bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal variants in Maturity Onset Diabetes of the Young (MODY) – A systematic review
Authors: Rafique Ibrar , Mir Asif , Saqib Muhammad Arif Nadeem , Naeem Muhammad , Marchand Luc , Polychronakos Constantin 
Published: November 2021

AbstractBackgroundMaturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms overlap with type 1 and type 2 diabetes. Reviews for clinical characteristics, diagnosis and treatments are available but a comprehensive list of genetic variants, is lacking. Therefore this study was designed to collect all the causal variants involved in MODY, reported to date.MethodsWe searched PubMed from its date of inception to December 2019. The search terms we used included disease names and name of all the known genes involved. The ClinVar database was also searched for causal variants in the known 14 MODY genes.ResultsThe record revealed 1647 studies and among them, 326 studies were accessed for full-text. Finally, 239 studies were included, as per our inclusion criteria. A total of 1017 variants were identified through literature review and 74 unpublished variants from Clinvar database. The gene most commonly affected wasGCK, followed byHNF1a. The traditional Sanger sequencing was used in 76 % of the cases and 65 % of the studies were conducted in last 10 years. Variants from countries like Jordan, Oman and Tunisia reported that the MODY types prevalent worldwide were not common in their countries.ConclusionsWe expect that this paper will help clinicians interpret MODY genetics results with greater confidence. Discrepancies in certain middle-eastern countries need to be investigated as other genes or factors, like consanguinity may be involved in developing diabetes.
What’s suffering got to do with it? A qualitative study of suffering in the context of Medical Assistance in Dying (MAID)
Authors: Pesut Barbara , Wright David Kenneth , Thorne Sally , Hall Margaret I. , Puurveen Gloria , Storch Janet , Huggins Madison 
Published: November 2021

AbstractBackgroundIntolerable suffering is a common eligibility requirement for persons requesting assisted death, and although suffering has received philosophic attention for millennia, only recently has it been the focus of empirical inquiry. Robust theoretical knowledge about suffering is critically important as modern healthcare provides persons with different options at end-of-life to relieve suffering. The purpose of this paper is to present findings specific to the understanding and application of suffering in the context of MAID from nurses’ perspectives.MethodsA longitudinal qualitative descriptive study using semi-structured telephone interviews. Inductive analysis was used to construct a thematic account. The study received ethical approval and all participants provided written consent.ResultsFifty nurses and nurse practitioners from across Canada were interviewed. Participants described the suffering of dying and provided insights into the difficulties of treating existential suffering and the iatrogenic suffering patients experienced from long contact with the healthcare system. They shared perceptions of the suffering that leads to a request for MAID that included the unknown of dying, a desire for predictability, and the loss of dignity. Eliciting the suffering story was an essential part of nursing practice. Knowledge of the story allowed participants to find the balance between believing that suffering is whatever the persons says it is, while making sure that the MAID procedure was for the right person, for the right reason, at the right time. Participants perceived that the MAID process itself caused suffering that resulted from the complexity of decision-making, the chances of being deemed ineligible, and the heighted work of the tasks of dying.ConclusionsHealthcare providers involved in MAID must be critically reflective about the suffering histories they bring to the clinical encounter, particularly iatrogenic suffering. Further, eliciting the suffering stories of persons requesting MAID requires a high degree of skill; those involved in the assessment process must have the time and competency to do this important role well. The nature of suffering that patients and family encounter as they enter the contemplation, assessment, and provision of MAID requires further research to understand it better and develop best practices.
Specialist palliative care teams and characteristics related to referral rate: a national cross-sectional survey among hospitals in the Netherlands
Authors: Boddaert M.S. , Stoppelenburg A. , Hasselaar J. , van der Linden Y.M. , Vissers K.C.P. , Raijmakers N.J.H. , Brom L. 
Published: November 2021

Abstract
Background
Specialist palliative care teams (SPCTs) in hospitals improve quality of life and satisfaction with care for patients with advanced disease. However, referrals to SPCTs are often limited. To identify areas for improvement of SPCTs’ service penetration, we explored the characteristics and level of integration of palliative care programmes and SPCTs in Dutch hospitals and we assessed the relation between these characteristics and specialist palliative care referral rates.

Methods
We performed a secondary analysis of a national cross-sectional survey conducted among hospitals in the Netherlands from March through May 2018. For this survey, a previously developed online questionnaire, containing 6 consensus-based integration indicators, was sent to palliative care programme leaders in all 78 hospitals. For referral rate we calculated the number of annual inpatient referrals to the SPCT as a percentage of the number of total annual hospital admissions. Referral rate was dichotomized into high (≥ third quartile) and low (< third quartile). Characteristics of SPCTs with high and low referral rate were compared using univariate analyses. P-values < 0.05 were considered significant.

Results
In total, 63 hospitals (81%) participated in the survey, of which 62 had an operational SPCT. The palliative care programmes of these hospitals consisted of inpatient consultation services (94%), interdisciplinary staffing (61%), outpatient clinics (45%), dedicated acute care beds (21%) and community-based palliative care (27%). The median referral rate was 0.56% (IQR 0.23–1.0%), ranging from 0 to 3.7%. Comparing SPCTs with high referral rate (≥1%, n = 17) and low referral rate (< 1%, n = 45) showed significant differences for SPCTs’ years of existence, staffing, their level of education, participation in other departments’ team meetings, provision of education and conducting research. With regard to integration, significant differences were found for the presence of outpatient clinics and timing of referrals.

Conclusion
In the Netherlands, palliative care programmes and specialist palliative care teams in hospitals vary in their level of integration and development, with more mature teams showing higher referral rates. Appropriate staffing, dedicated outpatient clinics, education and research appear means to improve service penetration and timing of referral for patients with advanced diseases.
IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis
Authors: Vergis N. , Patel V. , Bogdanowicz K. , Czyzewska-Khan J. , Fiorentino F. , Day E. , Cross M. , Foster N. , Lord E. , Goldin R. , Forrest E. , Thursz M. 
Published: November 2021

Abstract
Background
Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this study is to explore the potential benefits of the IL-1β antibody, canakinumab, in the treatment of AH.

Methods
This is a multicentre, double-blind, randomised placebo-controlled trial. Participants will be diagnosed with AH using clinical criteria. Liver biopsy will then confirm that all histological features of AH are present. Up to 58 participants will be recruited into two groups from 15 centres in the UK. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is the difference between groups in the proportion of patients demonstrating histological improvement and will compare histological appearances at baseline with appearances at 28 days to assign a category of “improved” or “not improved”. Patients with evidence of ongoing disease activity will receive a second infusion of canakinumab or placebo. Participants will be followed up for 90 days. Secondary outcomes include mortality and change in MELD score at 90 days.

Discussion
This phase II study will explore the benefits of the IL-1β antibody, canakinumab, in the treatment of AH to provide proof of concept that inhibition of IL-1β signalling may improve histology and survival for patients with AH.

Trial registration
EudraCT 2017-003724-79. Prospectively registered on 13 April 2018.
Patient and public involvement (PPI) in prisons: the involvement of people living in prison in the research process – a systematic scoping review
Authors: Treacy Samantha , Martin Steven , Samarutilake Nelum , Van Bortel Tine 
Published: November 2021

Abstract
Background
Patient and Public Involvement (PPI) in health and social care research is increasingly prevalent and is promoted in policy as a means of improving the validity of research. This also applies to people living in prison and using social care services. Whilst evidence for the effectiveness of PPI was limited and reviews of its application in prisons were not found, the infancy of the evidence base and moral and ethical reasons for involvement mean that PPI continues to be advocated in the community and in prisons.

Objectives
To conduct a review of the literature regarding the involvement of people or persons living in prison (PLiP) in health and social care research focused on: (i) aims; (ii) types of involvement; (iii) evaluations and findings; (iv) barriers and solutions; and (v) feasibility of undertaking a systematic review.

Methods
A systematic scoping review was undertaken following Arksey and O’Malley’s (International Journal of Social Research Methodology 8: 19-32, 2005) five-stage framework. A comprehensive search was conducted involving ten electronic databases up until December 2020 using patient involvement and context related search terms. A review-specific spreadsheet was created following the PICO formula, and a narrative synthesis approach was taken to answer the research questions. PRISMA guidelines were followed in reporting.

Results
39 papers were selected for inclusion in the review. The majority of these took a ‘participatory’ approach to prisoner involvement, which occurred at most stages during the research process except for more ‘higher’ level research operations (funding applications and project management), and only one study was led by PLiPs. Few studies involved an evaluation of the involvement of PLiP, and this was mostly PLiP or researcher reflections without formal or independent analysis, and largely reported a positive impact. Barriers to the involvement of PLiP coalesced around power differences and prison bureaucracy.

Conclusion
Given the very high risk of bias arising from the available ‘evaluations’, it was not possible to derive firm conclusions about the effectiveness of PLiP involvement in the research process. In addition, given the state of the evidence base, it was felt that a systematic review would not be feasible until more evaluations were undertaken using a range of methodologies to develop the field further.
Role of Cel5H protein surface amino acids in binding with clay minerals and measurements of its forces
Authors: Math Renukaradhya K. , Bharatham Nagakumar , Javaregowda Palaksha K. , Yun Han Dae 
Published: November 2021

AbstractOur previous study on the binding activity between Cel5H and clay minerals showed highest binding efficiency among other cellulase enzymes cloned. Here, based on previous studies, we hypothesized that the positive amino acids on the surface of Cel5H protein may play an important role in binding to clay surfaces. To examine this, protein sequences of Bacillus licheniformis Cel5H (BlCel5H) and Paenibacillus polymyxa Cel5A (PpCel5A) were analyzed and then selected amino acids were mutated. These mutated proteins were investigated for binding activity and force measurement via atomic force microscopy (AFM). A total of seven amino acids which are only present in BlCel5H but not in PpCel5A were selected for mutational studies and the positive residues which are present in both were omitted. Of the seven selected surface lysine residues, only three mutants K196A(M2), K54A(M3) and K157T(M4) showed 12%, 7% and 8% less clay mineral binding ability, respectively compared with wild-type. The probable reason why other mutants did not show altered binding efficiency might be due to relative location of amino acids on the protein surface. Meanwhile, measurement of adhesion forces on mica sheets showed a well-defined maximum at 69 ± 19 pN for wild-type, 58 ± 19 pN for M2, 53 ± 19 pN for M3, and 49 ± 19 pN for M4 proteins. Hence, our results demonstrated that relative location of surface amino acids of Cel5H protein especially positive charged amino acids are important in the process of clay mineral-protein binding interaction through electrostatic exchange of charges.
Ossicular reconstruction of incudo-stapedial joint by glass ionomer—a study of 24 cases
Authors: Juvekar Meenesh , Sarkar Baisali 
Published: November 2021

Abstract
Background
Chronic otitis media is one of the major health issues worldwide resulting in partial or complete loss of conductive hearing mechanism including the tympanic membrane and ossicular assembly. The aim of the study is to assess hearing improvement after reconstructing the incudo-stapedial joint with glass ionomer cement. Here, a prospective observational study was done in a tertiary care hospital. Patients of chronic mucosal otitis media were operated, and intraoperatively incudo-stapedial joint discontinuity was restored using glass ionomer cement. Post-operative follow-up was done at 1-month, 3-month, 6-month, and 1-year intervals, and hearing was evaluated by doing pure tone audiometry with air conduction at 0.5, 1, 2, 3, 4, 6, and 8 kHz and bone conduction at 0.5, 1, 2, 3, and 4 kHz. Tabulation was done by calculating the air-bone gap in each patient.

Results
In our study, the patients showed statistically significant improvement in air conduction thresholds and near closure of air-bone gap post-operatively. The mean AC threshold is 15 dB with 91.67% patients having closure of ABG < 20 dB at the end of the 3rd month. Hearing was also evaluated at 6-month and 1-year intervals, which showed good improvement in hearing levels.

Conclusions
Glass ionomer is a simple, physiological, and cost-effective method of tympano-ossicular reconstruction with certain significant post-operative hearing improvement.
Study of kerosene caustic wash process for jet fuel production
Authors: Abdelhamid Ahmed Mohamed Selim , Mustafa Hamdy Abdel-Aziz 
Published: November 2021

AbstractCaustic wash is one of many industrial processes that are used to produce jet fuel. In this study, an analysis of the key parameters of the kerosene caustic wash process was conducted to improve the total performance of the treatment process. The investigated parameters are caustic concentration (from 0.03 to 3.0 wt%), caustic volume (from 110% of theoretical to 250%), number of treatment stages (one and two stages), wash water type (demineralized water and alkaline soft water), and wash water volume (10% and 30% of kerosene feed volume). Results revealed that the reaction between sodium hydroxide and naphthenic acids is a diffusion-controlled chemical reaction. The diluted caustic solutions (0.5 wt%) are better than the concentrated ones (3 wt%). Higher excess caustic volume has a slight effect on kerosene acidity. Performing the caustic treatment process in one stage is sufficient, and the two-stage process has no effect on acidity. Washing caustic-treated kerosene with demineralized water (pH=7) has a slight adverse effect on kerosene acidity. Increasing the demineralized water volume results in a slight increase in the acidity of the treated kerosene. Wash water should be slightly alkaline (pH 7.5–8) to prevent the reverse reaction of sodium naphthenates back into naphthenic acid. Increasing wash water volume (more than 10 vol% of kerosene feed) has no noticeable effect on the water content of treated kerosene.
Standards of Care
Authors: Velocci Beans 
Published: November 2021

AbstractIn the 1950s and early 1960s, Harry Benjamin and his colleague Elmer Belt corresponded at length about which transsexuals they would and would not approve for genital surgery. Benjamin defined transsexuality primarily through a desire for medical transition, but merely being a transsexual in this definition did not automatically result in surgical eligibility. Benjamin and Belt remained preoccupied with the possibility that transsexuals would regret their surgeries and seek legal or personal revenge, and thus their assessments of who should have surgery focused more on the possibility of a bad outcome than adherence to gender norms or classification as transsexual. The informal clinical practices they worked out to protect themselves in these early years of American trans medicine would ultimately go on to structure more formalized Standards of Care. Benjamin and Belt's fears, and their resulting decision-making processes, thus played a crucial role in the production of the category “transsexual.” Throughout their correspondence and clinical practice, the transsexual emerged as a threat to medical providers, and a subject incapable of making their own bodily decisions, needing to be protected from themselves. While assessments of gender identity and gendered behavior factored into these decisions, their decisions about who might regret transition treated gender as primarily practical and functional, and made an unshakable internal gender identity a necessary but insufficient criterion for granting a patient access to surgery.
Advances in diet-induced rodent models of metabolically acquired peripheral neuropathy
Authors: Eid Stéphanie A. , Feldman Eva L. 
Published: November 2021

ABSTRACT
Peripheral neuropathy (PN) is a severe complication that affects over 30% of prediabetic and 60% of type 2 diabetic (T2D) patients. The metabolic syndrome is increasingly recognized as a major driver of PN. However, basic and translational research is needed to understand the mechanisms that contribute to nerve damage. Rodent models of diet-induced obesity, prediabetes, T2D and PN closely resemble the human disease and have proven to be instrumental for the study of PN mechanisms. In this Perspective article, we focus on the development, neurological characterization and dietary fat considerations of diet-induced rodent models of PN. We highlight the importance of investigating sex differences and discuss some of the challenges in translation from bench to bedside, including recapitulating the progressive nature of human PN and modeling neuropathic pain. We emphasize that future research should overcome these challenges in the quest to better mimic human PN in animal models.
Aerobic scope does matter in the temperature–size rule, but only under optimal conditions
Authors: Walczyńska Aleksandra , Sobczyk Mateusz 
Published: November 2021

ABSTRACT
We united theoretical predictions of the factors responsible for the evolutionary significance of the temperature–size rule (TSR). We assumed that (i) the TSR is a response to temperature-dependent oxic conditions, (ii) body size decrease is a consequence of cell shrinkage in response to hypoxia, (iii) this response enables organisms to maintain a wide scope for aerobic performance, and (iv) it prevents a decrease in fitness. We examined three clones of the rotifer Lecane inermis exposed to three experimental regimes: mild hypoxia, severe hypoxia driven by too high of a temperature, and severe hypoxia driven by an inadequate oxygen concentration. We compared the following traits in normoxia- and hypoxia-exposed rotifers: nuclear size (a proxy for cell size), body size, specific dynamic action (SDA, a proxy of aerobic metabolism) and two fitness measures, the population growth rate and eggs/female ratio. The results showed that (i) under mildly hypoxic conditions, our causative reasoning was correct, except that one of the clones decreased in body size without a decrease in nuclear size, and (ii) in more stressful environments, rotifers exhibited clone- and condition-specific responses, which were equally successful in terms of fitness levels. Our results indicate the importance of the testing conditions. The important conclusions were that (i) a body size decrease at higher temperatures enabled the maintenance of a wide aerobic scope under clone-specific, thermally optimal conditions, and (ii) this response was not the only option to prevent fitness reduction under hypoxia.
Comparison of different thresholds of PSA density for risk stratification of PI-RADSv2.1 categories on prostate MRI
Authors: Girometti Rossano , Giannarini Gianluca , Panebianco Valeria , Maresca Silvio , Cereser Lorenzo , De Martino Maria , Pizzolitto Stefano , Pecoraro Martina , Ficarra Vincenzo , Zuiani Chiara , Valotto Claudio 
Published: November 2021

Objectives:
To compare the effect of different PSA density (PSAD) thresholds on the accuracy for clinically significant prostate cancer (csPCa) of the Prostate Imaging Reporting And Data System v.2.1 (PI-RADSv2.1).

Methods:
We retrospectively included 123 biopsy-naïve men who underwent multiparametric magnetic resonance imaging (mpMRI) and transperineal mpMRI-targeted and systematic prostate biopsy between April 2019 and October 2020. mpMRI, obtained on a 3.0T magnet with a PI-RADSv2.1-compliant protocol, was read by two radiologists (&gt;1500/&gt;500 mpMRI examinations). csPCa was defined as International Society of Urogenital Pathology grading group ≥2. Receiver operating characteristic analysis was used to calculate per-index lesion sensitivity, specificity, and area under the curve (AUC) of PI-RADSv.2.1 categories after adjusting for PSAD ≥0.10,≥0.15, and ≥0.20 ng/mL ml−1. Per-adjusted category cancer detection rate (CDR) was calculated, and decision analysis performed to compare PSAD-adjusted PI-RADSv.2.1 categories as a biopsy trigger.

Results:
csPCa prevalence was 43.9%. PSAD-adjustment increased the CDR of PI-RADSv2.1 category 4. Sensitivity/specificity/AUC were 92.6%/53.6%/0.82 for unadjusted PI-RADS, and 85.2%/72.4%/0.84, 62.9%/85.5%/0.83, and 92.4%/53.6%/0.82 when adjusting PI-RADS categories for a 0.10, 0.15, and 0.20 ng/ml ml−1 PSAD threshold, respectively. Triggering biopsy for PI-RADS four lesions and PSAD ≥0.10 ng/mL ml−1 was the strategy with greatest net benefit at 30 and 40% risk probability (0.307 and 0.271, respectively).

Conclusions:
PI-RADSv2.1 category four with PSAD ≥0.10 ng/mL ml−1 was the biopsy-triggering cut-off with the highest net benefit in the range of expected prevalence for csPCa.

Advances in knowledge:
0.10 ng/mL ml−1 is the PSAD threshold with higher clinical utility in stratifying the risk for prostate cancer of PI-RADSv.2.1 categories.