bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic stem cell transplantation for mantle cell lymphoma—update of the prospective trials of the East German Study Group Hematology/Oncology (OSHO#60 and #74)
Authors: Krüger William H. , Hirt Carsten , Basara Nadezda , Sayer Herbert G. , Behre Gerhard , Fischer Thomas , Grobe Norbert , Maschmeyer Georg , Neumann Thomas , Schneidewind Laila , Niederwieser Dietger , Dölken Gottfried , Schmidt Christian A. 
Published: April 2021

AbstractMantle cell lymphoma (MCL) is a non-Hodgkin’s lymphoma with an often aggressive course, incurable by chemotherapy. Consolidation with high-dose therapy and autologous stem cell transplantation (autoSCT) has a low transplant-related mortality but does not lead to a survival plateau. Allogeneic stem cell transplantation (alloSCT) is associated with a higher early mortality, but can cure MCL. To investigate alloSCT for therapy of MCL, we conducted two prospective trials for de novo MCL (OSHO#74) and for relapsed or refractory MCL (OSHO#60). Fifteen and 24 patients were recruited, respectively. Induction was mainly R-DHAP alternating with R-CHOP. Conditioning was either Busulfan/Cyclophosphamide or Treosulfan/Fludarabin. Either HLA-identical siblings or matched-unrelated donors with not more than one mismatch were allowed. ATG was mandatory in mismatched or unrelated transplantation. Progression-free survival (PFS) was 62% and overall survival (OS) was 68% after 16.5-year follow-up. Significant differences in PFS and OS between both trials were not observed. Patients below 56 years and patients after myeloablative conditioning had a better outcome compared to patients of the corresponding groups. Nine patients have died between day +8 and 5.9 years after SCT. Data from 7 long-term surviving patients showed an excellent Quality-of-life (QoL) after alloSCT. AlloSCT for MCL delivers excellent long-term survival data. The early mortality is higher than after autoSCT; however, the survival curves after alloSCT indicate the curative potential of this therapy. AlloSCT is a standard of care for all feasible patients with refractory or relapsed MCL and should offer to selected patients with de novo MCL and a poor risk profile. For defining the position of alloSCT in the therapeutic algorithm of MCL therapy, a randomized comparison of autoSCT and alloSCT is mandatory.
Open versus arthroscopic release for lateral patellar compression syndrome: a randomized-controlled trial
Authors: Hamawandi Sherwan A. , Amin Hazhar I. , Al-Humairi Ameer Kadhim 
Published: April 2021

Abstract
Introduction
Lateral patellar compression syndrome is one of the causes of anterior knee pain in young adults and resulted from tight lateral patellar retinaculum. The aim of our study is to compare between open and arthroscopic release of lateral patellar compression syndrome in relation of functional outcome, time of surgical procedure, length of hospital stays, intraoperative and postoperative complications as bleeding, infection, recurrence, and patellar instability with 2 years of follow-up.

Materials and methods
80 patients, age (21–49 years), were divided randomly into 2 groups (A and B). Group A (40 patients) were treated with open release. Group B (40 patients) were treated by arthroscopic release. All these patients are diagnosed as lateral patellar compression syndrome depending on clinical features and MRI. All patients were assessed by Lysholm knee scoring scale before surgery and at periods of 2, 6 weeks, 6, 12, and 24 months after surgery.

Results
There is significant difference in functional outcome, measured by Lysholm knee scoring scale, between preoperative and postoperative assessment periods in both groups (P < 0.001). There is significantly better functional outcome at 2 years of follow-up with arthroscopic release (P = 0.018). There is no recurrence in both groups, but there were 4 patients develop medial patellar instability in the group of open release.

Conclusion
Both open and arthroscopic lateral release for patients with isolated lateral patellar compression syndrome can be effective surgical procedures, but arthroscopic release can achieve better functional outcome.
Trial registration: NCT, NCT04130412. Retrospectively registered on 3rd of June, 2020 at ClinicalTrials.gov.
Long-term follow-up of conservative treatment of Charcot feet
Authors: Gratwohl Viviane , Jentzsch Thorsten , Schöni Madlaina , Kaiser Dominik , Berli Martin C. , Böni Thomas , Waibel Felix W. A. 
Published: April 2021

Abstract
Background
Charcot arthropathy (CN) can ultimately lead to limb loss despite appropriate treatment. Initial conservative treatment is the accepted treatment in case of a plantigrade foot. The aim of this retrospective study was to investigate the mid- to long-term clinical course of CN initially being treated conservatively, and to identify risk factors for reactivation and contralateral development of CN as well as common complications in CN.

Methods
A total of 184 Charcot feet in 159 patients (median age 60.0 (interquartile range (IQR) 15.5) years, 49 (30.1%) women) were retrospectively analyzed by patient chart review. Rates of limb salvage, reactivation, contralateral development and common complications were recorded. Statistical analysis was performed to identify possible risk factors for limb loss, CN reactivation, contralateral CN development, and ulcer development.

Results
Major amputation-free survival could be achieved in 92.9% feet after a median follow-up of 5.2 (IQR 4.25, range 2.2–11.25) years. CN recurrence occurred in 13.6%. 32.1% had bilateral CN involvement. Ulcers were present in 72.3%. 88.1% patients were ambulating in orthopaedic footwear without any further aids. Presence of Diabetes mellitus was associated with reactivation of CN, major amputation and ulcer recurrence. Smoking was associated with ulcer development and necessity of amputations.

Conclusions
With consistent conservative treatment of CN with orthopaedic footwear or orthoses, limb preservation can be achieved in 92.9% after a median follow-up of 5.2 years. Patients with diabetic CN are at an increased risk of developing complications and CN reactivation. To prevent ulcers and amputations, every effort should be made to make patients stop smoking.

Level of Evidence
III, long-term retrospective cohort study
Domiciliary Cough Monitoring for the Prediction of COPD Exacerbations
Authors: Crooks Michael G. , den Brinker Albertus C. , Thackray-Nocera Susannah , van Dinther Ralph , Wright Caroline E. , Morice Alyn H. 
Published: April 2021

Abstract
Introduction
Acute exacerbations of COPD (AE-COPD) are a leading cause of health service utilisation and are associated with morbidity and mortality. Identifying the prodrome of AE-COPD by monitoring symptoms and physiological parameters (telemonitoring) has proven disappointing and false alerts limit clinical utility. We report objective monitoring of cough counts around AE-COPD and the performance of a novel alert system identifying meaningful change in cough frequency.

Methods
This prospective longitudinal study of cough monitoring included chronic obstructive pulmonary disease (COPD) patients experienced in telemonitoring that had two or more AE-COPD in the past year. Participants underwent cough monitoring and completed a daily questionnaire for 90 days. The automated system identified deteriorating trends in cough and this was compared with alerts generated by an established telemonitoring questionnaire.

Results
28 patients [median age 66 (range 46–86), mean FEV-1% predicted 36% (SD 18%)] completed the study and had a total of 58 exacerbations (43 moderate and 15 severe). Alerts based on cough monitoring were generated mean 3.4 days before 45% of AE-COPD with one false alert every 100 days. In contrast, questionnaire-based alerts occurred in the prodrome of 88% of AE-COPD with one false alert every 10 days.

Conclusion
An alert system based on cough frequency alone predicted 45% AE-COPD; the low false alert rate with cough monitoring suggests it is a practical and clinically relevant tool. In contrast, the utility of questionnaire-based symptom monitoring is limited by frequent false alerts.
Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant
Authors: Morice Alyn H. , Birring Surinder S. , Smith Jaclyn A. , McGarvey Lorcan P. , Schelfhout Jonathan , Martin Nguyen Allison , Xu Zhi Jin , Wu Wen-Chi , Muccino David R. , Sher Mandel R. 
Published: April 2021

Abstract
Purpose
This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population.

Methods
Patients with RCC/UCC lasting for ≥ 1 year and cough severity visual analog scale (VAS) score of > 40 mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30 days before screening and chronic cough treatments within 1 year before screening. Data were summarized using descriptive statistics.

Results
Patients (N = 253; female, 76%; mean age, 60 years) had severe (mean cough severity VAS, 57.5 mm) and long-lasting (median duration, 11 years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%).

Conclusion
Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions.
Trial registration: ClinicalTrials.gov, NCT02612610; registered November 20, 2015
Linear elements are stable structures along the chromosome axis in fission yeast meiosis
Authors: Ding Da-Qiao , Matsuda Atsushi , Okamasa Kasumi , Hiraoka Yasushi 
Published: April 2021

AbstractThe structure of chromosomes dramatically changes upon entering meiosis to ensure the successful progression of meiosis-specific events. During this process, a multilayer proteinaceous structure called a synaptonemal complex (SC) is formed in many eukaryotes. However, in the fission yeast Schizosaccharomyces pombe, linear elements (LinEs), which are structures related to axial elements of the SC, form on the meiotic cohesin-based chromosome axis. The structure of LinEs has been observed using silver-stained electron micrographs or in immunofluorescence-stained spread nuclei. However, the fine structure of LinEs and their dynamics in intact living cells remain to be elucidated. In this study, we performed live cell imaging with wide-field fluorescence microscopy as well as 3D structured illumination microscopy (3D-SIM) of the core components of LinEs (Rec10, Rec25, Rec27, Mug20) and a linE-binding protein Hop1. We found that LinEs form along the chromosome axis and elongate during meiotic prophase. 3D-SIM microscopy revealed that Rec10 localized to meiotic chromosomes in the absence of other LinE proteins, but shaped into LinEs only in the presence of all three other components, the Rec25, Rec27, and Mug20. Elongation of LinEs was impaired in double-strand break-defective rec12− cells. The structure of LinEs persisted after treatment with 1,6-hexanediol and showed slow fluorescence recovery from photobleaching. These results indicate that LinEs are stable structures resembling axial elements of the SC.
Polyhedral separation via difference of convex (DC) programming
Authors: Astorino Annabella , Francesco Massimo Di , Gaudioso Manlio , Gorgone Enrico , Manca Benedetto 
Published: April 2021

AbstractWe consider polyhedral separation of sets as a possible tool in supervised classification. In particular, we focus on the optimization model introduced by Astorino and Gaudioso (J Optim Theory Appl 112(2):265–293, 2002) and adopt its reformulation in difference of convex (DC) form. We tackle the problem by adapting the algorithm for DC programming known as DCA. We present the results of the implementation of DCA on a number of benchmark classification datasets.
Process-property correlations in laser-induced graphene electrodes for electrochemical sensing
Authors: Behrent Arne , Griesche Christian , Sippel Paul , Baeumner Antje J. 
Published: April 2021

AbstractLaser-induced graphene (LIG) has emerged as a promising electrode material for electrochemical point-of-care diagnostics. LIG offers a large specific surface area and excellent electron transfer at low-cost in a binder-free and rapid fabrication process that lends itself well to mass production outside of the cleanroom. Various LIG micromorphologies can be generated when altering the energy input parameters, and it was investigated here which impact this has on their electroanalytical characteristics and performance. Energy input is well controlled by the laser power, scribing speed, and laser pulse density. Once the threshold of required energy input is reached a broad spectrum of conditions leads to LIG with micromorphologies ranging from delicate irregular brush structures obtained at fast, high energy input, to smoother and more wall like albeit still porous materials. Only a fraction of these LIG structures provided high conductance which is required for appropriate electroanalytical performance. Here, it was found that low, frequent energy input provided the best electroanalytical material, i.e., low levels of power and speed in combination with high spatial pulse density. For example, the sensitivity for the reduction of K3[Fe(CN)6] was increased almost 2-fold by changing fabrication parameters from 60% power and 100% speed to 1% power and 10% speed. These general findings can be translated to any LIG fabrication process independent of devices used. The simple fabrication process of LIG electrodes, their good electroanalytical performance as demonstrated here with a variety of (bio)analytically relevant molecules including ascorbic acid, dopamine, uric acid, p-nitrophenol, and paracetamol, and possible application to biological samples make them ideal and inexpensive transducers for electrochemical (bio)sensors, with the potential to replace the screen-printed systems currently dominating in on-site sensors used.
Robotic rehabilitation for end-effector device and botulinum toxin in upper limb rehabilitation in chronic post-stroke patients: an integrated rehabilitative approach
Authors: Paolucci Teresa , Agostini Francesco , Mangone Massimiliano , Bernetti Andrea , Pezzi Letizia , Liotti Vitalma , Recubini Elena , Cantarella Cristina , Bellomo Rosa Grazia , D’Aurizio Carlo , Saggini Raoul 
Published: April 2021

Abstract
Background
Determine the effects of an integrated rehabilitation protocol, including botulinum toxin and conventional rehabilitation exercise plus end-effector (EE) robotic training for functional recovery of the upper limb (UL) compared to training with the robot alone in post-chronic stroke patients with mild to severe spasticity, compared to training with the robot alone.

Methods
In this prospective, observational case-control study, stroke patients were allocated into 2 groups: robot group (RG, patients who underwent robotic treatment with EE) and robot-toxin group (RTG, patients who in addition have carried out the injection of botulinum toxin for UL recovery). All patients were assessed by Fugl-Meyer Assessment (FMA), Motricity Index (MI), modified Ashworth scale (MAS), numeric rating scale (NRS), Box and Block Test (BBT), Frenchay Arm Test (FAT), and Barthel Index (BI) at baseline (T0), T1 (end of treatment), and T2 (3 months of follow-up).

Results
Forty-four patients were included and analyzed (21RG; 23RTG). From the analysis between groups, the results suggested how there was a statistically significant difference in favor of RTG, specifically ΔT0-T1 and ΔT0-T2 for B&B p = 0.009 and p = 0.035; ΔT0-T1 and ΔT0-T2 for FAT with p = 0.016 and p = 0.031; ΔT0-T1 for MAS shoulder p = 0.016; ΔT0-T1 and ΔT0-T2 with p = 0.010 and p = 0.005 for MAS elbow; and ΔT0-T1 and ΔT0-T2 with p = 0.001 and p = 0.013 for MAS wrist.

Conclusion
Our results suggest, in line with the literature, a good efficacy in the reduction of spasticity and in the improvement of the function of the UL, with the reduction of pain, adopting a rehabilitation protocol integrated with BoTN, robot-assisted training, and traditional physiotherapy.
Economic evaluation of orphan drug Lutetium-Octreotate vs. Octreotide long-acting release for patients with an advanced midgut neuroendocrine tumour in the Netherlands
Authors: Hagendijk Marije E. , van der Schans Simon , Boersma Cornelis , Postma Maarten J. , van der Pol Simon 
Published: April 2021

AbstractObjectivesMultiple studies showed positive effects of Lutetium-Octreotate (LO) treatment in neuroendocrine tumours. LO has been used in the Netherlands since the 1980s and recently received the orphan status shortly after the acquisition by Novartis. Since then, the official list price has increased sixfold. From a value-based pricing perspective, we analysed the impact of the increase in price on the incremental cost-effectiveness ratio (ICER) of LO treatment compared to optimal best supportive care, a high dose of Octreotide long-acting release (O-LAR), using the clinical data of the NETTER-1 trial.MethodsA Markov model was developed to evaluate the costs per quality-adjusted life-year (QALY) for LO treatment compared to O-LAR from the healthcare perspective. A scenario analysis was conducted to compare the cost-effectiveness with the initial and increased price level of the LO-treatment.ResultsAt the increased price level, the cost-effectiveness analysis rendered a deterministic ICER of €53,500 per QALY, while at the initial pricing, the ICER was €19,000 per QALY. The probabilistic sensitivity analysis (PSA) showed that LO had a high probability of being cost-effective at both the increased and initial price level, considering a cost-effectiveness threshold of €80,000.ConclusionsEven at the increased price level, LO treatment can still be considered cost-effective using the applicable Dutch willingness-to-pay threshold of 80,000 euro per QALY. Considering the public scrutiny in relation to this price increase, these outcomes raise the question whether traditional cost-effectiveness methods are sufficient in fully capturing the societal acceptance of prices of new medicines.
Children’s participation and agency in Italian residential care for children: Adult-child interactions at dinnertime
Authors: Saglietti Marzia , Zucchermaglio Cristina 
Published: April 2021

AbstractThis paper analyzes the impact of adults’ interactive moves and strategies on children’s participation and agency at dinnertime in two Italian residential care facilities, one of the most widely used alternative care life-context for children and youth coming from vulnerable families. Participants are 14 children and 11 educators living in two residential care facilities in Rome (Italy). Adopting an interactional and multimodal analytic approach, this paper focuses on two dinnertime activities: the routine activity of praying before eating and the very frequent one of talking about rules and transgressions. The comparative analysis of the two facilities shows how, in stable patterns of adult-child interactions recurring across different activities in the same facility, adults’ strategies and interactive maneuvers differently impact on children’s participation and agency and consequent socialization practices. In the conclusion, we emphasize the relevance and implications of this study for either research in educational sciences and for professionals operating in alternative care and related fields.
Acceptability and Feasibility of Pharmacy-Based Delivery of Pre-Exposure Prophylaxis in Kenya: A Qualitative Study of Client and Provider Perspectives
Authors: Roche Stephanie D. , Wairimu Njeri , Mogere Peter , Kamolloh Kevin , Odoyo Josephine , Kwena Zachary A. , Bukusi Elizabeth A. , Ngure Kenneth , Baeten Jared M. , Ortblad Katrina F. 
Published: April 2021

AbstractAs countries scale up pre-exposure prophylaxis (PrEP) for HIV prevention, diverse PrEP delivery models are needed to expand access to populations at HIV risk that are unwilling or unable to access clinic-based PrEP care. To identify factors that may influence implementation of retail pharmacy-based PrEP delivery in Kenya, we conducted in-depth interviews with 40 pharmacy clients, 16 pharmacy providers, 16 PrEP clients, and 10 PrEP providers from two provinces. Most participants expressed strong support for expanding PrEP to retail pharmacies, though conditioned their acceptance on assurances that care would be private, respectful, safe, and affordable. Participant-reported determinants of feasibility centered primarily on ensuring that the intervention is compatible with retail pharmacy operations (e.g., staffing levels, documentation requirements). Future research is needed to develop and test tailored packages of implementation strategies that are most effective at integrating PrEP delivery into routine pharmacy practice in Kenya and other high HIV prevalence settings.
Optimal algorithms for scheduling under time-of-use tariffs
Authors: Chen Lin , Megow Nicole , Rischke Roman , Stougie Leen , Verschae José 
Published: April 2021

AbstractWe consider a natural generalization of classical scheduling problems to a setting in which using a time unit for processing a job causes some time-dependent cost, the time-of-use tariff, which must be paid in addition to the standard scheduling cost. We focus on preemptive single-machine scheduling and two classical scheduling cost functions, the sum of (weighted) completion times and the maximum completion time, that is, the makespan. While these problems are easy to solve in the classical scheduling setting, they are considerably more complex when time-of-use tariffs must be considered. We contribute optimal polynomial-time algorithms and best possible approximation algorithms. For the problem of minimizing the total (weighted) completion time on a single machine, we present a polynomial-time algorithm that computes for any given sequence of jobs an optimal schedule, i.e., the optimal set of time slots to be used for preemptively scheduling jobs according to the given sequence. This result is based on dynamic programming using a subtle analysis of the structure of optimal solutions and a potential function argument. With this algorithm, we solve the unweighted problem optimally in polynomial time. For the more general problem, in which jobs may have individual weights, we develop a polynomial-time approximation scheme (PTAS) based on a dual scheduling approach introduced for scheduling on a machine of varying speed. As the weighted problem is strongly NP-hard, our PTAS is the best possible approximation we can hope for. For preemptive scheduling to minimize the makespan, we show that there is a comparably simple optimal algorithm with polynomial running time. This is true even in a certain generalized model with unrelated machines.