulsions can be safely treated with an open approach. Contrary to other ligaments that favor reconstruction over repair, PCL avulsions may be better treated with early repair, so it is important to avoid delay in intervention. The most common complication in both open and arthroscopic approaches is arthrofibrosis, which is less common in the open approach. Early range of motion is encouraged to prevent arthrofibrosis. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Mass spectrometry–based assessment of M protein in peripheral blood during maintenance therapy in multiple myeloma
Authors: Kubicki Tadeusz , Dytfeld Dominik , Barnidge David , Sakrikar Dhananjay , Przybyłowicz-Chalecka Anna , Jamroziak Krzysztof , Robak Paweł , Czyż Jarosław , Tyczyńska Agata , Druzd-Sitek Agnieszka , Giannopoulos Krzysztof , Wróbel Tomasz , Nowicki Adam , Szczepaniak Tomasz , Łojko-Dankowska Anna , Matuszak Magdalena , Gil Lidia , Puła Bartosz , Szukalski Łukasz , Końska Agnieszka , Zaucha Jan Maciej , Walewski Jan , Mikulski Damian , Czabak Olga , Robak Tadeusz , Jiang Ken , Cooperrider Jennifer H. , Jakubowiak Andrzej J. , Derman Benjamin A. 
Published: May 2024

Abstract
Mass spectrometry (MS) can detect multiple myeloma–derived monoclonal proteins in the peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during posttransplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of posttransplant maintenance with either carfilzomib, lenalidomide, and dexamethasone, or with lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in the PB in the posttransplant setting, despite unavailability of pretreatment calibration samples. There was high agreement between MRD by MS in the PB and paired bone marrow (BM) MRD results at the 10–5 threshold, assessed by either next-generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which, in landmark analysis, reached statistical significance after 18 cycles after transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared with MRD negativity by only 1 modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10–5 threshold. Overall, posttransplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293.
Blockage of BCL-XL overcomes venetoclax resistance across BCL2+ lymphoid malignancies irrespective of BIM status
Authors: Dolnikova Alexandra , Kazantsev Dmitry , Klanova Magdalena , Pokorna Eva , Sovilj Dana , Kelemen Cristina Daniela , Tuskova Liliana , Hoferkova Eva , Mraz Marek , Helman Karel , Curik Nikola , Machova Polakova Katerina , Andera Ladislav , Trneny Marek , Klener Pavel 
Published: May 2024

Abstract
Venetoclax (VEN), a B-cell lymphoma 2 (BCL2) inhibitor, has a promising single-agent activity in mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), and large BCLs, but remissions were generally short, which call for rational drug combinations. Using a panel of 21 lymphoma and leukemia cell lines and 28 primary samples, we demonstrated strong synergy between VEN and A1155463, a BCL-XL inhibitor. Immunoprecipitation experiments and studies on clones with knockout of expression or transgenic expression of BCL-XL confirmed its key role in mediating inherent and acquired VEN resistance. Of note, the VEN and A1155463 combination was synthetically lethal even in the cell lines with lack of expression of the proapoptotic BCL2L11/BIM and in the derived clones with genetic knockout of BCL2L11/BIM. This is clinically important because BCL2L11/BIM deletion, downregulation, or sequestration results in VEN resistance. Immunoprecipitation experiments further suggested that the proapoptotic effector BAX belongs to principal mediators of the VEN and A1155463 mode of action in the BIM-deficient cells. Lastly, the efficacy of the new proapoptotic combination was confirmed in vivo on a panel of 9 patient–derived lymphoma xenografts models including MCL (n = 3), B-ALL (n = 2), T-ALL (n = 1), and diffuse large BCL (n = 3). Because continuous inhibition of BCL-XL causes thrombocytopenia, we proposed and tested an interrupted 4 days on/3 days off treatment regimen, which retained the desired antitumor synergy with manageable platelet toxicity. The proposed VEN and A1155463 combination represents an innovative chemotherapy-free regimen with significant preclinical activity across diverse BCL2+ hematologic malignancies irrespective of the BCL2L11/BIM status.
FTH1 overexpression using a dCasRx translation enhancement system protects the kidney from calcium oxalate crystal-induced injury
Authors: He Ziqi , Dong Caitao , Song Tianbao , Zhou Jiawei , Xu Tao , He Ruyuan , Li Sheng 
Published: May 2024

AbstractThe engineered clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein (Cas) system is currently widely applied in genetic editing and transcriptional regulation. The catalytically inactivated CasRx (dCasRx) has the ability to selectively focus on the mRNA coding region without disrupting transcription and translation, opening up new avenues for research on RNA modification and protein translation control. This research utilized dCasRx to create a translation-enhancement system for mammals called dCasRx-eIF4GI, which combined eukaryotic translation initiation factor 4G (eIF4GI) to boost translation levels of the target gene by recruiting ribosomes, without affecting mRNA levels, ultimately increasing translation levels of different endogenous proteins. Due to the small size of dCasRx, the dCasRx-eIF4GI translation enhancement system was integrated into a single viral vector, thus optimizing the delivery and transfection efficiency in subsequent applications. Previous studies reported that ferroptosis, mediated by calcium oxalate (CaOx) crystals, significantly promotes stone formation. In order to further validate its developmental potential, it was applied to a kidney stone model in vitro and in vivo. The manipulation of the ferroptosis regulatory gene FTH1 through single-guide RNA (sgRNA) resulted in a notable increase in FTH1 protein levels without affecting its mRNA levels. This ultimately prevented intracellular ferroptosis and protected against cell damage and renal impairment caused by CaOx crystals. Taken together, this study preliminarily validated the effectiveness and application prospects of the dCasRx-eIF4GI translation enhancement system in mammalian cell-based disease models, providing novel insights and a universal tool platform for protein translation research and future therapeutic approaches for nephrolithiasis.