bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Because it is a rare disease…it needs to be brought to attention that there are things out of the norm”: a qualitative study of patient and physician experiences of Wilson disease diagnosis and management in the US
Authors: Bailey Karen M , Sahota Navdeep , To Uyen , Hedera Peter 
Published: June 2023

Abstract
Background
Wilson disease (WD) is a genetic disorder of copper metabolism that leads to copper accumulation in various organs, primarily the liver and brain, resulting in heterogenous hepatic, neurologic, and psychiatric symptoms. Diagnosis can occur at any age, requiring lifelong treatment, which can involve liver transplantation. This qualitative study aims to understand the wider patient and physician experience of the diagnosis and management of WD in the US.

Methods
Primary data were collected from 1:1 semi structured interviews with US-based patients and physicians and thematically analyzed with NVivo.

Results
Twelve WD patients and 7 specialist WD physicians (hepatologists and neurologists) were interviewed. Analysis of the interviews revealed 18 themes, which were organized into 5 overarching categories: (1) Diagnosis journey, (2) Multidisciplinary approach, (3) Medication, (4) The role of insurance, and (5) Education, awareness, and support. Patients who presented with psychiatric or neurological symptoms reported longer diagnostic journeys (range 1 to 16 years) than those presenting with hepatic symptoms or through genetic screening (range 2 weeks to 3 years). All were also affected by geographical proximity to WD specialists and access to comprehensive insurance. Exploratory testing was often burdensome for patients, but receipt of a definitive diagnosis led to relief for some. Physicians emphasized the importance of multidisciplinary teams beyond hepatology, neurology, and psychiatry and recommended a combination of chelation, zinc, and a low-copper diet; however, only half the patients in this sample were on a chelator, and some struggled to access prescription zinc due to insurance issues. Caregivers often advocated for and supported adolescents with their medication and dietary regimen. Patients and physicians recommended more education and awareness for the healthcare community.

Conclusions
WD requires the coordination of care and medication among several specialists due to its complex nature, but many patients do not have access to multiple specialties due to geographical or insurance barriers. Because some patients cannot be treated in Centers of Excellence, easy access to reliable and up-to-date information is important to empower physicians, patients, and their caregivers in managing the condition, along with general community outreach programs.
CATI: an efficient gene integration method for rodent and primate embryos by MMEJ suppression
Authors: Chen Hongyu , Liu Xingchen , Li Lanxin , Tan Qingtong , Li Shiyan , Li Li , Li Chunyang , Fu Jiqiang , Lu Yong , Wang Yan , Sun Yidi , Luo Zhen-Ge , Lu Zongyang , Sun Qiang , Liu Zhen 
Published: June 2023

AbstractThe efficiency of homology-directed repair (HDR) plays a crucial role in the development of animal models and gene therapy. We demonstrate that microhomology-mediated end-joining (MMEJ) constitutes a substantial proportion of DNA repair during CRISPR-mediated gene editing. Using CasRx to downregulate a key MMEJ factor, Polymerase Q (Polq), we improve the targeted integration efficiency of linearized DNA fragments and single-strand oligonucleotides (ssODN) in mouse embryos and offspring. CasRX-assisted targeted integration (CATI) also leads to substantial improvements in HDR efficiency during the CRISPR/Cas9 editing of monkey embryos. We present a promising tool for generating monkey models and developing gene therapies for clinical trials.
Improvement in patient-reported outcomes and work productivity following 3-year ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: results from the PsABio real-world study
Authors: Gossec Laure , Siebert Stefan , Bergmans Paul , de Vlam Kurt , Gremese Elisa , Joven-Ibáñez Beatríz , Korotaeva Tatiana V. , Lavie Frederic , Noël Wim , Nurmohamed Michael T. , Sfikakis Petros P. , Sharaf Mohamed , Theander Elke , Smolen Josef S. 
Published: June 2023

Abstract
Background
To evaluate the real-world effect of the IL-12/23 inhibitor ustekinumab or of a tumour necrosis factor inhibitor (TNFi) on patient-reported outcomes (PRO) and their association with effectiveness endpoints in psoriatic arthritis (PsA) patients over 3 years.

Methods
In PsABio (NCT02627768), a prospective, observational study, patients with PsA that were prescribed first- to third-line ustekinumab or a TNFi, and remained on that drug for 3 years, were analysed for change in baseline in PROs (EuroQol-5 dimensions health state VAS [EQ-5D VAS], 12-item Psoriatic Arthritis Impact of Disease questionnaire [PsAID-12; range 0–10], Work Productivity and Activity Impairment for Psoriatic Arthritis questionnaire [WPAI; results expressed as a percentage for each domain]), and the association between PROs and WPAI with effectiveness endpoints, clinical disease activity index for psoriatic arthritis (cDAPSA), low disease activity (LDA)/remission, minimal disease activity (MDA) and very low disease activity (VLDA).

Results
In 437 patients (mean age 49.1 years, 47.8% female), at 3 years, ustekinumab and TNFi treatment led to comparable improvements in EQ-5D VAS; mean change from baseline (95% confidence intervals [CI]) was 11.0 (6.5; 15.4) and 18.9 (14.0; 23.9), respectively. Both groups improved PsAID-12 after 3 years; mean change from baseline (95% CI) was −2.9 (−3.2; −2.5) and −3.5 (−3.9; −3.2), respectively. At baseline, due to their PsA, TNFi-treated patients had lower work productivity compared to ustekinumab-treated patients; mean productivity reduction (95% CI) was 58.8 [52.4; 65.2] and 43.3 [35.6; 51.1]. Over 3 years, TNFi-treated patients had a greater improvement in work productivity compared to ustekinumab-treated patients, ultimately leaving work productivity to be comparable between groups; mean improvement (95% CI) was 44.5% (38.4; 50.6) and 24.9% (15.8; 34.0), respectively. A similar trend was observed in activity impairment. Patients in both treatment groups who achieved effectiveness endpoints, cDAPSA LDA/remission, MDA, and VLDA had greater improvement in PROs and WPAI than patients who did not achieve these endpoints.

Conclusions
At 3 years, improvements in PROs following ustekinumab or TNFi treatment were generally comparable; however, TNFi-treated patients achieved a greater improvement in work productivity, although this group started from a lower baseline. Achievement of effectiveness endpoints, independent of treatment group, also improved PROs.

Trial registration
ClinicalTrials.gov, NCT02627768. Registered on 11 December 2015
More than skin-deep: visceral fat is strongly associated with disease activity, function and metabolic indices in psoriatic disease
Authors: Blake Tim , Gullick Nicola J. , Hutchinson Charles E. , Bhalerao Abhir , Wayte Sarah , Weedall Andrew , Barber Thomas M. 
Published: June 2023

Abstract
Objective
To compare body composition between patients with psoriatic disease (PsD), including cutaneous psoriasis (PsO) and psoriatic arthritis (PsA), and controls, and to explore associations between disease activity and measures of function and metabolic derangement.

Methods
Body composition was assessed by air displacement plethysmography (ADP) and MRI-derived fat segmentation using an automated pipeline (FatSegNet). Function was assessed by Health Assessment Questionnaire (HAQ) and metabolic status by fasting lipid profile, insulin and adiponectin. Active and inactive PsO and PsA were defined by body surface area (BSA) and Psoriasis Area Severity Index (PASI) and minimal disease activity (MDA), respectively.

Results
Thirty patients (median disease duration 15 years; median age 52 years) and 30 BMI-matched controls were enrolled. Compared with controls, all MRI-derived body composition parameters—whole-body volume, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal adipose tissue (AAT), VAT/AAT and VAT/SAT—were higher in the PsD group, specifically, those with active disease. Body mass, body fat, whole-body volume and whole-body VAT were correlated with higher triglycerides, cholesterol:HDL (high-density lipoprotein), insulin resistance and lower adiponectin as well as higher HAQ and lower MDA.

Conclusions
In this pilot study, patients with PsD revealed excessive total adipose tissue and a greater volume of metabolically unfavourable ectopic fat, including VAT, compared with BMI-matched controls, which also correlated with HAQ, disease activity and overall dysmetabolism. We also provide the first evidence in patients with PsD for the clinical application of FatSegNet: a novel, automated and rapid deep learning pipeline for providing accurate MRI-based measurement of fat segmentation. Our findings suggest the need for a more integrated approach to the management of PsD, which considers both the metabolic and inflammatory burden of disease. More specifically, visceral fat is a surrogate marker of uncontrolled PsD and may be an important future target for both pharmacological and lifestyle interventions.
Differential response to donepezil in MRI subtypes of mild cognitive impairment
Authors: Diaz-Galvan Patricia , Lorenzon Giulia , Mohanty Rosaleena , Mårtensson Gustav , Cavedo Enrica , Lista Simone , Vergallo Andrea , Kantarci Kejal , Hampel Harald , Dubois Bruno , Grothe Michel J. , Ferreira Daniel , Westman Eric 
Published: June 2023

Abstract
Background
Donepezil is an approved therapy for the treatment of Alzheimer’s disease (AD). Results across clinical trials have been inconsistent, which may be explained by design-methodological issues, the pathophysiological heterogeneity of AD, and diversity of included study participants. We investigated whether response to donepezil differs in mild cognitive impaired (MCI) individuals demonstrating different magnetic resonance imaging (MRI) subtypes.

Methods
From the Hippocampus Study double-blind, randomized clinical trial, we included 173 MCI individuals (donepezil = 83; placebo = 90) with structural MRI data, at baseline and at clinical follow-up assessments (6–12-month). Efficacy outcomes were the annualized percentage change (APC) in hippocampal, ventricular, and total grey matter volumes, as well as in the AD cortical thickness signature. Participants were classified into MRI subtypes as typical AD, limbic-predominant, hippocampal-sparing, or minimal atrophy at baseline. We primarily applied a subtyping approach based on continuous scale of two subtyping dimensions. We also used the conventional categorical subtyping approach for comparison.

Results
Donepezil-treated MCI individuals showed slower atrophy rates compared to the placebo group, but only if they belonged to the minimal atrophy or hippocampal-sparing subtypes. Importantly, only the continuous subtyping approach, but not the conventional categorical approach, captured this differential response.

Conclusions
Our data suggest that individuals with MCI, with hippocampal-sparing or minimal atrophy subtype, may have improved benefit from donepezil, as compared with MCI individuals with typical or limbic-predominant patterns of atrophy. The newly proposed continuous subtyping approach may have advantages compared to the conventional categorical approach. Future research is warranted to demonstrate the potential of subtype stratification for disease prognosis and response to treatment.

Trial registration
ClinicalTrial.gov NCT00403520. Submission Date: November 21, 2006.
Promises and Perils of Rortian Conversation
Authors: Bono James J. 
Published: June 2023

AbstractAs a contribution to the Common Knowledge symposium “Whatever Happened to Richard Rorty?,” this essay elucidates how Isabelle Stengers's signature idea of an “ecology of practices” offers a way to establish claims to expertise and—within limits that are, in effect, the limits of specific scientific practices—claims of authority within science that Rorty would have denied. The problems facing Rorty's understanding of science also imperil his vision of a society admirably seeking to realize what he calls “social hope.” Once again, Stengers's ecology of practices, together with her cosmopolitical perspective, offers grounds for questioning Rorty's utopian belief that endless conversation should lead to continual expansion of the “we” who constitute liberal society. Her idea also provides tools for engaging, in mutually respectful and sensitive encounters that reopen prospects for social hope, the multiplicity of voices, perspectives, and practices of the “others” who have been excluded from liberal society.
Rorty Reframed
Authors: Fuller Steve 
Published: June 2023

Abstract
Richard Rorty is easily cast as the intellectual godfather of our post-truth condition. But unlike Nicholas Gaskill, whose article in Common Knowledge 28, no. 3, has engendered a continuing symposium in the journal, Professor Fuller sees Rorty's role as being to his credit rather than detriment. Rorty extended W. B. Gallie's idea of “essentially contested concepts” from the moral and political spheres to the epistemic, thereby rendering such terms as truth, reason, and evidence inherently vague, which means that they are defined not a priori but only in the context of exemplary concrete cases. Doing so invariably results in a “redescription” of what is observed that explains the “meta” level of understanding that philosophy brings to whatever it discusses. In this sense, all that the post-truth condition does is turn everyone into a philosopher.
Non-linear properties of the Achilles tendon determine ankle impedance over a broad range of activations in humans
Authors: Jakubowski Kristen L. , Ludvig Daniel , Perreault Eric J. , Lee Sabrina S. M. 
Published: June 2023

ABSTRACT
Regulating ankle mechanics is essential for controlled interactions with the environment and rejecting unexpected disturbances. Ankle mechanics can be quantified by impedance, the dynamic relationship between an imposed displacement and the torque generated in response. Ankle impedance in the sagittal plane depends strongly on the triceps surae and Achilles tendon, but their relative contributions remain unknown. It is commonly assumed that ankle impedance is controlled by changing muscle activation and, thereby, muscle impedance, but this ignores that tendon impedance also changes with activation-induced loading. Thus, we sought to determine the relative contributions from the triceps surae and Achilles tendon during conditions relevant to postural control. We used a novel technique that combines B-mode ultrasound imaging with joint-level perturbations to quantify ankle, muscle and tendon impedance simultaneously across activation levels from 0% to 30% of maximum voluntary contraction. We found that muscle and tendon stiffness, the static component of impedance, increased with voluntary plantarflexion contractions, but that muscle stiffness exceeded tendon stiffness at very low loads (21±7 N). Above these loads, corresponding to 1.3% of maximal strength for an average participant in our study, ankle stiffness was determined predominately by Achilles tendon stiffness. At approximately 20% MVC for an average participant, ankle stiffness was 4 times more sensitive to changes in tendon stiffness than to changes in muscle stiffness. We provide the first empirical evidence demonstrating that the nervous system, through changes in muscle activations, leverages the non-linear properties of the Achilles tendon to increase ankle stiffness during postural conditions.
Prevalence of and factors associated with depression, anxiety and stress among adolescents in Bangladesh during the COVID-19 pandemic: A population-based study
Authors: Haque Md Atiqul , Anjum Afifa , Mousum Sabrina , Salwa Marium , Ratan Zubair Ahmed , Khan Md Maruf Haque , Islam Mohammad Tanvir , Ahmed Helal Uddin , Amin Md Robed , Mamun Mohammad Abdullah Al 
Published: June 2023

Background: The COVID-19 pandemic has brought significant mental health challenges among adolescents in Bangladesh. This study aimed to investigate the prevalence of and associated factors of depression, anxiety and stress among adolescents of Bangladesh during the COVID-19 pandemic. Methods: This cross-sectional study used a two-stage cluster sampling procedure for collecting the sample. A total of 2030 adolescents were enrolled from urban and rural areas of all eight administrative divisions of Bangladesh. The Depression, Anxiety, and Stress-21 (DASS-21) scale was used to assess depression, anxiety, and stress in adolescents. In addition, data on sociodemographics, parenting style, food insecurity, and anthropometric measures were also obtained. Linear regression was done to measure the risk factors. Results: Depression, anxiety, and stress were identified in 18%, 14%, and 16% of adolescents, respectively. Sociodemographic characteristics such as female sex, higher age, urban resident, food insecurity, and poor parenting were significant risk factors for depression, anxiety, and stress during the COVID-19 pandemic. In addition, inconsistent parenting has been identified as a significant risk factor for depression only. Conclusions: During the COVID-19 pandemic in Bangladesh, depression, anxiety, and stress are found quite common among adolescents. Therefore, necessary action is required to prevent the mental health epidemic from spreading.
Outcomes from the first dedicated diagnostic and interventional nephrology (DIN) service in a UK renal unit
Authors: Morrison Samuel , Lee Ji Ching , Brazell Madeline , Ayub Haroon , Marsden Joanna , Pollock Caitlin , Waterman Harry , Smith Abbey , Davies Simon , Brennan Sophie , Whitehead Jennifer , Sweeney Debra , Allan Carol , Dodds Margaret , McCloskey Sarah , Andrews James , Clark Rauri , Ahmed Saeed , Srivastava Shalabh 
Published: June 2023

Background: We report the clinical outcomes, operational and training model from the first diagnostic and interventional nephrology (DIN) department in a UK renal unit. Methods: Patient outcomes were evaluated for an array of diagnostic and therapeutic interventional procedures performed at the DIN unit, SDIN (the Sunderland Diagnostic and Intervention Unit), within the first year of its establishment. Data was retrospectively collected for the period beginning 1st October 2019 to 1st October 2020 for patients who underwent the following procedures: ultrasound guided renal biopsy, Tunnelled Dialysis Catheter (TDC) insertion and exchange, Peritoneal Dialysis (PD) catheter insertion/exchange, and Areteriovenous Fistula (AVF) Point of Care Ultrasound (POCUS). These figures were compared to the cohort from the one-year period pre-SDIN, between the 1st October 2018 and 31st September 2019. All results are expressed as mean and percentages unless otherwise specified. Results: Renal Biopsy: 104 biopsies were performed with an improvement in median waiting time from 12 to 7 days with 98.4% being diagnostic. Tunnelled Dialysis Catheters: 99 TDCs were inserted or exchanged with the catheters remaining in place for a mean duration of 156 days. We report an incidence of 2 infections per 1000 catheter days within the 90-day observation period. Peritoneal dialysis catheters: 16 PD catheters were inserted and they remained in place for an average of 153 days. Eleven (69%) catheters had no complications within the 28-day observation period, 3 (19%) catheters required manipulation. AVF POCUS: 279 AVF POCUS scans were performed during the SDIN period. The waiting time from referral to scan was reduced from a mean of 35 days to 2 days. Conclusions: A comprehensive DIN service leads to significant improvements in training, service and patient outcomes and would be an ideal model for wider adaptation across the UK renal units.
Case Report: Multiple atherosclerotic plaques at its extreme in synchrony
Authors: Toshniwal Saket , Sahai Isha , Ghosh Benumadhab , Chaturvedi Anuj , Agrawal Gajendra , Acharya Sourya , Kumar Sunil , Khadse Satish , Khurana Kashish 
Published: June 2023

Peripheral vascular disease in association with renal artery stenosis is an important association which predicts the severity of the disease. An increase in the number of vessels affected by peripheral vascular disease increases the chances of renal artery stenosis. In our case, the patient had primarily presented with anginal chest pain with complaints of claudication which on further investigation was diagnosed to be a triple vessel coronary artery disease along with bilateral subclavian and bilateral renal stenosis. On detailed history taking, risk factors like hypertension and chronic smoking was found to be present in our case which predisposed to peripheral artery disease secondary to atherosclerosis which was diagnosed on further investigations. Although the association of renal artery stenosis is not very rare in cases of severe peripheral vascular diseases, the presence of a triple vessel coronary artery disease in synchrony is what makes it unique. Take away lesson from this case report is importance of early diagnosis of dyslipidemia causing atherosclerosis and its complications. Multiple atherosclerotic lesions in synchrony i.e, bilateral renal artery stenosis with bilateral subclavian artery stenosis with coronary artery triple vessel atherosclerotic disease like in our case and its severity should create awareness among health care individuals and early treatment measures including lifestyle modifications should be considered to avoid such drastic events.
Identification of predictive factors for surgical site infections in gastrointestinal surgeries: A retrospective cross-sectional study in a resource-limited setting
Authors: Al-hajri Abdu , Ghabisha Saif , Ahmed Faisal , Al-wageeh Saleh , Badheeb Mohamed , Alyhari Qasem , Altam Abdulfattah , Alsharif Afaf 
Published: June 2023

Background: Surgical site infection (SSI), albeit infrequent, drastically impact the quality of care. This article endeavors to investigate the predictive factors of SSIs following surgical interventions that involve the gastrointestinal (GI) tract within a single institution in a resource-limited setting. Methods: Over seven years from June 2015 to Oct 2022, patients who underwent GI surgery and developed SSI were retrospectively matched with an unaffected case-control cohort of patients. Standardized techniques for wound culture, laboratory evaluation of bacterial isolates, and antibiotic susceptibility tests were employed. Logistic regression analysis was utilized to investigate the predictive factors associated with 30-day postoperative SSI. Results: A total of 525 patients who underwent GI surgical procedures were included, among whom, 79 (15%) developed SSI. The majority of SSIs were superficial (67.10%), Escherichia coli was the most commonly isolated bacterium (54.4%), and a high percentage of multidrug-resistant organisms were observed (63.8%). In multivariate Cox regression analysis, illiteracy (Odds ratio [OR]:40.31; 95% confidence interval [CI]: 9.54-170.26), smoking (OR: 21.15; 95% CI: 4.63-96.67), diabetes (OR: 5.07; 95% CI: 2.27-11.35), leukocytosis (OR: 2.62; 95% CI: 1.24-5.53), hypoalbuminemia (OR: 3.70; 95% CI: 1.35-10.16), contaminated and dirty wounds (OR: 6.51; 95% CI:1.62-26.09), longer operative time (OR: 1.02; 95% CI: 1.01-1.03), emergency operations (OR: 12.58; 95% CI: 2.91-54.30), and extending antibiotic prophylaxis duration (OR: 3.01; 95% CI: 1.28-7.10) were the independent risk factors for SSI (all p < 0.05). Conclusions: This study highlights significant predictors of SSI, including illiteracy, smoking, diabetes, leukocytosis, hypoalbuminemia, contaminated and dirty wounds, longer operative time, emergency operations, and extending antibiotic prophylaxis duration. Identifying these risk factors can help surgeons adopt appropriate measures to reduce postoperative SSI and improve the quality of surgical care, especially in a resource-limited setting with no obvious and strict policy for reducing SSI.