bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Fanconi Anemia–Associated Head and Neck Cancer: Opportunities to Improve Outcomes
Authors: Lee Rex H. , Kang Hyunseok , Yom Sue S. , Smogorzewska Agata , Johnson Daniel E. , Grandis Jennifer R. 
Published: May 2021

AbstractFanconi anemia, the most frequent genetic cause of bone marrow failure, is characterized by an extreme predilection toward multiple malignancies, including a greater than 500-fold incidence of head and neck squamous cell carcinoma (HNSCC) relative to the general population. Fanconi anemia–associated HNSCC and esophageal SCC (FA-HNSCC) often present at advanced stages with poor survival. Surgical resection remains the primary treatment for FA-HNSCC, and there is often great reluctance to administer systemic agents and/or radiotherapy to these patients given their susceptibility to DNA damage. The paucity of FA-HNSCC case reports limits evidence-based management, and such cases have not been analyzed collectively in detail. We present a systematic review of FA-HNSCC treatments reported from 1966 to 2020, defining a cohort of 119 patients with FA-HNSCC including 16 esophageal SCCs (131 total primary tumors), who were treated with surgery, radiotherapy, systemic therapy (including cytotoxic agents, EGFR inhibitors, or immune checkpoint inhibitors), or a combination of modalities. We summarize the clinical responses and regimen-associated toxicities by treatment modality. The collective evidence suggests that when possible, surgical resection with curative intent should remain the primary treatment modality for FA-HNSCC. Radiation can be administered with acceptable toxicity in the majority of cases, including patients who have undergone stem cell transplantation. Although there is little justification for cytotoxic chemotherapy, EGFR inhibitors and tyrosine kinase inhibitors may be both safe and effective. Immunotherapy may also be considered. Most oncologists have little personal experience with FA-HNSCC. This review is intended as a comprehensive resource for clinicians.
Harnessing the hERG1/β1 Integrin Complex via a Novel Bispecific Single-chain Antibody: An Effective Strategy against Solid Cancers
Authors: Duranti Claudia , Iorio Jessica , Lottini Tiziano , Lastraioli Elena , Crescioli Silvia , Bagni Giacomo , Lulli Matteo , Capitani Chiara , Bouazzi Rayhana , Stefanini Matteo , Carraresi Laura , Iamele Luisa , De Jonge Hugo , Arcangeli Annarosa 
Published: May 2021

Abstract
mAbs, either mono- or bispecific (bsAb), represent one of the most successful approaches to treat many types of malignancies. However, there are certain limitations to the use of full length mAbs for clinical applications, which can be overcome by engineered antibody fragments. The aim of this study was to develop a small bsAb, in the format of a single-chain diabody (scDb), to efficiently target two proteins, the hERG1 potassium channel and the β1 subunit of integrin receptors, which specifically form a macromolecular complex in cancer cells. We provide evidence that the scDb we produced binds to the hERG1/β1 complex in cancer cells and tissues, but does not bind to the hERG1 channel in nonpathologic tissues, in particular the heart. The scDb-hERG1-β1 (i) downregulates the formation of the hERG1/β1 complex, (ii) inhibits Akt phosphorylation and HIF-1α expression, and (iii) decreases cell survival, proliferation, and migration in vitro. These effects only occur in cancer cells (either colon, pancreatic, or breast), but not in normal cells. In vivo, the scDb-hERG1-β1 shows a good pharmacokinetic profile, with a half-life of 13.5 hours and no general, cardiac, or renal toxicity when injected intravenously up to the dose of 8 mg/kg. The scDb-hERG1-β1 accumulates into subcutaneous xenografted tumors, arising from either colon or pancreatic human cancer cells, and induces a reduction of tumor growth and vascularization. Overall, the scDb-hERG1-β1 represents an innovative single-chain bispecific antibody for therapeutic applications in solid cancers that overexpress the hERG1/β1 integrin signaling complex.
M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) Delivering Efficacy in Multiple Myeloma Models
Authors: Sanderson Michael P. , Friese-Hamim Manja , Walter-Bausch Gina , Busch Michael , Gaus Stefanie , Musil Djordje , Rohdich Felix , Zanelli Ugo , Downey-Kopyscinski Sondra L. , Mitsiades Constantine S. , Schadt Oliver , Klein Markus , Esdar Christina 
Published: May 2021

Abstract
Large multifunctional peptidase 7 (LMP7/β5i/PSMB8) is a proteolytic subunit of the immunoproteasome, which is predominantly expressed in normal and malignant hematolymphoid cells, including multiple myeloma, and contributes to the degradation of ubiquitinated proteins. Described herein for the first time is the preclinical profile of M3258; an orally bioavailable, potent, reversible and highly selective LMP7 inhibitor. M3258 demonstrated strong antitumor efficacy in multiple myeloma xenograft models, including a novel model of the human bone niche of multiple myeloma. M3258 treatment led to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells both in vitro and in vivo. Furthermore, M3258 showed superior antitumor efficacy in selected multiple myeloma and mantle cell lymphoma xenograft models compared with the approved nonselective proteasome inhibitors bortezomib and ixazomib. The differentiated preclinical profile of M3258 supported the initiation of a phase I study in patients with multiple myeloma (NCT04075721).
Análise da velocidade e acurácia de movimentos em indivíduos após acidente vascular encefálico
Authors: Araújo Gabriela , Rossini Nataly , Ferrari Aline Sanchez , Monteiro Carlos Bandeira de Mello , Silva Talita Dias da , Massetti Thais , Fernani Deborah Cristina Gonçalves Luiz , Dantas Maria Tereza Artero Prado 
Published: May 2021

The Stroke might cause alterations in movement control due to the sequels of this process. Objective: Analyze the speed-accuracy trade-off of upper limb movement in individuals with sequels of Stroke through a computer software. Method: It is about a cross-sectional study, the sample was composed of 46 individuals divided into two groups: individuals post-stroke, between the ages of 35 and 83 years old, in which 10 were women and 14 were men; and 22 healthy controls aligned by age and sex, in which 8 were women and 14 were men, evaluated through the instruments: Mini mental state examination, Orpington prognostic scale, Fugl-Meyer Assessment Scale, dynamometer, box of blocks and throught the software “Fitts Reciprocal Aiming Task v.2.0. (Horizontal)”, that seeks to understand the motor control of the upper limb, verifying the speed and accuracy of movement through a computer task. Results: The individuals with sequels of Stroke showed a loss in the strength of the palmar grip and manual function. Besides, they showed a longer time in movement in all index of difficulty compared to Control group. However, they showed a similar behaviour to the healthy individuals throughout the execution of the index of difficulty. Conclusion: Thus, it can be concluded that the individuals with sequels of Stroke showed a deficit of the motor control of the upper limb, compared to the healthy individuals, however, these showed the same behavior, with a bigger deficit in the accuracy of movement.
Neurophysiological comparative response to clinical and surgical treatment of the ulnar neuropathy in leprosy
Authors: Borela Marianna Cossi Monseff , Cury Filho Milton , Kirchner Daniel Rocco , Salgado Manuel Henrique , Virmond Marcos da Cunha Lopes , Garbino José Antonio 
Published: May 2021

Leprosy neuropathy may develop into subacute and chronic inflammatory scenarios, called reactions, which may cause entrapments in the anatomic tunnels. Objective: This study describes the late nerve conduction findings in patients with ulnar neuropathy at the elbow that were submitted to clinical and surgery treatments. Methods: A total of 27 nerves of 21 patients with borderline leprosy during type 1 (reversal) reaction were selected in a non- competing retrospective cohort for three years. The nerves with treated clinically active neuropathy (Group A1) were randomized for inclusion of surgical treatment (Group A2) after one month of clinical treatment without clear signs of clinical and neurophysiological improvement. Fifteen nerves were randomly chosen for surgery while 12 were clinically treated, after steroids treatment without expected response. Nerve conduction was measured before and after treatment on four occasions. Results: The authors observed significant improvement in the following variables in the surgically treated nerves: compound motor action potential amplitude (CMAP) at elbow and above elbow and conduction velocity (CV) along the forearm. Conclusion: The improvement of CMAP amplitudes and conduction velocity (CV) along the forearm express the late effect of nerve decompression. Persistence of temporal dispersion (TD) along the elbow was related to the new reaction or to incomplete surgical solution. However, moderate reduction in CV along the elbow, without TD, was considered an indication of na expected partial remyelination. Previous gradation of the nerve lesion based on the CMAP amplitude was related to the most severe results.
The Impossibility of Automating Ambiguity
Authors: Birhane Abeba 
Published: May 2021

AbstractOn the one hand, complexity science and enactive and embodied cognitive science approaches emphasize that people, as complex adaptive systems, are ambiguous, indeterminable, and inherently unpredictable. On the other, Machine Learning (ML) systems that claim to predict human behaviour are becoming ubiquitous in all spheres of social life. I contend that ubiquitous Artificial Intelligence (AI) and ML systems are close descendants of the Cartesian and Newtonian worldview in so far as they are tools that fundamentally sort, categorize, and classify the world, and forecast the future. Through the practice of clustering, sorting, and predicting human behaviour and action, these systems impose order, equilibrium, and stability to the active, fluid, messy, and unpredictable nature of human behaviour and the social world at large. Grounded in complexity science and enactive and embodied cognitive science approaches, this article emphasizes why people, embedded in social systems, are indeterminable and unpredictable. When ML systems “pick up” patterns and clusters, this often amounts to identifying historically and socially held norms, conventions, and stereotypes. Machine prediction of social behaviour, I argue, is not only erroneous but also presents real harm to those at the margins of society.
Postoperative Complications Associated With Intra- Versus Extracorporeal Anastomosis for Laparoscopic Right Colectomy
Authors: Ishizuka Mitsuru , Shibuya Norisuke , Takagi Kazutoshi , Hachiya Hiroyuki , Tago Kazuma , Shimizu Takayuki , Matsumoto Takatsugu , Aoki Taku , Kubota Keiichi 
Published: May 2021

Objective To compare the postoperative complications of intracorporeal anastomosis (ICA) and extracorporeal anastomosis (ECA) in patients undergoing laparoscopic right colectomy (LRC). Background Although several studies have compared postoperative complications of ICA and ECA after LRC, most were retrospective studies. Methods We performed a comprehensive electronic search of the literature to identify studies that compared postoperative complications between ICA and ECA in patients who underwent LRC. We performed meta-analysis using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) of experiencing complications, and we analyzed heterogeneity using I2 statistics. Results Fifteen studies consist of randomized controlled trials, case-control studies, and propensity score matching studies involving a total of 3219 patients who underwent LRC were included. Among 1377 patients who received ICA, 255 (18.5%) had postoperative complications, whereas among 1652 patients who received ECA, 373 (22.6%) had such complications. The results of the meta-analysis revealed that ICA was associated with a significantly reduced risk of postoperative complications (RR, .73; 95% CI: .57-.95; P = .02; I2 = 57%) compared with ECA. Although there was no significant difference between the 2 groups in risk of anastomotic leakage (RR, .67; 95% CI: .39-1.17; P = .16; I2 = 8%), there was a significant difference between them in risk of surgical site infection (RR, .50; 95% CI: .34-.71; P = .0002; I2 = 0%). Conclusions Intracorporeal anastomosis is associated with a reduced risk of postoperative complications compared with ECA in patients undergoing LRC.
Living with myalgic encephalomyelitis/chronic fatigue syndrome: Experiences of occupational disruption for adults in Australia
Authors: Bartlett Chelsea , Hughes Julie L , Miller Laura 
Published: May 2021

Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood, highly stigmatised health condition that has widespread impacts on the individual. Currently, there is limited understanding of the ME/CFS experience from an occupational perspective within Australia. This study aimed to explore the lived experience of ME/CFS and subsequent disruption to occupational participation for adults living in Australia. Methods Using descriptive case study design, five participants with ME/CFS in Australia completed semi-structured interviews. Reflexive thematic analysis was used to analyse the qualitative data. Findings Themes identified were organised using the Person-Environment-Occupation model. Participants reported systemic changes to previous levels of physical, cognitive and affective functioning, resulting in significant occupational disruption and poor well-being. Occupational prioritisation was followed by a loss of occupations starting with leisure, then productivity and eventually self-care. Environmental barriers to participation included stigma and misunderstanding of ME/CFS, financial hardship, lack of appropriate health services and strains on personal support networks and relationships. Conclusion Changes to occupational performance following the onset of ME/CFS caused significant occupational disruption and resulted in limited participation which narrowed over time. There is a clear role for occupational therapy to intervene early to prevent significant negative impacts on occupational participation for people with ME/CFS.
Clinical trials site recruitment optimisation: Guidance from Clinical Trials: Impact and Quality
Authors: Zahren Christine , Harvey Sonia , Weekes Leanne , Bradshaw Charlotte , Butala Radhika , Andrews John , O’Callaghan Sally 
Published: May 2021

Background/Aims: Participants are integral to the success of any clinical research study, yet participant recruitment into clinical trials poses ongoing and complex challenges. It is widely accepted and recognised that clinical trial sites often find it difficult to meet recruitment goals, both in terms of accrual targets and timelines. This can impact the validity of trials or cause major delays for research. There are very few frameworks available to clinical trial sites to improve recruitment. The GREET project (Guidance to Recruitment: Examining Experiences at clinical Trial sites) sought to identify barriers to recruitment and produce formal guidance to optimise recruitment outcomes. Methods: Clinical Trials: Impact and Quality, a collaborative of sector stakeholders, convened a project team with comprehensive knowledge of the Australian clinical trials sector to undertake the GREET project. The project scope included exploration of recruitment issues at a site level across all phases of clinical trials and all types of trial sites. The scope excluded upstream issues such as protocol design and general public clinical trial awareness, participant retention and elements of recruitment outside a site’s capacity to directly influence or control. The project team’s extensive knowledge and experience conducting clinical trials in Australia was used to collaboratively identify a list of 24 key barriers and 12 enablers to site recruitment which formed the basis of the project. Key stakeholder groups were surveyed to challenge project team assumptions. A national and international environmental scan and literature review was conducted to identify best-practice recruitment solutions. Results: A total of 343 people responded to a survey sent to sites, sponsors, and contract research organisations, and 162 people responded to a survey sent to consumers via consumer networks. The key barriers and enablers initially identified by the project team aligned with the key outcomes of the surveys, which in turn assisted in the development of best-practice recommendations in the form of a Clinical Trial Site Recruitment Guide. Recommendations were grouped into four key themes; conducting accurate study feasibility; proactive planning during start-up; selecting optimal recruitment methods; and participant involvement. Early intervention was identified as a key facilitator in maximising improved recruitment outcomes. The GREET Clinical Trial Site Recruitment Guide is publicly accessible on the Clinical Trials: Impact and Quality website. Conclusion: Participant recruitment challenges experienced at a site level are widespread and varied, and there is no universal recruitment solution. However, this project identified that there are interventions and assessments that can be proactively implemented and selectively applied to facilitate improved recruitment outcomes.
Comparing individual and population differences in minute ventilation/carbon dioxide production slopes using centile growth curves and log-linear allometry
Authors: Nevill Alan M. , Myers Jonathan , Kaminsky Leonard A. , Arena Ross , Myers Tony D. 
Published: May 2021

Identifying vulnerable groups and/or individuals’ cardiorespiratory fitness (CRF) is an important challenge for clinicians/researchers alike. To quantify CRF accurately, the assessment of several variables is now standard practice including maximal oxygen uptake (VʹCO2) and ventilatory efficiency, the latter assessed using the minute ventilation/carbon dioxide production (VʹE/VʹCO2) slope. Recently, reference values (centiles) forVʹE/VʹCO2slopes for males and females aged 20 to 80 have been published, using cardiopulmonary exercise testing (CPX) data (treadmill protocol) from the Fitness Registry and the Importance of Exercise National Database (FRIEND Registry).In the current observational study we provide centile curves for the FRIEND RegistryVʹE/VʹCO2slopes, fitted using the generalised additive model for location, scale and shape (GAMLSS), to provide individuals with a more precise estimate of where theirVʹE/VʹCO2slopes fall within the population. We also confirm that by adopting allometric models (incorporating a log transformation), the resulting ANCOVAs provided more normal and homoscedastic residuals, with superior goodness-of-fit using the Akaike information criterion (AIC)=14 671 (compared with traditional ANCOVA's AIC=15 008) that confirms allometric models are vastly superior to traditional ANCOVA models.In conclusion, providing sex-by-age centile curves rather than referring to reference tables for ventilatory efficiency (VʹE/VʹCO2slopes) will provide more accurate estimates of where an individual's particularVʹE/VʹCO2slope falls within the population. Also, by adopting allometric models researchers are more likely to identify real and valid inferences when analysing population/group differences inVʹE/VʹCO2slopes.
High but stable incidence of adult-onset asthma in northern Sweden over the last decades
Authors: Räisänen Petri , Backman Helena , Hedman Linnea , Andersson Martin , Stridsman Caroline , Kankaanranta Hannu , Ilmarinen Pinja , Andersen Heidi , Piirilä Päivi , Lindberg Anne , Lundbäck Bo , Rönmark Eva 
Published: May 2021

BackgroundThe prevalence of asthma has increased both among children and adults during the latter half of the 20th century. The prevalence among adults is affected by the incidence of asthma not only in childhood but also in adulthood. Time trends in asthma incidence have been poorly studied.AimsThe aim of this study was to review the incidence of adult-onset asthma from 1996 to 2006 and 2006 to 2016 and compare the risk factor patterns.MethodsIn the Obstructive Lung Disease in Northern Sweden (OLIN) studies, two randomly selected population-based samples in the 20–69-year age group participated in postal questionnaire surveys about asthma in 1996 (n=7104, 85%) and 2006 (n=6165, 77%). A 10-year follow-up of the two cohorts with the same validated questionnaire was performed, and 5709 and 4552 responded, respectively. Different definitions of population at risk were used in the calculations of asthma incidence. The protocol followed a study performed between 1986 and 1996 in the same area.ResultsThe crude incidence rate of physician-diagnosed asthma was 4.4 per 1000 person-years (men 3.8, women 5.5) from 1996 to 2006, and 4.8 per 1000 person-years (men 3.7, women 6.2) from 2006 to 2016. When correcting for possible under-diagnosis at study entry, the incidence rate was 2.4 per 1000 person-years from 1996 to 2006 and 2.6 per 1000 person-years from 2006 to 2016. The incidence rates were similar across age groups. Allergic rhino-conjunctivitis was the main risk factor for incident asthma in both observation periods (risk ratio 2.4–2.6).ConclusionsThe incidence of adult-onset asthma has been stable over the last two decades and has remained at a similar level since the 1980s. The high incidence contributes to the increase in asthma prevalence.
Anesthetic effect of different doses of butorphanol in patients undergoing gastroscopy and colonoscopy
Authors: Lv Shun , Sun Defeng , Li Jinglin , Yang Lin , Sun Zhongliang , Feng Yan 
Published: May 2021

Abstract
Background
This study aimed to investigate the anesthetic effect of butorphanol with different doses in patients undergoing gastroscopy and colonoscopy.

Methods
480 patients undergoing gastroscopy and colonoscopy were recruited and randomly divided into four groups to receive different doses of butorphanol (Group A = 2.5 μg/kg, Group B = 5 μg/kg, Group C = 7.5 μg/kg and Group D = 10 μg/kg). Butorphanol was administered 5 min before propofol infusion. The primary outcome was the incidence of body movement. Secondary outcomes were postoperative recovery time, length of stay in the Post-Anesthesia Care Unit (PACU), the total dose of propofol, and the incidence of intraoperative hypoxemia, propofol injection pain, cough, postoperative nausea and vomiting, drowsiness, and dizziness.

Results
The incidence of body movement and the dose of propofol in Group C and D were lower than those in Group A and B (P < 0.05). The incidence and intensity of propofol injection pain and the incidence of cough in Group B, C, and D were lower than those in Group A (P < 0.05). The length of stay in PACU and the incidence of postoperative drowsiness and dizziness were higher in Group D than in Group A, B, and C (P < 0.05).

Conclusion
Intravenous pre-injection of 7.5 μg/kg butorphanol with propofol can be the optimal dosage for patients undergoing gastroscopy and colonoscopy.
Trial registration: Trial registration: Chinese Clinical Trial Registry, ChiCTR2000031506. Registered 3 April 2020—Retrospectively registered, http://www.medresman.org.cn.