bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for immune-related adverse events: what have we learned and what lies ahead?
Authors: Liu Xiaoyan , Shi Yuequan , Zhang Dongming , Zhou Qing , Liu Jia , Chen Minjiang , Xu Yan , Zhao Jing , Zhong Wei , Wang Mengzhao 
Published: November 2021

AbstractImmune checkpoint inhibitors (ICIs) have heralded the advent of a new era in oncology by holding the promise of prolonged survival in severe and otherwise treatment-refractory advanced cancers. However, the remarkable antitumor efficacy of these agents is overshadowed by their potential for inducing autoimmune toxic effects, collectively termed immune-related adverse events (irAEs). These autoimmune adverse effects are often difficult to predict, possibly permanent, and occasionally fatal. Hence, the identification of risk factors for irAEs is urgently needed to allow for prompt therapeutic intervention. This review discusses the potential mechanisms through which irAEs arise and summarizes the existing evidence regarding risk factors associated with the occurrence of irAEs. In particular, we examined available data regarding the effect of a series of clinicopathological and demographic factors on the risk of irAEs.
Customized exogenous ferredoxin functions as an efficient electron carrier
Authors: Song Zhan , Wei Cancan , Li Chao , Gao Xin , Mao Shuhong , Lu Fuping , Qin Hui-Min 
Published: November 2021

AbstractFerredoxin (Fdx) is regarded as the main electron carrier in biological electron transfer and acts as an electron donor in metabolic pathways of many organisms. Here, we screened a self-sufficient P450-derived reductase PRF with promising production yield of 9OHAD (9α-hydroxy4-androstene-3,17-dione) from AD, and further proved the importance of [2Fe–2S] clusters of ferredoxin-oxidoreductase in transferring electrons in steroidal conversion. The results of truncated Fdx domain in all oxidoreductases and mutagenesis data elucidated the indispensable role of [2Fe–2S] clusters in the electron transfer process. By adding the independent plant-type Fdx to the reaction system, the AD (4-androstene-3,17-dione) conversion rate have been significantly improved. A novel efficient electron transfer pathway of PRF + Fdx + KshA (KshA, Rieske-type oxygenase of 3-ketosteroid-9-hydroxylase) in the reaction system rather than KshAB complex system was proposed based on analysis of protein–protein interactions and redox potential measurement. Adding free Fdx created a new conduit for electrons to travel from reductase to oxygenase. This electron transfer pathway provides new insight for the development of efficient exogenous Fdx as an electron carrier.
Graphical Abstract
Relationship between hemodialysis and health-related quality of life: a cross-sectional study of diagnosis and duration of hemodialysis
Authors: Noto Shinichi , Miyazaki Masashi , Takeuchi Hidemi , Saito Shinya 
Published: November 2021

Abstract
Background
Hemodialysis is a medical technology implemented for various renal diseases and has a significant budget impact in Japan. Hemodialysis also affects health-related quality of life, as it interferes with daily life, but the effect of diagnosis and duration of hemodialysis is not clear. The purpose of this study was to examine the impact of hemodialysis on health-related quality of life, with a focus on diagnosis and duration of hemodialysis.

Methods
We conducted EQ-5D-5L surveys among hemodialysis patients at a single hemodialysis hospital between November 2015 and September 2017 and used a scoring algorithm that was developed in Japan to calculate the scores.

Results
A total of 274 subjects without missing data were included in the data analysis. The mean score of the entire group was 0.772 ± 0.215. Compared with other domains, pain/discomfort had the highest percentage of problems (59.1%). There were no differences in the distributions with respect to diagnostic names in any domain. Multiple regression analysis showed that hemodialysis duration was the only explanatory variable that had a mild significant effect on EQ-5D-5L scores, but it was not large.

Conclusions
QOL measured using the EQ-5D-5L survey score was not affected by age, gender, or diagnosis but was affected by hemodialysis duration. Future studies are needed to investigate the impact of prolonged hemodialysis on health-related quality of life.
Larvae of the blue crab Callinectes sapidus Rathbun, 1896 (Decapoda: Brachyura: Portunidae) in the Balearic Archipelago (NW Mediterranean Sea)
Authors: Png-Gonzalez Lydia , Papiol Vanesa , Balbín Rosa , Cartes Joan Enric , Carbonell Aina 
Published: November 2021

AbstractThe invasive blue crab Callinectes sapidus has been frequently recorded during the last years along the NW Mediterranean Sea, leading to established populations. Two megalopae of C. sapidus were found during two different oceanographic surveys in open waters of the Balearic Archipelago, in July 2005 and October 2011, previous to the first reference of adult specimens documented in the Balearic sub-basin. The analyzed environmental conditions of the sampling periods allowed us to hypothesize the likely introduction pathways, namely by maritime transport and surface currents. Furthermore, the recorded megalopae seem to enlarge the life history of C. sapidus in regard to its native area, where spawning peaks occur in late July and early August.
Flipped learning in the context of postgraduate public health higher education: a qualitative study involving students and their tutors
Authors: Akparibo Robert , Osei-Kwasi Hibbah Araba , Asamane Evans Atiah 
Published: November 2021

AbstractIn higher education institutions, there is a growing popularity of the use of flipped learning (FL) pedagogy to enhance the learning experience of students. At the undergraduate level, there is increasing evidence to demonstrate the potential benefits of this teaching and learning approach. However, at the level of the postgraduate education, evidence is limited on potential impact of FL on students’ learning experience. We conducted qualitative in-depth interviews and focus groups involving postgraduate students and tutors to explore their perspectives of FL. Campus-based students pursuing the masters of public health (MPH) course, and their tutors at the School of Health and Related Research (ScHARR), University of Sheffield, UK were sampled to participate in the study. Tutors generally demonstrated good knowledge and understanding of the concept of FL and its application, although different tutors use different terms to describe FL. Motivations for the use of FL among tutors were identified as: decision informed by available evidence; curriculum design suited for FL; knowledge/expertise acquired through participating in an online FL short course; advise from colleagues and perception of how higher education students should be learning. Students’ views about FL suitability for their courses were generally positive, with only a few students showing a dislike of this teaching and learning method. Our study results show that tutors and postgraduate students in public health higher education place high value on FL pedagogy, and reported positive experiences of their encounter with the FL pedagogy. The results are encouraging and suggest that higher education institutions running postgraduate masters’ degree courses, particularly public health, could consider adopting and using FL approach to enhance the learning experiences of their students.
Understanding the visual function symptoms and associated functional impacts of phakic presbyopia
Authors: Bentley Sarah , Findley Amy , Chiva-Razavi Sima , Naujoks Christel , Patalano Francesco , Johnson Chloe , Arbuckle Rob , Wolffsohn James S. 
Published: November 2021

Abstract
Background
Presbyopia is defined as the age-related deterioration in the ability to focus on close objects, causing difficulty with near vision tasks. The study aim was to understand the lived experience of phakic presbyopia and identify all relevant visual function symptoms and associated functional impacts.

Methods
Fifty individuals with clinician-confirmed phakic presbyopia (US n = 30, France n = 10, Germany n = 10) and seven healthcare professionals (HCPs) participated in in-depth, face-to-face, qualitative concept elicitation interviews. Verbatim transcripts were analyzed using thematic analysis methods.

Results
Visual function symptoms reported by participants with phakic presbyopia were categorized as: primary near vision functioning symptoms (impaired near visual acuity, n = 50/50, 100%; difficulty with near vision in dim light, n = 42/50, 84%; difficulty focusing at close distances, n = 30/50, 60%; difficulty seeing things when glare is present, n = 30/50, 60%) and secondary symptoms (eye strain, n = 37/50, 74%; dry eyes, n = 35/50, 70%; headaches, n = 30/50, 60%). Proximal impacts on functional vision included difficulty reading in near vision (n = 49/50, 98%, including printed text and handwriting), seeing objects in near vision n = 48/50, 96%, and performing activities of daily living that require near vision (n = 49/50, 98%, including using a smartphone or computer). Distal impacts on functional vision included emotional, work, financial and social impacts. HCP interviews supported participant findings.

Conclusion
Findings provide a comprehensive understanding of the lived experience of phakic presbyopia which informed the development of a presbyopia conceptual model and patient-reported outcome assessments of vision correction independence and near vision functioning. The sample did not include those whose vision cannot be adequately corrected with lenses or surgery.
Gender response to 10 weeks acupuncture-TENS application on patients who presented with post-injection sciatic pain
Authors: Okonkwo Uchenna Prosper , Ibeneme Sam Chidi , Ezenwankwo Elochukwu Fortune , Okeke Chukwuebuka Olisaemeka , Ani Kenneth Umezulike , Akobundu Uzoamaka Nwakaego , Onwuakagba Ifeoma Uchenna 
Published: November 2021

Abstract
Background
Studies to determine gender response to transcutaneous electrical nerve stimulation (TENS) application on individuals who presented with post-injection sciatic pain (PISP) following gluteal injection is not common. A total of 40 subjects comprising 20 males and 20 females who were purposively recruited and conveniently assigned to group A (male) and group B (female) completed the study. Acupuncture-like TENS (AL-TENS) was applied on the 20 male and 20 female subjects, 1 h per session, 3 times per week for the 10 weeks the study lasted.

Result
The pre-intervention baseline scores for the two groups were 8.80 + 1.05 (Female) and 8.60 + 1.27 (Male). The result revealed that after 10 weeks of intervention the VAS scores were 2.60+ 3.28 (p < 0.001) and 2.40 + 3.28 (p < 0.001) for the female and male subjects, respectively. The mean comparison of the female mean VAS scores (2.60 + 3.28) and male VAS scores 2.40 + 3.25 after 10 weeks of AL-TENS intervention shows no statistically significant difference (p > 0.85) in pain intensity (pain perception).

Conclusions
There was no gender variation in pain perception in subjects with post-injection sciatic pain (PISP) following gluteal muscle injection after 10 weeks of AL-TENS application. Therefore, gender-based variation should not be considered when applying AL-TENS as an instrument of intervention in subjects with PISP.

Trial registration
PACTR2018050034082
Effect of different direct-acting antiviral regimens for treatment of nondiabetic hepatitis C virus–infected Egyptian patients on insulin resistance and sensitivity
Authors: Yosef Tarek , Ibrahim Wesam Ahmed , El-Ghandour Ahmed , Attia Soha , El-Nakeep Sarah 
Published: November 2021

Abstract
Background
The association between hepatitis C virus (HCV), insulin resistance (IR), and metabolic syndrome has been extensively investigated. Direct-acting antivirals (DAAs) have a high sustained virologic response (SVR) rate, reaching > 90%. The effect of SVR after DAA treatment on metabolic parameters and IR in nondiabetic patients could be an important factor in the patient’s long-term outcome. The aim of the study is to evaluate the impact of different DAA regimens on IR and sensitivity in naïve chronic HCV-infected nondiabetic patients (before and after 12 weeks of treatment).

Methods
This prospective cohort study was conducted on 100 HCV-infected Child A nondiabetic patients eligible for DAA treatment in the Department of Gastroenterology and Hepatology, Ain Shams University, and Kobry El-Kobba Military Hospital among patients attending the outpatient clinic.
Patients were categorized into four groups according to the HCV regimens they received for 12 weeks.
All patient were subjected to the following tests before and 12 weeks after treatment: HCV quantitative PCR, Fibroscan, fasting insulin level (using insulin quantitative test kit), fasting and postprandial blood glucose (PPG), lipid profile, liver enzymes, BMI, and waist circumference.

Results
All patients achieved SVR at 12 weeks. In all treatment groups, lab was assessed before and after treatment, the 2-h PPG, high-density lipoprotein, and low-density lipoprotein levels showed statistically significant increases, whereas triglyceride, fasting glucose, hemoglobin A1C, and fasting plasma insulin levels showed statistically significant decreases. The homeostasis model assessment of insulin resistance (HOMA-IR) exhibited statistically significant decreases, whereas the quantitative insulin sensitivity check index (QUICKI) and Matsuda index showed statistically significant increases, across the four groups.

Conclusions
DAA treatment in naïve nondiabetic HCV-infected patients affects metabolic profile and insulin resistance/sensitivity, with similar effect among different DAA regimens.
Review of oncological findings and complications after elective neck dissection during total laryngectomy: a case series
Authors: Elsayed Mahmoud , Dwiddar Nada , Allam Amr , Ubayasiri Kishan , Simons Anthony , Sethi Neeraj 
Published: November 2021

AbstractBackgroundThis study aims to report the rate of occult lymph node metastasis during elective neck dissection in clinically and radiologically negative neck (cN0) for patients offered total laryngectomy as either primary or salvage treatment. We also compare the rate of complications and recurrence after elective neck dissection during total laryngectomy.A retrospective review of patients treated in a single teaching hospital in the UK between 2004 and 2020 was performed. We collected the following patient information: age, sex, TNM staging, tumour location and laterality, primary treatment received if recurrent, preoperative imaging, operative details of the elective neck dissection, pathology results, postoperative complications, and recurrence. Inclusion criteria are as follows: squamous cell carcinoma and cN0 neck. Exclusion criteria are as follows: second primary tumour in the head and neck, a total laryngectomy because of a dysfunctional larynx, or a previously performed neck dissection.ResultsOf the 105 included patients, 66 (63%) had primary surgery and 39 (37%) were offered salvage surgery. All cases in the primary group were offered elective neck dissection. Thirty-six patients of the salvage group were offered elective neck dissection. The rate of occult lymph node metastasis was 35% (23/66) and 5.6% (2/36) in the primary and salvage groups, respectively. There was no difference in the overall complication rate in both groups, although the specific incidence of pharyngocutaneous fistula in the salvage group was higher compared with the primary group, 14% vs 7.5%.ConclusionsWe conclude that elective neck dissection is indicated during primary total laryngectomy due to the high rate of occult lymph node metastasis, 35% (23/66) in our series. Conversely, from our data in the salvage setting, the rate of occult lymph node was very low at 5.6% (2/36). The impact on survival is not known. The decision over elective neck dissection may be made more judiciously on an individual basis in the salvage setting.
International Medullary Thyroid Carcinoma Grading System: A Validated Grading System for Medullary Thyroid Carcinoma
Authors: Xu Bin , Fuchs Talia L. , Ahmadi Sara , Alghamdi Mohammed , Alzumaili Bayan , Bani Mohamed-Amine , Baudin Eric , Chou Angela , De Leo Antonio , Fagin James A. , Ganly Ian , Glover Anthony , Hartl Dana , Kanaan Christina , Khneisser Pierre , Najdawi Fedaa , Nigam Aradhya , Papachristos Alex , Repaci Andrea , Spanheimer Philip M. , Solaroli Erica , Untch Brian R. , Barletta Justine A. , Tallini Giovanni , Al Ghuzlan Abir , Gill Anthony J. , Ghossein Ronald A. 
Published: November 2021

PURPOSE Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. PATIENTS AND METHODS Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm2, Ki67 proliferative index ≥ 5%, or tumor necrosis. RESULTS Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. CONCLUSION This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.
Evaluation of TP53 Variants Detected on Peripheral Blood or Saliva Testing: Discerning Germline From Somatic TP53 Variants
Authors: Schwartz Alison N. , Cahill Sophie R. , Stokes Samantha M. , Castillo Danielle , Tung Nadine M. , Weitzel Jeffrey N. , Rana Huma Q. , Garber Judy E. 
Published: November 2021

PURPOSE Multigene panel testing (MGPT) identifies TP53 pathogenic or likely pathogenic (P/LP) variants in patients with diverse phenotypes, of which only one is classic Li-Fraumeni syndrome. Low variant allelic fraction (VAF) in TP53 found on germline testing may suggest aberrant clonal expansion or constitutional mosaicism. We evaluated TP53-positive probands seen in a cancer genetics program to determine germline versus somatic status. METHODS We reviewed TP53-positive probands from 2012 to 2019 identified by MGPT on blood or saliva (N = 84). Available VAFs were collected. Probands with a familial variant, who met Li-Fraumeni syndrome testing criteria or who carried a founder variant, were considered germline. For those with uncertain germline status, TP53 variants were further examined using ancillary data of family members and somatic tissue. RESULTS Of the 84 probands, 54.7% had germline variants with 33.3% meeting criteria for germline status and 21.4% confirmed through ancillary testing. Aberrant clonal expansion comprised 13.1% with clonal hematopoiesis of indeterminate potential and 2.4% with a hematologic malignancy. Constitutional mosaicism was confirmed in 8.3% probands. Definitive status could not be determined in 3.6% despite ancillary assessment, and 17.9% did not have ancillary testing. CONCLUSION A TP53 P/LP variant found on peripheral blood or saliva MGPT does not always originate in the germline. In a clinical cancer genetics cohort, approximately half of the patients had TP53 P/LP germline variants; these patients plus those with constitutional mosaicism require intensified surveillance. A framework of multiple strategies enables discernment of germline from constitutional mosaic and acquired variants, which is essential for appropriate management.
Universal witnesses of vanishing energy gap
Authors: Szymański Konrad , Życzkowski Karol 
Published: November 2021

Abstract
Energy gap, the difference between the energy of the ground-state of a given Hamiltonian and the energy of its first excited state, is a parameter of a critical importance in analysis of phase transitions and adiabatic quantum computation. We present a concrete technique to determine an upper bound for the energy gap of a Hamiltonian H
0 based on properties of the set of expectation values of H
0 and an additional auxiliary Hamiltonian V. This formalism can be applied to obtain an effective criterion of gaplessness, which we illustrate with a concrete example of the XY model —a physical system with vanishing energy gap.
Shakespeare’s Starlings
Authors: Fugate Lauren , Miller John MacNeill 
Published: November 2021

AbstractScientists, environmentalists, and nature writers often report that all common starlings (Sturnus vulgaris) in North America descend from a flock released in New York City in 1890 by Eugene Schieffelin, a man obsessed with importing all the birds mentioned by Shakespeare. This article uses the methods of literary history to investigate this popular anecdote. Today starlings are much despised as an invasive species that displaces native birds and does almost a billion dollars worth of damage to agriculture annually. Because of the starling’s pest status, the Schieffelin story is considered a cautionary tale about the dangers of ecological ignorance. Diving into the history of the Schieffelin story reveals, however, that it is almost entirely fictional. Tracing how its elements emerged and changed over a century of retelling clarifies how the story came to shore up uncertainties in the bird’s environmental history and to distract from the lack of data supporting the starling’s supposedly disastrous impacts. In explaining how a fiction repeated over time attained the status of fact in debates about invasive species, this literary history suggests humanistic methods can serve as useful tools for understanding the value-laden narratives underpinning environmental attitudes and practices today.