bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telemedicine in Thai-otorhinolaryngology patients in COVID-19 situation; primary surveys
Authors: Koopirom Phoom , Wiriyaamornchai Pannapa , Santeerapharp Alena 
Published: December 2022

Introduction COVID-19 pandemic has put a strain on various aspects of hospital management due to high rates of infection and increased preventive measures around the world. Physicians and patients alike are susceptible to the ongoing virus causing concern leading to loss or postpone of follow up. Thailand has just start integration of digital solutions such as telemedicine which expected similar level of medical care and efficiency while reducing risk of exposure during the COVID-19 pandemic. Objective Evaluation the willingness to accept telemedicine in otorhinolaryngology patients during the peak COVID-19 outbreaks in our institution. Methods Collected data from all patients who had a schedule follow up for otorhinolaryngology department between the months of June to August, 2021 at out-patient Center. Results Total of 299 otorhinolaryngology patients included, 213 patients (71.2%) denied a virtual medical visit whereas 86 patients (28.8%) accepted. The obstructive sleep apnea (OSA) was the only group to have more acceptance of telemedicine, 79.5% than denying 20.5% with statistical significance ( p < 0.01). Age difference between the accepting and declining group also showed statistical significance, 48.5 years and 56 years respectively ( p < 0.01). Main Reasons for their decision, 48% of patients accepted due to experiencing clinical improvement and stability. The main reason for not accepting telemedicine was 80% of patients preferred a special otorhinolaryngologic examination on follow up. Conclusions This primary surveys among Thai otorhinolaryngology patients about telemedicine. The greater number of patients not interested in telemedicine due to requirement of otorhinolaryngologic examination. Which OSA follow-up patients have more attention in telemedicine.
14-day Holter monitoring for atrial fibrillation after ischemic stroke: The yield of guideline-recommended monitoring duration
Authors: Himmelreich Jelle CL , Lucassen Wim AM , Coutinho Jonathan M , Harskamp Ralf E , de Groot Joris R , CPM van Weert Henk 
Published: December 2022

Introduction: Current European Stroke Organisation (ESO) guidelines recommend >48 h of continuous electrocardiographic monitoring for atrial fibrillation (AF) in all patients with ischemic stroke or transient ischemic attack (TIA) with undetermined origin. We assessed the yield of the guideline-recommended monitoring for AF, as well as of extending monitoring up to 14 days. Patients and methods: We included consecutive patients with stroke/TIA without AF in an academic hospital in The Netherlands. We reported AF incidence and number needed to screen (NNS) in the overall sample after 48 h and 14 days of Holter monitoring. Results: Among 379 patients with median age 63 years (IQR 55–73), 58% male, Holter monitoring detected 10 cases of incident AF during a median of 13 (IQR 12–14) days of monitoring. Seven AF cases were detected within the first 48 hours (incidence 1.85%, 95% CI 0.74–3.81; NNS 54), and three additional AF cases were recorded among the 362 patients with >48 h of monitoring and without AF ⩽ 48 h (incidence 0.83%, 95% CI: 0.17–2.42; NNS 121). All AF cases were detected within the first 7 days of monitoring. Our sample was subject to sampling bias favoring inclusion of participants with low AF risk. Discussion: Strengths of this work were the broad inclusion criteria as recommended by ESO guidelines, and high Holter adherence among participants. The analysis was limited by inclusion of lower-risk cases and a relatively small sample size. Conclusion: In low-risk patients with recent stroke or TIA, ESO guideline-recommended screening for AF resulted in a low AF yield, with limited additional value of monitoring up to 14 days. Our results underline the need for a personalized approach in determining a patient’s optimum duration for post-stroke non-invasive ambulatory monitoring.
The Statistical Fragility of Platelet-Rich Plasma as Treatment for Plantar Fasciitis: A Systematic Review and Simulated Fragility Analysis
Authors: Gupta Arjun , Ortiz-Babilonia Carlos , Xu Amy L. , Rogers Davis , Vulcano Ettore , Aiyer Amiethab A. 
Published: December 2022

Background: Plantar fasciitis (PF) is the most common cause of heel pain and can be a source of extensive physical disability and financial burden. Platelet-rich plasma (PRP) offers a potentially definitive, regenerative treatment modality that, if effective, could change the current paradigm of PF care. However, randomized controlled trials (RCTs) on the clinical benefits of PRP for refractory PF offer inconsistent conclusions, potentially because of the broader limitations of using P value thresholds to declare statistical and clinical significance. In this study, we use the Continuous Fragility Index (CFI) and Quotient (CFQ) to appraise the statistical robustness of data from RCTs evaluating PRP for treatment of PF. Methods: RCTs comparing outcomes after PRP injection vs alternative treatment in patients with chronic PF were evaluated. Representative simulated data sets were generated for each reported outcome event using summary statistics. The CFI was determined by manipulating each data set until reversal of significance (α=0.05) was achieved. The corresponding CFQ was calculated by dividing the CFI by the sample size. Results: Of 259 studies screened, 20 studies (59 outcome events) were included in this analysis. From these simulations, the median CFI for all events was 9, suggesting that varying the treatment of 9 patients would be required to reverse trial significance. The corresponding CFQ was 0.177. Studies with reported P value <.05 were more statistically fragile (CFI=10, CFQ=0.122) than studies with reported P value >.05 (CFI=5, CFQ=0.179). Of 36 outcome events reporting lost to follow-up data, 10 events (27.8%) lost ≥9 patients. Conclusion: Our findings suggest that, on average, the statistical fragility of RCTs evaluating PRP for nonoperative PF therapy is at least comparable to that of the sports medicine literature. However, several included studies had concerningly low simulated fragility scores. Orthopaedic surgeons may benefit from preferentially relying on studies with higher CFI and CFQ values when evaluating the utility of PRP for chronic PF in their own clinical practice. Given the importance of RCT data in clinical decision making, fragility indices could help give context to the stability of statistical findings. Level of Evidence: Level I, systematic review.
Latissimus Dorsi Tendon Repair
Authors: Belk John W. , Bravman Jonathan T. , Frank Rachel M. , Seidl Adam J. , McCarty Eric C. 
Published: December 2022

Background: Latissimus dorsi tendon ruptures are rare injuries that can occur in overhead or throwing motions and are almost always sports related. Indications: Latissimus dorsi tendon ruptures are largely treated nonoperatively, although surgical repair is indicated for the young active patient looking to return to a high level of sport and for those with complete avulsion injuries or mid-substance tendon tears. Technique Description: Depending on the degree of tendon retraction, anteroinferior or posteroinferior axillary incision is made. After the tendon is mobilized, sutures are placed in a Krackow fashion through the bulk of the tendon, and the tendon footprint is prepared by gently decorticating the surface of the humerus, just anterior and inferior to the teres major insertion point. Two Arthrex Pec Buttons are then loaded into the superior and inferior limbs of the suture tape and 2 unicortical holes are drilled into the footprint of the insertion site. The superior button is placed first and then tensioned to allow the latissimus dorsi to be pulled to the bone. Next, the second button is placed, though this is not tensioned until later at the time of the biceps tenodesis. Finally, the procedure is visualized and well inspected to ensure appropriate location of the tendon and securing hardware. Results: After an appropriate rehabilitation protocol is followed for up to 6 months postoperatively, acute repair of a ruptured latissimus dorsi tendon allows for near to complete restoration of patient functionality and strength, with return to full activity possible within 6 to 8 months. Conclusion: Surgical repair of a ruptured latissimus dorsi tendon is effective in restoring upper extremity strength and functionality and is associated with high patient satisfaction. 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.
The OTUD1-Notch2-ICD axis orchestrates allogeneic T cell–mediated graft-versus-host disease
Authors: Cheng Qiao , Wang Dong , Lai Xiaoxuan , Liu Yin , Zuo Yibo , Zhang Wenli , Lei Lei , Chen Jia , Liu Hong , Wang Ying , Liu Haiyan , Zheng Hui , Wu Depei , Xu Yang 
Published: December 2022

Abstract
Disorders of the ubiquitin-proteasome system (UPS) are known to influence the incidence and mortality of various diseases. It remains largely unknown whether and how the UPS affects the onset and progression of acute graft-verus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study demonstrated that the deubiquitinase OTUD1 is an essential regulator of aGVHD. Activation of CD4+ T cells after allo-HSCT, elevated the protein levels of OTUD1, which in turn interacted with the Notch2-ICD (NICD) to cleave the ubiquitin of NICD at the K1770 site, thereby inducing NICD protein accumulations in T cells. OTUD1-driven NICD signaling promoted the differentiation and functions of Th1 and Th17 cells and amplified the cascade of aGVHD. Moreover, by screening a FDA-approved drugs library the study identified dapagliflozin as an inhibitor targeting the OTUD1/NICD axis. Dapagliflozin administration significantly prolonged the survival of aGVHD mice. This study characterized a previously unknown role of OTUD1 in T cell–mediated allogeneic responses and provided a promising therapeutic strategy to target OTUD1 for the alleviation of aGVHD.
Proximity proteomics identifies septins and PAK2 as decisive regulators of actomyosin-mediated expulsion of von Willebrand factor
Authors: El-Mansi Sammy , Robinson Christopher L. , Kostelnik Katja B. , McCormack Jessica J. , Mitchell Tom P. , Lobato-Márquez Damián , Rajeeve Vinothini , Cutillas Pedro , Cutler Daniel F. , Mostowy Serge , Nightingale Thomas D. 
Published: December 2022

AbstractIn response to tissue injury, within seconds the ultra-large glycoprotein von Willebrand factor (VWF) is released from endothelial storage organelles (Weibel−Palade bodies) into the lumen of the blood vasculature, where it leads to the recruitment of platelets. The marked size of VWF multimers represents an unprecedented burden on the secretory machinery of endothelial cells (ECs). ECs have evolved mechanisms to overcome this, most notably an actomyosin ring that forms, contracts, and squeezes out its unwieldy cargo. Inhibiting the formation or function of these structures represents a novel therapeutic target for thrombotic pathologies, although characterizing proteins associated with such a dynamic process has been challenging. We have combined APEX2 proximity labeling with an innovative dual loss-of-function screen to identify proteins associated with actomyosin ring function. We show that p21 activated kinase 2 (PAK2) recruits septin hetero-oligomers, a molecular interaction that forms a ring around exocytic sites. This cascade of events controls actomyosin ring function, aiding efficient exocytic release. Genetic or pharmacological inhibition of PAK2 or septins led to inefficient release of VWF and a failure to form platelet-catching strings. This new molecular mechanism offers additional therapeutic targets for the control of thrombotic disease and is highly relevant to other secretory systems that employ exocytic actomyosin machinery.
A nanobody against the VWF A3 domain detects ADAMTS13-induced proteolysis in congenital and acquired VWD
Authors: Kizlik-Masson Claire , Peyron Ivan , Gangnard Stéphane , Le Goff Gaelle , Lenoir Solen M , Damodaran Sandra , Clavel Marie , Roullet Stéphanie , Regnault Véronique , Rauch Antoine , Vincent Flavien , Jeanpierre Emmanuelle , Dupont Annabelle , Ternisien Catherine , Donnet Thibault , Christophe Olivier D. , van Belle Eric , Denis Cécile V. , Casari Caterina , Susen Sophie , Lenting Peter J. 
Published: December 2022

Abstract
von Willebrand factor (VWF) is a multimeric protein, the size of which is regulated via ADAMTS13-mediated proteolysis within the A2 domain. We aimed to isolate nanobodies distinguishing between proteolyzed and non-proteolyzed VWF, leading to the identification of a nanobody (designated KB-VWF-D3.1) targeting the A3 domain, the epitope of which overlaps the collagen-binding site. Although KB-VWF-D3.1 binds with similar efficiency to dimeric and multimeric derivatives of VWF, binding to VWF was lost upon proteolysis by ADAMTS13, suggesting that proteolysis in the A2 domain modulates exposure of its epitope in the A3 domain. We therefore used KB-VWF-D3.1 to monitor VWF degradation in plasma samples. Spiking experiments showed that a loss of 10% intact VWF could be detected using this nanobody. By comparing plasma from volunteers to that from congenital von Willebrand disease (VWD) patients, intact-VWF levels were significantly reduced for all VWD types, and most severely in VWD type 2A–group 2, in which mutations promote ADAMTS13-mediated proteolysis. Unexpectedly, we also observed increased proteolysis in some patients with VWD type 1 and VWD type 2M. A significant correlation (r = 0.51, P &lt; .0001) between the relative amount of high–molecular weight multimers and levels of intact VWF was observed. Reduced levels of intact VWF were further found in plasmas from patients with severe aortic stenosis and patients receiving mechanical circulatory support. KB-VWF-D3.1 is thus a nanobody that detects changes in the exposure of its epitope within the collagen-binding site of the A3 domain. In view of its unique characteristics, it has the potential to be used as a diagnostic tool to investigate whether a loss of larger multimers is due to ADAMTS13-mediated proteolysis.
Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial
Authors: Panopoulou Aikaterini , Cairns David A. , Holroyd Amy , Nichols Isabel , Cray Nikita , Pawlyn Charlotte , Cook Gordon , Drayson Mark , Boyd Kevin , Davies Faith E. , Jenner Matthew , Morgan Gareth J. , Owen Roger , Houlston Richard , Jackson Graham , Kaiser Martin F. 
Published: December 2022

Abstract
Prediction of individual patient benefit from lenalidomide (Len) maintenance after autologous stem cell transplant (ASCT) remains challenging. Here, we investigated extended molecular profiling for outcome prediction in patients in the National Cancer Research Institute Myeloma XI (MyXI) trial. Patients in the MyXI trial randomized to Len maintenance or observation after ASCT were genetically profiled for t(4;14), t(14;16), t(14;20), del(1p), gain(1q), and del(17p) and co-occurrence of risk markers was computed. Progression-free survival (PFS), subsequent progression (PFS2), and overall survival (OS) were calculated from maintenance randomization, and groups were compared using Cox proportional hazards regression. Of 556 patients, 17% with double-hit multiple myeloma (MM) (≥2 risk markers), 32% with single-hit (1 risk marker), and 51% without risk markers were analyzed. Single-hit MM derived the highest PFS benefit from Len maintenance, specifically, isolated del(1p), del(17p), and t(4;14), with ∼40-fold, 10-fold, and sevenfold reduced risk of progression or death (PFS), respectively, compared with observation. This benefit translated into improved PFS2 and OS for this group of patients compared with observation; median PFS was 10.9 vs 57.3 months for observation vs Len maintenance. Patients with isolated gain(1q) derived no benefit, and double-hit MM limited benefit (regardless or risk lesions involved) from Len maintenance. Extended genetic profiling identifies patients deriving exceptional benefit from Len maintenance and should be considered for newly diagnosed patients to support management discussions along their treatment pathway. This trial was registered at www.isrctn.com/ISRCTN49407852 as # ISRCTN49407852.
Prevention of acute GVHD using an orthogonal IL-2/IL-2Rβ system to selectively expand regulatory T cells in vivo
Authors: Ramos Teresa L. , Bolivar-Wagers Sara , Jin Sujeong , Thangavelu Govindarajan , Simonetta Federico , Lin Po-Yu , Hirai Toshihito , Saha Asim , Koehn Brent , Su Leon L. , Picton Lora K. , Baker Jeanette , Lohmeyer Juliane K. , Riddle Megan , Eide Cindy , Tolar Jakub , Panoskaltsis-Mortari Angela , Wagner John E. , Garcia K. Christopher , Negrin Robert S. , Blazar Bruce R. 
Published: December 2022

Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but limited by variable suppressive capacities and the need for a high therapeutic dose. Here, we sought to expand Treg in vivo by expressing an orthogonal interleukin 2 receptor β (oIL-2Rβ) that would selectively interact with oIL-2 cytokine and not wild-type (WT) IL-2. To test whether the orthogonal system would preferentially drive donor Treg expansion, we used a murine major histocompatibility complex–disparate GVHD model of lethally irradiated BALB/c mice given T cell–depleted BM from C57BL/6 (B6) mice alone or together with B6Foxp3+GFP+ Treg or oIL-2Rβ–transduced Treg at low cell numbers that typically do not control GVHD with WT Treg. On day 2, B6 activated T cells (Tcons) were injected to induce GVHD. Recipients were treated with phosphate-buffered saline (PBS) or oIL-2 daily for 14 days, then 3 times weekly for an additional 14 days. Mice treated with oIL-2Rβ Treg and oIL-2 compared with those treated with PBS had enhanced GVHD survival, in vivo selective expansion of Tregs, and greater suppression of Tcon expansion in secondary lymphoid organs and intestines. Importantly, oIL-2Rβ Treg maintained graft-versus-tumor (GVT) responses in 2 distinct tumor models (A20 and MLL-AF9). These data demonstrate a novel approach to enhance the efficacy of Treg therapy in allo-HSCT using an oIL-2/oIL-2Rβ system that allows for selective in vivo expansion of Treg leading to GVHD protection and GVT maintenance.
INR and vitamin K–dependent factor levels after vitamin K antagonist reversal with 4F-PCC or plasma
Authors: Hood Christopher , Goldstein Joshua N. , Milling Truman J. , Refaai Majed A. , Bajcic Paolo , Goldstein Brahm , Sarode Ravi 
Published: December 2022

Abstract
Restoration of the international normalized ratio (INR) to values &lt;1.5 is commonly targeted to achieve hemostasis in patients with major bleeding or undergoing urgent surgery who are treated using vitamin K antagonists (VKAs). However, the relationship between corrected INR and vitamin K–dependent factor (VKDF) levels for hemostasis is uncertain. We aim to examine the impact of 4-factor prothrombin complex concentrate (4F-PCC) or plasma on INR correction and VKDF restoration and evaluate the relationship between INR values and VKDF levels in patients with acute major bleeding or patients requiring an urgent surgical procedure. Adult patients treated with VKA with an elevated INR (≥2.0 within 3 hours before study treatment) who received 4F-PCC or plasma after major bleeding or before an urgent surgery or invasive procedure were included in this retrospective analysis of data from 2 prospective phase 3b randomized controlled trials. Of the 370 patients included in this analysis, 185 received 4F-PCC, and 185 received plasma. In the 4F-PCC group, 159 of 185 (85.9%) had an INR ≤1.5 at 30 minutes after the end of infusion compared with only 72 of 184 (39.1%) in the plasma group. After 4F-PCC treatment, all VKDF levels exceeded 50% activity regardless of the postinfusion INR value. However, after plasma administration, mean activity levels for factors II and X were &lt;50% at all time points assessed within 3 hours after starting the infusion, regardless of the postinfusion INR value. This retrospective analysis demonstrated that treatment with 4F-PCC among patients treated with VKA rapidly restores VKDFs to hemostatic levels irrespective of the postinfusion INR value, whereas treatment with plasma does not.
A Novel Braking Control Strategy for Hybrid Electric Buses Based on Vehicle Mass and Road Slope Estimation
Authors: Liu Zijun , Cheng Shuo , Liu Jinzhao , Wu Qiong , Li Liang , Liang Huawei 
Published: December 2022

AbstractProper braking force distribution strategies can improve both stability and economy performance of hybrid electric vehicles, which is prominently proved by many studies. To achieve better dynamic stable performance and higher energy recovery efficiency, an effective braking control strategy for hybrid electric buses (HEB) based on vehicle mass and road slope estimation is proposed in this paper. Firstly, the road slope and the vehicle mass are estimated by a hybrid algorithm of extended Kalman filter (EKF) and recursive least square (RLS). Secondly, the total braking torque of HEB is calculated by the sliding mode controller (SMC), which uses the information of brake intensity, whole vehicle mass, and road slope. Finally, comprehensively considering driver's braking intention and regulations of the Economic Commission for Europe (ECE), the optimal proportional relationship between regenerative braking and pneumatic braking is obtained. Furthermore, related simulations and experiments are carried out on the hardware-in-the-loop test bench. Results show that the proposed strategy can effectively improve the braking performance and increase the recovered energy through precise control of the braking torque.